CBFB-MYH11 Fusion Transcripts Distinguish Acute Myeloid Leukemias with Distinct Molecular Landscapes and Outcomes.

2021

2021 Sep 21

2473-9537

<p>Patients with inv(16)/CBFB-MYH11 AML are considered favorable risk, however, nearly one-third relapse despite intensive therapy. Despite efforts to define risk groups within this favorable risk cohort, CBFB-MYH11 AML patients continue to be treated as a uniform cohort. Through transcriptome sequencing of 186 patients with inv(16) AML, we demonstrate that fusion junction breakpoints (exon 5-exon 33 versus other) are highly associated with outcome. The presence of exon 17 KIT mutations provides additional prognostic significance. Additionally, we provide insights into the transcriptional landscapes that differentiate these distinct CBFB-MYH11 AML subtypes. Children's Oncology Group trials include CCG-2961 (registered at www.clinicaltrials.gov as NCT00002798), AAML03P1 (NCT00070174), AAML0531 (NCT00372593), and AAML1031 (NCT01371981).</p>

10.1182/bloodadvances.2021004965

Blood Adv

34547772

Quality of life in pediatric acute myeloid leukemia: Report from the Children's Oncology Group.

2019

2019 Jun 12

2045-7634

<p><strong>INTRODUCTION: </strong>Objectives were used to describe guardian proxy-report and child self-report quality of life (QoL) during chemotherapy for pediatric acute myeloid leukemia (AML) patients.</p>

<p><strong>METHODS: </strong>Patients enrolled on the phase 3 AML trial AAML1031 who were 2-18&nbsp;years of age with English-speaking guardians were eligible. Instruments used were the PedsQL Generic Core Scales, Acute Cancer Module, and Multidimensional Fatigue Scale. Assessments were obtained at the beginning of Induction 1 and following completion of cycles 2-4. Potential predictors of QoL included the total number of nonhematological grade 3-4 Common Terminology Criteria for Adverse Event (CTCAE) submissions.</p>

<p><strong>RESULTS: </strong>There were 505 eligible guardians who consented to participate and 348 of their children provided at least one self-report assessment. The number of submitted CTCAE toxicities was significantly associated with worse physical health summary scores (β&nbsp;±&nbsp;standard error (SE) -3.00&nbsp;±&nbsp;0.69; P&nbsp;&lt;&nbsp;0.001) and general fatigue (β&nbsp;±&nbsp;SE -2.50&nbsp;±&nbsp;0.66; P&nbsp;&lt;&nbsp;0.001). Older age was significantly associated with more fatigue (β&nbsp;±&nbsp;SE -0.58&nbsp;±&nbsp;0.25; P&nbsp;=&nbsp;0.022). Gender, white race, Hispanic ethnicity, private insurance status, risk status, bortezomib assignment, and duration of neutropenia were not significantly associated with QoL.</p>

<p><strong>DISCUSSION: </strong>The number of CTCAE toxicities was the primary factor influencing QoL among children with AML. Reducing toxicities should improve QoL; identifying approaches to ameliorate them should be a priority.</p>

10.1002/cam4.2337

Cancer Med

31190442

Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia.

2015

2949-62

2015 Sep 20

1527-7755

<p>Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and international collaborative efforts have evolved. This overview describes these efforts and includes a summary of the history and contributions of each of the main collaborative pediatric AML groups worldwide. The focus is on translational and clinical research, which includes past, current, and future clinical trials. Separate sections concern acute promyelocytic leukemia, myeloid leukemia of Down syndrome, and relapsed AML. A plethora of novel antileukemic agents that have emerged, including new classes of drugs, are summarized as well. Finally, an important aspect of the treatment of pediatric AML--supportive care--and late effects are discussed. The future is bright, with a wide range of emerging innovative therapies and with more and more international collaboration that ultimately aim to cure all children with AML, with fewer adverse effects and without late effects.</p>

10.1200/JCO.2015.62.8289

J. Clin. Oncol.

26304895