The impact of pre-existing HLA and red blood cell antibodies on transfusion support and engraftment in sickle cell disease after nonmyeloablative hematopoietic stem cell transplantation from HLA-matched sibling donors: A prospective, single-center, observational study

Abstract

Background: Hematopoietic stem cell transplantation (HSCT) is curative for patients with sickle cell disease (SCD). Prior to HSCT, patients with SCD commonly receive RBC transfusions with some becoming RBC or HLA alloimmunized. This alloimmunization may impact post-HSCT transfusion requirements and donor engraftment. Methods: The study population included patients with SCD transplanted on a single-center nonmyeloablative, HLA-matched sibling HSCT trial at the National Heart, Lung, and Blood Institute (NHLBI) who had a pre-HSCT sample available for HLA class I antibody testing. We evaluated transfusion requirements and engraftment outcomes comparing patients with and without pre-existing HLA and RBC antibodies. Findings: Of 36 patients studied, 10 (28%) had HLA class I antibodies and 11 (31%) had a history of RBC alloantibodies. Up to day +45 post-HSCT, patients with HLA antibodies received more platelet transfusions (median 2.5 vs 1, p = 0.042) and those with RBC alloantibodies received more RBC units (median 7 vs 4, p = 0.0059) compared to respective non-alloimmunized patients. HLA alloimmunization was not associated with neutrophil engraftment, donor chimerism, or graft rejection. However, RBC alloimmunization correlated with a decreased donor T cell chimerism at 1 year (median 24% vs 55%, p = 0.035). Interpretation: Pre-existing HLA and RBC alloantibodies are clinically significant for patients undergoing HLAmatched nonmyeloablative HSCT. Testing for both HLA and RBC antibodies is important to help estimate transfusion needs peri-HSCT. The association of lower donor T cell chimerism and pre-existing RBC alloantibodies needs further investigation.

Case report: Daratumumab treatment in pre-transplant alloimmunization and severe hemolytic anemia

“…RBC alloimmunization is not only a significant obstacle for transfusing patients with sickle cell disease due to the risk of severe hemolytic transfusion reactions, but also impacts transplant outcomes due to HLA alloimmunization ( 23 ). In a study by Nickel et al., HLA alloimmunization did not correspond with neutrophil engraftment, donor chimerism, or graft rejection in sickle cell patients, but RBC alloimmunization correlated with a decline in donor T cell chimerism at one year ( 24 ). Presence of donor specific HLA antibodies (DSA) indicates a 10 fold increase of primary graft failure and graft rejection, especially when MFI is > 10,000 ( 25 , 26 ).…”

Chronic granulomatous disease and McLeod syndrome: Stem cell transplant and transfusion support in a 2-year-old patient—a case report

“…A pre-conditioning regime using rituximab to deplete B cells and daratumumab to inhibit plasma cells was used to try to blunt the immune antibody response and reduce alloimmunization risk ( 11 ). rEPO was used early to increase hematocrit during conditioning as well as enhance repopulation of the erythroid cell line post-allogeneic transplant ( 17 ).…”

“…The transfusion service was notified that compatible RBC units were not currently available and a suitable donor could not be identified. The risk of alloimmunization from non-MLS compatible units could complicate the post-transplant course (9)(10)(11), so an autologous whole blood donation program was developed by the transfusion service in conjunction with a local blood supplier to collect and freeze autologous units for a child of this size (~11 kg).…”

Post–hematopoietic stem cell transplantation immune-mediated anemia: a literature review and novel therapeutics

“…In one cohort, RBC antibodies were detected in 9 of 61 patients post-HCT (15%), including 3 patients with pre-formed and 6 with new antibodies, 4 patients developed reticulocytopenia or hemolysis [59]. In a cohort of non-MA, matched-sibling HCT for SCT, 31% (11/31) of patients had a history of RBC alloantibodies, which was correlated with a decreased donor T cell chimerism at 1 year than non-alloimmunized patients (median 24% vs 55%, p=.035) [60]. As the number of HCT in SCD is increasing, it remains a challenge to prevent and treat RBC alloimmunization peri-HCT.…”

“… 58 In a cohort of patients undergoing matched-sibling HSCT without MA conditioning, 31% (11 of 31) had a history of RBC alloantibodies, which was correlated with decreased donor T-cell chimerism at 1 year compared with patients without alloimmunization (median, 24% vs 55%; P = .035). 59 As the number of HSCTs in sickle cell disease is increasing, it remains a challenge to prevent and treat RBC alloimmunization peri-HSCT.…”