Trial Outcomes & Findings for Scleroderma: Cyclophosphamide or Transplantation (NCT NCT00114530)

Last Updated: 2023-04-12

Results Overview

The GRCS is an analytic tool that accounts for multiple disease manifestations simultaneously. It does not measure clinical disease activity or severity but reflects how participants compared to one another based on a hierarchy of ordered outcomes: death, event-free survival (EFS), forced vital capacity (FVC), Health Assessment Questionnaire - Disability Index (HAQ-DI), and Modified Rodnan Skin Score (mRSS). Participants alive ranked higher than those who died; those who survived event-free ranked higher than EFS failures. EFS failure included death, respiratory failure (decrease from baseline of \>30% in DLCO % predicted or \>20% in FVC % predicted ), renal failure (chronic dialysis \> 6 month or renal transplant), or cardiac failure (clinical congestive heart failure or left ventricular ejection fraction \<30%). The lowest 3 GRCS components are ordinal; improvement, stability, or worsening from baseline (±10% change in FVC % predicted, ±0.4 change in HAQ-DI, ±25% change in mRSS).

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

75 participants

Primary outcome timeframe

54 Months Post-Randomization

Results posted on

2023-04-12

Participant Flow

Participant milestones

Participant milestones
Measure	mHSCT Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).
Overall Study STARTED	36	39
Overall Study COMPLETED	27	19
Overall Study NOT COMPLETED	9	20

Reasons for withdrawal

Reasons for withdrawal
Measure	mHSCT Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).
Overall Study Death	3	11
Overall Study Lost to Follow-up	1	1
Overall Study Physician Decision	1	1
Overall Study Withdrawal by Subject	2	6
Overall Study Breast Cancer	1	0
Overall Study Subject decision after endpoint failure	0	1
Overall Study Ineligible	1	0

Baseline Characteristics

Scleroderma: Cyclophosphamide or Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	mHSCT n=36 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=39 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	Total n=75 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	35 Participants n=5 Participants	38 Participants n=7 Participants	73 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	44.9 years STANDARD_DEVIATION 10.90 • n=5 Participants	46.9 years STANDARD_DEVIATION 10.43 • n=7 Participants	45.9 years STANDARD_DEVIATION 10.63 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	29 Participants n=7 Participants	48 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	10 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	32 Participants n=5 Participants	34 Participants n=7 Participants	66 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	29 Participants n=5 Participants	31 Participants n=7 Participants	60 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Canada	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United States	35 participants n=5 Participants	37 participants n=7 Participants	72 participants n=5 Participants
Health Assessment Questionnaire - Disability Index (HAQ-DI)	1.2 units on a scale STANDARD_DEVIATION 0.65 • n=5 Participants	1.4 units on a scale STANDARD_DEVIATION 0.86 • n=7 Participants	1.3 units on a scale STANDARD_DEVIATION 0.77 • n=5 Participants
Short Form 36 Health Survey (SF-36) Physical Component Score	29.5 units on a scale STANDARD_DEVIATION 9.20 • n=5 Participants	28.9 units on a scale STANDARD_DEVIATION 9.46 • n=7 Participants	29.2 units on a scale STANDARD_DEVIATION 9.27 • n=5 Participants
Short Form 36 Health Survey (SF-36) Mental Component Score	44.7 units on a scale STANDARD_DEVIATION 10.70 • n=5 Participants	44.6 units on a scale STANDARD_DEVIATION 9.86 • n=7 Participants	44.6 units on a scale STANDARD_DEVIATION 10.21 • n=5 Participants
Diffusion in Liters of Carbon Monoxide (DLCO) (Percent-Predicted)	53.9 Percent predicted STANDARD_DEVIATION 7.63 • n=5 Participants	52.7 Percent predicted STANDARD_DEVIATION 8.19 • n=7 Participants	53.3 Percent predicted STANDARD_DEVIATION 7.90 • n=5 Participants
Forced Vital Capacity (FVC) (Percent-Predicted)	74.5 percent predicted STANDARD_DEVIATION 14.77 • n=5 Participants	73.8 percent predicted STANDARD_DEVIATION 16.98 • n=7 Participants	74.2 percent predicted STANDARD_DEVIATION 15.86 • n=5 Participants
Modified Rodnan Skin Score (mRSS)	28.5 units on a scale STANDARD_DEVIATION 8.72 • n=5 Participants	30.8 units on a scale STANDARD_DEVIATION 10.55 • n=7 Participants	29.7 units on a scale STANDARD_DEVIATION 9.72 • n=5 Participants
Disease-Modifying Anti-Rheumatic Drug (DMARD) Use Within 6 Months of Randomization	26 Participants n=5 Participants	25 Participants n=7 Participants	51 Participants n=5 Participants
Disease-Modifying Anti-Rheumatic Drug (DMARD) Use	27 Participants n=5 Participants	32 Participants n=7 Participants	59 Participants n=5 Participants

PRIMARY outcome

Timeframe: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Outcome measures

Outcome measures
Measure	mHSCT n=36 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=39 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Global Rank Composite Score (GRCS) (Month 54, ITT)	17.0 Sum of subject-pair comparison scores Interval -58.0 to 52.0	-6.0 Sum of subject-pair comparison scores Interval -58.0 to 52.0	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Population: Per-protocol (PP). The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm, or receiving at least 9 of 12 planned doses in the cyclophosphamide arm.

Outcome measures

Outcome measures
Measure	mHSCT n=33 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=34 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Global Rank Composite Score (GRCS) (Month 54, PP)	16 Sum of subject-pair comparison scores Interval -56.0 to 46.0	-11.0 Sum of subject-pair comparison scores Interval -56.0 to 46.0	—	—

SECONDARY outcome

Timeframe: 48 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Outcome measures

Outcome measures
Measure	mHSCT n=36 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=39 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Global Rank Composite Score (GRCS) (Month 48, ITT)	20.0 Sum of subject-pair comparison scores Interval -58.0 to 55.0	-8.0 Sum of subject-pair comparison scores Interval -58.0 to 55.0	—	—

SECONDARY outcome

Timeframe: 48 Months Post-Randomization

Outcome measures

Outcome measures
Measure	mHSCT n=33 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=34 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Global Rank Composite Score (GRCS) (Month 48, PP)	17.0 Sum of subject-pair comparison scores Interval -56.0 to 49.0	-13.0 Sum of subject-pair comparison scores Interval -56.0 to 49.0	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Event-free survival (EFS) is defined as survival without significant organ damage or death. EFS failure includes any one of the following: death, respiratory failure (decrease from baseline of \>30% in diffusion in liters of carbon monoxide (DLCO) % predicted or \>20% in forced vital capacity (FVC) % predicted, documented on at least 2 successive occasions at least 1 month apart), renal failure (requiring chronic dialysis \> 6 months or transplantation), or the occurrence of cardiomyopathy (clinical congestive heart failure or left ventricular ejection fraction \<30%, documented on at least 2 successive occasions at least 1 month apart). EFS failures include participants who failed any component of the EFS definition between randomization and Month 54 post-randomization.

Outcome measures

Outcome measures
Measure	mHSCT n=36 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=39 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Event-Free Survival (EFS) (Month 54, ITT) EFS Failure	10 Participants	20 Participants	—	—
Event-Free Survival (EFS) (Month 54, ITT) Survived Event Free	26 Participants	19 Participants	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Event-free survival (EFS) is defined as survival without significant organ damage or death. EFS failure includes any one of the following: death, respiratory failure (decrease from baseline of \>30% in DLCO % predicted or \>20% in FVC % predicted, documented on at least 2 successive occasions at least 1 month apart), renal failure (requiring chronic dialysis \> 6 months or transplantation), or the occurrence of cardiomyopathy (clinical congestive heart failure or left ventricular ejection fraction \<30%, documented on at least 2 successive occasions at least 1 month apart). EFS failures include participants who failed any component of the EFS definition between randomization and Month 54 post-randomization.

Outcome measures

Outcome measures
Measure	mHSCT n=33 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=34 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Event-Free Survival (EFS) (Month 54, PP) EFS Failure	7 Participants	17 Participants	—	—
Event-Free Survival (EFS) (Month 54, PP) Survived Event Free	26 Participants	17 Participants	—	—

SECONDARY outcome

Timeframe: 48 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Event-free survival (EFS) is defined as survival without significant organ damage or death. EFS failure includes any one of the following: death, respiratory failure (decrease from baseline of \>30% in DLCO % predicted or \>20% in FVC % predicted, documented on at least 2 successive occasions at least 1 month apart), renal failure (requiring chronic dialysis \> 6 months or transplantation), or the occurrence of cardiomyopathy (clinical congestive heart failure or left ventricular ejection fraction \<30%, documented on at least 2 successive occasions at least 1 month apart). EFS failures include participants who failed any component of the EFS definition between randomization and Month 48 post-randomization.

Outcome measures

Outcome measures
Measure	mHSCT n=36 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=39 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Event-Free Survival (EFS) (Month 48, ITT) EFS Failure	10 Participants	20 Participants	—	—
Event-Free Survival (EFS) (Month 48, ITT) Survived Event Free	26 Participants	19 Participants	—	—

SECONDARY outcome

Timeframe: 48 Months Post-Randomization

Event-free survival (EFS) is defined as survival without significant organ damage or death. EFS failure includes any one of the following: death, respiratory failure (decrease from baseline of \>30% in DLCO % predicted or \>20% in FVC % predicted, documented on at least 2 successive occasions at least 1 month apart), renal failure (requiring chronic dialysis \> 6 months or transplantation), or the occurrence of cardiomyopathy (clinical congestive heart failure or left ventricular ejection fraction \<30%, documented on at least 2 successive occasions at least 1 month apart). EFS failures include participants who failed any component of the EFS definition between randomization and Month 48 post-randomization.

Outcome measures

Outcome measures
Measure	mHSCT n=33 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=34 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Event-Free Survival (EFS) (Month 48, PP) EFS Failure	7 Participants	17 Participants	—	—
Event-Free Survival (EFS) (Month 48, PP) Survived Event Free	26 Participants	17 Participants	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Death, occurring at any time between randomization and Month 54 post-randomization, which is possibly, probably, or definitely resulting from treatment given in the study.

Outcome measures

Outcome measures
Measure	mHSCT n=36 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=39 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Treatment-Related Mortality (Month 54, ITT)	1 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Death, occurring at any time between randomization and Month 54 post-randomization, which is possibly, probably, or definitely resulting from treatment given in the study.

Outcome measures

Outcome measures
Measure	mHSCT n=33 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=34 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Treatment-Related Mortality (Month 54, PP)	1 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: 48 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Death, occurring at any time between randomization and Month 48 post-randomization, which is possibly, probably, or definitely resulting from treatment given in the study.

Outcome measures

Outcome measures
Measure	mHSCT n=36 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=39 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Treatment-Related Mortality (Month 48, ITT)	1 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: 48 Months Post-Randomization

Death, occurring at any time between randomization and Month 48 post-randomization, which is possibly, probably, or definitely resulting from treatment given in the study.

Outcome measures

Outcome measures
Measure	mHSCT n=33 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=34 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Treatment-Related Mortality (Month 48, PP)	1 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Any death, regardless of relationship to treatment, between randomization and Month 54 post-randomization.

Outcome measures

Outcome measures
Measure	mHSCT n=36 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=39 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
All-Cause Mortality (Month 54, ITT)	6 Participants	11 Participants	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Any death, regardless of relationship to treatment, between randomization and Month 54 post-randomization.

Outcome measures

Outcome measures
Measure	mHSCT n=33 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=34 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
All-Cause Mortality (Month 54, PP)	3 Participants	8 Participants	—	—

SECONDARY outcome

Timeframe: 48 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Any death, regardless of relationship to treatment, between randomization and Month 48 post-randomization.

Outcome measures

Outcome measures
Measure	mHSCT n=36 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=39 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
All-Cause Mortality (Month 48, ITT)	6 Participants	11 Participants	—	—

SECONDARY outcome

Timeframe: 48 Months Post-Randomization

Any death, regardless of relationship to treatment, between randomization and Month 48 post-randomization.

Outcome measures

Outcome measures
Measure	mHSCT n=33 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=34 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
All-Cause Mortality (Month 48, PP)	3 Participants	8 Participants	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

HAQ-DI is a self-reported questionnaire of functionality that includes questions in 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities). The final score ranges from 0 to 3, where a higher HAQ-DI score indicates a worse outcome. Analysis was based on an ordinal response variable, defined as follows: a decrease of \>0.4 from baseline in the HAQ-DI score was considered disease improvement, an increase of \>0.4 was considered disease worsening, and any change less than 0.4 was considered "no change." Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.

Outcome measures

Outcome measures
Measure	mHSCT n=26 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=19 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure n=10 Participants Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure n=20 Participants Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Change From Baseline to Month 54 in Health Assessment Questionnaire - Disability Index (HAQ-DI) (ITT) Improvement	17 Participants	6 Participants	2 Participants	0 Participants
Change From Baseline to Month 54 in Health Assessment Questionnaire - Disability Index (HAQ-DI) (ITT) No Change	8 Participants	11 Participants	5 Participants	11 Participants
Change From Baseline to Month 54 in Health Assessment Questionnaire - Disability Index (HAQ-DI) (ITT) Worsening	1 Participants	2 Participants	3 Participants	9 Participants

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Outcome measures

Outcome measures
Measure	mHSCT n=26 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=17 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure n=7 Participants Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure n=17 Participants Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Change From Baseline to Month 54 in Health Assessment Questionnaire - Disability Index (HAQ-DI) (PP) Improvement	17 Participants	6 Participants	2 Participants	0 Participants
Change From Baseline to Month 54 in Health Assessment Questionnaire - Disability Index (HAQ-DI) (PP) No Change	8 Participants	10 Participants	5 Participants	9 Participants
Change From Baseline to Month 54 in Health Assessment Questionnaire - Disability Index (HAQ-DI) (PP) Worsening	1 Participants	1 Participants	0 Participants	8 Participants

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

The SF-36 measures health-related quality of life. It has 36 items and 2 component scores, the Physical Component Score and the Mental Component Score. Each component was transformed into a 0-100 scale (higher numbers indicate greater quality of life) and normalized to have a mean of 50 and standard deviation of 10 for the 1998 general US population. Analysis was based on ordinal response, defined as follows for each component: a \>= 10 point increase indicated disease improvement, a \>= 10 point decrease indicated disease worsening, and a change \<10 points indicated "no change". Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.

Outcome measures

Outcome measures
Measure	mHSCT n=26 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=19 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure n=10 Participants Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure n=20 Participants Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (ITT) Physical Component Score: Improvement	19 Participants	6 Participants	1 Participants	0 Participants
Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (ITT) Physical Component Score: No Change	6 Participants	9 Participants	6 Participants	16 Participants
Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (ITT) Physical Component Score: Worsening	1 Participants	4 Participants	3 Participants	4 Participants
Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (ITT) Mental Component Score: Improvement	10 Participants	2 Participants	1 Participants	1 Participants
Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (ITT) Mental Component Score: No Change	12 Participants	12 Participants	5 Participants	12 Participants
Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (ITT) Mental Component Score: Worsening	4 Participants	5 Participants	4 Participants	7 Participants

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Outcome measures

Outcome measures
Measure	mHSCT n=26 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=17 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure n=7 Participants Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure n=17 Participants Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (PP) Physical Component Score: Improvement	19 Participants	6 Participants	1 Participants	0 Participants
Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (PP) Physical Component Score: Worsening	1 Participants	2 Participants	0 Participants	3 Participants
Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (PP) Physical Component Score: No Change	6 Participants	9 Participants	6 Participants	14 Participants
Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (PP) Mental Component Score: Improvement	10 Participants	2 Participants	1 Participants	1 Participants
Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (PP) Mental Component Score: No Change	12 Participants	12 Participants	5 Participants	10 Participants
Change From Baseline to Month 54 in Short Form 36 Health Survey (SF-36) (PP) Mental Component Score: Worsening	4 Participants	3 Participants	1 Participants	6 Participants

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Diffusion in liters of carbon monoxide (DLCO) is a measure of lung function. Predicted values for DLCO were computed using the Crapo Morris equations and adjusted per the Cotes formula for anemia, if a participant's hemoglobin was \<13 or \>17 gm/dL, and altitude (Calgary site only). Analysis was based on an ordinal response variable, defined as follows: an increase from baseline of \>15% in DLCO % Predicted indicated disease improvement, a decrease of \>15% indicated disease worsening, and a change of \<=15% was considered "no change". Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.

Outcome measures

Outcome measures
Measure	mHSCT n=26 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=19 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure n=10 Participants Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure n=20 Participants Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Change From Baseline to Month 54 in Diffusion in Liters of Carbon Monoxide (DLCO) (ITT) No Change	19 Participants	8 Participants	0 Participants	2 Participants
Change From Baseline to Month 54 in Diffusion in Liters of Carbon Monoxide (DLCO) (ITT) Worsening	3 Participants	6 Participants	10 Participants	18 Participants
Change From Baseline to Month 54 in Diffusion in Liters of Carbon Monoxide (DLCO) (ITT) Improvement	4 Participants	5 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Outcome measures

Outcome measures
Measure	mHSCT n=26 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=17 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure n=7 Participants Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure n=17 Participants Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Change From Baseline to Month 54 in Diffusion in Liters of Carbon Monoxide (DLCO) (PP) Improvement	4 Participants	5 Participants	0 Participants	0 Participants
Change From Baseline to Month 54 in Diffusion in Liters of Carbon Monoxide (DLCO) (PP) No Change	19 Participants	8 Participants	0 Participants	2 Participants
Change From Baseline to Month 54 in Diffusion in Liters of Carbon Monoxide (DLCO) (PP) Worsening	3 Participants	4 Participants	7 Participants	15 Participants

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Forced Vital Capacity (FVC) is the amount of air that can be forcibly exhaled after a full breath and is a measure of lung function. Predicted FVC was based on institutional standards. Analysis was based on an ordinal response variable, defined as follows: an increase from baseline of \>10% in FVC % Predicted indicated disease improvement, a decrease of \>10% indicated disease worsening, and a change of \<=10% was considered "no change". Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.

Outcome measures

Outcome measures
Measure	mHSCT n=26 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=19 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure n=10 Participants Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure n=20 Participants Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Change From Baseline to Month 54 in Forced Vital Capacity (FVC) (ITT) Improvement	12 Participants	7 Participants	0 Participants	1 Participants
Change From Baseline to Month 54 in Forced Vital Capacity (FVC) (ITT) No Change	13 Participants	8 Participants	2 Participants	2 Participants
Change From Baseline to Month 54 in Forced Vital Capacity (FVC) (ITT) Worsening	1 Participants	4 Participants	8 Participants	17 Participants

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Outcome measures

Outcome measures
Measure	mHSCT n=26 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=17 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure n=7 Participants Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure n=17 Participants Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Change From Baseline to Month 54 in Forced Vital Capacity (FVC) (PP) Worsening	1 Participants	2 Participants	5 Participants	14 Participants
Change From Baseline to Month 54 in Forced Vital Capacity (FVC) (PP) Improvement	12 Participants	7 Participants	0 Participants	1 Participants
Change From Baseline to Month 54 in Forced Vital Capacity (FVC) (PP) No Change	13 Participants	8 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness. Skin thickness in 17 anatomic areas was rated on a 0-3 scale and scores are summed to obtain the mRSS (range from 0 - 51), with higher mRSS scores indicating worse disease activity. Analysis was based on an ordinal response variable, defined as follows: if the baseline mRSS was \<=20, a decrease \>=5 points from baseline indicated disease improvement and an increase \>= 5 points indicated disease worsening; if the baseline mRSS was \>20, then a decrease of \>25% indicated disease improvement and an increase of \>25% indicated disease worsening. Participants who do not meet the disease criteria outlined above were considered "no change". Data for participants without a Month 54 assessment was imputed using a last observation carried forward approach; improvement/worsening was assessed at each participant's last available study visit that occurred prior to or at Month 54, without confirmation at the next visit.

Outcome measures

Outcome measures
Measure	mHSCT n=26 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=19 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure n=10 Participants Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure n=20 Participants Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Change From Baseline to Month 54 in Modified Rodnan Skin Score (mRSS) (ITT) Improvement	26 Participants	14 Participants	5 Participants	5 Participants
Change From Baseline to Month 54 in Modified Rodnan Skin Score (mRSS) (ITT) Worsening	0 Participants	2 Participants	4 Participants	5 Participants
Change From Baseline to Month 54 in Modified Rodnan Skin Score (mRSS) (ITT) No Change	0 Participants	3 Participants	1 Participants	10 Participants

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Outcome measures

Outcome measures
Measure	mHSCT n=26 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=17 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure n=7 Participants Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure n=17 Participants Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Change From Baseline to Month 54 in Modified Rodnan Skin Score (mRSS) (PP) Worsening	0 Participants	0 Participants	1 Participants	2 Participants
Change From Baseline to Month 54 in Modified Rodnan Skin Score (mRSS) (PP) Improvement	26 Participants	14 Participants	5 Participants	5 Participants
Change From Baseline to Month 54 in Modified Rodnan Skin Score (mRSS) (PP) No Change	0 Participants	3 Participants	1 Participants	10 Participants

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Any events that met the criteria outlined below or were reported as adverse events between randomization and Month 54 post-randomization are summarized. 1) Development of new or worsening arrhythmias that require medical treatment for \>= 3 months or require ablative therapy or pacemaker insertion. (Note that for a participant who has medically controlled arrhythmia at randomization, worsening was defined as breakthrough episodes severe enough to prompt change in medication, an increase in the dose of a medication, or addition of a new medication to maintain control of the arrhythmia.) 2) Congestive heart failure (CHF) requiring clinical treatment for \>= 3 months develops. 3) Clinically significant pericardial effusion (excess fluid around the heart) that required pericardial window.

Outcome measures

Outcome measures
Measure	mHSCT n=36 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=39 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
New or Worsening Arrhythmias, Congestive Heart Failure, or Pericardial Effusion (ITT) Development of new or worsening arrhythmias	6 Participants	4 Participants	—	—
New or Worsening Arrhythmias, Congestive Heart Failure, or Pericardial Effusion (ITT) CHF requiring clinical treatment	0 Participants	4 Participants	—	—
New or Worsening Arrhythmias, Congestive Heart Failure, or Pericardial Effusion (ITT) Clinically significant pericardial effusion	2 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Any events that met the criteria outlined below or were reported as adverse events between randomization and Month 54 post-randomization are summarized. 1) Development of new or worsening arrhythmias that require medical treatment for \>= 3 months or require ablative therapy or pacemaker insertion. (Note that for a participant who has medically controlled arrhythmia at randomization, worsening will be defined as breakthrough episodes severe enough to prompt change in medication, an increase in the dose of a medication or addition of a new medication to maintain control of the arrhythmia.) 2) Congestive heart failure (CHF) requiring clinical treatment for \>= 3 months develops. 3) Clinically significant pericardial effusion (excess fluid around the heart) that required pericardial window.

Outcome measures

Outcome measures
Measure	mHSCT n=33 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=34 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
New or Worsening Arrhythmias, Congestive Heart Failure, or Pericardial Effusion (PP) Development of new or worsening arrhythmias	6 Participants	4 Participants	—	—
New or Worsening Arrhythmias, Congestive Heart Failure, or Pericardial Effusion (PP) Clinically significant pericardial effusion	2 Participants	0 Participants	—	—
New or Worsening Arrhythmias, Congestive Heart Failure, or Pericardial Effusion (PP) CHF requiring clinical treatment	0 Participants	4 Participants	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Any pulmonary arterial hypertension (PAH) events that occurred between randomization and Month 54 post-randomization were summarized. Development of PAH occurred if the participant met the following criteria, where the measurement value(s) could not be explained by other causes such as congestive heart failure or pulmonary emboli: 1) a post-baseline peak systolic pulmonary artery pressure \> 55 mmHg by echocardiogram or 2) a mean pulmonary artery pressure \> 30 mmHg at rest measured by right heart catheterization. If the post-baseline peak systolic pulmonary artery pressure was between 40 to 55 mmHg by echocardiogram, a right heart catheterization was done to confirm a diagnosis of pulmonary artery hypertension. The endpoint was met if the mean pulmonary artery pressure was \> 30 mmHg at rest by right heart catheterization. Additionally, any adverse event reported as PAH was included in the analysis.

Outcome measures

Outcome measures
Measure	mHSCT n=36 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=39 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
New or Worsening Pulmonary Hypertension (ITT)	0 Participants	5 Participants	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Any pulmonary arterial hypertension (PAH) events that occurred between randomization and Month 54 post-randomization were summarized. Development of PAH occurred if the participant met the following criteria, where the measurement value(s) could not be explained by other causes such as congestive heart failure or pulmonary emboli: 1) a post-baseline peak systolic pulmonary artery pressure \> 55 mmHg by echocardiogram or 2) a mean pulmonary artery pressure \> 30 mmHg at rest measured by right heart catheterization. If the post-baseline peak systolic pulmonary artery pressure was between 40 to 55 mmHg by echocardiogram, a right heart catheterization would be done to confirm a diagnosis of pulmonary artery hypertension. The endpoint was met if the mean pulmonary artery pressure was \> 30 mmHg at rest by right heart catheterization. Additionally, any adverse event reported as PAH was included in the analysis.

Outcome measures

Outcome measures
Measure	mHSCT n=33 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=34 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
New or Worsening Pulmonary Hypertension (PP)	0 Participants	5 Participants	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Documented scleroderma renal crisis (hypertensive or non-hypertensive) occurring from randomization to Month 54 post-randomization was summarized. A hypertensive scleroderma renal crisis occurred if a participant obtained both of the following: New-onset hypertension, defined as systolic blood pressure (SBP) \>= 140 mmHg, diastolic blood pressure (DBP) \>= 90 mmHg, a rise in SBP \>= 30 mmHg compared to baseline, or a rise in DBP \>= 20 mmHg compared to baseline, and one of the following features: 1) increase of \>= 50 % above baseline in serum creatinine, 2) proteinuria (\>= 2+ by dipstick confirmed by protein:creatinine ratio \> 2.5), 3) hematuria (\>= 2+ by dipstick or \> 10 RBCs/HPF, without menstruation), 4) thrombocytopenia (\< 100,000 plts/mm3), or 5) hemolysis (determined by blood smear or increased reticulocyte count). Additionally, any adverse event reported as a scleroderma renal crisis was included in the analysis.

Outcome measures

Outcome measures
Measure	mHSCT n=36 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=39 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Occurrence of Scleroderma Renal Crisis (ITT)	2 Participants	3 Participants	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Outcome measures

Outcome measures
Measure	mHSCT n=33 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=34 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Occurrence of Scleroderma Renal Crisis (PP)	0 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Number of participants who experienced any event of myositis that occurred from randomization to Month 54 post-randomization. Documented myositis occurred if the participant had 1) elevated creatine phosphokinase (CPK), electromyography, and/or biopsy and 2) required \> 30 mg per day prednisone for over 1 month or another therapy such as methotrexate (MTX) for treatment of myositis. Additionally, any adverse event reported as myositis was included in the analysis.

Outcome measures

Outcome measures
Measure	mHSCT n=36 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=39 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Documented Myositis (ITT)	1 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Outcome measures

Outcome measures
Measure	mHSCT n=33 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=34 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Documented Myositis (PP)	1 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Population: Intention to treat (ITT). The ITT population includes all randomized participants.

Initiation of disease-modifying antirheumatic drugs (DMARDs). Participants were not expected to receive additional disease-modifying therapy for systemic sclerosis (SSc) in the absence of disease progression. In general, this includes the administration of any therapy clearly given for the purpose of treating the underlying SSc. It does not include concomitant treatments permitted in the protocol, such as use of methotrexate (15 g or less), anti-malarials, or minocycline for arthritis only. Systemic corticosteroids given at \> 10 mg/day (prednisone or prednisone equivalent), without clearly defined non-SSc indications, and methotrexate given for non-arthritis indications are examples of qualifying DMARDs.

Outcome measures

Outcome measures
Measure	mHSCT n=36 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=39 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Initiating Use of Disease-Modifying Antirheumatic Drugs (DMARDs) by Month 54 (ITT)	3 Participants	15 Participants	—	—

SECONDARY outcome

Timeframe: 54 Months Post-Randomization

Outcome measures

Outcome measures
Measure	mHSCT n=33 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=34 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Initiating Use of Disease-Modifying Antirheumatic Drugs by Month 54 (DMARDs) (PP)	3 Participants	15 Participants	—	—

SECONDARY outcome

Timeframe: Randomization through end of study follow-up (up to Month 72 post-randomization)

Population: Safety population. The safety population includes all participants for whom study treatment was initiated. For the mHSCT arm, treatment was initiated with the first dose of granulocyte colony stimulating factor for mobilization, and for the cyclophosphamide arm, treatment was initiated with the first dose of IV cyclophosphamide.

Regimen-related toxicities are defined as Grade 3 or higher adverse events reported by site physicians as possibly, probably, or definitely related to study therapy.

Outcome measures

Outcome measures
Measure	mHSCT n=34 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=37 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Regimen-Related Toxicities Possibly Related	106 Events	23 Events	—	—
Regimen-Related Toxicities Probably Related	98 Events	13 Events	—	—
Regimen-Related Toxicities Definitely Related	90 Events	5 Events	—	—

SECONDARY outcome

Timeframe: Randomization through end of study follow-up (up to Month 72 post-randomization).

Regimen-related toxicities are defined as Grade 3 or higher adverse events reported by site physicians as possibly, probably, or definitely related to study therapy.

Outcome measures

Outcome measures
Measure	mHSCT n=34 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=37 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Number of Subjects With Regimen-Related Toxicities Possibly Related	33 Participants	10 Participants	—	—
Number of Subjects With Regimen-Related Toxicities Probably Related	27 Participants	10 Participants	—	—
Number of Subjects With Regimen-Related Toxicities Definitely Related	26 Participants	3 Participants	—	—

SECONDARY outcome

Timeframe: Randomization through end of study follow-up (up to Month 72 post-randomization).

Infectious complications include any events that code to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class of "Infections and infestations" or events that a site has classified as an infectious event. These can include bacteremia, septicemia, fungemia, fever associated with infection, infectious pneumonia, idiopathic pneumonia syndrome, clinical infection (i.e. infection diagnosed with clinical features without identification of an organism) and other local/organ site-specific infections.

Outcome measures

Outcome measures
Measure	mHSCT n=34 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=37 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Infectious Complications	131 Events	112 Events	—	—

SECONDARY outcome

Timeframe: Randomization through end of study follow-up (up to Month 72 post-randomization).

Outcome measures

Outcome measures
Measure	mHSCT n=34 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide n=37 Participants Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Number of Subjects With Infectious Complications	33 Participants	31 Participants	—	—

SECONDARY outcome

Timeframe: 28 days post-transplant

Population: Per-protocol (PP) - mHSCT arm only. The PP population is defined as those participants who completed the assigned treatment protocol: undergoing autologous CD34-selected hematopoietic progenitor cell transplantation in the mHSCT arm.

Time to absolute neutrophil count (ANC) engraftment is defined as the number of days post-transplant until required levels of ANC are attained (for the mHSCT arm only). If engraftment did not occur within 28 days post-transplant, then the variable was set to 28 days. ANC engraftment required an ANC of \> 500 cells/microliter, maintained for 3 consecutive days.

Outcome measures

Outcome measures
Measure	mHSCT n=34 Participants Participants were administered granulocyte colony stimulating factor (G-CSF) and had hematopoietic stem cells removed from their blood. They then underwent high-dose immunosuppressive therapy using a conditioning regimen of total body irradiation (800 cGy given over 2 days with lung and kidney shielding limiting exposure to 200cGy), cyclophosphamide (60 mg/kg/day for 2 days), IV Methylprednisolone (1 mg/kg/day for 3 days), and equine antithymocyte globulin (ATGAM) (15 mg/kg/day for 3 days). Purified autologous stem cell were infused at a dose of \>2.5x106 CD34+ cells/kg. After transplantation, participants received additional doses of IV Methylprednisolone (1 mg/kg/day for 3 days) and ATGAM (15 mg/kg/day for 3 days.)	Cyclophosphamide Participants received 12 monthly pulses of high-dose intravenous cyclophosphamide (an initial dose of 500 mg/m\^2, followed by 11 doses of 750 mg/m\^2).	mHSCT- EFS Failure Subjects in the mHSCT group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.	Cyclophosphamide- EFS Failure Subjects in the Cyclophosphamide group who failed the event-free survival (EFS) endpoint, defined as survival without significant organ damage or death.
Time to Absolute Neutrophil Count Engraftment	10 Days Interval 8.0 to 12.0	—	—	—

Adverse Events

mHSCT

Serious events: 25 serious events

Other events: 33 other events

Deaths: 7 deaths

Cyclophosphamide

Serious events: 19 serious events

Other events: 37 other events

Deaths: 14 deaths

Serious adverse events

Other adverse events

Additional Information

Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place