title: Intensified PEG-L-asparaginase and antimetabolite-based therapy for treatment of higher risk precursor-B acute lymphoblastic leukemia: a report from the Children's Oncology Group.
abstract: The Pediatric Oncology Group 9203 pilot protocol was designed to determine the feasibility of delivering 29 biweekly doses of polyethylene glycol (PEG)-L-asparaginase, on a backbone of intensive multiagent antimetabolite-based consolidation and maintenance in higher risk B-precursor acute lymphoblastic leukemia. Between June 1992 and August 1993, 34 patients were enrolled on this limited institution pilot. The 5-year event-free survival (+/-standard error) and overall survival (+/-standard error) were 68+/-8% and 76+/-7%, respectively. Excessive toxicities attributed to PEG-L-asparaginase and myelosuppression associated with cytosine arabinoside were encountered during consolidation resulting in early study closure and modification of therapy for those already enrolled. Ninety-two percent of methotrexate/cytosine arabinoside cycles were associated with grades 3 to 4 myelosuppression, and 24% resulted in delays in therapy of more than 7 days. Fifteen PEG-L-asparaginase related toxicities occurred in 13 patients (8 allergy, 4 pancreas, 2 central nervous system, and 1 hemorrhage). Intensification of therapy with PEG-L-asparaginase resulted in event-free survival and overall survival comparable to other studies of the same time period without the use of agents associated with long-term complications, such as anthracyclines, epipodophyllotoxins, and alkylating agents. However, excessive toxicity occurred with intensified PEG-L-asparaginase and antimetabolite based therapy delivered on this schedule.
authors.affiliation: Keesler Medical Center, Keesler AFB, Biloxi, MS, USA. Wanda.Salzer@amedd.army.mil
authors.forename: Wanda L
authors.initials: WL
authors.lastname: Salzer
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Shuster
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wang
authors.forename: Allen
authors.initials: A
authors.lastname: Chauvenet
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Asselin
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Camitta
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001215:Asparaginase / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase