Introduction: Hematopoietic cell transplantation (HCT) is the only curative therapy for sickle cell disease (SCD), though is not widely utilized due to inadequate donor availability. Our center has previously reported improved outcomes with a reduced intensity, haploidentical bone marrow transplant (haplo-BMT) with post-transplant Cytoxan and thiotepa (de la Fuente et al, Biol Blood Marrow Transplant 2019). All patients treated with this protocol require red blood cell (RBC) support for anemia. Alloimmunization to minor RBC antigens can be a barrier to therapies including HCT, especially in those patients with multiple antibodies or those requiring rare RBC units. We report on our experience thus far in seven patients with SCA on this protocol.
Materials and Methods: After IRB approval, we report in a cohort of 10 patients who completed haplo-BMT with our ongoing platform (ClinicalTrials.gov Identifier: NCT01850108). Phenotypic matching of RBCs beyond ABO and Rh(D) is necessary since patients with SCD commonly produce antibodies against minor RBC antigens, which can result in transfusion reactions such as delayed hemolysis and hyperhemolysis. Our institutional practice is to obtain minor RBC phenotyping on both the patient and their donor prior to transplant. The blood bank provides RBCs that are phenotypically matched for Rh and Kell antigens regardless of antibody status. If a patient has a history of an antibody or a positive screen, the blood bank provides extended phenotypic matching to include Fya, Fyb, Jka, Jkb, and MNS if possible. Outcomes data were analyzed using the CIBMTR database and EMR.
Results: A total of 10 patients underwent haplo-BMT, 7 for sickle cell anemia and 3 for beta thalassemia major. Two patients had alloantibodies prior to haplo-BMT, both of whom had SCA. Three patients were ABO identical with their donor; five patients received minor ABO incompatible transplants, and two received major ABO incompatible transplants. Indications for transplant included transfusion dependence (5 patients), cerebrovascular accidents (4 patients), recurrent pain crises (1 patient), visual impairment (1 patient), and seizures (1 patient). The median recipient age at transplant was 17.8 years for the 8 males and 2 females included. Median donor age was 37.5 years, including 4 males and 6 females, with 7 parental donors and 3 sibling donors. No grade 1 acute graft-versus-host disease (GvHD) was noted, though 30% (3/10) had grades II-IV disease. Limited chronic GvHD occurred in 20% (2/10) patients, without any cases of extensive disease. A median of 3.5 RBC (range 0 - 14) transfusions and a median of 10 (range 1 - 24) platelet transfusions were required from date of transplant until neutrophil engraftment. None of the patients had delayed erythroid engraftment.
Conclusion: We report successful haploidentical HCT in 7 patients with sickle cell anemia. Providing appropriate phenotypically matched RBCs is especially important in the era of emerging cures for sickle cell anemia, including gene therapy and haploidentical HCT. Alloimmunization is an understudied barrier to HSCT and must be carefully assessed when planning for HCT or other curative therapies required RBC transfusion support.
1. de la Fuente J, Dhedin N, Koyama T, et al. Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide Plus Thiotepa Improves Donor Engraftment in Patients with Sickle Cell Anemia: Results of an International Learning Collaborative. Biol Blood Marrow Transplant 2019;25:1197-1209.
2. Bolanos-Meade J, Fuchs EJ, Luznik L, et al. HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease. Blood 2012;120:4285-91.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
