Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia

Hagop M. Kantarjian, Susan O'Brien, Terry L. Smith, Jorge Cortes, Francis J. Giles, Miloslav Beran, Sherry Pierce, Yang Huh, Michael Andreeff, Charles Koller, Chul S. Ha, Michael J. Keating, Sharon Murphy, Emil J. Freireich

Research output: Contribution to journalArticle

Abstract

Purpose: To evaluate the efficacy and toxicity of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a dose-intensive regimen, in adult acute lymphocytic leukemia (ALL). Patients and Methods: Adults with newly diagnosed ALL referred since 1992 were entered onto the study; treatment was initiated in 204 patients between 1992 and January 1998. No exclusions were made because of older age, poor performance status, organ dysfunction, or active infection. Median age was 39.5 years; 37% were at least 50 years old. Mature B-cell disease (Burkitt type) was present in 9%, T-cell disease in 17%. Leukocytosis of more than 30 x 109/L was found in 26%, Philadelphia chromosome-positive disease in 16% (20% of patients with assessable metaphases), CNS leukemia at the time of diagnosis in 7%, and a mediastinal mass in 7%. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy. Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). Results: Overall, 185 patients (91%) achieved complete remission (CR) and 12 (6%) died during induction therapy. Estimated 5-year survival and 5-year CR rates were 39% and 38%, respectively. The incidence of CNS relapse was low (4%). Compared with 222 patients treated with vincristine, doxorubicin, and dexamethasone (VAD) regimens, our patients had a better CR rate (91% v 75%, P < .01) and CR rate after one course (74% v 55%, P < .01) and better survival (P < .01), and a smaller percentage had more than 5% day 14 blasts (34% v 48%, P = .01). Previous prognostic models remained predictive for outcome with Hyper-CVAD therapy. Conclusion: Hyper-CVAD therapy is superior to our previous regimens and should be compared with established regimens in adult ALL.

Original languageEnglish (US)
Pages (from-to)547-561
Number of pages15
JournalJournal of Clinical Oncology
Volume18
Issue number3
StatePublished - Feb 1 2000
Externally publishedYes

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Vincristine
Therapeutics
Methotrexate
Doxorubicin
Dexamethasone
B-Cell Leukemia
6-Mercaptopurine
Philadelphia Chromosome
Survival
Antibiotic Prophylaxis
Cytarabine
Leukocytosis
Granulocyte Colony-Stimulating Factor
Metaphase
Prednisone
Cyclophosphamide
Leukemia
B-Lymphocytes
Maintenance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kantarjian, H. M., O'Brien, S., Smith, T. L., Cortes, J., Giles, F. J., Beran, M., ... Freireich, E. J. (2000). Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. Journal of Clinical Oncology, 18(3), 547-561.

Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. / Kantarjian, Hagop M.; O'Brien, Susan; Smith, Terry L.; Cortes, Jorge; Giles, Francis J.; Beran, Miloslav; Pierce, Sherry; Huh, Yang; Andreeff, Michael; Koller, Charles; Ha, Chul S.; Keating, Michael J.; Murphy, Sharon; Freireich, Emil J.

In: Journal of Clinical Oncology, Vol. 18, No. 3, 01.02.2000, p. 547-561.

Research output: Contribution to journalArticle

Kantarjian, HM, O'Brien, S, Smith, TL, Cortes, J, Giles, FJ, Beran, M, Pierce, S, Huh, Y, Andreeff, M, Koller, C, Ha, CS, Keating, MJ, Murphy, S & Freireich, EJ 2000, 'Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia', Journal of Clinical Oncology, vol. 18, no. 3, pp. 547-561.
Kantarjian, Hagop M. ; O'Brien, Susan ; Smith, Terry L. ; Cortes, Jorge ; Giles, Francis J. ; Beran, Miloslav ; Pierce, Sherry ; Huh, Yang ; Andreeff, Michael ; Koller, Charles ; Ha, Chul S. ; Keating, Michael J. ; Murphy, Sharon ; Freireich, Emil J. / Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. In: Journal of Clinical Oncology. 2000 ; Vol. 18, No. 3. pp. 547-561.
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abstract = "Purpose: To evaluate the efficacy and toxicity of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a dose-intensive regimen, in adult acute lymphocytic leukemia (ALL). Patients and Methods: Adults with newly diagnosed ALL referred since 1992 were entered onto the study; treatment was initiated in 204 patients between 1992 and January 1998. No exclusions were made because of older age, poor performance status, organ dysfunction, or active infection. Median age was 39.5 years; 37{\%} were at least 50 years old. Mature B-cell disease (Burkitt type) was present in 9{\%}, T-cell disease in 17{\%}. Leukocytosis of more than 30 x 109/L was found in 26{\%}, Philadelphia chromosome-positive disease in 16{\%} (20{\%} of patients with assessable metaphases), CNS leukemia at the time of diagnosis in 7{\%}, and a mediastinal mass in 7{\%}. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy. Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). Results: Overall, 185 patients (91{\%}) achieved complete remission (CR) and 12 (6{\%}) died during induction therapy. Estimated 5-year survival and 5-year CR rates were 39{\%} and 38{\%}, respectively. The incidence of CNS relapse was low (4{\%}). Compared with 222 patients treated with vincristine, doxorubicin, and dexamethasone (VAD) regimens, our patients had a better CR rate (91{\%} v 75{\%}, P < .01) and CR rate after one course (74{\%} v 55{\%}, P < .01) and better survival (P < .01), and a smaller percentage had more than 5{\%} day 14 blasts (34{\%} v 48{\%}, P = .01). Previous prognostic models remained predictive for outcome with Hyper-CVAD therapy. Conclusion: Hyper-CVAD therapy is superior to our previous regimens and should be compared with established regimens in adult ALL.",
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T1 - Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia

AU - Kantarjian, Hagop M.

AU - O'Brien, Susan

AU - Smith, Terry L.

AU - Cortes, Jorge

AU - Giles, Francis J.

AU - Beran, Miloslav

AU - Pierce, Sherry

AU - Huh, Yang

AU - Andreeff, Michael

AU - Koller, Charles

AU - Ha, Chul S.

AU - Keating, Michael J.

AU - Murphy, Sharon

AU - Freireich, Emil J.

PY - 2000/2/1

Y1 - 2000/2/1

N2 - Purpose: To evaluate the efficacy and toxicity of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a dose-intensive regimen, in adult acute lymphocytic leukemia (ALL). Patients and Methods: Adults with newly diagnosed ALL referred since 1992 were entered onto the study; treatment was initiated in 204 patients between 1992 and January 1998. No exclusions were made because of older age, poor performance status, organ dysfunction, or active infection. Median age was 39.5 years; 37% were at least 50 years old. Mature B-cell disease (Burkitt type) was present in 9%, T-cell disease in 17%. Leukocytosis of more than 30 x 109/L was found in 26%, Philadelphia chromosome-positive disease in 16% (20% of patients with assessable metaphases), CNS leukemia at the time of diagnosis in 7%, and a mediastinal mass in 7%. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy. Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). Results: Overall, 185 patients (91%) achieved complete remission (CR) and 12 (6%) died during induction therapy. Estimated 5-year survival and 5-year CR rates were 39% and 38%, respectively. The incidence of CNS relapse was low (4%). Compared with 222 patients treated with vincristine, doxorubicin, and dexamethasone (VAD) regimens, our patients had a better CR rate (91% v 75%, P < .01) and CR rate after one course (74% v 55%, P < .01) and better survival (P < .01), and a smaller percentage had more than 5% day 14 blasts (34% v 48%, P = .01). Previous prognostic models remained predictive for outcome with Hyper-CVAD therapy. Conclusion: Hyper-CVAD therapy is superior to our previous regimens and should be compared with established regimens in adult ALL.

AB - Purpose: To evaluate the efficacy and toxicity of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a dose-intensive regimen, in adult acute lymphocytic leukemia (ALL). Patients and Methods: Adults with newly diagnosed ALL referred since 1992 were entered onto the study; treatment was initiated in 204 patients between 1992 and January 1998. No exclusions were made because of older age, poor performance status, organ dysfunction, or active infection. Median age was 39.5 years; 37% were at least 50 years old. Mature B-cell disease (Burkitt type) was present in 9%, T-cell disease in 17%. Leukocytosis of more than 30 x 109/L was found in 26%, Philadelphia chromosome-positive disease in 16% (20% of patients with assessable metaphases), CNS leukemia at the time of diagnosis in 7%, and a mediastinal mass in 7%. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy. Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). Results: Overall, 185 patients (91%) achieved complete remission (CR) and 12 (6%) died during induction therapy. Estimated 5-year survival and 5-year CR rates were 39% and 38%, respectively. The incidence of CNS relapse was low (4%). Compared with 222 patients treated with vincristine, doxorubicin, and dexamethasone (VAD) regimens, our patients had a better CR rate (91% v 75%, P < .01) and CR rate after one course (74% v 55%, P < .01) and better survival (P < .01), and a smaller percentage had more than 5% day 14 blasts (34% v 48%, P = .01). Previous prognostic models remained predictive for outcome with Hyper-CVAD therapy. Conclusion: Hyper-CVAD therapy is superior to our previous regimens and should be compared with established regimens in adult ALL.

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