title: Treatment of Philadelphia chromosome-positive early chronic phase chronic myelogenous leukemia with daily doses of interferon alpha and low-dose cytarabine.
abstract: OBJECTIVE
  To evaluate the efficacy of the combination of interferon alpha (IFN-alpha) 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. Both IFN-alpha and ara-C induce cytogenetic responses as single-agent therapy in CML.
  
  
  METHODS
  One hundred forty patients with Ph-positive early chronic-phase CML received subcutaneous injections of IFN-alpha 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-alpha 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 rote 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-alpha 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-alpha plus ara-C combination. The incidence of CHR was higher with IFN-alpha plus daily ara-C compared with IFN-alpha plus intermittent ara-C and IFN-alpha 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-alpha regimens (7 v 10 v 12 months; P < .01). However, with the present follow-up, the survival and time to blastic transformation were similar.
  
  
  CONCLUSIONS
  The combination of IFN-alpha 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-alpha compared with our previous studies.
authors.affiliation: Department of Leukemia, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: S
authors.initials: S
authors.lastname: O'Brien
authors.forename: T L
authors.initials: TL
authors.lastname: Smith
authors.forename: M B
authors.initials: MB
authors.lastname: Rios
authors.forename: J
authors.initials: J
authors.lastname: Cortes
authors.forename: M
authors.initials: M
authors.lastname: Beran
authors.forename: C
authors.initials: C
authors.lastname: Koller
authors.forename: F J
authors.initials: FJ
authors.lastname: Giles
authors.forename: M
authors.initials: M
authors.lastname: Andreeff
authors.forename: S
authors.initials: S
authors.lastname: Kornblau
authors.forename: S
authors.initials: S
authors.lastname: Giralt
authors.forename: M J
authors.initials: MJ
authors.lastname: Keating
authors.forename: M
authors.initials: M
authors.lastname: Talpaz
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005819:Genetic Markers; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D015466:Leukemia, Myeloid, Chronic-Phase / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D005819:Genetic Markers; D016898:Interferon-alpha; D003561:Cytarabine