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Successful matched unrelated donor stem cell transplant in Hemoglobin Bart's disease

Bone Marrow Transplantation volume 51, pages 1522–1523 (2016)Cite this article

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Alpha thalassemia is the most common inherited disorder of hemoglobin synthesis in Southeast Asia, with the carrier rate ranging from 5 to 15%.1 Alpha thalassemia is divided into four clinical subsets that reflect the extent of impairment in α-globin chain production: silent carrier (−α/αα), α-thalassemia trait (−α/−α or −/αα), hemoglobin H disease (−/−α) and hemoglobin Bart’s (−/−). Hemoglobin Bart’s usually leads to hydrops fetalis syndrome during the mid-trimester of fetal life because of the absolute failure of α-globin chain synthesis. The affected fetus has severe intrauterine hypoxia due to extreme anemia. Most affected babies are born prematurely and require intensive care. The surviving infants will require long-term management with regular blood transfusion and iron chelation treatment, similar to patients with beta thalassemia major.2, 3 Improvements in DNA technology allow antenatal diagnosis and counseling for couples at risk as early as 8 to 10 weeks after conception. More neonates with hemoglobin Bart’s disease are surviving with the advancement of neonatal care and intrauterine transfusion, but have no curative options. Here, we present a patient with hemoglobin Bart’s diagnosed and treated in utero, who underwent successful allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-matched unrelated donor at 5 months of age.

Our patient was born to parents of south Asian descent. He was the product of his mother’s fifth pregnancy. The previous four pregnancies had resulted in normal deliveries of healthy infants at term. Our patient was found to have fetal cardiomegaly and pericardial effusion on prenatal ultrasound done at 27 weeks. Hemoglobin Bart’s disease was highly suspected, as the mother is a known alpha thalassemia trait carrier. The patient had percutaneous umbilical vein sampling, which revealed, on hemoglobin electrophoresis, that the majority of hemoglobin was hemoglobin Bart’s with a small amount of Portland hemoglobin and no hemoglobin A or hemoglobin F. The diagnosis of hemoglobin Bart’s disease was confirmed through molecular testing, which revealed deletion of all four alpha globin genes on chromosome 16. Further, infectious disease work-up was negative for CMV, toxoplasmosis and parvovirus. The patient was then closely followed with weekly amniotic fluid index, hydrops checks and biweekly non-stress tests. Fetal echocardiogram done at 30 weeks gestation re-demonstrated the pericardial effusion and the four dilated heart chambers with good function, suggestive of compensated high cardiac output failure. A single intrauterine transfusion was given at 35 weeks gestation, as the middle cerebral arterial doppler time-averaged mean velocity was >2 s.d. above the mean. The baby was born via a normal vaginal delivery at 38 weeks gestation. APGAR scores at 1 and 5 min were 9 and 9, respectively. Initial cardiac examination was within normal limit. Echocardiogram obtained on day-of-life 1 demonstrated a slightly dilated chamber, large patent ductus arteriosus with bidirectional flow, small patent foramen ovale and a small rim of pericardial effusion. A treatment plan of transfusions and iron monitoring was decided upon, with counseling about HSCT.

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Acknowledgements

MYE is supported by the National Institutes of Health grant T32 CA009614. CMC is supported by the National Cancer Institute grant K08 CA174750.

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Authors and Affiliations

  1. Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    M Y Elsaid, C M Capitini, C A Diamond, M Porte, M Otto & K B DeSantes

  2. Division of Hematology, Oncology & Bone Marrow Transplant, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    M Y Elsaid, C M Capitini, C A Diamond, M Otto & K B DeSantes

  3. Division of Neonatology, American Family Children’s Hospital, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    M Porte

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  1. M Y Elsaid
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Correspondence to K B DeSantes.

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Elsaid, M., Capitini, C., Diamond, C. et al. Successful matched unrelated donor stem cell transplant in Hemoglobin Bart's disease. Bone Marrow Transplant 51, 1522–1523 (2016). https://doi.org/10.1038/bmt.2016.153

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