Background/Case Studies: Hematopoietic stem cell transplant (HSCT) is currently the only curative option for patients with sickle cell disease (SCD). Alloimmunization in this population is frequent and can complicate transfusion management during HSCT period.
Study
Design/Methods: The transfusion management strategies for a pediatric SCD patient with severe clinical phenotype, and history of multiple alloantibodies (9) and hyperhemolysis syndrome who successfully underwent HSCT are described.
Results/Findings: The 12-year-old patient underwent haploidentical HSCT following myeloablative conditioning. He received daratumumab, rituximab, bortezomib and had 5 plasma exchanges for desensitization to donor specific anti-HLA antibodies and for the erythrocytes alloimmunization. The patient is known for an anti-e, despite the presence of an RHCE*01.01 allele which predicts a C-, c+, E-, weak e+ phenotype. Because of the patient significant alloimmunization history (anti-M, S, C, e (variant), K, Fy3, Fya, Jkb, s (variant) and probable auto anti-N), it was decided to match units for the RHCE*01.01 allele and all donors matching the patient extended phenotype were targeted for RHCE genotyping. Donors homozygous or heterozygous for RHCE*01.01 were then selected for compatibility analyses and ranked based on strength of reactions. Discordance between zygosity and strength of reactions were observed, as the most compatible donors were heterozygous for RHCE*01.01. Various strategies were also implemented to limit donor exposure. Notably, transfusion decisions were based on anemia tolerance. In total, the patient received 7 red blood cell units from 2 different donors (heterozygote RHCE*01/RHCE*01.01) during HSCT process without transfusion reaction or development of alloantibodies (see Table 1). No reaction during compatibility analyses were observed for donor 1 whereas weak reactions with unabsorbed serum were detected for donor 2, but none with allo-adsorbed serum. Five months post-HSCT, hemoglobin level is stable above 130 g/L and chimerism is 100%. Conclusions: This case highlights the feasibility and safety of HSCT for heavily alloimmunized SCD patients with early involvement of transfusion medicine specialists. Genotyping of donors is useful for identifying compatible blood for those patients but has some limitations. Further research on the clinical impact of genotypic matching is needed.
Importance of research: Hematopoietic stem cell transplant (HSCT) is currently the only curative option for patients with sickle cell disease, but it can be complicated by prior alloimmunization of patients. This case illustrates the different strategies used for the successful transplant of a heavily alloimmunized pediatric patient without transfusion reaction or development of new alloantibodies. It also highlights the advantages and limitations of genotyping for selection of compatible blood donors.
