Fludarabine and pharmacokinetic-targeted busulfan before allografting for adults with acute lymphoid leukemia

Biol Blood Marrow Transplant. 2011 Oct;17(10):1505-11. doi: 10.1016/j.bbmt.2011.02.011. Epub 2011 Mar 6.

Abstract

We aimed to evaluate the safety and efficacy of fludarabine (FLU) and pharmacokinetic-targeted busulfan (BU) as conditioning regimen for hematopoietic cell transplantation (HCT) in adult patients with acute lymphoid leukemia (ALL). Forty-four patients with ALL (27 in first complete remission [CR1] and 17 in more advanced disease stage: 4 with primary induction failure [PIF], 12 in CR2, and 1 in CR3) received FLU and pharmacokinetic-targeted BU as preparative therapy for HCT. Grafts were T-replete, filgrastim-mobilized peripheral blood stem cells (PBSC). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus (TAC) and short-course methotrexate in 36 patients, TAC and sirolimus in 3, and TAC and mycophenolate mofetil in 5. Primary engraftment was achieved in all 44 patients. The cumulative incidence of transplant-related mortality (TRM) was 2% (95% confidence interval [CI] 0%-16%) at 100 days and 18% (95% CI 10%-34%) at 2 years. The 2-year cumulative incidence of relapse was 19% (95% CI 8%-41%) for those transplanted in CR1, and 48% (29%-80%) for those with more advanced disease. After a median follow-up of 32 months (range: 15-69 months), the 2-year overall survival (OS) was 54% (95% CI 39%-69%). Relapse-free survival (RFS) at 2 years was 63% (95% CI 45%-81%) for patients transplanted in CR1 and 34% (95% CI 11%-57%) for patients transplanted in more advanced disease. When compared to irradiation-containing regimens, FLU and PK-targeted BU appear safer and similarly effective in controlling ALL, providing a treatment option for adult patients with ALL.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Busulfan / administration & dosage
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Graft Survival*
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / prevention & control
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Retrospective Studies
  • Survival Rate
  • Tacrolimus / administration & dosage
  • Transplantation Conditioning*
  • Transplantation, Homologous
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives

Substances

  • Immunosuppressive Agents
  • Vidarabine
  • Busulfan
  • fludarabine
  • Tacrolimus
  • Methotrexate