First name
John
Middle name
E
Last name
Levine

Title

Adolescent and young adult (AYA) versus pediatric patients with acute leukemia have a significantly increased risk of acute GVHD following unrelated donor (URD) stem cell transplantation (SCT): the Children's Oncology Group experience.

Year of Publication

2022

Date Published

2022 Jan 06

ISSN Number

1476-5365

Abstract

<p>Adolescent and young adult (AYA) patients with acute leukemia (AL) have inferior outcomes in comparison to younger patients, and are more likely to develop acute and chronic GVHD than younger children following HLA matched sibling donor stem cell transplant (SCT). We compared the incidence of grade II-IV acute GVHD, chronic GVHD, and survival in AYA (age 13-21 years) to younger children (age 2-12 years) who received an unrelated donor SCT for acute leukemia on Children's Oncology Group trials between 2004-2017. One hundred and eighty-eight children and young adults ages 2-21 years underwent URD SCT. Sixty-three percent were aged 2-12 and 37% were age 13-21. Older age was a risk factor for grade II-IV acute GVHD in multivariate analysis with a hazard ratio (HR) of 1.95 [95% confidence interval (CI) 1.23-3.10], but not for chronic GVHD, HR 1.25 [95% CI 0.57-2.71]. Younger patients relapsed more often (34.5 ± 4.4% vs. 22.8 ± 4.0%, p = 0.032), but their Event-Free Survival (42.6 ± 4.7% vs. 51.8 ± 6.1%, p = 0.18) and Overall Survival at 5 years (48.5 ± 4.9% vs. 51.5 ± 6.4%, p = 0.56) were not different than AYA patients. AYA patients who receive an URD SCT for acute leukemia are significantly more likely to develop grade II-IV acute GVHD, though survival is similar.</p>

DOI

10.1038/s41409-021-01558-6

Alternate Title

Bone Marrow Transplant

PMID

34992254

Title

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

Year of Publication

2020

Date Published

2020 Feb 06

ISSN Number

1592-8721

Abstract

<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>

DOI

10.3324/haematol.2019.220962

Alternate Title

Haematologica

PMID

32029509

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