Cytarabine dose reduction in patients with low-risk acute myeloid leukemia: A report from the Children's Oncology Group.

2021

e29313

2021 Sep 02

1545-5017

<p><strong>BACKGROUND: </strong>The optimal number of chemotherapy courses for low-risk (LR) pediatric acute myeloid leukemia (AML) is not known.</p>

<p><strong>OBJECTIVE: </strong>To compare outcomes for four (21.6&nbsp;g/m cytarabine) versus five (45.6&nbsp;g/m cytarabine) chemotherapy courses for LR-AML using data from Children's Oncology Group (COG) AAML0531 and AAML1031.</p>

<p><strong>METHODS: </strong>We compared relapse risk (RR), disease-free survival (DFS), and overall survival (OS), and the differential impact in LR subgroups for patients receiving four versus five chemotherapy courses. Cox (OS and DFS) and risk (RR) regressions were used to estimate hazard ratios (HR) to compare outcomes.</p>

<p><strong>RESULTS: </strong>A total of 923 LR-AML patients were included; 21% received five courses. Overall, LR-AML patients who received four courses had higher RR (40.9% vs. 31.4%; HR&nbsp;=&nbsp;1.40, 95% confidence interval [CI]: 1.06-1.85), and worse DFS (56.0% vs. 67.0%; HR&nbsp;=&nbsp;1.45, 95% CI: 1.10-1.91). There was a similar decrement in OS though it was not statistically significant (77.0% vs. 83.5%; HR&nbsp;=&nbsp;1.45, 95% CI: 0.97-2.17). Stratified analyses revealed the detrimental effects of cytarabine dose de-escalation to be most pronounced in the LR-AML subgroup with uninformative cytogenetic/molecular features who were minimal residual disease (MRD) negative after the first induction course (EOI1). The absolute decrease in DFS with four courses for patients with favorable cytogenetic/molecular features and positive MRD was similar to that observed for patients with uninformative cytogenetic/molecular features and negative MRD at EOI1, though not statistically significant.</p>

<p><strong>CONCLUSIONS: </strong>Our results support de-escalation of cytarabine exposure through the elimination of a fifth chemotherapy course only for LR-AML patients who have both favorable cytogenetic/molecular features and negative MRD after the first induction cycle.</p>

10.1002/pbc.29313

Pediatr Blood Cancer

34472213

Bortezomib with standard chemotherapy for children with acute myeloid leukemia does not improve treatment outcomes: a report from the Children's Oncology Group.

2020

2020 Feb 06

1592-8721

<p>New therapeutic strategies are needed for pediatric acute myeloid leukemia to reduce disease recurrence and treatment-related morbidity. The Children's Oncology Group Phase III AAML1031 trial tested whether the addition of bortezomib to standard chemotherapy improves survival in pediatric patients with newly diagnosed acute myeloid leukemia. AAML1031 randomized patients younger than 30 years of age with de novo acute myeloid leukemia to standard treatment with or without bortezomib. All patients received the identical chemotherapy backbone with either four intensive chemotherapy courses or three courses followed by allogeneic hematopoietic stem cell transplantation for high-risk patients. For those randomized to the intervention arm, bortezomib 1.3 mg/m2 was given on days 1, 4 and 8 of each chemotherapy course. For those randomized to the control arm, bortezomib was not administered. In total, 1097 patients were randomized to standard chemotherapy (n=542) or standard chemotherapy with bortezomib (n=555). Remission induction rate did not differ between bortezomib and control treatment arms (89% vs 91%, p=0.531). Bortezomib failed to improve three-year event-free survival (44.8+/-4.5% vs 47.0+/-4.5%, p=0.236) or overall survival (63.6+/-4.5 vs 67.2+/-4.3, p=0.356) compared with the control arm. However, bortezomib was associated with significantly more peripheral neuropathy (p=0.006), and intensive care unit admissions (p=0.025) during the first course. The addition of bortezomib to standard chemotherapy increased toxicity but did not improve survival. These data do not support the addition of bortezomib to standard chemotherapy in children with de novo acute myeloid leukemia. (NCT01371981; https://www.cancer.gov/clinicaltrials/NCT01371981).</p>

10.3324/haematol.2019.220962

Haematologica

32029509