Treatment of philadelphia chromosome-positive early chronic phase chronic myelogenous leukemia with daily doses of interferon alpha and low- dose cytarabine

Hagop M. Kantarjian, Susan O'Brien, Terry L. Smith, Mary Beth Rios, Jorge Cortes, Miloslav Beran, Charles Koller, Francis J. Giles, Michael Andreeff, Steven Kornblau, Sergio Giralt, Michael J. Keating, Moshe Talpaz

Research output: Contribution to journalArticle

Abstract

Purpose: To evaluate the efficacy of the combination of interferon alpha (IFN-α) and daily low-dose cytarabine (ara-C) in the treatment of patients with early chronic-phase chronic myelogenous leukemia (CML) (within 1 year of diagnosis). Improving the degree of hematologic and cytogenetic response in patients with Philadelphia chromosome (Ph)-positive CML may improve prognosis. Bath IFN-α and ara-C induce cytogenetic responses as single- agent therapy in CML. Patients and Methods: One hundred forty patients with Ph-positive early chronic-phase CML received subcutaneous injections of IFN- α 5 megaunits/m2 daily and ara-C 10 mg daily. Their median age was 46 years; 53% had good-risk disease, 33% had intermediate-risk disease, and 14% had poor-risk disease. Their results were compared with those of patients receiving IFN-α with or without intermittent ara-C (7 days/mo). Results: A complete hematologic response (CHR) was achieved in 92% of patients. A cytogenetic response was seen in 74%: it was major in 50% (Ph-positive < 35%) and complete in 31% (Ph-positive 0%). With a median follow-up of 42 months, the 4-year estimated survival rate was 70% (95% confidence interval, 61% to 79%). Significant side effects included fatigue (43%; grade 3/4, 11%), weight loss (19%; grade 3/4, 11%), muscle and bone aches (20%; grade 3/4, 7%), oral ulcers (4%), diarrhea (6%), and neurologic changes (27%, grade 3/4, 6%). The median dose of IFN-α was 3.7 megaunits/m2 daily, mainly because of reductions for myelosuppression (70% of cases); the median ara-C dose was 7.5 mg daily. Prognostic risk groups were predictive for response to the IFN-α plus ara-C combination. The incidence of CHR was higher with IFN-α plus daily ara-C compared with IFN-α plus intermittent ara-C and IFN-α alone (no ara-C) (92% v 84% v 80%, P = .01), as were the incidences of cytogenetic response (74% v 73% v 58%; P = .003) and major cytogenetic response (50% v 38% v 38%; P = .06). The median time to achievement of major cytogenetic response was significantly shorter than that for previous IFN-α regimens (7 v 10 v 12 months; P < .01). However, with the present follow-up, the survival and time to blastic transformation were similar. Conclusion: The combination of IFN-α plus daily low-dose ara-C seems to be promising for the treatment of CML. High rates of CHR and cytogenetic response were observed with acceptable toxicity and a lower daily dose of IFN-α compared with our previous studies.

Original languageEnglish (US)
Pages (from-to)284-292
Number of pages9
JournalJournal of Clinical Oncology
Volume17
Issue number1
StatePublished - Jan 1 1999
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Philadelphia Chromosome
Cytarabine
Interferon-alpha
Cytogenetics
Therapeutics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Oral Ulcer
Incidence
Subcutaneous Injections
Baths
Nervous System
Fatigue
Weight Loss
Diarrhea

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Treatment of philadelphia chromosome-positive early chronic phase chronic myelogenous leukemia with daily doses of interferon alpha and low- dose cytarabine. / Kantarjian, Hagop M.; O'Brien, Susan; Smith, Terry L.; Rios, Mary Beth; Cortes, Jorge; Beran, Miloslav; Koller, Charles; Giles, Francis J.; Andreeff, Michael; Kornblau, Steven; Giralt, Sergio; Keating, Michael J.; Talpaz, Moshe.

In: Journal of Clinical Oncology, Vol. 17, No. 1, 01.01.1999, p. 284-292.

Research output: Contribution to journalArticle

Kantarjian, HM, O'Brien, S, Smith, TL, Rios, MB, Cortes, J, Beran, M, Koller, C, Giles, FJ, Andreeff, M, Kornblau, S, Giralt, S, Keating, MJ & Talpaz, M 1999, 'Treatment of philadelphia chromosome-positive early chronic phase chronic myelogenous leukemia with daily doses of interferon alpha and low- dose cytarabine', Journal of Clinical Oncology, vol. 17, no. 1, pp. 284-292.
Kantarjian, Hagop M. ; O'Brien, Susan ; Smith, Terry L. ; Rios, Mary Beth ; Cortes, Jorge ; Beran, Miloslav ; Koller, Charles ; Giles, Francis J. ; Andreeff, Michael ; Kornblau, Steven ; Giralt, Sergio ; Keating, Michael J. ; Talpaz, Moshe. / Treatment of philadelphia chromosome-positive early chronic phase chronic myelogenous leukemia with daily doses of interferon alpha and low- dose cytarabine. In: Journal of Clinical Oncology. 1999 ; Vol. 17, No. 1. pp. 284-292.
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abstract = "Purpose: To evaluate the efficacy of the combination of interferon alpha (IFN-α) and daily low-dose cytarabine (ara-C) in the treatment of patients with early chronic-phase chronic myelogenous leukemia (CML) (within 1 year of diagnosis). Improving the degree of hematologic and cytogenetic response in patients with Philadelphia chromosome (Ph)-positive CML may improve prognosis. Bath IFN-α and ara-C induce cytogenetic responses as single- agent therapy in CML. Patients and Methods: One hundred forty patients with Ph-positive early chronic-phase CML received subcutaneous injections of IFN- α 5 megaunits/m2 daily and ara-C 10 mg daily. Their median age was 46 years; 53{\%} had good-risk disease, 33{\%} had intermediate-risk disease, and 14{\%} had poor-risk disease. Their results were compared with those of patients receiving IFN-α with or without intermittent ara-C (7 days/mo). Results: A complete hematologic response (CHR) was achieved in 92{\%} of patients. A cytogenetic response was seen in 74{\%}: it was major in 50{\%} (Ph-positive < 35{\%}) and complete in 31{\%} (Ph-positive 0{\%}). With a median follow-up of 42 months, the 4-year estimated survival rate was 70{\%} (95{\%} confidence interval, 61{\%} to 79{\%}). Significant side effects included fatigue (43{\%}; grade 3/4, 11{\%}), weight loss (19{\%}; grade 3/4, 11{\%}), muscle and bone aches (20{\%}; grade 3/4, 7{\%}), oral ulcers (4{\%}), diarrhea (6{\%}), and neurologic changes (27{\%}, grade 3/4, 6{\%}). The median dose of IFN-α was 3.7 megaunits/m2 daily, mainly because of reductions for myelosuppression (70{\%} of cases); the median ara-C dose was 7.5 mg daily. Prognostic risk groups were predictive for response to the IFN-α plus ara-C combination. The incidence of CHR was higher with IFN-α plus daily ara-C compared with IFN-α plus intermittent ara-C and IFN-α alone (no ara-C) (92{\%} v 84{\%} v 80{\%}, P = .01), as were the incidences of cytogenetic response (74{\%} v 73{\%} v 58{\%}; P = .003) and major cytogenetic response (50{\%} v 38{\%} v 38{\%}; P = .06). The median time to achievement of major cytogenetic response was significantly shorter than that for previous IFN-α regimens (7 v 10 v 12 months; P < .01). However, with the present follow-up, the survival and time to blastic transformation were similar. Conclusion: The combination of IFN-α plus daily low-dose ara-C seems to be promising for the treatment of CML. High rates of CHR and cytogenetic response were observed with acceptable toxicity and a lower daily dose of IFN-α compared with our previous studies.",
author = "Kantarjian, {Hagop M.} and Susan O'Brien and Smith, {Terry L.} and Rios, {Mary Beth} and Jorge Cortes and Miloslav Beran and Charles Koller and Giles, {Francis J.} and Michael Andreeff and Steven Kornblau and Sergio Giralt and Keating, {Michael J.} and Moshe Talpaz",
year = "1999",
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TY - JOUR

T1 - Treatment of philadelphia chromosome-positive early chronic phase chronic myelogenous leukemia with daily doses of interferon alpha and low- dose cytarabine

AU - Kantarjian, Hagop M.

AU - O'Brien, Susan

AU - Smith, Terry L.

AU - Rios, Mary Beth

AU - Cortes, Jorge

AU - Beran, Miloslav

AU - Koller, Charles

AU - Giles, Francis J.

AU - Andreeff, Michael

AU - Kornblau, Steven

AU - Giralt, Sergio

AU - Keating, Michael J.

AU - Talpaz, Moshe

PY - 1999/1/1

Y1 - 1999/1/1

N2 - Purpose: To evaluate the efficacy of the combination of interferon alpha (IFN-α) and daily low-dose cytarabine (ara-C) in the treatment of patients with early chronic-phase chronic myelogenous leukemia (CML) (within 1 year of diagnosis). Improving the degree of hematologic and cytogenetic response in patients with Philadelphia chromosome (Ph)-positive CML may improve prognosis. Bath IFN-α and ara-C induce cytogenetic responses as single- agent therapy in CML. Patients and Methods: One hundred forty patients with Ph-positive early chronic-phase CML received subcutaneous injections of IFN- α 5 megaunits/m2 daily and ara-C 10 mg daily. Their median age was 46 years; 53% had good-risk disease, 33% had intermediate-risk disease, and 14% had poor-risk disease. Their results were compared with those of patients receiving IFN-α with or without intermittent ara-C (7 days/mo). Results: A complete hematologic response (CHR) was achieved in 92% of patients. A cytogenetic response was seen in 74%: it was major in 50% (Ph-positive < 35%) and complete in 31% (Ph-positive 0%). With a median follow-up of 42 months, the 4-year estimated survival rate was 70% (95% confidence interval, 61% to 79%). Significant side effects included fatigue (43%; grade 3/4, 11%), weight loss (19%; grade 3/4, 11%), muscle and bone aches (20%; grade 3/4, 7%), oral ulcers (4%), diarrhea (6%), and neurologic changes (27%, grade 3/4, 6%). The median dose of IFN-α was 3.7 megaunits/m2 daily, mainly because of reductions for myelosuppression (70% of cases); the median ara-C dose was 7.5 mg daily. Prognostic risk groups were predictive for response to the IFN-α plus ara-C combination. The incidence of CHR was higher with IFN-α plus daily ara-C compared with IFN-α plus intermittent ara-C and IFN-α alone (no ara-C) (92% v 84% v 80%, P = .01), as were the incidences of cytogenetic response (74% v 73% v 58%; P = .003) and major cytogenetic response (50% v 38% v 38%; P = .06). The median time to achievement of major cytogenetic response was significantly shorter than that for previous IFN-α regimens (7 v 10 v 12 months; P < .01). However, with the present follow-up, the survival and time to blastic transformation were similar. Conclusion: The combination of IFN-α plus daily low-dose ara-C seems to be promising for the treatment of CML. High rates of CHR and cytogenetic response were observed with acceptable toxicity and a lower daily dose of IFN-α compared with our previous studies.

AB - Purpose: To evaluate the efficacy of the combination of interferon alpha (IFN-α) and daily low-dose cytarabine (ara-C) in the treatment of patients with early chronic-phase chronic myelogenous leukemia (CML) (within 1 year of diagnosis). Improving the degree of hematologic and cytogenetic response in patients with Philadelphia chromosome (Ph)-positive CML may improve prognosis. Bath IFN-α and ara-C induce cytogenetic responses as single- agent therapy in CML. Patients and Methods: One hundred forty patients with Ph-positive early chronic-phase CML received subcutaneous injections of IFN- α 5 megaunits/m2 daily and ara-C 10 mg daily. Their median age was 46 years; 53% had good-risk disease, 33% had intermediate-risk disease, and 14% had poor-risk disease. Their results were compared with those of patients receiving IFN-α with or without intermittent ara-C (7 days/mo). Results: A complete hematologic response (CHR) was achieved in 92% of patients. A cytogenetic response was seen in 74%: it was major in 50% (Ph-positive < 35%) and complete in 31% (Ph-positive 0%). With a median follow-up of 42 months, the 4-year estimated survival rate was 70% (95% confidence interval, 61% to 79%). Significant side effects included fatigue (43%; grade 3/4, 11%), weight loss (19%; grade 3/4, 11%), muscle and bone aches (20%; grade 3/4, 7%), oral ulcers (4%), diarrhea (6%), and neurologic changes (27%, grade 3/4, 6%). The median dose of IFN-α was 3.7 megaunits/m2 daily, mainly because of reductions for myelosuppression (70% of cases); the median ara-C dose was 7.5 mg daily. Prognostic risk groups were predictive for response to the IFN-α plus ara-C combination. The incidence of CHR was higher with IFN-α plus daily ara-C compared with IFN-α plus intermittent ara-C and IFN-α alone (no ara-C) (92% v 84% v 80%, P = .01), as were the incidences of cytogenetic response (74% v 73% v 58%; P = .003) and major cytogenetic response (50% v 38% v 38%; P = .06). The median time to achievement of major cytogenetic response was significantly shorter than that for previous IFN-α regimens (7 v 10 v 12 months; P < .01). However, with the present follow-up, the survival and time to blastic transformation were similar. Conclusion: The combination of IFN-α plus daily low-dose ara-C seems to be promising for the treatment of CML. High rates of CHR and cytogenetic response were observed with acceptable toxicity and a lower daily dose of IFN-α compared with our previous studies.

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