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Allografting

Long-term disease-free survival after nonmyeloablative cyclophosphamide/fludarabine conditioning and related/unrelated allotransplantation for acute myeloid leukemia/myelodysplasia

Bone Marrow Transplantation volume 45, pages 1300–1308 (2010)Cite this article

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Abstract

A total of 50 consecutive patients (median age, 57.5 years) with AML (n=30) or myelodysplasia (MDS, n=20) underwent HLA matched related donor (MRD, n=27) or unrelated donor (MUD, n=23) peripheral blood hematopoietic cell transplantation after nonmyeloablative CY/fludarabine (Flu) conditioning. GVHD prophylaxis included CsA (n=19)±mycophenolate mofetil (n=31). At a median follow-up of 59 months, 21 patients (42%) were alive without evidence of disease. By Kaplan–Meier analysis, year 1–4 disease-free survival (DFS) and OS estimates were 0.50/0.58, 0.40/0.46, 0.37/0.43 and 0.37/0.41. MUD recipients were engrafted quickly (13.5 days) compared to MRD recipients (16 days) and relapsed/progressed less frequently (P=0.005). Overall grade 3/4 acute GVHD (aGVHD) occurred in 26% in the absence of antecedent mucositis and was associated with chronic GVHD (cGVHD) and poor OS. Extensive cGVHD developed in 51.2% of 100 day survivors. Rates of aGVHD, cGVHD and survival were similar between MRD and MUD recipients. Of 14 survivors with cGVHD, 5 (35.7%) experienced resolution off immunosuppression, suggesting that tolerance with HLA matched grafts is possible at an advanced age by this method. This study provides further evidence for prolonged DFS after CY/Flu MRD allotransplantation for AML/MDS, and extends the findings to older patients and those with unrelated donors.

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Acknowledgements

We acknowledge the work of Judy Amlin, Kelly Ward, and Elizabeth Taylor, who took excellent care of the participants in this study, and Patty Fredenburgh for care coordination. We also thank the community physicians for their kind referral of patients, for the dedicated nursing staff in the BMT Units at Indiana University and the Clarian Health System, and the supportive administration at Indiana University School of Medicine and the IU and Melvin and Bren Simon Cancer Center.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    R P Nelson Jr, J E Schwartz, M J Robertson, C A Fausel, J A Baute, E A Cox, L L Wood, S Srivastava, S S Farag, K Cornetta & L D Cripe

  2. Division of Biostatistics, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    M Yu

  3. Division of Hematology/Oncology, University of New Mexico, Albuquerque, NM, USA

    R Hromas

  4. Division of Pediatric Hematology and Oncology, Department of Pediatrics, IU Melvin and Bren Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA

    R P Nelson Jr, G H Vance, K A Robertson & P R Haut

  5. Department of Medical and Molecular Genetics, IU Melvin and Bren Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA

    G H Vance, S R Dlouhy, S S Farag & K Cornetta

  6. Department of Pathology and Laboratory Medicine, IU Melvin and Bren Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA

    R Abonour

  7. Department of Microbiology and Immunology, IU Melvin and Bren Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA

    S S Farag & K Cornetta

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Nelson, R., Yu, M., Schwartz, J. et al. Long-term disease-free survival after nonmyeloablative cyclophosphamide/fludarabine conditioning and related/unrelated allotransplantation for acute myeloid leukemia/myelodysplasia. Bone Marrow Transplant 45, 1300–1308 (2010). https://doi.org/10.1038/bmt.2009.348

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