title: Preliminary experience with a new chemotherapy regimen for adults with acute lymphoblastic leukemia.
abstract: We treated 11 consecutive adult patients who presented with acute lymphoblastic leukemia to the University of Chicago with a novel, intensified chemotherapy regimen to evaluate the feasibility and toxicity of this program. Following a 5-drug induction therapy (course A), patients received sequential courses (B and C) of high-dose antimetabolite therapies, in part to replace cranial irradiation for CNS prophylaxis. All patients achieved a complete remission. The regimen was designed with a goal of administering all post-remission therapy in the outpatient setting. With the exception of the initial induction course (A), 3(1/3)8 total patient courses were administered in the outpatient clinic. As expected, the induction and consolidation courses (A and B) of this regimen were associated with grade 4 hematologic toxicity and significant but manageable infectious toxicity. Another novel aspect of the regimen included a combined intravenous and oral dosing schedule designed to sustain methotrexate levels > or = 1.0 microM for 30 hours (course C). There was minimal toxicity with the CNS prophylaxis/high-dose methotrexate course (C). Methotrexate levels at 30 hours ranged from 0.31-4.0 microM, with a median of 1.0 microM (n=37). This study demonstrates that this novel post-remission regimen is feasible in adults and that high concentrations of methotrexate can be sustained in the outpatient setting. The Cancer and Leukemia Group B is presently evaluating the efficacy of this regimen in a large phase II trial (CALGB study 19802).
authors.affiliation: Section of Hematology/Oncology, Department of Medicine and the Cancer Research Center, University of Chicago, Chicago, IL 60637-1470, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Cataland
authors.forename: C K
authors.initials: CK
authors.lastname: Daugherty
authors.forename: E C
authors.initials: EC
authors.lastname: Weseman
authors.forename: R A
authors.initials: RA
authors.lastname: Larson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D002423:Cause of Death; D003520:Cyclophosphamide / Q000008:administration & dosage; D020732:Cytogenetic Analysis; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000097:blood / Q000493:pharmacokinetics; D008875:Middle Aged; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy* / Q000401:mortality
chemical_list: D003520:Cyclophosphamide; D008727:Methotrexate