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Factors that contribute to long-term survival in patients with leukemia not in remission at allogeneic hematopoietic cell transplantation

Factors that contribute to long-term survival in patients with leukemia not in remission at allogeneic hematopoietic cell transplantation,10.1186/1756

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Factors that contribute to long-term survival in patients with leukemia not in remission at allogeneic hematopoietic cell transplantation  
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Hideo Koh, Hirohisa Nakamae, Kiyoyuki Hagihara, Takahiko Nakane, Masahiro Manabe, Yoshiki Hayashi, Mitsutaka Nishimoto, Yukari Umemoto, Mika Nakamae, Asao Hirose, Eri Inoue, Atsushi Inouehttp://academic.research.microsoft.com/io.ashx?type=5&id=47617038&selfId1=0&selfId2=0&maxNumber=12&query=
Background  There has been insufficient examination of the factors affecting long-term survival of more than 5 years in patients with leukemia that is not in remission at transplantation. Method  We retrospectively analyzed leukemia not in remission at allogeneic hematopoietic cell transplantation (allo-HCT) performed at our institution between January 1999 and July 2009. Forty-two patients with a median age of 39 years received intensified conditioning (n = 9), standard (n = 12) or reduced-intensity conditioning (n = 21) for allo-HCT. Fourteen patients received individual chemotherapy for cytoreduction during the three weeks prior to reduced-intensity conditioning. Diagnoses comprised acute leukemia (n = 29), chronic myeloid leukemia-accelerated phase (n = 2), myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) (n = 10) and plasma cell leukemia (n = 1). In those with acute leukemia, cytogenetic abnormalities were intermediate (44%) or poor (56%). The median number of blast cells in bone marrow (BM) was 26.0% (range; 0.2-100) before the start of chemotherapy for allo-HCT. Six patients had leukemic involvement of the central nervous system. Stem cell sources were related BM (7%), related peripheral blood (31%), unrelated BM (48%) and unrelated cord blood (CB) (14%). Results  Engraftment was achieved in 33 (79%) of 42 patients. Median time to engraftment was 17 days (range: 9-32). At five years, the cumulative probabilities of acute graft-versus-host disease (GVHD) and chronic GVHD were 63% and 37%, respectively. With a median follow-up of 85 months for surviving patients, the five-year Kaplan-Meier estimates of leukemia-free survival rate and overall survival (OS) were 17% and 19%, respectively. At five years, the cumulative probability of non-relapse mortality was 38%. In the univariable analyses of the influence of pre-transplant variables on OS, poor-risk cytogenetics, number of BM blasts (>26%), MDS overt AML and CB as stem cell source were significantly associated with worse prognosis (p = .03, p = .01, p = .02 and p < .001, respectively). In addition, based on a landmark analysis at 6 months post-transplant, the five-year Kaplan-Meier estimates of OS in patients with and without prior history of chronic GVHD were 64% and 17% (p = .022), respectively. Conclusion  Graft-versus-leukemia effects possibly mediated by chronic GVHD may have played a crucial role in long-term survival in, or cure of active leukemia.
Journal: Journal of Experimental & Clinical Cancer Research - J EXP CLIN CANCER RES , vol. 30, no. 1, pp. 1-7, 2011
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