title: 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.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Paolo
authors.initials: P
authors.lastname: Strati
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Sergej
authors.initials: S
authors.lastname: Konoplev
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Jorgensen
authors.forename: Raja
authors.initials: R
authors.lastname: Luthra
authors.forename: Lynne
authors.initials: L
authors.lastname: Abruzzo
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintas-Cardama
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage; D001752:Blast Crisis / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D000069439:Dasatinib; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D013844:Thiazoles / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D003561:Cytarabine; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D000068877:Imatinib Mesylate; D003520:Cyclophosphamide; D000069439:Dasatinib; D008727:Methotrexate
keywords: HCVAD; blast phase; chronic myeloid leukemia; lymphoid variant; tyrosine kinase inhibitors