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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)373-380
Number of pages8
JournalCancer
Volume120
Issue number3
DOIs
StatePublished - Feb 1 2014
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Vincristine
Doxorubicin
Cyclophosphamide
Dexamethasone
Blast Crisis
Stem Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Transplants
Protein-Tyrosine Kinases
Multivariate Analysis
Survival
Residual Neoplasm
Cytogenetics
Flow Cytometry
Imatinib Mesylate
Dasatinib

Keywords

  • blast phase
  • chronic myeloid leukemia
  • HCVAD
  • lymphoid variant
  • tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Strati, P., Kantarjian, H., Thomas, D., O'Brien, S., Konoplev, S., Jorgensen, J. L., ... Cortes, J. (2014). HCVAD plus imatinib or dasatinib in lymphoid blastic phase chronic myeloid leukemia. Cancer, 120(3), 373-380. https://doi.org/10.1002/cncr.28433

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

In: Cancer, Vol. 120, No. 3, 01.02.2014, p. 373-380.

Research output: Contribution to journalArticle

Strati, P, Kantarjian, H, Thomas, D, O'Brien, S, Konoplev, S, Jorgensen, JL, Luthra, R, Abruzzo, L, Jabbour, E, Quintas-Cardama, A, Borthakur, G, Faderl, S, Ravandi, F & Cortes, J 2014, 'HCVAD plus imatinib or dasatinib in lymphoid blastic phase chronic myeloid leukemia', Cancer, vol. 120, no. 3, pp. 373-380. https://doi.org/10.1002/cncr.28433
Strati P, Kantarjian H, Thomas D, O'Brien S, Konoplev S, Jorgensen JL et al. HCVAD plus imatinib or dasatinib in lymphoid blastic phase chronic myeloid leukemia. Cancer. 2014 Feb 1;120(3):373-380. https://doi.org/10.1002/cncr.28433
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. / HCVAD plus imatinib or dasatinib in lymphoid blastic phase chronic myeloid leukemia. In: Cancer. 2014 ; Vol. 120, No. 3. pp. 373-380.
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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.",
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AU - Konoplev, Sergej

AU - Jorgensen, Jeffrey L.

AU - Luthra, Raja

AU - Abruzzo, Lynne

AU - Jabbour, Elias

AU - Quintas-Cardama, Alfonso

AU - Borthakur, Gautam

AU - Faderl, Stefan

AU - Ravandi, Farhad

AU - Cortes, Jorge

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N2 - 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.

AB - 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.

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