Is HLA-Haploidentical Hematopoietic Stem Cell Transplantation a Valid Alternative Option for Patients with Combined Paroxysmal Nocturnal Hemoglobinuria and Aplastic Anemia (AA/PNH Syndrome)?

Background In the era of eculizumab, indentifying patients with PNH who may benefit from allogeneic stem cell transplantation(SCT) is challenging, especially for those who have no HLA-matched donors. Several recent studies have shown that HLA-haploidentical SCT for patients with hematological malignancy can achieved comparable outcomes with HLA-identical sibling transplantation. There are very few reports on the use of HLA-haploidentical SCT for AA/PNH. The aim of the present study was to assess the long-term clinical outcome of HLA-haploidentical SCT in patients with AA/PNH.

Methods Total of 9 AA/PNH patients received HLA-haploidentical SCT between Oct 2010 and Oct 2014 at our institution. The patients were aged 13 to 54(median 24 years). The median interval from the diagnosis to transplantation was 48 months (range 2-180). Of the 9 HLA-haploidentical donors, 3 were siblings, 2 fathers, 2 mothers, 1 son and 1 daughter. 8 patients received myeloablative conditioning regimen consisting of busulfan, cyclophosphamide and ATG (anti-thymocyte globulin), 1 patient who underwent salvage HLA-haploidentical SCT after the graft failure of double umbilical cord blood transplantation received conditioning including reduced-intensity total body irradiation, cyclophosphomide and ATG. G-CSF-mobilized bone marrow and peripheral blood stem cells were transplanted as graft. Prophylaxis for graft-versus-host disease(GVHD) consisted of cyclosporine or tacrolimus + mycophenolate mofetil + short-term methotrexate.

Results All 9 patients were engrafted successfully. The median time of neutrophils (ANC) reached to 0.5×10⁹/L and platelets (PLT) reached to 20×10⁹/L were 12 (range 11-26) days and 15 (range 11-120) days, respectively. 2 patients developed grade Ⅱ acute GVHD, 2 patients developed limited chronic GVHD. After a median follow-up time of 14.0 (range 4.0-30.8) months, the 2-year OS probability was 72.9±16.5%. 2 patients died of treatment-related mortality, including severe pulmonary infection (n=1) and transplant-associated thrombotic microangiopathy (n=1),respectively. No patients were documented to have a recurrence of a PNH clone after SCT.

Conclusion This study showed that long-term outcomes of HLA-haploidentical SCT in patients with AA/PNH were comparable to that of HLA-matched donor SCT ( the 2-year OS probability was 80.5±10.2%, P=0.02) at our institution. HLA-haploidentical SCT should be considered as a valid alternative therapeutic option for AA/PNH patients without HLA-matched donors.