Second-generation tyrosine kinase inhibitors combined with stem cell transplantation in patients with imatinib-refractory chronic myeloid leukemia

摘要

BACKGROUND: Allogeneic stem cell transplantation (allo-SCT) remains a curative therapy for chronic myeloid leukemia with advanced diseases, but limited data exist on the efficacy of short-time 2nd-generation tyrosine kinase inhibitors (TKIs) used before and after allo-SCT for patients failing imatinib therapy. METHODS: We present a single-center report of a series of 12 imatinib-refractory patients in advanced phases, 9 of whom harbored BCR-ABL1 mutations. All of them were treated with 2nd TKI, followed by allo-SCT. RESULTS: Dasatinib or nilotinib reinduced complete hematologic responses in 11 patients and complete cytogenetic responses in 4 patients. All patients engrafted successfully. Five patients experienced acute graft-versus-host-disease (GVHD), including 4 with grade III-IV disease. Four patients experienced chronic GVHD, including 1 with extensive disease. Post-transplant prophylactic dasatinib or nilotinb was administrated in 9 patients and discontinued 1 year later, all of whom sustained complete molecular remission, even after a median follow-up of 13 months after withdrawal of the TKI. No hematologic relapse was observed. Four patients died: 1 of primary disease and 3 of transplant-related complications. After a median follow-up of 28 months (range, 12-37 months) after SCT, 8 (66.7%) of 12 patients are alive, including 7 with complete molecular remission. CONCLUSIONS: Allo-SCT has a satisfactory outcome when combined with 2nd-generation TKI, which could provide a good quality of remission before transplantation and prevent relapse after transplantation.