title: Phase II study of all-trans retinoic acid in the accelerated phase or early blastic phase of chronic myeloid leukemia: a study of the Eastern Cooperative Oncology Group (E1993).
abstract: The aims of this study were to evaluate the safety and efficacy of all-trans retinoic acid (ATRA) in the treatment of the accelerated and blastic phase of chronic myeloid leukemia (CML) and to evaluate in vitro correlates of biological activity. ATRA was administered in an intermittent schedule to patients with CML in the accelerated or blastic phases for a 6 week induction period, which was continued if there was evidence of clinical response or stable disease. If the patient was progressing at 6 weeks, interferon-alpha could be added to the ATRA. Laboratory correlative studies were performed prior to treatment and at intervals during treatment to evaluate effects on maturation and differentiation, and on CML progenitor cell growth by assessment of colony-forming cells (CFC). Eighteen patients were enrolled. There was 1 complete response, 1 partial response and 2 with hematological improvement. A fifth patient was stable on ATRA and interferon for several months. Laboratory data for the responders demonstrated high sensitivity of primary CFC to ATRA prior to treatment and low serial CFC counts on ATRA therapy. ATRA demonstrated clinical and hematological activity in 5 of 18 patients with the accelerated phase of CML, and there was evidence of a biological effect in laboratory studies of 3 of the 5 patients' progenitor cells. Combination therapy with other differentiating agents may be useful in this disease.
authors.affiliation: Albert Einstein College (NY), Bronx, NY, USA. jpd4401@aol.com
authors.forename: Janice P
authors.initials: JP
authors.lastname: Dutcher
authors.forename: Sandra
authors.initials: S
authors.lastname: Lee
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gallagher
authors.forename: Adel Z
authors.initials: AZ
authors.lastname: Makary
authors.forename: John D
authors.initials: JD
authors.lastname: Hines
authors.forename: Harold
authors.initials: H
authors.lastname: Londer
authors.forename: John P
authors.initials: JP
authors.lastname: Farnen
authors.forename: John M
authors.initials: JM
authors.lastname: Bennett
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Paietta
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: Olga
authors.initials: O
authors.lastname: Goloubeva
authors.forename: Peter H
authors.initials: PH
authors.lastname: Wiernik
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001752:Blast Crisis; D003131:Combined Modality Therapy; D020732:Cytogenetic Analysis; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D016019:Survival Analysis; D013997:Time Factors; D014212:Tretinoin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014212:Tretinoin