Feasibility of In-utero Hematopoietic Stem Cell Transplantation as a Conjunctive Treatment During In-utero Blood Transfusion for Hemoglobin Bart's Hydrops Fetalis Syndrome in Hong Kong
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Rate of maternal complications
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Rate of maternal complications
时间窗: during pregnancy (up to week 40)
Maternal participant tolerance of bone marrow or peripheral blood stem cells harvest with prior granulocyte colony-stimulating factor (G-CSF) administration: \- Maternal participant tolerance defined as not requiring interventions for preterm labor, bleeding, infection or prolonged hospitalization. Any side effects or adverse outcome related to the procedure or related medications observed will be well documented.
Rate of survival of fetus
时间窗: during pregnancy (up to week 40)
Safety of in utero HSCT when performed at the same time as in utero blood transfusion for the fetal participant: \- Safety for fetal participant defined by survival 24 hours after procedure, fetal survival till birth, neonatal survival through discharge of hospitalization and no evidence of graft versus host disease.
次要结局
未报告次要终点
研究者
Tak Yeung LEUNG
Professor
Chinese University of Hong Kong