PB1270 - Hematopoietic stem cell transplantation in a newborn suffering from severe combined immunodeficiency and severe hemophilia A

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Sarah Schober, MD

Medical Doctor
University Children’s Hospital Tuebingen, Department I – General Pediatrics, Hematology/Oncology, Tuebingen, Germany
Tuebingen, Baden-Wurttemberg, Germany

Co-Author(s)

UH

Ursula Holzer

Consultant
University Children’s Hospital Tuebingen, Department I – General Pediatrics, Hematology/Oncology, Tuebingen, Germany
Tuebingen, Baden-Wurttemberg, Germany
PL

Peter Lang

Acting Medical Director
University Children’s Hospital Tuebingen, Department I – General Pediatrics, Hematology/Oncology, Tuebingen, Germany
Tuebingen, Baden-Wurttemberg, Germany
MD

Michaela Döring

Consultant
University Children’s Hospital Tuebingen, Department I – General Pediatrics, Hematology/Oncology, Tuebingen, Germany
Tuebingen, Baden-Wurttemberg, Germany
Martin Olivieri (he/him/his)

Head of the Paediatric Thrombosis and Haemostasis Unit
Paediatric Thrombosis and Haemostasis Unit, Paediatric Haemophilia Center, Dr. von Hauner Children's Hospital, LMU Clinic, Munich, Germany
Munich, Bayern, Germany
VI

Vanya Icheva

Consultant
University Children’s Hospital Tuebingen, Department II – Pediatric Cardiology, Intensive Care Medicine and Pulmonology, Tuebingen, Germany
Tuebigen, Baden-Wurttemberg, Germany

Background: SCID and severe hemophilia A are two rare congenital diseases (incidence SCID 1:50 000 newborns, hemophilia A 1:5 000 male newborns). The coincidence of these potentially life-threatening diseases in newborns has not been reported so far. Today, SCID can be cured by HSCT. However, managing a newborn with severe hemophilia A during HSCT is challenging.

Aims: We describe a newborn with SCID, genetically verified by a homozygous pathogen missense variant in RAG1 gene at 5 weeks of age. In addition, the boy suffered from severe hemophilia A caused by an inversion of intron 22. Both parents were consanguine.

Methods: The patient received T-cell depleted peripheral stem cells from a matched unrelated donor after a myeloablative conditioning regimen at the age of three months. The first substitution of extended half-life factor VIII product (Efmoroctocog alfa) was required during implantation of the central venous catheter. During the initial phase of HSCT factor VIII was supplemented twice a week with 250IE. During the aplastic period with platelet count < 100,000/µl, factor substitution was adjusted to achieve factor VIII levels > 50%. After hematopoietic reconstitution, factor VIII substitution was reduced to 250IE twice a week, and finally to once a week. There were no bleeding complications and no inhibitor was detected.

Results: HSCT is feasible without bleeding complications applying an individual substitution regimen depending on platelet count. So far, the patient did not develop any factor VIII inhibitor although intron 22 inversion is associated with an inhibitor risk of about 25%.

Conclusion(s): One could assume that the risk for developing inhibitors is lower in patients with impaired immune system. After HSCT, the inhibitor risk presumably remains lower as the healthy donor cells were exposed to normal factor VIII levels. However, this is speculative and further studies are needed to investigate hemophilia patients suffering from immunodeficiencies and undergoing HSCT.