Is intensive chemotherapy and allogeneic stem cell transplantation mandatory for curing Philadelphia chromosome-positive acute lymphoblastic leukemia in young patients in the era of multitarget agents?

Expert Rev Hematol. 2024 Jul;17(7):353-359. doi: 10.1080/17474086.2024.2357273. Epub 2024 May 20.

Abstract

Introduction: The treatment outcomes for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) have improved with various tyrosine kinase inhibitors (TKIs) and bispecific T-cell engagers. Although allogeneic stem cell transplantation (allo-SCT) is the standard treatment for young patients with Ph+ALL, its role remains debatable in the era of TKIs and blinatumomab.

Areas covered: There are some issues regarding Ph+ALL. First, do young patients require intensive chemotherapy (IC) in the era of multitarget agents? Second, which TKI is preferred for frontline therapy? Third, should allo-SCT be performed in patients achieving complete remission with ponatinib and IC? Fourth, can chemo-free treatment lead to a cure without allo-SCT? We searched relevant literature from the last 30 years on PubMed; reviewed the role of chemo-free therapies and combinations of ponatinib and IC; and assessed the necessity of allo-SCT in young patients with Ph+ALL.

Expert opinion: Allo-SCT may not be needed, even in young patients with Ph+ALL treated with ponatinib-based IC or combined ponatinib and blinatumomab as frontline therapy. When adopting a ponatinib-based chemo-minimized regimen for induction, allo-SCT is needed with posttransplant ponatinib maintenance. Continuous exposure to ponatinib at pre- or post-transplant is regarded as one of the most important factor for the success of treatment.

Keywords: Philadelphia chromosome; acute lymphoblastic leukemia; allogeneic stem cell transplantation; intensive chemotherapy; ponatinib.

Publication types

  • Review

MeSH terms

  • Antibodies, Bispecific / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Combined Modality Therapy
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Imidazoles
  • Molecular Targeted Therapy
  • Philadelphia Chromosome*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridazines / therapeutic use
  • Transplantation, Homologous*
  • Treatment Outcome

Substances

  • Protein Kinase Inhibitors
  • ponatinib
  • Antibodies, Bispecific
  • blinatumomab
  • Pyridazines
  • Imidazoles