Second-generation tyrosine kinase inhibitors before allogeneic stem cell transplantation in patients with chronic myeloid leukemia resistant to imatinib.

Philadelphia-positive chronic myeloid leukemia (Ph+ CML) patients who are resistant to imatinib are commonly treated with second-generation tyrosine kinase inhibitors (TKIs). Limited data exist on the possible effects of these drugs on subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT).The outcome of 12 imatinib-resistant CML patients treated with dasatinib or nilotinib or both before allo-HSCT, was retrospectively analyzed. Patients were treated with second-generation TKIs for 1-17 months (median, 8). At the time of transplant, 3 patients were in complete cytogenetic response (CCgR), 3 patients in partial cytogenetic response (PCgR) and 6 patients were in less than PCgR. Donors were HLA-matched related in 4 cases and unrelated in 8 cases. Stem cell source was peripheral blood, bone marrow or cord blood in 6, 5 and 1 cases, respectively. All patients engrafted successfully and all but one achieved a full donor chimerism. Three patients experienced acute and chronic graft-versus-host disease. No cases of transplant-related mortality were recorded. Best response to allo-HSCT was complete molecular response (CMR) in 9 patients, major molecular response (MMR) in 1 patient and CCgR in 2 patients. Median follow-up was 16.5 months. At the last evaluation, 9 patients were in continuous CMR and 1 patient was in MMR; 2 patients had died of disease progression. Second-generation TKIs given before allo-HSCT do not negatively affect transplant engraftment and response rate, nor increases transplant-related toxicity.