Factors predicting long-term survival after T-cell depleted reduced intensity allogeneic stem cell transplantation for acute myeloid leukemia

Charles Craddock, Sandeep Nagra, Andrew Peniket, Cassandra Brookes, Laura Buckley, Emmanouil Nikolousis, Nick Duncan, Sudhir Tauro, John Yin, Effie Liakopoulou, Panos Kottaridis, John Snowden, Donald Milligan, Gordon Cook, Beni Tholouli, Tint Littlewood, Karl Peggs, Paresh Vyas, Fiona Clark, Mark CookStephen MacKinnon, Nigel Russell

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    Abstract

    Background

    Reduced intensity conditioning regimens permit the delivery of a potentially curative graft-versus-leukemia effect in older patients with acute myeloid leukemia. Although T-cell depletion is increasingly used to reduce the risk of graft-versus-host disease its impact on the graft-versus-leukemia effect and long-term outcome post-transplant is unknown.

    Design and Methods

    We have characterized pre- and post-transplant factors determining overall survival in 168 patients with acute myeloid leukemia transplanted using an alemtuzumab based reduced intensity conditioning regimen with a median duration of follow-up of 37 months.

    Results

    The 3-year overall survival for patients transplanted in CR1 or CR2/CR3 was 50% (95% CI, 38% to 62%) and 44% (95% CI, 31% to 56%), respectively compared to 15% (95% CI, 2% to 36%) for patients with relapsed/refractory disease. Multivariate analysis demonstrated that both survival and disease relapse were influenced by status at transplant (P=0.008) and presentation cytogenetics (P=0.01). Increased exposure to cyclosporine A (CsA) in the first 21 days post-transplant was associated with an increased relapse risk (P<0.0001) and decreased overall survival (P<0.0001).

    Conclusions

    Disease stage, presentation karyotype and post-transplant CsA exposure are important predictors of outcome in patients undergoing a T-cell depleted reduced intensity conditioning allograft for acute myeloid leukemia. These data confirm the presence of a potent graft-versus-leukemia effect after a T-cell depleted reduced intensity conditioning allograft in acute myeloid leukemia and identify CsA exposure as a manipulable determinant of outcome in this setting.

    Original languageEnglish
    Pages (from-to)989-995
    Number of pages7
    JournalHaematologica
    Volume95
    Issue number6
    DOIs
    Publication statusPublished - Jun 2010

    Keywords

    • reduced intensity conditioning
    • graft-versus-leukemia
    • acute myeloid leukemia
    • ACUTE MYELOGENOUS LEUKEMIA
    • BONE-MARROW-TRANSPLANTATION
    • VERSUS-HOST-DISEASE
    • MYELODYSPLASTIC SYNDROME
    • CYCLOSPORINE-A
    • CONDITIONING REGIMEN
    • COMPLETE REMISSION
    • CLINICAL-TRIALS
    • TOTAL-BODY
    • RISK

    Cite this

    Craddock, C., Nagra, S., Peniket, A., Brookes, C., Buckley, L., Nikolousis, E., Duncan, N., Tauro, S., Yin, J., Liakopoulou, E., Kottaridis, P., Snowden, J., Milligan, D., Cook, G., Tholouli, B., Littlewood, T., Peggs, K., Vyas, P., Clark, F., ... Russell, N. (2010). Factors predicting long-term survival after T-cell depleted reduced intensity allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica, 95(6), 989-995. https://doi.org/10.3324/haematol.2009.013920