Phase II trial of HyperCVAD and Dasatinib in patients with relapsed Philadelphia chromosome positive acute lymphoblastic leukemia or blast phase chronic myeloid leukemia

Ohad Benjamini, Theresa Liu Dumlao, Hagop Kantarjian, Susan O'Brien, Guillermo Garcia-Manero, Stefan Faderl, Jeffrey Jorgensen, Rajyalakshmi Luthra, Rebecca Garris, Deborah Thomas, Partow Kebriaei, Richard Champlin, Elias Jabbour, Jan Burger, Jorge Cortes, Farhad Ravandi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)282-287
Number of pages6
JournalAmerican Journal of Hematology
Volume89
Issue number3
DOIs
StatePublished - Mar 1 2014
Externally publishedYes

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Blast Crisis
Philadelphia Chromosome
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Dasatinib
Survival
Pericardial Effusion
Homologous Transplantation
Pleural Effusion
Combination Drug Therapy
Cytogenetics
Protein-Tyrosine Kinases
Phosphotransferases
Blood Platelets

ASJC Scopus subject areas

  • Hematology

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Phase II trial of HyperCVAD and Dasatinib in patients with relapsed Philadelphia chromosome positive acute lymphoblastic leukemia or blast phase chronic myeloid leukemia. / Benjamini, Ohad; Dumlao, Theresa Liu; Kantarjian, Hagop; O'Brien, Susan; Garcia-Manero, Guillermo; Faderl, Stefan; Jorgensen, Jeffrey; Luthra, Rajyalakshmi; Garris, Rebecca; Thomas, Deborah; Kebriaei, Partow; Champlin, Richard; Jabbour, Elias; Burger, Jan; Cortes, Jorge; Ravandi, Farhad.

In: American Journal of Hematology, Vol. 89, No. 3, 01.03.2014, p. 282-287.

Research output: Contribution to journalArticle

Benjamini, O, Dumlao, TL, Kantarjian, H, O'Brien, S, Garcia-Manero, G, Faderl, S, Jorgensen, J, Luthra, R, Garris, R, Thomas, D, Kebriaei, P, Champlin, R, Jabbour, E, Burger, J, Cortes, J & Ravandi, F 2014, 'Phase II trial of HyperCVAD and Dasatinib in patients with relapsed Philadelphia chromosome positive acute lymphoblastic leukemia or blast phase chronic myeloid leukemia', American Journal of Hematology, vol. 89, no. 3, pp. 282-287. https://doi.org/10.1002/ajh.23624
Benjamini, Ohad ; Dumlao, Theresa Liu ; Kantarjian, Hagop ; O'Brien, Susan ; Garcia-Manero, Guillermo ; Faderl, Stefan ; Jorgensen, Jeffrey ; Luthra, Rajyalakshmi ; Garris, Rebecca ; Thomas, Deborah ; Kebriaei, Partow ; Champlin, Richard ; Jabbour, Elias ; Burger, Jan ; Cortes, Jorge ; Ravandi, Farhad. / Phase II trial of HyperCVAD and Dasatinib in patients with relapsed Philadelphia chromosome positive acute lymphoblastic leukemia or blast phase chronic myeloid leukemia. In: American Journal of Hematology. 2014 ; Vol. 89, No. 3. pp. 282-287.
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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

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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.

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