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Allogeneic hematopoietic stem cell transplantation from a 2-HLA-haplotype-mismatched family donor for posttransplant relapse: a prospective phase I/II study

Bone Marrow Transplantation volume 56, pages 70–83 (2021)Cite this article

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Abstract

HLA haploidentical hematopoietic stem cell transplantation (HSCT), i.e., HSCT from a 1-HLA-haplotype-mismatched family donor, has been successfully performed even as a second transplantation for posttransplant relapse. Is the haploidentical the limit of HLA mismatches in HSCT? In order to explore the possibility of HLA-mismatched HSCT from family donors beyond haploidentical relatives, we conducted a prospective phase I/II study of 2-HLA-haplotype-mismatched HSCT (2-haplo-mismatch HSCT). We enrolled 30 patients with posttransplant relapse (acute myeloid leukemia: 18, acute lymphoblastic leukemia: 11, non-Hodgkin lymphoma: 1). 2-haplo-mismatch HSCT was performed as the second to sixth transplantations. The donors were siblings (n = 12), cousins (n = 16), and second cousins (n = 2). The conditioning regimen consisted of fludarabine, cytarabine, melphalan, low-dose anti-thymocyte globulin, and 3 Gy of total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, methylprednisolone, and mycophenolate mofetil. All patients achieved neutrophil engraftment, except for a case of early death. The cumulative incidences of grades II–IV and III–IV acute GVHD were 36.7% and 16.7%, respectively. The overall survival at 1 year, relapse, and non-relapse mortality rates was 30.1%, 38.9%, and 44.3%, respectively. Considering the poor prognosis of posttransplant relapse, 2-haplo-mismatch HSCT can be an alternative option in a second or third transplantation.

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Fig. 1: Incidence of engraftment, donor chimerism, and acute GVHD.
Fig. 2: Overall survival (OS) rate.
Fig. 3: Incidences of relapse and non-relapse mortality (NRM).
Fig. 4: Recovery of lymphocyte fractions and immunoglobulins.

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Acknowledgements

The authors would like to thank Ms. Ryoko Ishimoto for help with data management and Ms. Kimiko Yamamoto for excellent laboratory support. We also thank all physicians, nurses, pharmacists, physical therapists, and support personnel for their care of the patients in this study.

Funding

This work was supported in part by Health and Labour Sciences Research Grants for Clinical Cancer Research from the Ministry of Health, Labour and Welfare, Japan, Grants-in aid for Scientific Research (18K08376), and a Grant-in-Aid for Researchers, Hyogo College of Medicine.

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

    Kazuhiro Ikegame, Katsuji Kaida, Keiko Fukunaga, Yuko Osugi, Kyoko Yoshihara, Satoshi Yoshihara, Shinichi Ishii, Satoshi Fujino, Takaya Yamashita, Azusa Mayumi, Satoshi Maruyama, Masahiro Teramoto, Takayuki Inoue, Masaya Okada, Hiroya Tamaki, Hiroyasu Ogawa & Yosihiro Fujimori

  2. Division of Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

    Shinichi Ishii

  3. Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan

    Satoshi Fujino

  4. Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan

    Takaya Yamashita

  5. Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Azusa Mayumi

  6. Department of Hematology-Oncology, Chiba Cancer Center, Chiba, Japan

    Satoshi Maruyama

  7. Division of Hematology, Department of Internal Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan

    Masahiro Teramoto

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Contributions

KI designed the study, analyzed data, wrote, and edited the paper. KK, KF, YO, KY, SY, SI, SF, TY, AM, SM, MT, and TI treated patients. MO, HT, HO, and YF supported clinical management.

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Correspondence to Kazuhiro Ikegame.

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Ikegame, K., Kaida, K., Fukunaga, K. et al. Allogeneic hematopoietic stem cell transplantation from a 2-HLA-haplotype-mismatched family donor for posttransplant relapse: a prospective phase I/II study. Bone Marrow Transplant 56, 70–83 (2021). https://doi.org/10.1038/s41409-020-0980-8

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