Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932

Abstract

PURPOSE: AALL0932 evaluated two randomized maintenance interventions to optimize disease-free survival (DFS) while reducing the burden of therapy in children with newly diagnosed NCI standard-risk (SR) B-acute lymphoblastic leukemia (B-ALL). METHODS: AALL0932 enrolled 9,229 patients with B-ALL; 2,364 average-risk (AR) patients were randomly assigned (2 × 2 factorial design) at the start of maintenance therapy to vincristine/dexamethasone pulses every 4 (VCR/DEX4) or every 12 (VCR/DEX12) weeks, and a starting dose of once weekly oral methotrexate of 20 mg/m2 (MTX20) or 40 mg/m2 (MTX40). RESULTS: Five-year event-free survival and overall survival (OS) from enrollment, for all eligible and evaluable SR B-ALL patients (n = 9,226), were 92.0% (95% CI, 91.1% to 92.8%) and 96.8% (95% CI, 96.2% to 97.3%), respectively. The 5-year DFS and OS from the start of maintenance for randomly assigned AR patients were 94.6% (95% CI, 93.3% to 95.9%) and 98.5% (95% CI, 97.7% to 99.2%), respectively. The 5-year DFS and OS for patients randomly assigned to receive VCR/DEX4 (n = 1,186) versus VCR/DEX12 (n = 1,178) were 94.1% (95% CI, 92.2% to 96.0%) and 98.3% (95% CI, 97.2% to 99.4%) v 95.1% (95% CI, 93.3% to 96.9%) and 98.6% (95% CI, 97.7% to 99.6%), respectively ( P = .86 and .69). The 5-year DFS and OS for AR patients randomly assigned to receive MTX20 versus MTX40 were 95.1% (95% CI, 93.3% to 96.8%) and 98.8% (95% CI, 97.9% to 99.7%) versus 94.2% (95% CI, 92.2% to 96.1%) and 98.1% (95% CI, 97.0% to 99.2%), respectively ( P = .92 and .89). CONCLUSIONS: The NCI-SR AR B-ALL who received VCR/DEX12 had outstanding outcomes despite receiving one third of the vincristine/dexamethasone pulses previously used as standard of care on Children's Oncology Group (COG) trials. The higher starting dose of MTX of 40 mg/m2 once weekly did not improve outcomes when compared with 20 mg/m2 once weekly. The decreased frequency of vincristine/dexamethasone pulses has been incorporated into frontline COG B-ALL trials to decrease the burden of therapy for patients and their families.

Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia

“…In contrast to a previous magnetic resonance spectroscopy (MRS) and gas chromatography-mass spectrometry (GC–MS)-based untargeted metabolomics study which reported total depletion of asparagine at D29 in patients who received PEG-asparaginase between induction D4 and D6 17 , we detected asparagine in plasma and marrow samples from all children. Patients on both induction protocols (AALL0932 and AALL1131) received PEG-asparaginase on induction D4 12 , 33 ; our observation is consistent that of Angiolillo et al, who demonstrated that asparagine levels begin to recover 20–25 days after PEG-asparaginase administration 34 . Given the importance of asparagine depletion in ALL chemotherapy, it may be noteworthy that it was readily detected in plasma using this approach, and that plasma and marrow asparagine abundances correlated strongly.…”

Comparison of The Blood, Bone Marrow, and Cerebrospinal Fluid Metabolomes In Children with B-Cell Acute Lymphoblastic Leukemia

“…In contrast to a previous magnetic resonance spectroscopy (MRS) and gas chromatography-mass spectrometry (GC-MS)-based untargeted metabolomics study, which reported total depletion of asparagine at D29 in patients who received PEGasparaginase between induction D4 and D6 17 , we detected asparagine in plasma and marrow samples from all children. Patients on both induction protocols (AALL0932 and AALL1131) received PEGasparaginase on induction D4 12,33 ; our observation is consistent that of Angiolillo et al, who demonstrated that asparagine levels begin to recover approximately 20-25 days after PEG-asparginase administration 34 . Given the importance of asparagine depletion in ALL chemotherapy, it may be noteworthy that it was readily detected in plasma using this approach, and that plasma and marrow asparagine abundances correlated strongly.…”

Curing the Curable: Managing Low-Risk Acute Lymphoblastic Leukemia in Resource Limited Countries

“…For the lower-risk groups, reduction of VCR/steroid pulses has been studied. The COG AALL0932 for NCI-SR B-ALL found that reducing the intensity of VCR/steroid pulses from 4 weekly to 12 weekly maintained the same excellent outcomes (OS 98%), although this was not performed in the context of a non-inferiority trial [77]. In the Ma-Spore trials, VCR/steroid pulses in the SR and IR arms were also given 10 weekly (MS2003) and 12 weekly (MS2010), with excellent outcomes [18,19].…”