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

Abstract

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.

• Authors: Paolo Strati, Hagop Kantarjian, Deborah Thomas, Susan O'Brien, Sergej Konoplev, Jeffrey L Jorgensen, Raja Luthra, Lynne Abruzzo, Elias Jabbour, Alfonso Quintas-Cardama, Gautam Borthakur, Stefan Faderl, Farhad Ravandi, Jorge Cortes
• Journal: Cancer (Cancer) Vol. 120 Issue 3 Pg. 373-80 (Feb 01 2014) ISSN: 1097-0142 [Electronic] United States
• PMID: 24151050 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 American Cancer Society.

Chemical References

• Benzamides
• Piperazines
• Pyrimidines
• Thiazoles
• Cytarabine
• Vincristine
• Dexamethasone
• Doxorubicin
• Imatinib Mesylate
• Cyclophosphamide
• Dasatinib
• Methotrexate

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Benzamides (administration & dosage)
• Blast Crisis (drug therapy)
• Cyclophosphamide (administration & dosage)
• Cytarabine (administration & dosage)
• Dasatinib
• Dexamethasone (administration & dosage)
• Doxorubicin (administration & dosage)
• Female
• Hematopoietic Stem Cell Transplantation
• Humans
• Imatinib Mesylate
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, mortality, pathology)
• Male
• Methotrexate (administration & dosage)
• Middle Aged
• Piperazines (administration & dosage)
• Pyrimidines (administration & dosage)
• Thiazoles (administration & dosage)
• Vincristine (administration & dosage)