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Prognostic factors in salvage transplantation for graft failure following allogeneic hematopoietic stem cell transplantation

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Abstract

Although graft failure (GF) is a fatal complication after allogeneic stem cell transplantation (SCT), no mortality risk assessments after salvage SCT have been reported. We developed a comprehensive prognostic scoring system consisting of patient and comorbidity factors with 470 patients as a training cohort out of 940; these patients underwent salvage SCT for GF. The multivariate analysis demonstrated that older age, poorer performance status, a continuation of antimicrobial treatment, and severe organ dysfunction were independently associated with worse overall survival (OS) and non-relapse mortality (NRM). Based on each factor’s hazard ratio, weighted scores of 1–3 were assigned to these factors. Using the summed scores (0–8), a prognostic scoring system successfully stratified outcomes after salvage SCT in the cohort. For patients in the low (0–2, n = 122), intermediate (3–4, n = 209), and high score (5–8, n = 110) groups, the 1-year OS was 62.8%, 40.8%, and 14.2%, respectively (P < 0.001), whereas the 1-year NRM was 24.1%, 43.9%, and 72.7%, respectively (P < 0.001). The prognostic value of the scoring system was confirmed in the validation cohort (n = 470). Our scoring system is useful for predicting survival after salvage SCT.

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Fig. 1: Transplant outcomes after salvage stem cell transplantation according to the scoring system in each cohort.
Fig. 2: Transplant outcomes after salvage stem cell transplantation according to the scoring system stratified by modified-disease risk index.
Fig. 3: Transplant outcomes after salvage stem cell transplantation according to the scoring system stratified by the donor source.
Fig. 4: The prognostic impact of transplant characteristics in each risk group.

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Data availability

Clinical data were provided by the Transplant Registry Unified Management Program 2 of the Japanese Data Center for Hematopoietic Cell Transplantation. Restrictions are applicable to the availability of the data, which were used under license for this study.

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Acknowledgements

The authors thank all the physicians and staff at the transplant centers who provided the clinical data to the Transplant Registry Unified Management Program of the Japan Society of Hematopoietic Cell Transplantation. The authors also thank Enago (www.enago.jp) for the English language review. This work was supported in part by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development, AMED under Grant Number 18ek0510023h0002. KH, SK, SF, YN, KY, and HN designed this study on behalf of the transplant complication working group in the Japan Society for Hematopoietic Cell Transplantation. KH performed all analyses and wrote the first draft. SK, SF, YN, KY, NU, MO, KI, SY, NS, KM, YO, MS, ST, TK, TF, JK, YA, and HN contributed to data interpretation and correction of the draft. All authors approved the final manuscript.

Funding

This work was supported in part by the Practical Research Project for Allergic Diseases and Immunology (Research Technology of Medical Transplantation) from the Japan Agency for Medical Research and Development, AMED under Grant Number 18ek0510023h0002.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan

    Kaito Harada & Makoto Onizuka

  2. Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan

    Shun-ichi Kimura & Hideaki Nakasone

  3. Department of Hematology, Osaka International Cancer Institute, Osaka, Japan

    Shigeo Fuji

  4. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Yuho Najima & Naoki Shingai

  5. Department of Medical Oncology and Hematology, Kobe University Hospital, Kobe, Japan

    Kimikazu Yakushijin

  6. Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital, Tokyo, Japan

    Naoyuki Uchida

  7. Department of Hematology, Hyogo College of Medicine Hospital, Nishinomiya, Japan

    Kazuhiro Ikegame

  8. Clinical Oncology and Hematology, The Jikei University School of Medicine, Tokyo, Japan

    Shingo Yano

  9. Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan

    Ken-ichi Matsuoka

  10. Department of Hematology, Tohoku University Hospital, Sendai, Japan

    Yasushi Onishi

  11. Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan

    Masashi Sawa

  12. Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Japan

    Satoru Takada

  13. Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan

    Toshiro Kawakita

  14. Hematopoietic Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan

    Takahiro Fukuda

  15. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Junya Kanda

  16. Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan

    Yoshiko Atsuta

  17. Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yoshiko Atsuta

Authors
  1. Kaito Harada
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  2. Shun-ichi Kimura
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  3. Shigeo Fuji
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  18. Yoshiko Atsuta
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Correspondence to Kaito Harada.

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The authors declare no competing interests.

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Our study protocol was approved by the institutional review board of the Tokai University School of Medicine.

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Harada, K., Kimura, Si., Fuji, S. et al. Prognostic factors in salvage transplantation for graft failure following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 56, 2183–2193 (2021). https://doi.org/10.1038/s41409-021-01310-0

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