title: Toxicity profile of repeated doses of PEG-asparaginase incorporated into a pediatric-type regimen for adult acute lymphoblastic leukemia.
abstract: Despite having been long regarded as too toxic for adult patients, pediatric-like regimens containing L-asparaginase have resulted in improved outcomes for adults with acute lymphoblastic leukemia (ALL). To characterize the spectrum of toxicity of repeated doses of polyethylene glycolated-asparaginase (PEG-asp) in adults, we reviewed all doses (2000 IU/m(2) ) administered as part of a pediatric-inspired regimen in adult ALL at our center. Subjects aged 18-60 yr with ALL (n = 152, 69.1% male) contributed 522 dose cycles to the study. Hepatotoxicity was the most common adverse event: grades 3-4 transaminitis and hyperbilirubinemia occurred in 53.9% and 23.7% of subjects, respectively. Hepatotoxicity was reversible; no cases of fulminate hepatic failure were observed. Other toxicities affecting at least 5% of subjects were grades 3-4 triglyceridemia in 50.9%, hypofibrinogenemia (<100 mg/dL) in 47.9%, clinical pancreatitis in 12.6%, venous thromboembolism in 11.2%, allergic reaction in 7.2%, and any grade bleeding in 5.3%. PEG-asp was always discontinued after grades 3-4 pancreatitis or allergic reaction. Otherwise, toxicities did not preclude administration of additional cycles of the drug. Our results suggest that repeated PEG-asp dosing is safe in adults aged 18-60 yr, even after occurrence of a drug-related toxicity.
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Aldoss
authors.affiliation: Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Douer
authors.affiliation: Division of Biostatistics, Department of Information Sciences, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Carolyn E
authors.initials: CE
authors.lastname: Behrendt
authors.affiliation: Jane Ann Nohl Division of Hematology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: Preeti
authors.initials: P
authors.lastname: Chaudhary
authors.affiliation: Jane Ann Nohl Division of Hematology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Mohrbacher
authors.affiliation: Jane Ann Nohl Division of Hematology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: Janice
authors.initials: J
authors.lastname: Vrona
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Vinod
authors.initials: V
authors.lastname: Pullarkat
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001215:Asparaginase / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity / Q000209:etiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D006932:Hyperbilirubinemia / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000209:etiology / Q000473:pathology; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D054556:Venous Thromboembolism / Q000209:etiology / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase
keywords: PEG-asparaginase; acute lymphoblastic leukemia; adults; bleeding; hepatotoxicity; pancreatitis; toxicity; venous thromboembolism