Reduced-intensity chemotherapy with tyrosine kinase inhibitor followed by allogeneic transplantation is effective in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Korean J Intern Med. 2025 Jan;40(1):124-134. doi: 10.3904/kjim.2024.227. Epub 2025 Jan 1.

Abstract

Background/aims: To determine the effectiveness of tyrosine kinase inhibitor (TKI) plus reduced-intensity therapy in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL), this retrospective study compared treatment outcomes and induction mortality according to backbone regimen intensity.

Methods: The data of 132 patients diagnosed with Ph-positive ALL were retrospectively collected from five centers. Patients received imatinib plus intensive chemotherapy (modified VPD, KALLA1407, or hyper-CVAD) or reduced-intensity chemotherapy (EWALL) for curative purposes. This study analyzed 117 patients, of which 35,22,46, and 14 received modified VPD, KALLA1407, hyper-CVAD, and EWALL, respectively. All patients used imatinib as a TKI.

Results: The median age of the patients who received reduced-intensity chemotherapy was 64.4 years, while that of the patients with intensive regimens was 47.5 years. There was no induction death in the reduced-intensity group, while nine patients died in the intensive therapy group. Major molecular response achievement tended to be higher in the intensive chemotherapy group than in the reduced-intensity group. More patients in the intensive chemotherapy group received allogeneic stem cell transplantation (allo-SCT). There was no statistically significant difference in long-term survival between the two groups in terms of relapse-free survival and overall survival rates.

Conclusion: When imatinib plus reduced-intensity therapy was used as a frontline treatment, there was no inferiority in obtaining complete remission compared to imatinib plus intensive chemotherapy or significant difference in long-term survival. Since imatinib plus reduced-intensity therapy has limitations in obtaining a deep molecular response, proceeding to allo-SCT should be considered.

Keywords: Acute lymphoblastic leukemia; Philadelphia chromosome; Stem cell transplantation; Tyrosine kinase inhibitor.

Publication types

  • Multicenter Study
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Female
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Imatinib Mesylate* / administration & dosage
  • Imatinib Mesylate* / therapeutic use
  • Male
  • Middle Aged
  • Philadelphia Chromosome
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Protein Kinase Inhibitors* / administration & dosage
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Republic of Korea
  • Retrospective Studies
  • Time Factors
  • Transplantation, Homologous
  • Treatment Outcome
  • Tyrosine Kinase Inhibitors

Substances

  • Protein Kinase Inhibitors
  • Imatinib Mesylate
  • Tyrosine Kinase Inhibitors