Outcomes of Tyrosine Kinase Inhibitors Maintenance Therapy with or without Allogeneic Hematopoietic Stem Cell Transplantation in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia in First Complete Remission: A Systematic Review and Meta-Analysis

We conducted a systematic review and meta-analysis to compare outcomes of tyrosine kinase inhibitor (TKI) mainte-nance therapy with or without allogeneic hematopoietic stem cell transplantation (HSCT) in Philadelphia chromosome -positive (Ph + ) acute lymphoblastic leukemia (ALL) in first remission (CR1). A literature search was performed on PubMed, Cochrane, and Clinical trials.gov. After screening 1720 articles, 12 studies were included. Proportions and odds ratios (OR) with 95% confidence intervals (CI) were computed. I 2 provides an estimate of the percentage of variability in results across studies that is due to real differences and not due to chance. Of 1039 patients, 635 (61%) had TKI alone and 404 (39%) patients had HSCT followed by TKI. At 3 years, a trend towards poor overall survival (OS; OR 0.67, 95% CI 0.39-1.15, I 2 = 68%), (disease-free survival; OR 0.58, 95% CI 0.26-1.29, I 2 = 76%), and higher relapse rate (RR; OR = 2.52, 95% CI = 1.66-3.83, I 2 = 26%) was seen with TKI alone compared to HSCT-TKI. Although HSCT followed by TKI maintenance in Ph + ALL has long been considered standard of care, the introduction of potent third-generation TKIs and bispecific T-cell engagers such as Blinatumomab has significantly improved outcomes while sparing the need for HSCT in newly diagnosed patients.

Automated summary

We conducted a systematic review and meta-analysis to compare the outcomes of TKI maintenance therapy with or without HSCT in Ph+ ALL in CR1. It was found that TKI alone had a trend towards poor OS, disease-free survival, and higher relapse rate compared to HSCT followed by TKI. The introduction of potent third-generation TKIs and bispecific T-cell engagers has significantly improved outcomes in newly diagnosed patients while sparing the need for HSCT.