Faculty Collaboration Database

Toxicity associated with intensive postinduction therapy incorporating clofarabine in the very high-risk stratum of patients with newly diagnosed high-risk B-lymphoblastic leukemia: A report from the Children's Oncology Group study AALL1131. Cancer 2018 Mar 15;124(6):1150-1159

Date

12/22/2017

Pubmed ID

29266189

Pubmed Central ID

PMC5839964

DOI

10.1002/cncr.31099

Scopus ID

2-s2.0-85038428590 (requires institutional sign-in at Scopus site)   40 Citations

Abstract

BACKGROUND: Children, adolescents, and young adults with very high-risk (VHR) B acute lymphoblastic leukemia (B-ALL) have poor outcomes, and novel therapies are needed for this subgroup. The AALL1131 study evaluated postinduction therapy using cyclophosphamide (CPM), etoposide (ETOP), and clofarabine (CLOF) for patients with VHR B-ALL.

METHODS: Patients who were 1 to 30 years old and had VHR B-ALL received modified Berlin-Frankfurt-Münster therapy after induction and were randomized to 1) CPM, cytarabine, mercaptopurine, vincristine (VCR), and pegaspargase (control arm), 2) CPM, ETOP, VCR, and pegaspargase (experimental arm 1), or 3) CPM, ETOP, CLOF (30 mg/m² /d × 5), VCR, and pegaspargase (experimental arm 2) during the second half of consolidation and delayed intensification.

RESULTS: The rates of grade 4/5 infections and grade 3/4 pancreatitis were significantly increased in experimental arm 2. The dose of CLOF was, therefore, reduced to 20 mg/m² /d × 5, and myeloid growth factor was required after CLOF administration. Despite these changes, 4 of 39 patients (10.3%) developed grade 4 infections, with 1 of these patients developing a grade 5 acute kidney injury attributed to CLOF, whereas only 1 of 46 patients (2.2%) in experimental arm 1 developed grade 4 infections, and there were no grade 4/5 infections in the control arm (n = 20). Four patients in experimental arm 2 had prolonged cytopenias for >60 days, whereas none did in the control arm or experimental arm 1. Counts failed to recover for 2 of these patients, one having a grade 5 acute kidney injury and the other removed from protocol therapy; both events occurred 92 days after the start of consolidation part 2.

CONCLUSIONS: In AALL1131, CLOF, administered with CPM and ETOP, was associated with unacceptable toxicity. Cancer 2018;124:1150-9. © 2017 American Cancer Society.

Author List

Salzer WL, Burke MJ, Devidas M, Chen S, Gore L, Larsen EC, Borowitz M, Wood B, Heerema NA, Carroll AJ, Hilden JM, Loh ML, Raetz EA, Winick NJ, Carroll WL, Hunger SP

Author

Michael James Burke MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Kidney Injury
Adolescent
Adult
Antineoplastic Combined Chemotherapy Protocols
Bacterial Infections
Child
Child, Preschool
Disease-Free Survival
Dose-Response Relationship, Drug
Female
Humans
Infant
Male
Pancreatitis
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Remission Induction
Severity of Illness Index
Young Adult