Long-term follow-up of allogeneic hematopoietic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: impact of tyrosine kinase inhibitors on treatment outcomes

Biol Blood Marrow Transplant. 2012 Apr;18(4):584-92. doi: 10.1016/j.bbmt.2011.08.011. Epub 2011 Aug 23.

Abstract

The introduction of tyrosine kinase inhibitors (TKI) has revolutionized therapy for patients with acute lymphoblastic leukemia (ALL) who have the Philadelphia (Ph) chromosome. A retrospective analysis was conducted on 102 adults and 11 children who received a first-matched related (n = 60), matched unrelated (n = 40), mismatched cord blood (n = 12), or haploidentical (n = 1) allogeneic hematopoietic stem cell transplantation (HSCT) for Ph-positive (Ph+) ALL in first complete remission (n = 71), second complete remission (n = 11), or with active disease (n = 31) between 1990 and 2009. Sixty-seven patients received TKI with upfront ALL therapy, and 32 patients received TKI maintenance following HSCT. With median follow-up of 5 years among survivors (range: 1.1-20.4 years), overall survival (OS) was significantly better for patients transplanted in first remission compared with HSCT in advanced disease: 43% versus 16%, P = .002. Disease stage and age at time of HSCT, the development of acute graft-versus-host disease (aGVHD), and decade of HSCT were found to significantly impact OS, progression-free survival (PFS), and nonrelapse mortality (NRM) in multivariate analyses. Allogeneic HSCT provides durable remission for patients with Ph+ ALL in first remission. Neither TKI use pre- nor post-HSCT were found to significantly impact transplant outcomes in univariate and multivariate analyses.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation*
  • Histocompatibility / immunology
  • Humans
  • Male
  • Middle Aged
  • Philadelphia Chromosome*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Remission Induction
  • Retrospective Studies
  • Time Factors
  • Transplantation Conditioning*
  • Transplantation, Homologous

Substances

  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases