Effect of ABO Mismatch and RBC Alloimmunization on the Outcome of Hematopoietic Cell Transplantation for Sickle Cell Disease.

Abstract

Background: Hematopoietic cell transplantation (HCT) remains the only well-established curative option for sickle cell disease (SCD) patients. Nonmyeloablative (NMA) conditioning has been used to improve the outcomes and reduce toxicities in adult SCD patients. However, Recipient/Donor (R/D) ABO incompatibility and alloimmunization could be significant impediments to successful outcomes when transplanting SCD patients due to risks of hemolysis, delayed engraftment, poor graft function and graft failure (GF). Herein, we report our experience with allogeneic HSCT for SCD and the effects of RBC groups mismatch and alloimmunization on the outcome of transplanted patients.

Methods: We conducted a retrospective analysis of all SCD patients (age >14 year) that underwent HSCT from January 2015 to February 2022 at our center. All patients received Intravenous alemtuzumab (1 mg/kg divided over 5 days on days -7 to -3) and 300 cGy TBI on day -2 or -1 for conditioning. Pre-transplant preparation consisted of hydroxyurea at maximum tolerated dose for 2-3 months and one session of exchange transfusion. Peripherally mobilized CD34 stem cells targeting 10 × 10⁶ /kg of recipient weight were used. For graft versus host disease (GVHD) prophylaxis sirolimus was started on day -1 and continued for one year with tapering if lymphoid chimerism was > 50%. For Patients with major ABO incompatibility, we administered 2 doses of rituximab (375 mg/m2) and 3 sessions of plasmapheresis before starting the conditioning regimen targeting an isoheamagglutinin titer < 1/32. The primary objective was to determine the impact of RBC groups mismatch and alloimmunization on the outcome of transplanted patients. The secondary objective was to assess the impact of GF on overall survival (OS). Logistic regression was done to evaluate predictors for GF. Kaplan-Meier method was used for survival analysis.

Results: A total of 194 patients were included with a median age of 26 years. The median baseline Hgb and HbS were 93 g/L and 71.3%, respectively. Indications of stem cell transplantations were most commonly due to recurrent vaso-occlusive crisis in 52.5% of patients, CNS events in 19.6%, and acute chest syndrome in 17%. After a median follow up of 28.8 months (5-83), sixteen patients (8%) experienced graft failure (3 with primary GF and 13 with secondary GF). On univariate analysis, ABO minor incompatibility and RBC alloantibodies against donor non-ABO antigens were predictive for GF.On multivariate analysis RBC alloantibodies against donor non-ABO antigens (OR, 8.29; 95% CI, 2.01 to 34.05, P=0.0033) was the only factor predictive of GF. None of the 16 patients with major ABO incompatibility developed GF. Two-years OS for all patients was 95%. The 2 years OS for patients without GF was 98% compared to 74% in patients with GF, (P<0.0001).

Conclusion: In our SCD transplanted patients, RBC alloantibodies against donor non- ABO antigens were an independent risk factor for GF. Patients with GF had an inferior survival and strategies for decreasing GF risk are needed.