2001 Associates' Presentations
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A Novel Treatment for Philadelphia Chromosome Positive Leukemia
Stephen Medlin, D.O.
Marshfield Clinic, Marshfield, Wisconsin
Chronic Myelogenous Leukemia (CML) is a myeloproliferative disorder characterized by the uncontrolled proliferation of maturing myeloid cells. Cytogenetic studies are typically associated with an abnormal chromosome 22, also known as the Philadelphia chromosome. Standard therapies for CML include chemotherapy, bone marrow transplantation and interferon alpha.
Gleevec, a novel drug with limited systemic toxicity (STI-571) has been developed. It targets the abnormality produced by the t(9,22) chromosomal translocation present in about 85% of patients with CML and 20 to 30% of adult patients with acute lymphoblastic leukemia (ALL). Therefore, it is directed toward cells with the BCR-ABL ocutations that have enhanced tyrosine kinase activity. Gleevec has been demonstrated to produce a response rate of 70% and remission rate of 20% in Philadelphia chromosome positive patients with ALL. Patients with myeloid blast crises and chronic CML also respond to this medication.
We report the case of a patient who presents with a one-year history of weight loss, fatigue, and a two month history of left upper quadrant abdominal pain. Physical exam revealed an enlarged spleen, without lymphadenopathy. Laboratory data showed a WBC count of 360,000. Peripheral blood smear showed an excess of granulocytic cells with no blasts. Bone marrow aspirate was obtained and cytogenetics were positive for the Philadelphia chromosome.
The patient received interferon alpha, hydroxyurea and cytarabine followed by autologous stem cell transplant. His course was complicated by prolonged thrombocytopenia. Three months after transplant, he developed supraclavicular, axillary and inguinal lymphadenopathy. Nodal biopsy revealed lymphoblastic lymphoma secondary to lymphoblastic transformation of his CML. Within one month of startin STI-571, his lymphadenopathy resolved. He has now been in remission for the past eight months and is seeking a matched unrelated donor transplant or an unrelated cord blood transplant.
Gleevec is a novel drug which an be used in certain patients with CML and other Philadelphia Chromosome positive malignancies.
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Sharon Haase, MD, FACP
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Kelly Lang
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