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Severe intravascular haemolysis following minor group mismatched peripheral blood stem cell transplantation

Bone Marrow Transplantation volume 39, pages 805–806 (2007)Cite this article

A minor ABO incompatibility is defined by the presence of donor antibodies directed against the antigens of the recipient's red blood cells (RBCs). Delayed immune haemolysis may occur 7–10 days after transplantation, with an unpredictable and rather abrupt onset1 and can be associated with serious consequences, including multiorgan failure and death. This reaction is secondary to transient immune antibody production by donor passenger B lymphocytes carried within the graft and mounting an anamnestic immune response against recipient red cell antigens.2, 3, 4 The occurrence of delayed haemolysis is more often observed in certain settings such as when peripheral blood stem cells (PBSCs) are used instead of bone marrow as the source for stem cells for transplantation,4 and when nonmyeloablative regimen is used compared to myeloablative conditioning regimen.1, 5 It is also noted more often when cyclosporine (CsA) alone is used instead of CsA and methotrexate (MTX) for immunosuppression.2, 6 We report a case of severe delayed intravascular haemolysis and its complications, in a minor mismatched PBSC transplant (PBSCT) despite using myeloablative conditioning regimen and MTX along with CsA for graft-versus-host disease (GVHD) prophylaxis.

A 13-year-old girl, blood group A+, with Philadelphia-positive B cell acute lymphoblastic leukaemia with delayed relapse in second complete remission, underwent an allogeneic PBSCT from her HLA-matched mixed lymphocyte culture nonreactive sister with blood group O+. After conditioning using busulphan and cyclophosphamide, she received 170 ml of PBSC containing 6.1 × 108 viable non-T-cell-depleted cells/kg, from her donor who was primed with recombinant human granulocyte colony-stimulating factor (G-CSF) at 5 mcg/kg/day Q 12 hourly for 4 days (harvesting was performed on day 5). CsA and MTX were administered as GVHD prophylaxis. Neutrophil and platelet engraftment occurred on days 19 and 17, respectively. On day 12, she developed fever, abdominal and bilateral flank pain, with severe intravascular haemolysis as evidenced by a sudden drop in her haemoglobin (Hb) level to 6 g/dl, a lactate dehydrogenase level of 1968 IU/l (n=300–620), plasma Hb level of 600 mg/dl (N<5), a haptoglobin level of less than 50 mg/dl, unconjugated hyperbilirubinemia (maximal bilirubin level reached 32 mg/dl), haemoglobinuria and presence of schistocytes in peripheral smear with normal urea and creatinine levels. The direct Coombs' test was positive, further characterized by a complement-specific antiglobin serum as C3d. A maximal titre of 1:2500 IgM and IgG anti-A antibodies were found in the patient's serum. The patient was treated with adequate hydration, diuretics, morphine infusion, plasmapheresis, A+ fresh-frozen plasma (FFP) and exchange transfusion with 3 l of washed O+ RBCs. She recovered from this haemolytic reaction after 7 days; however, there was a mild derangement of coagulogram suggestive of compensated disseminated intravascular coagulation (DIC).

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Authors and Affiliations

  1. Department of Haematology, Delhi Cantonment, New Delhi, India

    V Nair, A Sharma, J Ratheesh, S Das & D K Mishra

  2. Department of Paediatric surgery, Delhi Cantonment, New Delhi, India

    R Kale

  3. Department of Microbiology, Delhi Cantonment, New Delhi, India

    N Grover

  4. Department of Radiology Army Hospital (Research and Referral), Delhi Cantonment, New Delhi, India

    C Mohan

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Correspondence to V Nair.

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Nair, V., Sharma, A., Ratheesh, J. et al. Severe intravascular haemolysis following minor group mismatched peripheral blood stem cell transplantation. Bone Marrow Transplant 39, 805–806 (2007). https://doi.org/10.1038/sj.bmt.1705674

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