title: Factors that contribute to long-term survival in patients with leukemia not in remission at allogeneic hematopoietic cell transplantation.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Koh
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Nakamae
authors.forename: Kiyoyuki
authors.initials: K
authors.lastname: Hagihara
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakane
authors.forename: Masahiro
authors.initials: M
authors.lastname: Manabe
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Nishimoto
authors.forename: Yukari
authors.initials: Y
authors.lastname: Umemoto
authors.forename: Mika
authors.initials: M
authors.lastname: Nakamae
authors.forename: Asao
authors.initials: A
authors.lastname: Hirose
authors.forename: Eri
authors.initials: E
authors.lastname: Inoue
authors.forename: Atsushi
authors.initials: A
authors.lastname: Inoue
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yoshida
authors.forename: Masato
authors.initials: M
authors.lastname: Bingo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamura
authors.forename: Ran
authors.initials: R
authors.lastname: Aimoto
authors.forename: Mizuki
authors.initials: M
authors.lastname: Aimoto
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Terada
authors.forename: Ki-Ryang
authors.initials: KR
authors.lastname: Koh
authors.forename: Takahisa
authors.initials: T
authors.lastname: Yamane
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ohsawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D007952:Leukemia, Plasma Cell / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy*; D012008:Recurrence; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D055815:Young Adult