This application involves a Phase II trial and related laboratory evaluation combining a two step biological approach for the treatment of chronic myelogenous leukemia (CML) using: 1) Interferon-alpha (IFN-alpha) and 2) A high affinity, recombinant humanized anti-CD33 monoclonal antibody, HuM195, that has been shown in studies performed at Memorial Sloan-Kettering Cancer Center to eliminate minimal residual disease as evidenced by the conversion of polymerase chain reaction (PCR) in patients with acute promyelocytic leukemia (APL). CML, a disease characterized by the Philadelphia (Ph) chromosome, can be followed on the molecular level by PCR for the BCR-ABL translocation. In this trial, the applicant will use IFN-alpha to cytoreduce patients with CML. Once a hematological remission is attained, he will administer HuM195 to achieve a long lasting cytogenetic remission. The antitumor effect will also be evaluated by bone marrow morphology and cytogenetics. Toxicity and immunogenicity of HuM195 will be determined. The ability to achieve a molecular remission will be tested by serial PCR assays, and correlated to response duration. In addition, laboratory studies will be done to investigate the mechanism of action of HuM195 and IFN-(ADCC) with cells from CML patients. Lastly, the applicants will explore whether HuM195 affects the adhesive properties of IFN-alpha on CML cells.