HSCT in a newborn suffering from SCID and severe haemophilia A

Introduction SCID (severe combined immunodeficiency) and severe haemophilia A are two very rare congenital diseases (incidence SCID 1:50 000 newborns, haemophilia A 1:5 000 male newborns). The coincidence of these two potentially life-threatening diseases in newborns has not been reported so far. Today, SCID can be cured by HSCT (haematopoietic stem cell transplantation). However, managing a newborn with severe haemophilia A during intensive HSCT treatment with increased bleeding risk is very challenging.

Method We describe a newborn with SCID, genetically verified by a homozygous pathogen missense variant in RAG1 gene at 5 weeks of age. Initially, SCID was suspected by a pathological newborn screening test. In addition, the boy suffered from severe haemophilia A caused by an inversion of intron 22, which was detected postnatally due to familial haemophilia predisposition. The parents were consanguine (cousins). So far there were no known SCID cases in the family. Fortunately, the boy had no severe infections since he was admitted to the HSCT ward at the age of 16 days.

Results As no matched sibling donor could be found, the patient received T-cell depleted peripheral stem cells from a matched unrelated donor after a myeloablative conditioning regimen (fludarabine, thiotepa, treosulfan, ATG) at the age of three months. The first substitution of elevated 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 (d+2 – d+16) with a platelet count < 100,000/µl, factor substitution was individually adjusted to achieve factor VIII levels > 50% (40IE/kg/BW daily to every other day). After haematopoietic reconstitution, with a platelet count > 100,000/µl, factor VIII substitution was reduced to 250IE twice a week, and finally in the absence of bleeding symptoms to once a week (follow up until d+61). With this individualized management there were no bleeding complications and no inhibitor was detected. There were no relevant side effects during HSCT.

Conclusion This is the first case report of a newborn suffering from SCID and severe haemophilia A. HSCT is feasible in this situation without bleeding complications if an individual substitution regimen is applied depending on the platelet count. So far, the patient did not develop any factor VIII inhibitor although intron 22 inversion is associated with an elevated inhibitor risk of about 25%. One could assume that the risk for developing inhibitors is lower in a patient with SCID as the immune system is impaired. After HSCT, the inhibitor risk presumably remains decreased due to the fact that the healthy donor cells were exposed to normal factor VIII levels. However, this is speculative and further studies are needed to investigate haemophilia patients undergoing HSCT and haemophilia patients suffering from immunodeficiencies.

Publikationsverlauf

Artikel online veröffentlicht:
20. Februar 2023