Salvage therapy for children with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia.

Background In the tyrosine kinase inhibitor (TKI) era, outcomes after salvage therapyfor relapsed or refractory Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) remain unclear. Procedure The clinical courses of 19 patients with relapse (n = 13) or induction failure (n = 6) in the Japanese Pediatric Leukemia/Lymphoma Study Group Ph+ ALL04 study were retrospectively reviewed. Results Fifteen male and four female patients had a median age of 8 (range 4–15) years at relapse or induction failure. Patients received imatinibin combination with hyperfractionatedcyclophosphamide, vincristine, doxorubicin, and dexamethasone ( hyper-CVAD) and methotrexate and cytarabine(MTX/Ara-C) (n = 9), imatinibin combination with other chemotherapy (n = 5), chemotherapy without imatinib(n = 2), imatinibalone (n = 2), or no additional chemotherapy (n = 1). Two patients underwent hematopoietic stem cell transplantation (HSCT) without achieving complete remission (CR) and died of leukemia. The remaining 17 patients achieved CR with salvage therapiesand underwent HSCT whilst in CR: 10 patients remain alive in CR, five died of transplantation-related complications, and two died of relapse. In six of seven patients with available data on minimal residual disease(MRD), imatinibin combination with the first course of hyper-CVADwas more effective in achieving a favorable MRD response compared with the Ph+ ALL04 induction regimen. Conclusion This study suggested that cross-resistanceto imatinibfailed to develop after conventional chemotherapy. Imatinibin combination with chemotherapy including hyper-CVAD+MTX/Ara-C was effective and safe for relapsed or refractory Ph+ ALL patients who received frontline therapy without imatinib.