Long-Term Follow-up of Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Impact of Tyrosine Kinase Inhibitors on Treatment Outcomes

The introduction of tyrosine kinase inhibitors (TKI) has revolutionized therapy for patients with acute lymphoblastic leukemia (ALL) who have the Philadelphia (Ph) chromosome. A retrospective analysis was conducted on 102 adults and 11 children who received a first-matched related (n = 60), matched unrelated (n = 40), mismatched cord blood (n = 12), or haploidentical (n = 1) allogeneic hematopoietic stem cell transplantation (HSCT) for Ph-positive (Ph+) ALL in first complete remission (n = 71), second complete remission (n = 11), or with active disease (n = 31) between 1990 and 2009. Sixty-seven patients received TKI with upfront ALL therapy, and 32 patients received TKI maintenance following HSCT. With median follow-up of 5 years among survivors (range: 1.1-20.4 years), overall survival (OS) was significantly better for patients transplanted in first remission compared with HSCT in advanced disease: 43% versus 16%, P = .002. Disease stage and age at time of HSCT, the development of acute graft-versus-host disease (aGVHD), and decade of HSCT were found to significantly impact OS, progression-free survival (PFS), and nonrelapse mortality (NRM) in multivariate analyses. Allogeneic HSCT provides durable remission for patients with Ph+ ALL in first remission. Neither TKI use pre- nor post-HSCT were found to significantly impact transplant outcomes in univariate and multivariate analyses.

Key Words: Philadelphia chromosome–positive acute lymphoblastic leukemia, Allogeneic hematopoietic stem cell transplantation, Tyrosine kinase inhibitor