Non-myeloablative conditioning with allogeneic hematopoietic cell transplantation for the treatment of high-risk acute lymphoblastic leukemia

Ron Ram, Rainer Storb, Brenda M. Sandmaier, David G. Maloney, Ann Woolfrey, Mary E.D. Flowers, Michael B. Maris, Ginna G. Laport, Thomas R. Chauncey, Thoralf Lange, Amelia A. Langston, Barry Storer, George E. Georges

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

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. Design and 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. (Clinicaltrials.gov identifier: NCT0036738).

Original languageEnglish (US)
Pages (from-to)1113-1120
Number of pages8
JournalHaematologica
Volume96
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • Acute lymphoblastic leukemia
  • Allogeneic hematopoietic cell transplantation
  • Imatinib
  • Non-myeloablative conditioning
  • Philadelphia chromosome-positive

ASJC Scopus subject areas

  • Hematology

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