Trial Outcomes & Findings for Haploidentical PBMC Transplant for Severe Congenital Anemias (NCT NCT00977691)

NCT ID: NCT00977691

Last Updated: 2025-01-17

Results Overview

Percentage of patients post transplant with sustained donor type hemoglobin on hemoglobin electrophoresis

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1/PHASE2

Target enrollment

23 participants

Primary outcome timeframe

1 year

Results posted on

2025-01-17

Participant Flow

A total of 23 adults underwent non-myeloablative haplo-HSCT at the National Institutes of Health (NIH) from December 2009 through September 2015.

Participant milestones

Participant milestones
Measure	PBSC Transplant With no Post-transplant Cyclophosphamide (PT-Cy) Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and no posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 50 mg/kg posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 100 mg/kg posttransplant cyclophosphamide (PT-Cy).
Overall Study STARTED	3	8	12
Overall Study COMPLETED	3	7	12
Overall Study NOT COMPLETED	0	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Haploidentical PBMC Transplant for Severe Congenital Anemias

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PBSC Transplant With no Post-transplant Cyclophosphamide (PT-Cy) n=3 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and no posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=8 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 50 mg/kg posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=12 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 100 mg/kg posttransplant cyclophosphamide (PT-Cy).	Total n=23 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	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants	23 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	9 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	14 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants	21 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants	20 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: 1 year

Percentage of patients post transplant with sustained donor type hemoglobin on hemoglobin electrophoresis

Outcome measures

Outcome measures
Measure	PBSC Transplant With no Post-transplant Cyclophosphamide (PT-Cy) n=3 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and no posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=8 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 50 mg/kg posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=12 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 100 mg/kg posttransplant cyclophosphamide (PT-Cy).
Patients With Donor Type Hemoglobin	0 Participants	3 Participants	6 Participants

SECONDARY outcome

Timeframe: Up to Year 5

Define the level of chimerism required to maintain graft survival and hematologic normalcy. Hematologic normalcy may be defined as: being free from sickle cell disease. The chimeric status of patients will be measured on days +14 (or when subject starts to engraft), +30, +60 and +100, and periodically after day +100, by microsatellite analysis of the peripheral blood. Engraftment of donor cells was assessed with the use of methods that detect informative polymorphisms in regions known to contain short tandem repeats. Peripheral-blood CD3+ T cells and CD14+CD15+ myeloid cells were selected for analysis with the use of immunomagnetic beads (Dynal).

Outcome measures

Outcome measures
Measure	PBSC Transplant With no Post-transplant Cyclophosphamide (PT-Cy) n=3 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and no posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=8 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 50 mg/kg posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=12 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 100 mg/kg posttransplant cyclophosphamide (PT-Cy).
Chimeric Value That is Required to Maintain Graft Survival and Hematologic Normalcy. Greater than or Equal to 20% Chimerism with hematologic normalcy	0 Participants	2 Participants	6 Participants
Chimeric Value That is Required to Maintain Graft Survival and Hematologic Normalcy. Less than or Equal to 20% Chimerism with no hematologic normalcy	3 Participants	6 Participants	6 Participants

SECONDARY outcome

Timeframe: Day100

Number of participants who developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV as defined by CIMBTR criteria for Organ Stages of Acute GVHD. Grades are defined as: Grade I: Skin = Maculopapular rash\< 25% of body surface area (BSA); Liver = Total Bilirubin 2-3 mg/dL; Lower GI = stool output/day is 500-999 mL/day. Grade II: Skin = rash on 25-50 percent body surface area; Liver = Total Bilirubin 3.1-6.0 mg/dL; Lower GI = Diarrhea 1001-1500 mL/day. Grade III: Skin = Rash on \>50% of body surface; Liver = Total Bilirubin 6.1 - 15.0 mg/dL; Lower GI = Diarrhea \> 1500 mL/day. Grade IV: Skin = Generalized erythroderma plus bullous formation; Liver = Total Bilirubin \>15 mg/dL; Lower GI = Severe abdominal pain with or without ileus. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.

Outcome measures

Outcome measures
Measure	PBSC Transplant With no Post-transplant Cyclophosphamide (PT-Cy) n=3 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and no posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=8 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 50 mg/kg posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=12 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 100 mg/kg posttransplant cyclophosphamide (PT-Cy).
Number of Participants Who Developed Acute GVHD Grades I, II, III, IV Grade III acute GvHD	0 Participants	0 Participants	0 Participants
Number of Participants Who Developed Acute GVHD Grades I, II, III, IV Grade IV acute GvHD	0 Participants	0 Participants	0 Participants
Number of Participants Who Developed Acute GVHD Grades I, II, III, IV Grade I acute GvHD	0 Participants	1 Participants	1 Participants
Number of Participants Who Developed Acute GVHD Grades I, II, III, IV Grade II acute GvHD	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Year 5

Number of incidences of participants who developed Limited Chronic Graft vs Host Disease (GVHD). Limited disease is characterized by localized skin involvement and/or evidence of hepatic dysfunction. Limited disease is associated with a favorable outcome without systemic therapy, while extensive disease patients have an unfavorable outcome.

Outcome measures

Outcome measures
Measure	PBSC Transplant With no Post-transplant Cyclophosphamide (PT-Cy) n=3 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and no posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=8 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 50 mg/kg posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=12 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 100 mg/kg posttransplant cyclophosphamide (PT-Cy).
Number of Participants Who Developed Limited Chronic GVHD	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Year 5

Number of participants with extensive, Chronic Graft vs Host Disease (GVHD). Extensive chronic GVHD is defined as GVHD occurring after day 100 that did not meet the definition of limited chronic GVHD. Extensive disease presents either with generalized skin involvement, or with localized skin involvement or hepatic dysfunction plus at least one of the following: * Liver histology showing chronic progressive hepatitis, bridging necrosis, or cirrhosis * Involvement of the eye (Schirmer's test with less than 5 mm wetting) (see "Diagnosis and classification of Sjögren's syndrome") * Involvement of minor salivary glands or oral mucosa (as demonstrated on labial or mucosal biopsy specimen) * Involvement of any other target organ

Outcome measures

Outcome measures
Measure	PBSC Transplant With no Post-transplant Cyclophosphamide (PT-Cy) n=3 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and no posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=8 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 50 mg/kg posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=12 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 100 mg/kg posttransplant cyclophosphamide (PT-Cy).
Number of Participants Who Develop Extensive GVHD	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Year 5

Number of participants with disease-free survival, as defined by: alive and free acute complications related to sickle cell disease.

Outcome measures

Outcome measures
Measure	PBSC Transplant With no Post-transplant Cyclophosphamide (PT-Cy) n=3 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and no posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=8 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 50 mg/kg posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=12 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 100 mg/kg posttransplant cyclophosphamide (PT-Cy).
Number of Participants With Disease-free Survival	0 Participants	2 Participants	6 Participants

SECONDARY outcome

Timeframe: Up to Year 5

Number of participants overall survival by year 5

Outcome measures

Outcome measures
Measure	PBSC Transplant With no Post-transplant Cyclophosphamide (PT-Cy) n=3 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and no posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=8 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 50 mg/kg posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=12 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 100 mg/kg posttransplant cyclophosphamide (PT-Cy).
Number of Participants Overall Survival Alive	1 Participants	7 Participants	11 Participants
Number of Participants Overall Survival Deceased	2 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Year 5

Number of participants with graft failure by year 5. Graft failure is defined by return of sickle cell disease.

Outcome measures

Outcome measures
Measure	PBSC Transplant With no Post-transplant Cyclophosphamide (PT-Cy) n=3 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and no posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=8 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 50 mg/kg posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=12 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 100 mg/kg posttransplant cyclophosphamide (PT-Cy).
Number of Participants With Graft Failure	3 Participants	6 Participants	6 Participants

SECONDARY outcome

Timeframe: Year 1

Number of participants that experienced a transplant related mortality, as defined as death from causes other than relapse (GVHD, toxicity, infection, other and unknown causes).

Outcome measures

Outcome measures
Measure	PBSC Transplant With no Post-transplant Cyclophosphamide (PT-Cy) n=3 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and no posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=8 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 50 mg/kg posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=12 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 100 mg/kg posttransplant cyclophosphamide (PT-Cy).
Number of Participants That Experienced a Transplant-related Mortality	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Year 5

Number of stem cell transplant participants that experienced rejection at each dose of post-transplant cyclophosphamide. Determine whether post-transplant cyclophosphamide is required and will reduce the incidence and severity of regimen failure.

Outcome measures

Outcome measures
Measure	PBSC Transplant With no Post-transplant Cyclophosphamide (PT-Cy) n=3 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and no posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=8 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 50 mg/kg posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=12 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 100 mg/kg posttransplant cyclophosphamide (PT-Cy).
Number of Stem Cell Transplant Participants That Experienced Rejection at Each Dose of Post-transplant Cyclophosphamide No post-transplant cyclophosphamide	3 Participants	0 Participants	0 Participants
Number of Stem Cell Transplant Participants That Experienced Rejection at Each Dose of Post-transplant Cyclophosphamide 50 mg/kg posttransplant cyclophosphamide	0 Participants	6 Participants	0 Participants
Number of Stem Cell Transplant Participants That Experienced Rejection at Each Dose of Post-transplant Cyclophosphamide 100 mg/kg posttransplant cyclophosphamide	0 Participants	0 Participants	6 Participants

SECONDARY outcome

Timeframe: Up to Year 5

Population: Participants with Sickle Cell Disease who survived beyond 6 months (participants with beta-thalassemia were excluded).

Determine whether specific haploidentical donors (i.e. parent versus sibling versus child) will decrease the incidence of regimen failure

Outcome measures

Outcome measures
Measure	PBSC Transplant With no Post-transplant Cyclophosphamide (PT-Cy) n=8 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and no posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=12 Participants Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 50 mg/kg posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 100 mg/kg posttransplant cyclophosphamide (PT-Cy).
Participants Who Engrafted or Rejected and Type of Haploidentical Donors Father	0 Participants	1 Participants	—
Participants Who Engrafted or Rejected and Type of Haploidentical Donors Mother	3 Participants	6 Participants	—
Participants Who Engrafted or Rejected and Type of Haploidentical Donors Brother	2 Participants	1 Participants	—
Participants Who Engrafted or Rejected and Type of Haploidentical Donors Sister	3 Participants	3 Participants	—
Participants Who Engrafted or Rejected and Type of Haploidentical Donors Son	0 Participants	1 Participants	—

Adverse Events

PBSC Transplant With no Post-transplant Cyclophosphamide (PT-Cy)

Serious events: 3 serious events

Other events: 0 other events

Deaths: 2 deaths

PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy)

Serious events: 7 serious events

Other events: 0 other events

Deaths: 1 deaths

PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy)

Serious events: 11 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Courtney Fitzhugh, MD, Investigator

National Heart Lung and Blood Institute

Phone: +1 301 402 6496

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	PBSC Transplant With no Post-transplant Cyclophosphamide (PT-Cy) n=3 participants at risk Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and no posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 50 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=8 participants at risk Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 50 mg/kg posttransplant cyclophosphamide (PT-Cy).	PBSC Transplant With 100 mg/kg Post-transplant Cyclophosphamide (PT- Cy) n=12 participants at risk Patients received a regimen consisting of alemtuzumab, 400 cGy total body irradiation (TBI), sirolimus, and 100 mg/kg posttransplant cyclophosphamide (PT-Cy).
General disorders Pain	33.3% 1/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	25.0% 2/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	33.3% 4/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Blood and lymphatic system disorders Anemia	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	12.5% 1/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Blood and lymphatic system disorders Myelodysplastic syndrome	33.3% 1/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Blood and lymphatic system disorders Sickle cell anemia with crisis	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	16.7% 2/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Cardiac disorders Cardiovascular disorder	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	12.5% 1/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Cardiac disorders Syncope	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	16.7% 2/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Cardiac disorders Ventricular tachycardia	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	12.5% 1/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Gastrointestinal disorders Colitis	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Gastrointestinal disorders Upper gastrointestinal Hemorrhage	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
General disorders Device related infection	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
General disorders Device related thrombosis	33.3% 1/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	12.5% 1/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
General disorders Extravasation	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	12.5% 1/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
General disorders Inflammation	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	12.5% 1/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Hepatobiliary disorders Hepatic hemorrhage	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Hepatobiliary disorders Portal hypertension	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Immune system disorders Hypersensitivity	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Infections and infestations Cytomegalovirus infection	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Infections and infestations Infection	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	50.0% 4/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	50.0% 6/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Infections and infestations Infective Myositis	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Infections and infestations Lung infection	33.3% 1/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	16.7% 2/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Infections and infestations Sepsis	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	25.0% 3/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Infections and infestations Upper respiratory tract infection	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	16.7% 2/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Injury, poisoning and procedural complications Fall	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Metabolism and nutrition disorders Dehydration	33.3% 1/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	12.5% 1/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Musculoskeletal and connective tissue disorders Arthralgia	33.3% 1/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Musculoskeletal and connective tissue disorders Musculoskeletal disorder	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Nervous system disorders Cerebrovascular accident	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	12.5% 1/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Nervous system disorders Headache	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	12.5% 1/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Nervous system disorders Memory impairment	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Nervous system disorders Seizure	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy while on Mycophenolate Mofetil	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	12.5% 1/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	33.3% 1/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	25.0% 2/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Respiratory, thoracic and mediastinal disorders Pulmonary Hypertension	33.3% 1/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	12.5% 1/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Vascular disorders Embolism	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	12.5% 1/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Vascular disorders Thrombosis	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	12.5% 1/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Endocrine disorders Hypothyroidism	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.
Infections and infestations Bacteremia	0.00% 0/3 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	0.00% 0/8 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.	8.3% 1/12 • 5 year Adverse events will be solicited from participant through questions from study personnel and information volunteered by the participant.