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16-05-2024 | Aplastic Anemia | Research

Significance of absolute neutrophil count before allogeneic hematopoietic stem cell transplantation in adult patients with aplastic anemia

Authors: Yukinori Nakamura, Yoshitaka Zaimoku, Hiroki Yamaguchi, Hirohito Yamazaki, Minoru Kanaya, Naoyuki Uchida, Noriko Doki, Masatoshi Sakurai, Nobuhiro Hiramoto, Shinichi Kako, Makoto Onizuka, Koichi Onodera, Yumiko Maruyama, Hiroyuki Ohigashi, Tetsuya Nishida, Satoshi Yoshihara, Ken-ichi Matsuoka, Tetsuya Eto, Yoshinobu Kanda, Takahiro Fukuda, Yoshiko Atsuta, Yasushi Onishi

Published in: Annals of Hematology

Abstract

The impact of absolute neutrophil count (ANC) before allogenic hematopoietic stem cell transplantation (HSCT) on the outcomes for patients with aplastic anemia (AA) remains unclear. We retrospectively evaluated the relationship between ANC before transplantation and patient outcomes, involving 883 adult Japanese patients with AA who underwent allogeneic HSCT as their first transplantation between 2008 and 2020. Patients were divided into three groups based on ANC: 0/µL (n = 116); 1–199 (n = 210); and ≥ 200 (n = 557). In the low ANC groups (ANC < 200), patient age was higher, previous anti-thymocyte globulin (ATG) treatments were infrequent, duration from diagnosis to transplantation was shorter, hematopoietic cell transplantation-comorbidity index (HCT-CI) was higher, ATG-based conditioning was used infrequently, and peripheral blood stem cell from related donor and cord blood were used frequently. In multivariate analysis, patient age, previous ATG treatment, HCT-CI, stem cell source, and ANC before transplantation were significantly associated with 5-year overall survival (OS) (“ANC ≥ 200”: 80.3% vs. “ANC 1–199”: 71.7% vs. “ANC 0”: 64.4%). The cumulative incidence of bacterial infection, invasive fungal disease, and early death before engraftment were significantly higher in the low ANC groups. Among patients with ANC of zero before transplantation, younger patient age, shorter duration from diagnosis to transplantation, HCT-CI of 0, and bone marrow from related donor as stem cell source were significantly associated with better OS. Consequently, ANC before allogeneic HSCT was found to be a significant prognostic factor in adult patients with AA. Physicians should pay attention to ANC before transplantation.

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Killick SB, Bown N, Cavenagh J et al (2016) Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol 172:187–207. https://doi.org/10.1111/bjh.13853CrossRefPubMed

Bacigalupo A (2017) How I treat acquired aplastic anemia. Blood 129:1428–1436. https://doi.org/10.1182/blood-2016-08-693481CrossRefPubMed

Iftikhar R, Chaudhry QUN, Anwer F et al (2021) Allogeneic hematopoietic stem cell transplantation in aplastic anemia: current indications and transplant strategies. Blood Rev 47:100772. https://doi.org/10.1016/j.blre.2020.100772CrossRefPubMed

Scheinberg P, Wu CO, Nunez O, Young NS (2009) Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia. Br J Haematol 144:206–216. https://doi.org/10.1111/j.1365-2141.2008.07450.xCrossRefPubMed

Chang MH, Kim KH, Kim HS et al (2010) Predictors of response to immunosuppressive therapy with antithymocyte globulin and cyclosporine and prognostic factors for survival in patients with severe aplastic anemia. Eur J Haematol 84:154–159. https://doi.org/10.1111/j.1600-0609.2009.01378.xCrossRefPubMed

Zhao X, Zhang L, Jing L et al (2015) The role of paroxysmal nocturnal hemoglobinuria clones in response to immunosuppressive therapy of patients with severe aplastic anemia. Ann Hematol 94:1105–1110. https://doi.org/10.1007/s00277-015-2348-5CrossRefPubMed

Townsley DM, Scheinberg P, Winkler T et al (2017) Eltrombopag added to standard immunosuppression for aplastic anemia. N Engl J Med 376:1540–1550. https://doi.org/10.1056/NEJMoa1613878CrossRefPubMedPubMedCentral

Peffault de Latour R, Kulasekararaj A, Iacobelli S et al (2022) Eltrombopag added to immunosuppression in severe aplastic anemia. N Engl J Med 386:11–23. https://doi.org/10.1056/NEJMoa2109965CrossRefPubMed

Zaimoku Y, Patel BA, Shalhoub R et al (2022) Predicting response of severe aplastic anemia to immunosuppression combined with eltrombopag. Haematologica 107:126–133. https://doi.org/10.3324/haematol.2021.278413CrossRefPubMed

10.

Yagasaki H, Shichino H, Ohara A et al (2014) Immunosuppressive therapy with horse anti-thymocyte globulin and cyclosporine as treatment for fulminant aplastic anemia in children. Ann Hematol 93:747–752. https://doi.org/10.1007/s00277-013-1984-xCrossRefPubMed

11.

Liu J, Lu XY, Cheng L et al (2019) Clinical outcomes of immunosuppressive therapy for severe aplastic anemia patients with absolute neutrophil count of zero. Hematology 24:492–497. https://doi.org/10.1080/16078454.2019.1631424CrossRefPubMed

12.

Nishiwaki K, Sano K, Kamiyama Y et al (2018) [Reduced-intensity umbilical cord blood transplantation for adult patients with fulminant aplastic anemia]. Rinsho Ketsueki 59:64–68. https://doi.org/10.11406/rinketsu.59.64CrossRefPubMed

13.

Makishima K, Obara N, Sakamoto T et al (2020) [Haploidentical transplantation from a related donor as first-line treatment for fulminant aplastic anemia]. Rinsho Ketsueki 61:1464–1468. https://doi.org/10.11406/rinketsu.61.1464CrossRefPubMed

14.

Wu LQ, Huang LF, Yang H et al (2023) Comparison of haploidentical-allogeneic hematopoietic stem cell transplantation and intensive immunosuppressive therapy for patients with severe aplastic anemia with an absolute neutrophil count of zero: a retrospective study. Ann Hematol 102:2015–2023. https://doi.org/10.1007/s00277-023-05256-9CrossRefPubMed

15.

Atsuta Y (2016) Introduction of Transplant Registry Unified Management Program 2 (TRUMP2): scripts for TRUMP data analyses, part I (variables other than HLA-related data). Int J Hematol 103:3–10. https://doi.org/10.1007/s12185-015-1894-xCrossRefPubMed

16.

Przepiorka D, Weisdorf D, Martin P et al (1995) 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplantat 15(6):825–828

17.

Shulman HM, Sullivan KM, Weiden PL et al (1980) Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 69:204–217. https://doi.org/10.1016/0002-9343(80)90380-0CrossRefPubMed

18.

Holtan SG, DeFor TE, Lazaryan A et al (2015) Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood 125:1333–1338. https://doi.org/10.1182/blood-2014-10-609032CrossRefPubMedPubMedCentral

19.

Sorror ML, Maris MB, Storb R et al (2005) Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 106:2912–2919. https://doi.org/10.1182/blood-2005-05-2004CrossRefPubMedPubMedCentral

20.

De Pauw B, Walsh TJ, Donnelly JP et al (2008) Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 46:1813–1821. https://doi.org/10.1086/588660CrossRefPubMed

21.

Gooley TA, Leisenring W, Crowley J, Storer BE (1999) Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 18:695–706. https://doi.org/10.1002/(sici)1097-0258(19990330)18:6%3C695::aid-sim60%3E3.0.co;2-oCrossRefPubMed

22.

Kanda Y (2013) Investigation of the freely available easy-to-use software EZR for medical statistics. Bone Marrow Transpl 48:452–458. https://doi.org/10.1038/bmt.2012.244CrossRef

23.

Champlin RE, Perez WS, Passweg JR et al (2007) Bone marrow transplantation for severe aplastic anemia: a randomized controlled study of conditioning regimens. Blood 109:4582–4585. https://doi.org/10.1182/blood-2006-10-052308CrossRefPubMedPubMedCentral

24.

Bacigalupo A, Socié G, Schrezenmeier H et al (2012) Bone marrow versus peripheral blood as the stem cell source for sibling transplants in acquired aplastic anemia: survival advantage for bone marrow in all age groups. Haematologica 97:1142–1148. https://doi.org/10.3324/haematol.2011.054841CrossRefPubMedPubMedCentral

25.

Kumar R, Kimura F, Ahn KW et al (2016) Comparing outcomes with bone marrow or peripheral blood stem cells as graft source for matched sibling transplants in severe aplastic anemia across different economic regions. Biol Blood Marrow Transpl 22:932–940. https://doi.org/10.1016/j.bbmt.2016.01.012CrossRef

26.

Kuwatsuka Y, Kanda J, Yamazaki H et al (2016) A comparison of outcomes for cord blood transplantation and unrelated bone marrow transplantation in adult aplastic anemia. Biol Blood Marrow Transpl 22:1836–1843. https://doi.org/10.1016/j.bbmt.2016.07.002CrossRef

27.

Onishi Y, Mori T, Yamazaki H et al (2023) Comparison of Haploidentical Stem Cell transplantation with Post-transplantation Cyclophosphamide versus umbilical cord blood transplantation in adult patients with aplastic Anemia. Transpl Cell Ther 29. https://doi.org/10.1016/j.jtct.2023.09.009. :766.e1-766.e8

28.

Zhang Y, Chen X, Yang D et al (2022) The prognostic impact of previously infectious complications on allogeneic hematopoietic stem cell transplantation for patients with severe aplastic anemia: a single-center, retrospective study. Front Immunol 13:1004787. https://doi.org/10.3389/fimmu.2022.1004787CrossRefPubMedPubMedCentral

29.

Xu S, Wu L, Zhang Y et al (2018) Allogeneic hematopoietic stem cell transplantation for the treatment of severe aplastic anemia patients with infection: a single-center retrospective study. Biol Blood Marrow Transpl 24:2532–2539. https://doi.org/10.1016/j.bbmt.2018.07.018CrossRef

30.

Liu L, Miao M, Chen X et al (2021) Outcomes of severe aplastic anemia patients with infection proceeding with allogeneic hematopoietic stem cell transplantation, versus patients without infection. Bone Marrow Transplant 56:2591–2594. https://doi.org/10.1038/s41409-021-01398-4

Title: Significance of absolute neutrophil count before allogeneic hematopoietic stem cell transplantation in adult patients with aplastic anemia
Authors: Yukinori Nakamura
Yoshitaka Zaimoku
Hiroki Yamaguchi
Hirohito Yamazaki
Minoru Kanaya
Naoyuki Uchida
Noriko Doki
Masatoshi Sakurai
Nobuhiro Hiramoto
Shinichi Kako
Makoto Onizuka
Koichi Onodera
Yumiko Maruyama
Hiroyuki Ohigashi
Tetsuya Nishida
Satoshi Yoshihara
Ken-ichi Matsuoka
Tetsuya Eto
Yoshinobu Kanda
Takahiro Fukuda
Yoshiko Atsuta
Yasushi Onishi
Publication date: 16-05-2024
Publisher: Springer Berlin Heidelberg
Keywords: Aplastic Anemia
Stem Cell Transplantation
Stem Cell Transplantion
Stem Cell Transplantation
Graft-Versus-Host Disease
Graft-Versus-Host Disease
Published in: Annals of Hematology
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-024-05800-1

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