Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole potential cure for paroxysmal nocturnal hemoglobinuria (PNH); however, the data on its utility in PNH are limited. This retrospective analysis of patients with PNH who underwent allo-HSCT in 11 Polish centers between 2002 and 2016 comprised 78 patients with PHN, including 27 with classic PNH (cPNH) and 51 with bone marrow failure-associated PNH (BMF/PNH). The cohort was 59% male, with a median age of 29 years (range, 12 to 65 years). There was a history of thrombosis in 12% and a history of hemolysis in 81%, and 92% required erythrocyte transfusions before undergoing allo-HSCT. No patient received eculizumab, and 26% received immunosuppressive treatment. The median time from diagnosis to allo-HSCT was 12 months (range, 1 to 127 months). Almost all patients (94%) received reduced-toxicity conditioning, 66% with treosulfan. The stem cell source was peripheral blood in 72% and an identical sibling donor in 24%. Engraftment occurred in 96% of the patients. With a median follow-up of 5.1 years in patients with cPNH and 3.2 years in patients with BMF/PNH, 3-year overall survival (OS) was 88.9% in the former and 85.1% in the latter (P=not significant [NS]). The 3-year OS for patients with/without thrombosis was 50%/92% (P=NS) in the cPNH group and 83.3%/85.3% (P=NS) in the BMF/PNH group. The 3-year OS for in the BMF/PNH patients with/without hemolysis was 93.9%/62.9% (hazard ratio, .13; P=.016). No other factors impacted OS. After allo-HSCT, the frequency of the PNH clone was reduced to 0%, <1%, and <2.4% in 48%, 48%, and 4% of cPNH patients and in 84%, 11%, and 5% of BMF/PNH patients, respectively. The frequency of acute graft-versus-host disease (GVHD) grade II-IV was 23%, and the cumulative 1-year incidence of extensive chronic GVHD was 10.8% in the BMF/PNH group and 3.7% in the cPNH group. Allo-HSCT is a valid option for PNH patients, effectively eliminating the PNH clone with satisfactory overall survival and acceptable toxicity. Reduced-toxicity conditioning with treosulfan is effective and safe in patients with cPNH and BMF/PNH.
Highlights
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematologic disorder
Our study cohort comprised 78 patients diagnosed with PNH, including 27 with classic PNH (cPNH) and 51 with bone marrow failure-associated PNH (BMF/PNH), who underwent allo-HSCT between 2002 and 2016 at 11 Polish Acute Leukemia Group (PALG) centers
The study covers a cohort of 78 patients with PNH who underwent allo-HSCT, making it one of the largest analysis of such patients published to date
Summary
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematologic disorder. The acquired somatic mutation of the PIG-A (phosphatidylinositol glycan anchor biosynthesis, class A) gene leading to deficiency of glycosylphosphatidylinositol-anchored complement regulatory proteins (eg, CD55 and CD59), is the pathobiological mechanism underlying the development of PNH. Allogeneic hematopoietic stem cell transplantation (allo-HSCT), which has the potential to be curative by eradicating the PNH clone through the combined effect of conditioning cytotoxicity and immunoreactivity of donor T cells [9], offers a putative option for patients lacking access to complement inhibitors or unwilling to be treated for life without a guarantee of improvement of their disease. Allo-HSCT can be an option for patients in a resource-constrained setting, considering the high cost of C5 inhibitors. It must be kept in mind, that survival following allo-HSCT is challenged by substantial complications, and in approximately one-third of survivors, quality of life is impacted by symptoms of GVHD
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