Delayed massive immune hemolysis mediated by minor ABO incompatibility after allogeneic peripheral blood progenitor cell transplantation

Abstract

BACKGROUND: Bone marrow transplantation with minor ABO incompatibility may be followed by moderate delayed hemolysis of the recipient's red cells by donor‐derived ABO antibodies. This reaction may be more severe after transplantation of peripheral blood progenitor cells (PBPCs). CASE REPORT: A 16‐year‐old boy underwent an allogeneic PBPC transplant from his HLA‐mismatched mother as treatment for acute myeloblastic leukemia that had proved resistant to induction chemotherapy. Transfusion of the unmanipulated PBPCs proceeded without any complication, despite the difference in ABO blood group (donor, O Rh‐positive; recipient, A Rh‐positive). On Day 7, a rapid drop in hemoglobin to 4 g per dL was observed, which was attributed to a massive hemolysis. All the recipient's group A red cells were destroyed within 36 hours. This delayed and rapidly progressive hemolytic anemia was not associated with the transfusion of the donor's plasma. Rather, the anti‐A titer increased in parallel with marrow recovery, which suggested an active synthesis of these antibodies by immunocompetent cells from the donor against the recipient's red cells. The mother's anti‐A titer was retrospectively found to be 2048. Her unusually high titer is probably due to prior sensitization during pregnancies. On Day 12, the patient developed grade IV graft‐versus‐host disease, which proved resistant to all treatments instituted and led to his death on Day 35. CONCLUSION: PBPC transplantation with minor ABO incompatibility may be associated with significant risk of massive delayed hemolysis.

Transplantation of ABO-incompatible bone marrow and peripheral blood stem cell components

“…[10][11][12][13][14][15][16][17] Indirect measurements of hemolysis such as rise in bilirubin after transplantation, shown by others to be affected by ABO-incompatible transplantation, 25 did not differ between groups defined by source of HSC or direction of ABO incompatibility. The only patient with a markedly elevated LDH (Ͼ4ϫ normal) showed schistocytes in the peripheral blood smear consistent with extravascular hemolysis occurring 20 days after transplantation.…”

“…However, authors of several recently published case reports of hemolysis occurring after minor or bidirectional ABO-incompatible PBSC transplantation suggest that these recipients are at greater risk of this complication than are marrow recipients, and that the occurrence and severity of the hemolysis may be explained by the much greater number of lymphocytes contained in the PBSC inoculum. [13][14][15][16][17] We conducted a retrospective analysis of related-donor allogeneic transplants to determine whether patients receiving PBSC transplantation were more likely to experience hemolytic complications of ABO-incompatible transplantation than were patients undergoing bone marrow transplantation. We were unable to demonstrate evidence of hemolysis after use of either source of HSC.…”

Impact of ABO blood group mismatch in alemtuzumab-based reduced-intensity conditioned haematopoietic SCT

“…3,7,22,48 PBSC and RIC have both been associated with increased severity of passenger lymphocyte syndrome in patients with MN ABO mismatch, thought secondary to increased numbers of immunocompetent CD3+ T cells and CD19+ B cells transplanted along with a PBSC graft. [49][50][51][52] . In a subgroup analysis of our PBSC RIC patients, however, we found no increased RBC requirement.…”

Hematopoietic stem cell transplantation between red cell incompatible donor–recipient pairs

“…41 The case reports of delayed hemolysis after PBSC transplantation involved patients who received regimens without metho-trexate or for whom some doses of this drug were withheld. [18][19][20][21] However, the incidence of hemolysis after transplantation in the absence of methotrexate is also not defined. Not all patients will experience delayed hemolysis and the risk factors could include both donor and recipient factors.…”

“…Authors of several recently published case reports of hemolysis occurring after minor or bidirectional ABO-incompatible PBSC transplantation suggest that PBSC recipients are at greater risk of this complication than are marrow recipients, and that both the frequency of occurrence and severity of the hemolysis may be explained by the much greater number of lymphocytes contained in a PBSC inoculum. [17][18][19][20][21] However, an increased risk of delayed hemolysis after PBSC transplantation has not been observed by this author for a large series of patients, 22 but these patients received methotrexate or similar medication as part of the GVHD regimen.…”