Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: Dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation

Marcos De Lima, Athanasios Anagnostopoulos, Mark Munsell, Munir Shahjahan, Naoto Ueno, Cindy Ippoliti, Borje S. Andersson, James Gajewski, Daniel Couriel, Jorge Cortes, Michele Donato, Joyce Neumann, Richard Champlin, Sergio Giralt

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    311 Scopus citations

    Abstract

    Intensity of the preparative regimen is an important component of allogeneic transplantations for myelodysplasia (MDS) or acute myelogenous leukemia (AML). We compared outcomes after a truly nonablative regimen (120 mg/m2 fludarabine, 4 g/m2 cytarabine, and 36 mg/m 2 idarubicin [FAI]) and a more myelosuppressive, reduced-intensity regimen (100 to 150 mg/m2 fludarabine and 140 or 180 mg/m2 melphalan [FM]). We performed a retrospective analysis of 94 patients with MDS (n = 26) and AML (n = 68) treated with FM (n = 62) and FAI (n = 32). The FAI group had a higher proportion of patients in complete remission (CR) at transplantation (44% versus 16%, P = .006), patients in first CR (28% versus 3%, P = .008), and HLA-matched sibling donors (81% versus 40%, P = .001). Median follow-up is 40 months. FM was significantly associated with a higher degree of donor cell engraftment, higher cumulative incidence of treatment-related mortality (TRM; P = .036), and lower cumulative incidence of relapse-related mortality (P = .029). Relapse rate after FAI and FM was 61% and 30%, respectively. Actuarial 3-year survival rate was 30% after FAI and 35% following FM. In a multivariate analysis of patient- and treatment-related prognostic factors, progression-free survival was improved after FM, for patients in CR at transplantation, and for those with intermediate-risk cytogenetics. Survival was improved for patients in CR at transplantation. In conclusion, FM provided better disease control though at a cost of increased TRM and morbidity.

    Original languageEnglish (US)
    Pages (from-to)865-872
    Number of pages8
    JournalBlood
    Volume104
    Issue number3
    DOIs
    StatePublished - Aug 1 2004

    ASJC Scopus subject areas

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

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    De Lima, M., Anagnostopoulos, A., Munsell, M., Shahjahan, M., Ueno, N., Ippoliti, C., Andersson, B. S., Gajewski, J., Couriel, D., Cortes, J., Donato, M., Neumann, J., Champlin, R., & Giralt, S. (2004). Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: Dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood, 104(3), 865-872. https://doi.org/10.1182/blood-2003-11-3750