Benefit of Allogeneic Transplantation in Patients Age ≥ 60 Years with Acute Myeloid Leukemia Is Limited to Those in First Complete Remission at Time of Transplant

  • Fotios V. Michelis
    Affiliations
    Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Hans A. Messner
    Affiliations
    Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Eshetu G. Atenafu
    Affiliations
    Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Dennis D. Kim
    Affiliations
    Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • John Kuruvilla
    Affiliations
    Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Jeffrey H. Lipton
    Affiliations
    Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Jieun Uhm
    Affiliations
    Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • David Loach
    Affiliations
    Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
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  • Vikas Gupta
    Correspondence
    Correspondence and reprint requests: Vikas Gupta, MD, FRCP, FRCPath, Princess Margaret Cancer Centre, Suite 5-217, 610-University Avenue, Toronto M5G 2M9, Canada.
    Affiliations
    Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
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Open ArchivePublished:December 16, 2013DOI:https://doi.org/10.1016/j.bbmt.2013.12.560

      Abstract

      We evaluated the impact of age and remission status on 242 consecutive patients who underwent allogeneic hematopoietic cell transplantation for acute myeloid leukemia (AML) in our program between 1999 and 2011. Median age of all patients was 48 years (range, 18 to 71). Based on age and remission status, patients were divided into 4 groups: first complete remission (CR1) age <60 years (n = 116), second complete remission (CR2) age <60 years (n = 78), CR1 age ≥60 years (n = 32), and CR2 age ≥60 years (n = 16). Donors were matched related (n = 155, 64%) or matched unrelated (n = 87, 36%). Median follow-up of survivors was 65 months (range, 12 to 145). In a univariate analysis, 3-year overall survival rates of the 4 groups were 57%, 43%, 39%, and 16% ( P = .003), respectively. In a multivariable analysis, hazard ratios of nonrelapse mortality and survival were 2.08 ( P = .06) and 1.52 ( P = .23), respectively, in patients ≥60 years in CR2 compared with ≥ 60 years in CR1. Although a plateau in survival was observed for patients ≥60 years in CR1 similar to those <60 years in CR1 and CR2, no long-term survivors were seen in patients ≥60 years in CR2. Our data suggest disappointing outcomes in AML patients ≥60 years of age transplanted in CR2. Therefore, if a transplant is indicated, early referral is recommended in patients ≥60 years with AML.

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      References

        • Gupta V.
        • Tallman M.S.
        • Weisdorf D.J.
        Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns.
        Blood. 2011; 117: 2307-2318
        • Koreth J.
        • Schlenk R.
        • Kopecky K.J.
        • et al.
        Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials.
        JAMA. 2009; 301: 2349-2361
        • Burnett A.K.
        • Goldstone A.
        • Hills R.K.
        • et al.
        Curability of patients with acute myeloid leukemia who did not undergo transplantation in first remission.
        J Clin Oncol. 2013; 31: 1293-1301
        • Horan J.T.
        • Logan B.R.
        • Agovi-Johnson M.A.
        • et al.
        Reducing the risk for transplantation-related mortality after allogeneic hematopoietic cell transplantation: how much progress has been made?.
        J Clin Oncol. 2011; 29: 805-813
        • Krauter J.
        • Wagner K.
        • Stadler M.
        • et al.
        Prognostic factors in allo-SCT of elderly patients with AML.
        Bone Marrow Transplant. 2011; 46: 545-551
        • Farag S.S.
        • Maharry K.
        • Zhang M.J.
        • et al.
        Comparison of reduced-intensity hematopoietic cell transplantation with chemotherapy in patients age 60-70 years with acute myelogenous leukemia in first remission.
        Biol Blood Marrow Transplant. 2011; 17: 1796-1803
        • Alatrash G.
        • de Lima M.
        • Hamerschlak N.
        • et al.
        Myeloablative reduced-toxicity i.v. busulfan-fludarabine and allogeneic hematopoietic stem cell transplant for patients with acute myeloid leukemia or myelodysplastic syndrome in the sixth through eighth decades of life.
        Biol Blood Marrow Transplant. 2011; 17: 1490-1496
        • Gyurkocza B.
        • Storb R.
        • Storer B.E.
        • et al.
        Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia.
        J Clin Oncol. 2010; 28: 2859-2867
        • McClune B.L.
        • Weisdorf D.J.
        • Pedersen T.L.
        • et al.
        Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome.
        J Clin Oncol. 2010; 28: 1878-1887
        • Walter R.B.
        • Buckley S.A.
        • Pagel J.M.
        • et al.
        Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission.
        Blood. 2013; 122: 1813-1821
        • Kurosawa S.
        • Yamaguchi T.
        • Miyawaki S.
        • et al.
        Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse.
        Haematologica. 2010; 95: 1857-1864
        • Michelis F.V.
        • Atenafu E.G.
        • Gupta V.
        • et al.
        Duration of first remission, hematopoietic cell transplantation-specific comorbidity index and patient age predict survival of patients with AML transplanted in second CR.
        Bone Marrow Transplant. 2013; 48: 1450-1455
        • Slovak M.L.
        • Kopecky K.J.
        • Cassileth P.A.
        • et al.
        Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study.
        Blood. 2000; 96: 4075-4083
        • Sorror M.L.
        • Sandmaier B.M.
        • Storer B.E.
        • et al.
        Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation.
        J Clin Oncol. 2007; 25: 4246-4254
        • Khabori M.A.
        • El-Emary M.
        • Xu W.
        • et al.
        Impact of intensity of conditioning therapy in patients aged 40-60 years with AML/myelodysplastic syndrome undergoing allogeneic transplantation.
        Bone Marrow Transplant. 2011; 46: 516-522
        • Bacigalupo A.
        • Ballen K.
        • Rizzo D.
        • et al.
        Defining the intensity of conditioning regimens: working definitions.
        Biol Blood Marrow Transplant. 2009; 15: 1628-1633
        • Gupta V.
        • Daly A.
        • Lipton J.H.
        • et al.
        Nonmyeloablative stem cell transplantation for myelodysplastic syndrome or acute myeloid leukemia in patients 60 years or older.
        Biol Blood Marrow Transplant. 2005; 11: 764-772
        • Pepe M.S.
        • Mori M.
        Kaplan-Meier, marginal or conditional probability curves in summarizing competing risks failure time data?.
        Stat Med. 1993; 12: 737-751
        • Brunner A.M.
        • Kim H.T.
        • Coughlin E.
        • et al.
        Outcomes in patients age 70 or older undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancies.
        Biol Blood Marrow Transplant. 2013; 19: 1374-1380
        • Peffault de Latour R.
        • Brunstein C.G.
        • Porcher R.
        • et al.
        Similar overall survival using sibling, unrelated donor, and cord blood grafts after reduced-intensity conditioning for older patients with acute myelogenous leukemia.
        Biol Blood Marrow Transplant. 2013; 19: 1355-1360