title: Non-myeloablative conditioning with allogeneic hematopoietic cell transplantation for the treatment of high-risk acute lymphoblastic leukemia.
abstract: BACKGROUND
  Allogeneic hematopoietic cell transplantation is a potentially curative treatment for patients with acute lymphoblastic leukemia. However, the majority of older adults with acute lymphoblastic leukemia are not candidates for myeloablative conditioning regimens. A non-myeloablative preparative regimen is a reasonable treatment option for this group. We sought to determine the outcome of non-myeloablative conditioning and allogeneic transplantation in patients with high-risk acute lymphoblastic leukemia.
  
  
  METHODS
  Fifty-one patients (median age 56 years) underwent allogeneic hematopoietic cell transplantation from sibling or unrelated donors after fludarabine and 2 Gray total body irradiation. Twenty-five patients had Philadelphia chromosome-positive acute lymphoblastic leukemia. Eighteen of these patients received post-grafting imatinib.
  
  
  RESULTS
  With a median follow-up of 43 months, the 3-year overall survival was 34%. The 3-year relapse/progression and non-relapse mortality rates were 40% and 28%, respectively. The cumulative incidences of grades II and III-IV acute graft-versus-host disease were 53% and 6%, respectively. The cumulative incidence of chronic graft-versus-host disease was 44%. Hematopoietic cell transplantation in first complete remission and post-grafting imatinib were associated with improved survival (P=0.005 and P=0.03, respectively). Three-year overall survival rates for patients with Philadelphia-negative acute lymphoblastic leukemia in first remission and beyond first remission were 52% and 8%, respectively. For patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in first remission who received post-grafting imatinib, the 3-year overall survival rate was 62%; for the subgroup without evidence of minimal residual disease at transplantation, the overall survival was 73%.
  
  
  CONCLUSIONS
  For patients with high-risk acute lymphoblastic leukemia in first complete remission, non-myeloablative conditioning and allogeneic hematopoietic cell transplantation, with post-grafting imatinib for Philadelphia chromosome-positive disease, can result in favorable long-term survival.
authors.affiliation: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Ram
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Ann
authors.initials: A
authors.lastname: Woolfrey
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
authors.forename: Michael B
authors.initials: MB
authors.lastname: Maris
authors.forename: Ginna G
authors.initials: GG
authors.lastname: Laport
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Chauncey
authors.forename: Thoralf
authors.initials: T
authors.lastname: Lange
authors.forename: Amelia A
authors.initials: AA
authors.lastname: Langston
authors.forename: Barry
authors.initials: B
authors.lastname: Storer
authors.forename: George E
authors.initials: GE
authors.lastname: Georges
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity; D001549:Benzamides; D002648:Child; D018450:Disease Progression; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use / Q000633:toxicity; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use / Q000633:toxicity; D012008:Recurrence; D012307:Risk Factors; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate