Transplantation without Hemolysis in a Kell Antigen Positive Patient Undergoing Peripheral Hematopoietic Stem Cell Transplant from a Donor with Anti-Kell Antibodies.

Red blood cell (RBC) antibody formation, with or without hemolysis, is a well known post-transplant complication of ABO and non-ABO mismatched patients and is seen in both solid organ and hematopoietic stem cell transplants (HSCT). Hemolysis secondary to donor lymphocytes transfused during transplant, which produce antibodies directed toward the patient’s remaining red blood cells, is most commonly reported among HSCT donor-recipients with minor ABO blood group mismatching. Passenger Lymphocyte Syndrome (PLS) has been noted to occur in non-ABO group mismatched HSCTs involving the following blood group systems: Rh, Kidd, Lewis, MNS and Duffy. We present a case of a patient with acute myeloid leukemia (AML) in first complete remission who was Kell antigen positive and underwent a non-myeloablative peripheral blood HSCT from a 10/10 HLA matched, related donor who had anti-Kell antibodies. The patient was a 69-year-old male with AML in first remission who consented for transplant with non-myeloablative conditioning on CALGB 100103. At the time of transplantation, the patient was ABO type A positive, had a negative antibody screen, and was positive for the Kell (K1) antigen. The patient had not been transfused RBC or platelets for 4 months prior to HSCT. The related donor was found to be A positive and had anti-Kell that was reactive 1+ at antihuman globulin phase (GEL) prior to filgrastim mobilized peripheral blood HSC collection. The patient received a conditioning regimen of fludarabine 30mg/m² daily (days -7 to -3) and bulsulfan 0.8mg/kg IV every 6 hours for 8 doses (days -4 to -3). GVHD prophylaxis consisted of methotrexate (5mg/m²) on day +1, +3, and +6 and tacrolimus starting on day -2. After HSCT, no RBC or platelet transfusions were required throughout the patient’s course. Neutrophil and platelet engraftment occurred by day +20. Chimerism studies on peripheral blood[c1] at day +30 revealed 61% donor CD3 T cells, 99% CD14 and CD15, myeloid cells, 90% CD19, B cells, and 96% donor whole blood. Weekly direct antiglobulin tests were performed (day +7 through day +21) with monitoring of hemoglobin, hematocrit, LDH, total and direct bilirbuin, BUN, and creatinine to evaluate for hemolysis. No evidence of hemolysis was seen in the immediate post-transplant period, and the patient’s antibody screen has remained negative to date through day +100. In conclusion, this case demonstrates that peripheral blood HSCT may be done safely in the setting of non-ABO incompatibility due to Kell in the donor-recipient direction. Given the increasing use of non-myeloablative conditioning regimens and peripheral blood HSCT, both of which increase the risk of PLS, the case highlights that the risks of hemolysis for HSCT are evolving and demonstrates the successful implementation of one strategy for monitoring at risk patients.