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Leuk Res. 2018 Mar;66:49-56. doi: 10.1016/j.leukres.2017.12.013. Epub 2018 Jan 3.

Pegaspargase-related high-grade hepatotoxicity in a pediatric-inspired adult acute lymphoblastic leukemia regimen does not predict recurrent hepatotoxicity with subsequent doses.

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Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Michigan Medicine, F4811D University Hospital South, 1500 East Medical Center Drive, SPC 5271, Ann Arbor, MI, 48109-5000, United States. Electronic address:
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, CA, United States.
Division of Oncology and Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States.
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, United States.
Division of Hematology, University of Southern California, Los Angeles, CA, United States.


Pediatric acute lymphoblastic leukemia (ALL) regimens, including higher cumulative asparaginase doses, have been investigated in adult ALL to improve outcomes. Preliminary results are promising, but hepatotoxicity rates with long-acting pegaspargase are greater in adults than children. However, adult pegaspargase-related hepatotoxicity is not as clearly defined despite being the commonest adult toxicity. We studied the frequency and characteristics of high-grade pegaspargase-related hepatotoxicity in newly diagnosed adults on a pediatric-inspired regimen that included six planned pegaspargase doses, 2000 IU/m2/dose intravenously, with doses given at least four weeks apart and not discontinued or dose-reduced for previous hepatotoxicity. Pegaspargase-related toxicity was monitored weekly after 185 delivered doses and reported by NCI CTCAE v3.0. Fifty-one patients, aged 18-57, received 192 pegaspargase doses (3.8 doses/patient). High-grade hyperbilirubinemia occurred in 16 (31.4%) patients and 23 (12.4%) doses; high-grade transaminitis occurred in 33 (64.7%) patients and 62 (33.5%) doses. Of 11 patients with high-grade hyperbilirubinemia who received at least one subsequent pegaspargase dose, six (54.5%) experienced recurrent toxicity; of 24 patients with high-grade transaminitis who received at least one subsequent pegaspargase dose, 15 (62.5%) developed recurrent toxicity. Pegaspargase at this dose and interval is associated with high hepatotoxicity rates, but patients can be rechallenged despite earlier pegaspargase-related hepatotoxicity.


ALL; Adult; Characteristics; Clinical research; Hepatotoxicity; Pegaspargase

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