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.

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.

Trial registration: ClinicalTrials.gov NCT00036738.

Figures

Figure 1.

Cumulative incidences (n=51) of (A) acute graft-versus-host disease (GVHD): 53% grade II, 6% grade III–IV; (B) chronic extensive GVHD: 42% incidence at 3 years; (C) non-relapse mortality, 28% incidence at 3 years.

Figure 2.

Cumulative relapse rate for Ph– ALL, in first complete remission (CR1) (n=13) versus beyond CR1 (n=13) and Ph+ ALL CR1 (n=19) versus beyond CR1 (n=6). Molecular disease relapse (PCR or flow cytometry positive) without morphological evidence of disease was included as relapse.

Figure 3.

Overall survival for (A) Ph– ALL, in first complete remission (CR1) (n=13) versus beyond CR1 (n=13) and (B) Ph+ ALL patients receiving imatinib after hematopoietic cell transplantation, CR1 (n=13) versus beyond CR1 (n=5).