Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has the capacity to produce durable remissions and long-term disease-free survival in patients with high-risk acute myeloid leukemia and myelodysplasia

Sudhir Tauro, Charles Craddock, Karl Peggs, Gulnaz Begum, Premini Mahendra, Gordon Cook, Judith Marsh, Donald Milligan, Anthony Goldstone, Ann Hunter, Asim Khwaja, Raj Chopra, Timothy Littlewood, Andrew Peniket, Anne Parker, Graham Jackson, Geoff Hale, Mark Cook, Nigel Russell, Stephen Mackinnon

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    Abstract

    Purpose The toxicity of allogeneic stem-cell transplantation can be substantially reduced using a reduced-intensity conditioning (RIC) regimen. This has increased the proportion of patients with myeloid malignancies eligible for allogeneic transplantation. However, the capacity of RIC allografts to produce durable remissions in patients with acute myeloid leukemia (AML) and myelodysplasia (MDS) has not yet been defined, and consequently, the role of RIC allografts in the management of these diseases remains conjectural. Patients and Methods Seventy-six patients with high-risk AML or MDS received an allograft using a fludarabine/ melphalan RIC regimen incorporating alemtuzumab. The median age of the cohort was 52 years (range, 18 to 71 years). Results The 100-day transplantation-related mortality rate was 9%, and no patient developed greater than grade 2 graft-versus-host disease. With a median follow-up of 36 months (range, 13 to 70 months), 27 patients were alive and in remission, with 3-year actuarial overall survival (OS) and disease-free survival (DFS) rates of 41% and 37%, respectively. The 3-year OS and DFS rates of patients with AML in complete remission at the time of transplantation were 48% and 42%, respectively. Disease relapse was the most common cause of treatment failure and occurred at a median time of 6 months after transplantation. All but one patient destined to relapse did so within 24 months of transplantation. Conclusion The extended follow-up in this series identifies a high risk of early disease relapse but provides evidence that RIC allografts can produce sustained DFS in a significant number of patients with AML who would be ineligible for allogeneic transplantation with myeloablative conditioning. S.T. and C.C. contributed equally to this article.
    Original languageEnglish
    Pages (from-to)9387-9393
    Number of pages7
    JournalJournal of Clinical Oncology
    Volume23
    Issue number36
    DOIs
    Publication statusPublished - 2005

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    Tauro, S., Craddock, C., Peggs, K., Begum, G., Mahendra, P., Cook, G., Marsh, J., Milligan, D., Goldstone, A., Hunter, A., Khwaja, A., Chopra, R., Littlewood, T., Peniket, A., Parker, A., Jackson, G., Hale, G., Cook, M., Russell, N., & Mackinnon, S. (2005). Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has the capacity to produce durable remissions and long-term disease-free survival in patients with high-risk acute myeloid leukemia and myelodysplasia. Journal of Clinical Oncology, 23(36), 9387-9393. https://doi.org/10.1200/JCO.2005.02.0057