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Decision analysis of allogeneic bone marrow transplantation versus immunosuppressive therapy for young adult patients with aplastic anemia

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Abstract

Background

Allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling donor is recommended as an initial treatment for young patients. However, immunosuppressive therapy (IST) with cyclosporine and anti-thymocyte globulin may be a viable option even when an HLA-identical sibling donor is available.

Methods

We constructed a Markov model to simulate the 10-year clinical course of patients aged 21–40 years with newly diagnosed severe aplastic anemia. Immediate BMT and IST were compared as an initial treatment assuming the availability of an HLA-identical sibling donor. Transition probabilities after treatment were determined based on a registry data analysis for BMT and a long-term prospective study for IST.

Results

Quality-adjusted life years (QALYs) after treatment selection were 6.77 for BMT and 6.74 for IST. One-way sensitivity analysis revealed that the utility for being alive without GVHD after BMT, that for being alive with partial response after IST, and the response rate after initial IST strongly affected the results.

Conclusions

BMT and IST produced similar QALY for young patients with severe aplastic anemia. An estimation of the response rate to the initial IST may enable an individualized comparison between BMT and IST.

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References

  1. Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, et al. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016;172(2):187–207.

    Article  PubMed  Google Scholar 

  2. Bacigalupo A. How I treat acquired aplastic anemia. Blood. 2017;129(11):1428–36.

    Article  CAS  PubMed  Google Scholar 

  3. Schrezenmeier H, Brümmendorf TH, Deeg HJ, Höchsmann B, Machherndl-Spandl S, Panse J, et al. Aplastische Anämie. 2018. https://www.onkopedia.com/de/onkopedia/guidelines/aplastische-anaemie/@@guideline/html/index.html. Accessed 10 Feb 2022.

  4. Buchbinder D, Nugent DJ, Brazauskas R, Wang Z, Aljurf MD, Cairo MS, et al. Late effects in hematopoietic cell transplant recipients with acquired severe aplastic anemia: a report from the late effects working committee of the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2012;18(12):1776–84.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Liu L, Zhang Y, Jiao W, Zhou H, Wang Q, ** S, et al. Comparison of efficacy and health-related quality of life of first-line haploidentical hematopoietic stem cell transplantation with unrelated cord blood infusion and first-line immunosuppressive therapy for acquired severe aplastic anemia. Leukemia. 2020;34(12):3359–69.

    Article  CAS  PubMed  Google Scholar 

  6. Zhang MX, Wang Q, Wang XQ. Hematopoietic stem-cell transplantation versus immunosuppressive therapy in patients with adult acquired severe aplastic anemia: a cost-effectiveness analysis. Int J Gen Med. 2021;14:3529–37.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Onishi Y, Mori T, Yamazaki H, Takenaka K, Yamaguchi H, Shingai N, et al. Cyclosporine/methotrexate versus tacrolimus/methotrexate with or without anti-thymocyte globulin as GVHD prophylaxis in adult patients with aplastic anemia. Ann Hematol. 2021;100(1):217–28.

    Article  CAS  PubMed  Google Scholar 

  8. Kako S, Yamazaki H, Ohashi K, Ozawa Y, Ota S, Kanda Y, et al. Mixed chimerism and secondary graft failure in allogeneic hematopoietic stem cell transplantation for aplastic anemia. Biol Blood Marrow Transplant. 2020;26(3):445–50.

    Article  CAS  PubMed  Google Scholar 

  9. Inamoto Y, Matsuda T, Tabuchi K, Kurosawa S, Nakasone H, Nishimori H, et al. Outcomes of patients who developed subsequent solid cancer after hematopoietic cell transplantation. Blood Adv. 2018;2(15):1901–13.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Yokota A, Ozawa S, Masanori T, Akiyama H, Ohshima K, Kanda Y, et al. Secondary solid tumors after allogeneic hematopoietic SCT in Japan. Bone Marrow Transplant. 2012;47(1):95–100.

    Article  CAS  PubMed  Google Scholar 

  11. Ohwada C, Sakaida E, Igarashi A, Kobayashi T, Doki N, Mori T, et al. A prospective, longitudinal observation of the incidence, treatment, and survival of late acute and chronic graft-versus-host disease by national institutes of health criteria in a Japanese cohort. Biol Blood Marrow Transplant. 2020;26(1):162–70.

    Article  PubMed  Google Scholar 

  12. Tichelli A, Schrezenmeier H, Socie G, Marsh J, Bacigalupo A, Duhrsen U, et al. A randomized controlled study in patients with newly diagnosed severe aplastic anemia receiving antithymocyte globulin (ATG), cyclosporine, with or without G-CSF: a study of the SAA Working Party of the European Group for Blood and Marrow Transplantation. Blood. 2011;117(17):4434–41.

    Article  CAS  PubMed  Google Scholar 

  13. Tichelli A, de Latour RP, Passweg J, Knol-Bout C, Socie G, Marsh J, et al. Long-term outcome of a randomized controlled study in patients with newly diagnosed severe aplastic anemia treated with antithymocyte globulin and cyclosporine, with or without granulocyte colony-stimulating factor: a severe aplastic anemia working party trial from the European Group of Blood and Marrow Transplantation. Haematologica. 2020;105(5):1223–31.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Scheinberg P. Acquired severe aplastic anaemia: how medical therapy evolved in the 20th and 21st centuries. Br J Haematol. 2021;194(6):954–69.

    Article  CAS  PubMed  Google Scholar 

  15. Valdez JM, Scheinberg P, Nunez O, Wu CO, Young NS, Walsh TJ. Decreased infection-related mortality and improved survival in severe aplastic anemia in the past two decades. Clin Infect Dis. 2011;52(6):726–35.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Voso MT, Fenu S, Latagliata R, Buccisano F, Piciocchi A, Aloe-Spiriti MA, et al. Revised International prognostic scoring system (IPSS) predicts survival and leukemic evolution of myelodysplastic syndromes significantly better than IPSS and WHO prognostic scoring system: validation by the Gruppo Romano Mielodisplasie Italian Regional Database. J Clin Oncol. 2013;31(21):2671–7.

    Article  PubMed  Google Scholar 

  17. Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8.

    Article  CAS  PubMed  Google Scholar 

  18. Kurosawa S, Oshima K, Yamaguchi T, Yanagisawa A, Fukuda T, Kanamori H, et al. Quality of life after allogeneic hematopoietic cell transplantation according to affected organ and severity of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2017;23(10):1749–58.

    Article  PubMed  Google Scholar 

  19. Socie G, Salooja N, Cohen A, Rovelli A, Carreras E, Locasciulli A, et al. Nonmalignant late effects after allogeneic stem cell transplantation. Blood. 2003;101(9):3373–85.

    Article  CAS  PubMed  Google Scholar 

  20. Koreth J, Pidala J, Perez WS, Deeg HJ, Garcia-Manero G, Malcovati L, et al. Role of reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation in older patients with de novo myelodysplastic syndromes: an international collaborative decision analysis. J Clin Oncol. 2013;31(21):2662–70.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Bacigalupo A, Oneto R, Schrezenmeier H, Hochsmann B, Dufour C, Kojima S, et al. First line treatment of aplastic anemia with thymoglobuline in Europe and Asia: outcome of 955 patients treated 2001–2012. Am J Hematol. 2018;93(5):643–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Groth M, Singer S, Niedeggen C, Petermann-Meyer A, Roth A, Schrezenmeier H, et al. Development of a disease-specific quality of life questionnaire for patients with aplastic anemia and/or paroxysmal nocturnal hemoglobinuria (QLQ-AA/PNH)-report on phases I and II. Ann Hematol. 2017;96(2):171–81.

    Article  CAS  PubMed  Google Scholar 

  23. Weisshaar K, Ewald H, Halter J, Gerull S, Schonfeld S, Senft Y, et al. Development of a patient-reported outcome questionnaire for aplastic anemia and paroxysmal nocturnal hemoglobinuria (PRO-AA/PNH). Orphanet J Rare Dis. 2020;15(1):249.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Scheinberg P, Nunez O, Weinstein B, Biancotto A, Wu CO, Young NS. Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med. 2011;365(5):430–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hayakawa J, Kanda J, Akahoshi Y, Harada N, Kameda K, Ugai T, et al. Meta-analysis of treatment with rabbit and horse antithymocyte globulin for aplastic anemia. Int J Hematol. 2017;105(5):578–86.

    Article  CAS  PubMed  Google Scholar 

  26. de Latour RP, Kulasekararaj A, Iacobelli S, Terwel SR, Cook R, Griffin M, et al. Eltrombopag added to immunosuppression in severe aplastic anemia. N Engl J Med. 2022;386(1):11–23.

    Article  Google Scholar 

  27. Katagiri T, Sato-Otsubo A, Kashiwase K, Morishima S, Sato Y, Mori Y, et al. Frequent loss of HLA alleles associated with copy number-neutral 6pLOH in acquired aplastic anemia. Blood. 2011;118(25):6601–9.

    Article  CAS  PubMed  Google Scholar 

  28. Sugimori C, Chuhjo T, Feng X, Yamazaki H, Takami A, Teramura M, et al. Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia. Blood. 2006;107(4):1308–14.

    Article  CAS  PubMed  Google Scholar 

  29. Bacigalupo A, Brand R, Oneto R, Bruno B, Socie G, Passweg J, et al. Treatment of acquired severe aplastic anemia: bone marrow transplantation compared with immunosuppressive therapy—The European Group for Blood and Marrow Transplantation experience. Semin Hematol. 2000;37(1):69–80.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by a Grant from the Ministry of Health, Labor and Welfare of Japan (20FC1018).

Author information

Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan

    Yoshinobu Kanda

  2. Jichi Medical University Saitama Medical Center, Saitama, Japan

    Yoshinobu Kanda & Shinichi Kako

  3. NTT Medical Center Tokyo, Tokyo, Japan

    Kensuke Usuki

  4. Hiroshima Red Cross Hospital & Atomic-Bomb Survivors Hospital, Hiroshima, Japan

    Mitsuhiro Inagaki

  5. Saitama Medical University, Saitama, Japan

    Akiko Ohta

  6. The Jikei University School of Medicine, Tokyo, Japan

    Yoji Ogasawara

  7. University of Tsukuba, Tsukuba, Ibaraki, Japan

    Naoshi Obara

  8. The University of Tokyo, Tokyo, Japan

    Mineo Kurokawa

  9. International University of Health and Welfare, Otawara, Tochigi, Japan

    Naoki Shimada

  10. Kitasato University, Kanagawa, Japan

    Takahiro Suzuki

  11. Japanese Red Cross Aichi Medical Center Nagoya First Hospital, Nagoya, Japan

    Asahito Hama

  12. Nippon Medical School, Tokyo, Japan

    Hiroki Yamaguchi

  13. Kanazawa University Hospital, Kanazawa, Japan

    Shinji Nakao & Hirohito Yamazaki

Authors
  1. Yoshinobu Kanda
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  2. Kensuke Usuki
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  6. Naoshi Obara
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Contributions

YK designed research, performed research, analyzed data, and wrote the paper. KU, SN and HY designed research, analyzed data, and wrote the paper. MI, AO, YO, NO, SK, MK, NS, TS, AH, HY designed research and wrote the paper.

Corresponding author

Correspondence to Yoshinobu Kanda.

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Conflict of interest

Y.K. received research support from Kyowa Kirin, Chugai Pharmaceutical, and Shionogi, and received honoraria from Sanofi, Novartis Pharma, Kyowa Kirin, Chugai Pharmaceutical, and Shionogi. K.U. received research funding from Novartis Pharma, Chugai, Astellas, and Kyowa Kirin, speaker bureaus for Novartis Pharma, Astellas, Kyowa Kirin, Sanofi, and Chugai, and consulting bureaus for Chugai, Sanofi, Kyowa Kirin, and Astellas, and Alnylam Japan. M.I. received honoraria from Sanofi, Novartis Pharma, and Kyowa Kirin. S.K. received honoraria from Sanofi, Novartis Pharma, Kyowa Kirin, and Chugai Pharmaceutical. M.K. received research funding from Astellas Pharma, Kyowa Kirin, Chugai Pharmaceutical, and Shionogi and received honoraria from Sanofi, Kyowa Kirin, Chugai Pharmaceutical, and Astellas Pharma. T.S. received honoraria from Sanofi, Novartis Pharma, Kyowa Kirin, and Chugai Pharmaceutical. H.Y. received research funding from Astellas Pharma, and received honoraria from Novartis Pharma, Kyowa Kirin, and Chugai Pharmaceutical. S.N. received honoraria from Sanofi, Novartis Pharma, Kyowa Kirin, and Chugai Pharmaceutical. H.Y. received honoraria from Novartis Pharma and Kyowa Kirin.

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Kanda, Y., Usuki, K., Inagaki, M. et al. Decision analysis of allogeneic bone marrow transplantation versus immunosuppressive therapy for young adult patients with aplastic anemia. Int J Hematol 117, 660–668 (2023). https://doi.org/10.1007/s12185-022-03530-6

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  • DOI: https://doi.org/10.1007/s12185-022-03530-6

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