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Influence of melphalan plus fludarabine-conditioning regimen in elderly patients aged ⩾55 years with hematological malignancies

Bone Marrow Transplantation volume 51, pages 157–160 (2016)Cite this article

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Some recent clinical developments allow the extension of hematopoietic stem cell transplantation (HSCT) to elderly patients.1 Reduced-intensity conditioning (RIC) regimen-based HSCT was introduced for these patients. Although various RIC regimens have been used and subsequently reported, the high treatment-related toxicity, early mortality and lower survival rate of elderly recipients remain unresolved. Several groups have reported that conditioning regimens employing fludarabine plus melphalan (FM) are efficacious and well tolerated.2, 3 We previously investigated the appropriate melphalan dose in combination with fludarabine in a prospective phase 1 study,4 and our findings led us to recommend a melphalan dose of ⩾135 mg/m2 to induce initial full-donor chimerism. Although another group reported that melphalan administered to elderly patients at doses up to 180 mg/m2 is safe and efficacious,5 most of these reports included a wide range of melphalan doses. The optimal melphalan dose combined with fludarabine for elderly patients is still unclear.

We performed a retrospective, multicenter analysis. Data were provided by the Nagoya Blood and Marrow Transplantation Group, and the registry data were managed using the Transplant Registry Unified Management Program.6 Between April 2002 and March 2011, 371 elderly patients aged ⩾55 years underwent their first allogeneic HSCT at nine Nagoya Blood and Marrow Transplantation Group-affiliated hospitals. We included 113 patients with AML, ALL/lymphoblastic lymphoma and myelodysplastic syndrome who fulfilled the following criteria: the conditioning regimen included fludarabine (125 mg/m2) and melphalan (130–180 mg/m2; FM). GvHD prophylaxis was either cyclosporine or tacrolimus (Tac), which was combined with a short course of methotrexate (MTX). The grafts comprised either bone marrow or granulocyte CSF-mobilized PBSC. Patients receiving TBI or undergoing in vivo or ex vivo T-cell depletion were excluded. We compared two groups according to melphalan dose as follows: FM 160–180 (melphalan >140 mg/m2) and FM 130–140 (melphalan ⩽140 mg/m2) based on the Center for International Blood and Marrow Transplant Research criteria, which define melphalan ⩽140 mg/m2 as RIC regimens.7 The disease risk was defined according to the disease risk index, which combined cytogenetic risk and stage risk.8 Acute GvHD was classified according to clinical criteria,9 and chronic GvHD was graded as limited or extensive.10 The Institutional Review Board approved this study, which was conducted in accordance with the Declaration of Helsinki.

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Acknowledgements

We would like to thank all of the physicians and staff at the cooperating centers for contributing patient data for this study.

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Authors and Affiliations

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

    K Miyao, M Sawa & T Kato

  2. Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan

    Y Kuwatsuka

  3. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Y Ozawa, N Kawashima & K Miyamura

  4. Department of Hematology and Oncology, Konan Kosei Hospital, Konan, Japan

    A Kohno & Y Morishita

  5. Division of Hematology, Meitetsu Hospital, Nagoya, Japan

    H Sao

  6. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    T Nishida & M Murata

  7. Department of Hematology, Nagoya Medical Center, Nagoya, Japan

    H Iida

  8. Department of Hematology, Hamamatsu Medical Center, Hamamatsu, Japan

    K Naito

  9. First Department of Internal Medicine, Gifu University, Gifu, Japan

    H Tsurumi

  10. Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan

    H Taji

  11. Department of Hematology, Fujita Health University, Toyoake, Japan

    S Mizuta

  12. Department of Medical Oncology and Immunology, Nagoya City University, Nagoya, Japan

    S Kusumoto

  13. Department of Hematology and Oncology, Mie University, Tsu, Japan

    K Nakase

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  1. K Miyao
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Correspondence to K Miyao.

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Miyao, K., Sawa, M., Kuwatsuka, Y. et al. Influence of melphalan plus fludarabine-conditioning regimen in elderly patients aged ⩾55 years with hematological malignancies. Bone Marrow Transplant 51, 157–160 (2016). https://doi.org/10.1038/bmt.2015.235

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