TY - JOUR
T1 - Phase II trial of HyperCVAD and Dasatinib in patients with relapsed Philadelphia chromosome positive acute lymphoblastic leukemia or blast phase chronic myeloid leukemia
AU - Benjamini, Ohad
AU - Dumlao, Theresa Liu
AU - Kantarjian, Hagop
AU - O'Brien, Susan
AU - Garcia-Manero, Guillermo
AU - Faderl, Stefan
AU - Jorgensen, Jeffrey
AU - Luthra, Rajyalakshmi
AU - Garris, Rebecca
AU - Thomas, Deborah
AU - Kebriaei, Partow
AU - Champlin, Richard
AU - Jabbour, Elias
AU - Burger, Jan
AU - Cortes, Jorge
AU - Ravandi, Farhad
PY - 2014/3
Y1 - 2014/3
N2 - Dasatinib is a second generation tyrosine kinase inhibitor, with activity in imatinib resistant Ph-positive ALL. We have treated 34 patients with relapsed Philadelphia chromosome positive acute lymphoblastic leukemia (ALL) (n=19) or lymphoid blast phase of chronic myelogenous leukemia (CML-LB) (n=15) with the combination of dasatinib and the hyperCVAD regimen. Prior regimens included hyperCVAD plus imatinib (n=11, 4 had transplant in first CR), other combination chemotherapy (n=12), monotherapy with kinase inhibitors other than dasatinib (n=9), and investigational agents (n=2). Pretreatment ABL mutations were noted in 10 patients. The overall response rate was 91%, with 24 patients (71%) achieving complete response (CR), and 7(21%) CR with incomplete platelet recovery (CRp). Two patients died during induction and one had progressive disease. Twenty-six patients (84%) achieved complete cytogenetic remission after one cycle of therapy. Overall, 13 patients (42%) achieved complete molecular response, and 11 patients (35%) had major molecular response (BCR-ABL/ABL<0.1%). Nine patients proceeded to allogeneic transplantation. Grades 3 and 4 toxicities included hemorrhage, pleural and pericardial effusions and infections. The median follow-up for patients with CML-LB is 37.5 months (range, 7-70 months) with a 3-year overall survival of 70%; 68% remained in CR at 3 years. For ALL patients, the median follow-up is 52 months (range, 45-59 months) with a 3-year survival of 26%; 30% remain in CR at 3 years. The combination of HyperCVAD regimen with dasatinib is effective in patients with relapsed Ph-positive ALL and CML-LB.
AB - Dasatinib is a second generation tyrosine kinase inhibitor, with activity in imatinib resistant Ph-positive ALL. We have treated 34 patients with relapsed Philadelphia chromosome positive acute lymphoblastic leukemia (ALL) (n=19) or lymphoid blast phase of chronic myelogenous leukemia (CML-LB) (n=15) with the combination of dasatinib and the hyperCVAD regimen. Prior regimens included hyperCVAD plus imatinib (n=11, 4 had transplant in first CR), other combination chemotherapy (n=12), monotherapy with kinase inhibitors other than dasatinib (n=9), and investigational agents (n=2). Pretreatment ABL mutations were noted in 10 patients. The overall response rate was 91%, with 24 patients (71%) achieving complete response (CR), and 7(21%) CR with incomplete platelet recovery (CRp). Two patients died during induction and one had progressive disease. Twenty-six patients (84%) achieved complete cytogenetic remission after one cycle of therapy. Overall, 13 patients (42%) achieved complete molecular response, and 11 patients (35%) had major molecular response (BCR-ABL/ABL<0.1%). Nine patients proceeded to allogeneic transplantation. Grades 3 and 4 toxicities included hemorrhage, pleural and pericardial effusions and infections. The median follow-up for patients with CML-LB is 37.5 months (range, 7-70 months) with a 3-year overall survival of 70%; 68% remained in CR at 3 years. For ALL patients, the median follow-up is 52 months (range, 45-59 months) with a 3-year survival of 26%; 30% remain in CR at 3 years. The combination of HyperCVAD regimen with dasatinib is effective in patients with relapsed Ph-positive ALL and CML-LB.
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U2 - 10.1002/ajh.23624
DO - 10.1002/ajh.23624
M3 - Article
C2 - 24779033
AN - SCOPUS:84896811150
SN - 0361-8609
VL - 89
SP - 282
EP - 287
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 3
ER -