Presence of Anti-D and Passive Transfer of Anti-D in Bone Marrow Transplant Patients Does Not Affect Transplant Outcomes

Introduction: Red cell alloimmunization can lead to worse outcomes after bone marrow transplant in alloimmunized patients. Anti-D alloimmunization remains a pertinent issue as RhD negative patients may receive RhD positive blood products in emergency or resource limited setting leading to alloimmunization against anti-D. Platelet shortages in particular lead to transfusion of RhD positive platelets to RhD negative potential BMT candidates. Some institutions have adapted a protocol to given Rho(D) immune globulin (RhIg), similar to standard of care for pregnancy, to prevent anti-D alloimmunization in BMT patients while other institutions have not. RhIg has a half life of 26 days but can be detected in circulating up to 6 months after administration. In patients with circulating RhD positive red blood cell, RhIg can lead to clinically significant hemolysis. In BMT patients who receive RhD positive transplant and product RhD positive red blood cells after engraftment, there can be interaction between the red cell and RhIg. Whether the presence of anti-D alloimmunization or RhIg administration would affects BMT outcomes in RhD negative patients receiving an RhD positive BMT is unknown.

Methods: We performed a retrospective analysis of all patients who underwent HSCT and had a positive antibody screen for anti-D between 2016 to 2023. “Anti-D alloimmunization” defined patients who were alloimmunized against the D antigen. “Passive transfer of anti-D (PTAD)” defined patients who had presence of anti-D due to recent administration of RhIg. At our institution, RhD negative patients who are BMT candidates will receive a dose of RhIg within 72 hours of receiving any RhD positive platelet transfusions to prevent alloimmunization.

Variables collected include diagnosis, blood type of patient and donor, date of transplant, timeline of positive antibody screen being positive, conditioning regimen, HLA matched or mismatched, dates of RhIg administration, rationale for RhIg administration. Transplant outcomes included grade of acute graft versus host disease (aGVHD), time to development of aGVHD, day to granulocyte engraftment (absolute neutrophil count greater than 500/mm³), days to platelet engraftment (platelet count greater than 20 x 10⁹/L), days to chronic graft versus host disease (cGVHD), days to death or relapse.

Patients were divided into 3 groups: 1) Anti-D (either anti-D alloimmunization of PTAD) present pre-transplant and received a BMT from RhD positive donor (ADpreBMT+RhD). In the patients with PTAD, the dose of RhIg had to be within 6 months prior to the BMT date as RhIg can be detected for as long as 6 months after being administered. 2) Anti-D present pre-transplant but did not receive a BMT from RhD positive donor (ADpreBMT) 3) Anti-D present post-transplant (ADpostBMT) as the control group. Groups were compared using either ANOVA or Kruskal-Wallis using Graphpad Prism.

Results: A total of 22 BMT patients had positive screens for anti-D. 5 patients had true anti-D alloimmunization of which 2 received a BMT from RhD positive donors. 17 patients had passive transfer of anti-D due to RhIg administration of which 9 were pre-BMT and 8 were post-BMT. The range of RhIg administration prior to transplant date was 23 to 147 days among the 9 patients and 5 had received a BMT from RhD positive donors.

All 22 patients were divided into the group 3 groups, ADPreBMT+RhD (n=7), ADPreBMT (n=7), ADpostBMT (n=8). There were no difference in days to aGVHD or grade of aGVHD between the groups (p=0.48, p=0.79, respectively). There were no differences in days to death or disease relapse (p=0.21). There were no differences in days to platelet and granulocyte engraftment (p=0.1, p=0.23, respectively).

Conclusion: BMT patients who were alloimmunized to anti-D and received an RhD positive transplant did not appear to have worse outcomes than those who received RhD positive transplants. Patients who received RhIg with the 6 months prior to BMT from an RhD positive donor, did not have significantly worse outcomes. However, our study was limited in its small sample size and single institutional study. The use of RhIg to prevent alloimmunization in this patient population warrants further study. Further studies are also needed to understand the long term clinical significance of transfusing RhD positive platelets to RhD negative BMT patients in times of platelet shortages.