In-utero Hematopoietic Stem Cell Transplantation for the Treatment of Fetuses With Bart's Hydrops Fetalis Syndrome

NCT ID: NCT05797272

Last Updated: 2023-04-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-01
• Study Completion Date: 2027-09-30

Brief Summary

This is a prospective observational pilot study on pregnant women who are diagnosed to have Bart's hydrops fetalis syndrome (BHFS) affected fetuses and opt for continuation of pregnancy will be invited to consider undergoing in-utero hematopoietic stem cell transplantation under a research protocol, aiming to determine whether in-utero hematopoietic stem cell transplantation (HSCT) for fetuses with confirmed BHFS at the time of in-utero transfusion (IUT) of red blood cells could be feasible in Hong Kong. The participants will undergo bone marrow or peripheral blood stem cells harvest and an IUT combined with maternal stem cells.

Detailed Description

Alpha thalassemia major or hemoglobin BHFS is thought to be incompatible of life. A prevalence study conducted in Hong Kong showed 4.6% of the screened population are heterozygous carriers of deletional type alpha thalassemia, who would have 25% risk of conceiving fetuses with BHFS if both couple are carrier. Fetuses with BHFS often develop severe anaemia in utero, feature with cardiomegaly, high peak systolic velocity in middle cerebral artery (MCA PSV), thickened placenta, and eventually hydrops, which can lead to intrauterine fetal demise or early neonatal death; while the mother may also be at risk of maternal mirror syndrome which will cause significant morbidity and even mortality. As a result, when the foetuses are diagnosed with BHFS, most couple will terminate the pregnancy.

With the advance of technology, if the couples are both known to be alpha thalassemia carrier (alpha-alpha couples), they may consider pre-implantation genetic diagnosis. However, even though preimplantation genetic testing for monogenic disease (PGT-M) is a mature technique over the decades, it is still technically challenging, requires assisted reproductive technology even if the couple are fertile and relative costly. As a result, most of the alpha-alpha couples still conceive naturally. Prenatal ultrasonic surveillance is usually offered for the couples and prenatal diagnosis is required for genetic analysis to confirm BHFS when there is ultrasound feature of fetal anaemia.

Thus, the investigators propose this pilot study to determine whether in-utero hematopoietic stem cell transplantation for fetuses with confirmed alpha thalassemia major at the time of IUT of red blood cells could be feasible in Hong Kong.

Conditions

Haemoglobin Barts Hydrops

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fetuses with BHFS

Fetuses of pregnant women confirmed with BHFS

Group Type: EXPERIMENTAL

in-utero HSCT

Intervention Type: PROCEDURE

Pregnant women who are diagnosed to have BHFS affected fetuses and opt for continuation of pregnancy will undergo in-utero HSCT.

Interventions

in-utero HSCT

Pregnant women who are diagnosed to have BHFS affected fetuses and opt for continuation of pregnancy will undergo in-utero HSCT.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Pregnancy before 26 weeks and 0 day of gestational age with a diagnosis of BHFS confirmed by chorionic villus sampling, amniocentesis or cordocentesis;
• The parents elected to pursue IUT and are willing to undergo subsequent IUT for the remainder of gestation.

Exclusion Criteria

A) Fetal subjects:

• Fetuses having a second major anatomic anomaly (not related to the underlying thalassemia) that contributes a significant morbidity or mortality risk;
• Fetuses having a genetic or chromosomal abnormalities other than BHFS that contributes a significant morbidity or mortality risk;
• Echocardiogram or ultrasound findings that indicate a high risk of fetal demise after fetal intervention;
• Fetuses diagnosed with in-utero death prior to the actual intervention.

B) Maternal subjects:

• Maternal age < 18 years, mentally handicapped or severely ill;
• Maternal participants having one or more morbidities that would preclude bone marrow or peripheral blood stem cells harvest and fetal intervention including, but not limited to, bleeding disorder, maternal cardiac disease, maternal mirror syndrome, symptomatic maternal anemia, or if they develop preterm premature rupture of membranes or active preterm labor;
• Unable to understand English or Chinese to give consent.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Tak Yeung LEUNG

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tak Yeung LEUNG, MD

Role: PRINCIPAL_INVESTIGATOR

Chinese University of Hong Kong

Locations

The Chinese University of Hong Kong

Shatin, , Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Tak Yeung LEUNG, MD

Role: CONTACT

tyleung@cuhk.edu.hk

852-35052806

Facility Contacts

Tak Yeung LEUNG, MD

Role: primary

tyleung@cuhk.edu.hk

852-35052806

Other Identifiers

2021.551-T

Identifier Type: -

Identifier Source: org_study_id