Comparison of allogeneic hematopoietic stem cell transplantation and TKI combined with chemotherapy for adult philadelphia chromosome positive acute lymphoblastic leukemia: a systematic review and meta-analysis
Topic: Immunotherapy

Objective: This study seeks to clarify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) is necessary for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in post-remission based on a comparison with tyrosine kinase inhibitor (TKI) combined with chemotherapy. Methods: We searched the Pubmed, Embase, and Web of Science databases and limited the date range for the studies from January 2010 to August 2020. A hazard ratio (HR) with a 95% confidence interval (CI) was employed to assess overall survival (OS) and relapse-free survival (RFS), and an odds ratio (OR) with a 95% CI was used to evaluate the ratio of non-relapsed mortality (NRM) and non-relapsed survival (NRS). All analyses were conducted with Stata software 16.0 and Revman 5.3. Results: Fifteen studies, totaling 959 patients, were included in our analysis. Among those patients, 473 underwent allo-HSCT, and 486 received TKI plus chemotherapy. The pooled results showed no difference in OS between outcomes for patients receiving TKI plus chemotherapy and those treated with allo-HSCT (HR = 0.76, 95% CI [0.51-1.12], p = 0.16). Patients undergoing allo-HSCT did better than those receiving TKI plus chemotherapy regarding RFS (HR = 0.48, 95% CI [0.37-0.63], p = 0.00), and NRS (OR = 2.64, 95% CI [1.25-5.57], p = 0.00). The NRM rate of the TKI plus chemotherapy group was significantly lower than the allo-HSCT group (OR = 2.33, 95% CI [1.51-3.59], p = 0.00). Conclusion: TKI combined with chemotherapy can be considered a post-remission treatment option for adult Ph+ ALL patients who are ineligible for allo-HSCT. However, more prospective studies with large sample sizes should be carried out in the future. Keywords: Philadelphia chromosome positive acute lymphoblastic leukemia; allogeneic hematopoietic stem cell transplantation; meta-analysis; tyrosine kinase inhibitor.

PICO
Population: Adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in post-remission
Intervention: Allogeneic hematopoietic stem cell transplantation (allo-HSCT)
Comparison: Tyrosine kinase inhibitor (TKI) combined with chemotherapy
Outcomes: Overall survival (OS), relapse-free survival (RFS), non-relapsed mortality (NRM), and non-relapsed survival (NRS)

Included studies:
title: Outcome of Philadelphia positive acute lymphoblastic leukemia with or without allogeneic stem cell transplantation in a retrospective study
title: Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosomepositive acute lymphoblastic leukemia
title: Phase II study of imatinib-based chemotherapy for newly diagnosed BCRABL-positive acute lymphoblastic leukemia
title: Final analysis of the JALSG Ph+ ALL202 study: tyrosine kinase inhibitor-combined chemotherapy for Ph+ ALL
title: Long-term follow-up of the imatinib GRAAPH-2003 study in newly diagnosed patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: a GRAALL study
title: Treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia with imatinib combined with a paediatric-based protocol
title: Retrospective analysis of Philadelphia chromosome-positive acute lymphoblastic leukemia treated with allogeneic hematopoietic stem cell transplant versus chemotherapy combined with tyrosine kinase inhibitor
title: Allogeneic stem cell transplantation versus tyrosine kinase inhibitors combined with chemotherapy in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia
title: Combination chemotherapy plus dasatinib leads to comparable overall survival and relapse-free survival rates as allogeneic hematopoietic stem cell transplantation in Philadelphia positive acute lymphoblastic leukemia
title: Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia
title: US intergroup study of chemotherapy plus dasatinib and allogeneic stem cell transplant in Philadelphia chromosome positive ALL
title: Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia
title: Nilotinib combined with multi-agent chemotherapy in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a singlecenter prospective study with long-term follow-up
title: Combination of hyperCVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: long-term follow-up of a single-centre, phase 2 study