Allogeneic Hematopoietic Stem Cell Transplantation for Paroxysmal Nocturnal Hemoglobinuria: Multicenter Analysis by the Polish Adult Leukemia Group.

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.

• Authors: Miroslaw Markiewicz, Joanna Drozd-Sokolowska, Przemyslaw Biecek, Monika Dzierzak-Mietla, Piotr Boguradzki, Mateusz Staniak, Beata Piatkowska-Jakubas, Agnieszka Piekarska, Magdalena Tormanowska, Kazimierz Halaburda, Marek Ussowicz, Anna Waszczuk-Gajda, Grzegorz Basak, Lukasz Bołkun, Justyna Rybka, Maria Sadus-Wojciechowska, Sebastian Giebel, Anna Szmigielska-Kaplon, Ewa Mendek-Czajkowska, Katarzyna Warzybok, Adrian Burdacki, Jadwiga Dwilewicz-Trojaczek
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 26 Issue 10 Pg. 1833-1839 (10 2020) ISSN: 1523-6536 [Electronic] United States
• PMID: 32512214 (Publication Type: Journal Article, Multicenter Study)
• Copyright: Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Topics

• Adolescent
• Adult
• Aged
• Child
• Female
• Graft vs Host Disease
• Hematopoietic Stem Cell Transplantation
• Hemoglobinuria, Paroxysmal (therapy)
• Humans
• Leukemia
• Male
• Middle Aged
• Poland
• Retrospective Studies
• Transplantation Conditioning
• Treatment Outcome
• Young Adult