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?

IntroductionThe 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 coveredThere 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 opinionAllo-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.