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Unrelated donor bone marrow transplantation with treosulfan-based myeloablative conditioning for paroxysmal nocturnal hemoglobinuria- successful treatment despite multiple transplant-related risk factors for hemolysis including major Kidd group incompatibility

Bone Marrow Transplantation volume 37, pages 231–232 (2006)Cite this article

Although allogeneic bone marrow transplantation (BMT) has the potential to cure patients with paroxysmal nocturnal hemoglobinuria (PNH), experience with transplantation from matched unrelated donor (MUD) in PNH is limited to five reports describing a total number of 18 transplants with 50% survival1, 2, 3, 4, 5 (Table 1). The significance of additional transplant-related risk factors for hemolysis, including potentially severe hemolysis due to Kidd group incompatibility, is unknown. Also an optimal preparative regimen in PNH has not yet been established.

Table 1 Published reports on allogeneic transplantations for PNH from unrelated donors
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We report MUD BMT for 35-year-old male PNH patient with refractory hemolysis and multiple BMT-related risk factors for hemolysis. Severe hemolytic anaemia was diagnosed 18 months prior to transplantation. Diagnosis of PNH was confirmed by flow-cytometric detection of complement inhibitor CD55 (DAF- decay accelerating factor) and CD59 (MIRL-membrane inhibitor of reactive lysis) defect present on 95% of erythrocytes and granulocytes. The patient was initially treated for 9 months with steroids (prednisone, methylprednisolone). Iron and folic acid were initially supplied to remedy their insufficiency. Pretransplantation substitutive therapy consisted of 10 transfusions of filtered washed RBCs performed with increasing frequency. At admission prior to BMT obvious signs of severe, progressive, refractory hemolysis were present: LDH 1886 U/l, haptoglobin 0.077 g/l and following morphological values: Hb 7.8 g/dl, Er 2.2 T/l, reticulocytes 98 promille. The donor was a 10-allele HLA-matched 38-year-old male. BMT-related risk factors for hemolysis were major Kidd group incompatibility (Jk(b) antigen present in donor and anti-Jk(b) alloantibodies detectable in recipient in titer 1:2); minor AB0 incompatibility (group 0 in donor with anti-B titer 1:16, group B in recipient); Rh difference (donor positive, recipient negative). Other risk factors included seronegative CMV status in the donor and seropositive in the recipient, arterial hypertension, steroid-related diabetes mellitus and probable former thrombotic episode (leading to nasal septum perforation). Myeloablative conditioning consisted of Treosulfan 3 × 14 g/m2 on days from −6 to −4, Fludarabine 5 × 30 mg/m2 on days from −6 to −2, Thymoglobulin total dose 4.5 mg/kg on days from −3 to −1. The rationale for use of treosulfan-based conditioning was its favorably low nonhematological toxicity profile and myeloablative efficiency demonstrated previously in a dose-finding study,6 although it was not used before for PNH. The nonmyeloablative conditioning regimens consisting of fludarabine with either TBI5, 7 or cyclophosphamide8, 9 were reported to have enough potential to eliminate the PNH clone and allow engraftment.

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  1. Department of Hematology and Bone Marrow Transplantation, Silesian Medical Academy, Katowice, Poland

    M Markiewicz, M Wojciechowska, I Wyleżoł, K Woźniczka, S Giebel, J Wojnar, M Krawczyk-Kuliś & J Hołowiecki

  2. Hematology Department, Institute of Hematology and Transfusiology, Warsaw, Poland

    E Mendek-Czajkowska

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  1. M Markiewicz
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Markiewicz, M., Wojciechowska, M., Wyleżoł, I. et al. Unrelated donor bone marrow transplantation with treosulfan-based myeloablative conditioning for paroxysmal nocturnal hemoglobinuria- successful treatment despite multiple transplant-related risk factors for hemolysis including major Kidd group incompatibility. Bone Marrow Transplant 37, 231–232 (2006). https://doi.org/10.1038/sj.bmt.1705210

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