HCVAD plus imatinib or dasatinib in lymphoid blastic phase chronic myeloid leukemia

• Published in: Cancer Vol. 120; no. 3; pp. 373 - 380
• Main Authors: Strati, Paolo, Kantarjian, Hagop, Thomas, Deborah, O'Brien, Susan, Konoplev, Sergej, Jorgensen, Jeffrey L., Luthra, Raja, Abruzzo, Lynne, Jabbour, Elias, Quintas‐Cardama, Alfonso, Borthakur, Gautam, Faderl, Stefan, Ravandi, Farhad, Cortes, Jorge
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 01.02.2014
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Benzamides - administration & dosage; Biological and medical sciences; Blast Crisis - drug therapy; blast phase; chronic myeloid leukemia; Cyclophosphamide - administration & dosage; Cytarabine - administration & dosage; Dasatinib; Dexamethasone - administration & dosage; Doxorubicin - administration & dosage; Female; HCVAD; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - mortality; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; lymphoid variant; Male; Medical sciences; Methotrexate - administration & dosage; Middle Aged; Piperazines - administration & dosage; Pyrimidines - administration & dosage; Thiazoles - administration & dosage; Tumors; tyrosine kinase inhibitors; Vincristine - administration & dosage; Antineoplastic agent; Genetic variability; lymphoid variant; HCVAD; Blast transformation; Blast; tyrosine kinase inhibitors; Myeloproliferative syndrome; Cancerology; Lymphoproliferative syndrome; chronic myeloid leukemia; Protein-tyrosine kinase; Dasatinib; Imatinib; Enzyme; Tyrosine kinase inhibitor; Transferases; Enzyme inhibitor; Chronic myelogenous leukemia; Genotype; Malignant hemopathy; Variant; Chronic lymphocytic leukemia; blast phase; Multikinase inhibitor; Cancer
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.28433

BACKGROUND Chronic myeloid leukemia (CML) may progress to blast phase (BP) at the rate of 1% to 1.5% per year. With the use of single‐agent tyrosine kinase inhibitors, median overall survival ranges between 7 and 11 months. METHODS The outcome was analyzed for 42 patients with lymphoid BP‐CML who were treated with hyperfractionated cyclophosphamide, vincristine, Adriamycin, dexamethasone (HCVAD) plus imatinib or dasatinib. RESULTS Complete hematological response was achieved in 90% of patients, complete cytogenetic remission in 58%, and complete molecular remission in 25%. Flow cytometry minimal residual disease negativity was achieved by 42% of evaluable patients after induction. Eighteen patients received allogeneic stem cell transplant (SCT) while in first complete hematological response. Median remission duration was 14 months and was longer among SCT recipients (P = .01) on multivariate analysis. Median overall survival was 17 months (range, 7‐27 months) and was longer among SCT recipients (P < .001) and patients treated with dasatinib (P = .07) on multivariate analysis. Although a high rate of hematologic toxicity (100%) and infectious complications (59%) were observed, the related rate of treatment discontinuation was low (7% and 9%, respectively). CONCLUSIONS HCVAD combined with tyrosine kinase inhibitors is an effective regimen for the management of BP‐CML, particularly when followed by allogeneic SCT. Cancer 2014;120:373–380 © 2013 American Cancer Society. HCVAD (hyperfractionated cyclophosphamide, vincristine, Adriamycin, dexamethasone) combined with tyrosine kinase inhibitor is an effective regimen for the management of lymphoid blastic phase chronic myeloid leukemia. Better results are observed when the regimen is followed by allogeneic stem cell transplantation.