The impact of tyrosine kinase inhibitors on allogeneic hematopoietic stem cell transplantation for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

In the tyrosine kinase inhibitor (TKI) era, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still the most potential approach for cure of adult patients with Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ ALL). TKI plus chemotherapy has strikingly increased response rates and depth of response, and facilitated allo-HSCT, which decreases relapse and improves survival eventually. Meanwhile, for those with older age or comorbidities at diagnosis, TKI in combination with reduced-intensity chemotherapy or chemotherapy-free strategy reduces treatment-related mortality, deferred intensive chemotherapy increases molecular responses and reduced-intensity conditioning (RIC) allo-HSCT improves survival finally. Of note, according to minimal residual disease (MRD) and BCR/ABL1 kinase domain mutation screening, prophylactic or preemptive maintenance therapy with a sensitive TKI decreases relapse further. Regarding transplantation-related mortality and impaired quality of life related to complications of allo-HSCT, autologous-HSCT (auto-HSCT) among those with early and persistent molecular remission and the most potent TKI ponatinib plus intensive chemotherapy has exhibited non-inferior survival to allo-HSCT. Even so, risk-adapted strategy isn't available now. Lastly, outcomes of relapse after allo-HSCT are dismal due to TKIs exposure, and new therapeutic interventions combined with TKIs shed light on this thorny problem.