TY - JOUR
T1 - Toxicity associated with intensive postinduction therapy incorporating clofarabine in the very high-risk stratum of patients with newly diagnosed high-risk B-lymphoblastic leukemia
T2 - A report from the Children's Oncology Group study AALL1131
AU - Salzer, Wanda L.
AU - Burke, Michael J.
AU - Devidas, Meenakshi
AU - Chen, Si
AU - Gore, Lia
AU - Larsen, Eric C.
AU - Borowitz, Michael
AU - Wood, Brent
AU - Heerema, Nyla A.
AU - Carroll, Andrew J.
AU - Hilden, Joanne M.
AU - Loh, Mignon L.
AU - Raetz, Elizabeth A.
AU - Winick, Naomi J.
AU - Carroll, William L.
AU - Hunger, Stephen P.
N1 - Publisher Copyright:
© 2017 American Cancer Society
PY - 2018/3/15
Y1 - 2018/3/15
N2 - 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.
AB - 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.
KW - acute
KW - childhood
KW - clofarabine
KW - lymphoblastic leukemia
KW - toxicity
UR - http://www.scopus.com/inward/record.url?scp=85038428590&partnerID=8YFLogxK
U2 - 10.1002/cncr.31099
DO - 10.1002/cncr.31099
M3 - Article
C2 - 29266189
AN - SCOPUS:85038428590
SN - 0008-543X
VL - 124
SP - 1150
EP - 1159
JO - Cancer
JF - Cancer
IS - 6
ER -