Higher busulfan dose intensity does not improve outcomes of patients undergoing allogeneic haematopoietic cell transplantation following fludarabine, busulfan-based reduced toxicity conditioning

Authors

  • Mehdi Hamadani,

    Corresponding author
    1. Osborn Hematopoietic Malignancy and Transplantation Program, MBRCC, West Virginia University, Morgantown, WV, USA
    • Assistant Professor of Medicine, Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia University, Morgantown, WV 26506, USA.
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  • Michael Craig,

    1. Osborn Hematopoietic Malignancy and Transplantation Program, MBRCC, West Virginia University, Morgantown, WV, USA
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  • Gary S. Phillips,

    1. The Ohio State University, Center for Biostatistics, Columbus, OH, USA
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  • Jame Abraham,

    1. Osborn Hematopoietic Malignancy and Transplantation Program, MBRCC, West Virginia University, Morgantown, WV, USA
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  • William Tse,

    1. Osborn Hematopoietic Malignancy and Transplantation Program, MBRCC, West Virginia University, Morgantown, WV, USA
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  • Aaron Cumpston,

    1. Osborn Hematopoietic Malignancy and Transplantation Program, MBRCC, West Virginia University, Morgantown, WV, USA
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  • Laura Gibson,

    1. Osborn Hematopoietic Malignancy and Transplantation Program, MBRCC, West Virginia University, Morgantown, WV, USA
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  • Scot C. Remick,

    1. Osborn Hematopoietic Malignancy and Transplantation Program, MBRCC, West Virginia University, Morgantown, WV, USA
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  • Pamela Bunner,

    1. Osborn Hematopoietic Malignancy and Transplantation Program, MBRCC, West Virginia University, Morgantown, WV, USA
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  • Sonia Leadmon,

    1. Osborn Hematopoietic Malignancy and Transplantation Program, MBRCC, West Virginia University, Morgantown, WV, USA
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  • Patrick Elder,

    1. Division of Hematology/Oncology, Blood and Marrow Transplantation Section, and the Comprehensive Cancer Center, The Ohio State University, Columbus OH, USA
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  • Craig Hofmeister,

    1. Division of Hematology/Oncology, Blood and Marrow Transplantation Section, and the Comprehensive Cancer Center, The Ohio State University, Columbus OH, USA
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  • Sam Penza,

    1. Division of Hematology/Oncology, Blood and Marrow Transplantation Section, and the Comprehensive Cancer Center, The Ohio State University, Columbus OH, USA
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  • Yvonne Efebera,

    1. Division of Hematology/Oncology, Blood and Marrow Transplantation Section, and the Comprehensive Cancer Center, The Ohio State University, Columbus OH, USA
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  • Leslie Andritsos,

    1. Division of Hematology/Oncology, Blood and Marrow Transplantation Section, and the Comprehensive Cancer Center, The Ohio State University, Columbus OH, USA
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  • Ramiro Garzon,

    1. Division of Hematology/Oncology, Blood and Marrow Transplantation Section, and the Comprehensive Cancer Center, The Ohio State University, Columbus OH, USA
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  • Don M. Benson Jr.,

    1. Division of Hematology/Oncology, Blood and Marrow Transplantation Section, and the Comprehensive Cancer Center, The Ohio State University, Columbus OH, USA
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  • William Blum,

    1. Division of Hematology/Oncology, Blood and Marrow Transplantation Section, and the Comprehensive Cancer Center, The Ohio State University, Columbus OH, USA
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  • Steven M. Devine

    1. Division of Hematology/Oncology, Blood and Marrow Transplantation Section, and the Comprehensive Cancer Center, The Ohio State University, Columbus OH, USA
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  • Financial Disclosure and Propriety Statement: Nothing to disclose.

Abstract

We evaluated the impact of busulfan dose intensity in patients undergoing reduced toxicity/intensity conditioning allogeneic transplantation in a multicenter retrospective study of 112 consecutive patients. Seventy-five patients were conditioned with busulfan (0.8 mg/kg/dose IV × 8 doses), fludarabine (30 mg/m2/day, days −7 to −3), and 6 mg/kg of ATG [reduced intensity conditioning (RIC) group], while 37 patients received a more-intense conditioning with busulfan (130 mg/m2/day IV, days −6 to −3), fludarabine (40 mg/m2/day, days −6 to −3) and 6 mg/kg of ATG [reduced toxicity conditioning (RTC) group]. At baseline both groups were matched for median age, unrelated donor allografts, and human leukocyte antigen-mismatched allografts. More patients in RIC group had high-risk disease, and higher median comorbidity index. There were no graft rejections. Median time to neutrophil (17 days vs. 15 days; p = 0.003) and platelet engraftment (16 days vs. 11 days; p < 0.001) was significantly longer in the RIC group. RTC group had significantly more bacterial (62.2% vs. 32%; p = 0.004) and fungal infections (13.5% vs. 1.3% p = 0.01). For RIC and RTC groups rates of grades II–IV acute GVHD (34% vs. 40%; p-value = 0.54), and chronic GVHD (45% vs. 57%; p-value = 0.30) were not significantly different. In similar order at 1 year the cumulative-incidence of non-relapse mortality (NRM; 12% vs. 21%; p-value = 0.21) and relapse rates (38% vs. 39%; p = 0.96) were not significantly different. Patients in RIC and RTC groups had similar 1-year overall survival (61% vs. 50%, p = 0.11) and progression-free survival (50% vs. 36%, p-value = 0.39). Our data suggest that the merits of higher busulfan dose intensity in the context of fludarabine/busulfan-based RTC may be offset by higher early morbidity. Copyright © 2011 John Wiley & Sons, Ltd.

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