Prior treatment with the tyrosine kinase inhibitors dasatinib and nilotinib allows stem cell transplantation (SCT) in a less advanced disease phase and does not increase SCT toxicity in patients with chronic myelogenous leukemia and Philadelphia positive acute lymphoblastic leukemia

Indications:8 patients with imatinib-failed chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia undergoing allogeneic stem cell transplantation.

Patients:21 patients were studied, 15 male and 6 female, aged 16 to 59 years, median age 45 years. Tasigna: 8 patients. Dasatinib: 13 patients. All 21 patients underwent allogeneic (human leukocyte antigen-matched sibling, n=7; matched-unrelated, n=13 and haploidentical, n=1) granulocyte-colony stimulating factor mobilized peripheral blood (19); and bone marrow (2) SCT. Patients were followed-up for 1-31 months (median, 14 months).

TypeofStudy:This retrospective study analyzed described the efficacy and safety of prior tyrosine kinase inhibitor (Tasigna or dasatinib) therapy in patients with chronic myeloid leukemia or Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) undergoing allogeneic stem cell transplantation (SCT). Letter to the Editor.

DosageDuration:400 mg bid (=800 mg daily), orally. Duration: 31 to 720 days (median, 24 days) prior to SCT.

Results:Results are given for the whole group of patients receiving TKI therapy without separate data for Tasigna. Following initiation of TKI therapy, 3/21 patients achieved complete hematologic response, of which 1/3 patient with PCyR mutation lost his CyR gene while waiting for unrelated donor SCT. 3/6 patients showed no response, of which 1/3 progressed to blast crisis (BC) prior to SCT. 5/10 patients with BC status or Ph+ ALL in relapse achieved complete hematologic response and underwent SCT. However, 2/5 patients had relapse prior to SCT and were transplanted in BC. 1/5 patient achieved minor hematologic response and managed to maintain it until SCT. 4/10 patients with BC showed no hematological response. All 4 patients received additional combination cancer chemotherapy, of which 3/4 patients achieved minor hematological response. Overall, 9/16 patients with advanced CML/Ph(+) ALL achieved hematological response while 7/16 patients maintained the same response prior until SCT. All 21 patients had successful engraftment. 1/21 patient had primary non-engraftment salvaged with additional bone marrow from the original donor. 1/21 patient had late graft rejection with concomitant molecular relapse salvaged with a second allogeneic SCT. Transplant-related complications were infrequent. 8/21 and 2/21 patients developed mucositis and liver veno-occlusive disease, respectively. Acute GVHD occurred in 8/21 patients with no resultant deaths. Chronic GVHD was noted in 10/21 patients and resulted in death in 1/10 patient. 19/21 patients achieved complete hematologic response following SCT. 2/21 patients had progressive disease immediately following SCT. 15/21 patients survived; whereas 6/21 died, of which 5/6 patients died of disease progression and 1/6 patient died from chronic GVHD. Overall, cumulative incidence of relapse was noted in 7/21 patients. The 2-year estimates of respective overall survival and disease-free survival were 64% and 46%. The most significant poor prognostic factor was SCT during BC or active Ph+ ALL disease. Any hematological response to Tasigna, dasatinib or chemotherapy was associated with improved outcome. Tasigna and dasatinib were safe and effective salvage therapy following imatinib failure and prior to SCT.

AdverseEffects:No adverse events were mentioned.

AuthorsConclusions:In summary, prior treatment with dasatinib and nilotinib may allow SCT in patients with CML or Ph+ ALL in a less advanced disease phase and probably does not increase the incidence of transplant-related organ toxcity, engraftment failure or GVHD. Treatment may be safe and effective salvage therapy for patients after failure of imatinib and before SCT.

FreeText:All patients received either Tasigna or dasatinib during an open-label, single-arm phase 2 study following failure of imatinib therapy. Patients underwent subsequent allogeneic SCT with myeloablative or reduced-intensity conditioning. Concomitant therapy: dasatinib, n=3; combination cancer chemotherapy; myeloablative regimens (total body irradiation, cyclophosphamide, and busulfan); anti-thymocyte globulin; and graft-versus-host (GVHD) disease prophylaxis (cyclosporine A and methotrexate).