The purpose of this study is to determine if PEG-Intron is better tolerated and more efficacious than standard interferons (Roferon, Intron) in patients with Philadelphia-positive Chronic Myelogenous Leukemia. These patients should have previously received standard interferon therapy and have been intolerant, resistant, or have relapsed disease.

It has been shown that patients who experience complete hematologic or at least a partial cytogenetic response to interferon will have improved survival times. In addition, evidence exists that even patients who do not demonstrate a cytogenetic response to interferon treatment can still benefit from treatment, in terms of survival, compared to patients not treated with interferon. This indicates that if a patient is better able to tolerate interferon, he or she may have improved survival even without cytogenetic response. Preliminary studies suggest that PEG-Intron is more convenient for patients (administered once weekly rather than daily), is better tolerated than interferon, and can produce hematologic remission in interferon-a resistant patients. Phase II studies are needed to ascertain the overall hematologic and cytogenetic response rates to PEG-Intron in such patients.

Inclusion Criteria:

• Chronic phase CML, documented by the presence of Philadelphia chromosome or bcr/abl rearrangement at time of diagnosis, confirmed by either cytogenetics or PCR.
• WBC >/= 3000/ul </=100,000/ul.
• Patients must have received prior interferon therapy & proven to have primary refractory disease, secondary resistance or intolerance to interferon-a
• Patient must have ECOG status of 0, 1, or 2
• Labs: SGOT/SGPT<2xULN; serum bilirubin<2xULN; serum creatinine <2.0mg/dl
• Recovered from effects of major surgery
• Life expectancy > 12 wks.
• Signed informed consent.
• Women of childbearing potential must have negative serum pregnancy test within 72 hrs prior to administration of PEG-Intron & use effective contraception during the study.

Exclusion Criteria:

• NO accelerated Phase CML patients with peripheral blood: blasts>/=15%, basophils>/=20%, blasts+promyelocytes>/=30%, platelets<100,000/ul (unrelated to therapy). Blastic phase CML:>/=30% in peripheral blood/bone marrow.
• NO patients with known hypersensitivity to interferon-a.
• NO severe cardiovascular disease, i.e. arrhythmias requiring chronic treatment or congestive heart failure (NYHA classification III/IV).
• NO history of neuropsychiatric disorder requiring hospitalization.
• NO patients requiring therapy for refractory thyroid dysfunction
• NO patients with uncontrolled diabetes mellitus.
• NO patients who have had treatment for a 2nd malignancy in the past 5 yrs, except for localized basal cell/squamous cell carcinoma of the skin or cervical carcinoma in situ.
• NO pregnant or lactating patients.
• NO patients known to be actively using alcohol or drugs
• NO patients receiving any experimental therapy within 30 days of enrollment in study.