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

Central nervous system disease in pediatric acute myeloid leukemia: A report from the Children's Oncology Group.

2017

2017 Apr 28

1545-5017

<p><strong>BACKGROUND: </strong>The prognostic impact of central nervous system (CNS) involvement in children with acute myeloid leukemia (AML) has varied in past trials, and controversy exists over the degree of involvement requiring intensified CNS therapy. Two recent Children's Oncology Group protocols, AAML03P1 and AAML0531, directed additional intrathecal (IT) therapy to patients with CNS2 (≤5 white blood cell [WBC] with blasts) or CNS3 (&gt;5 WBC with blasts or CNS symptoms) disease at diagnosis.</p>

<p><strong>METHODS: </strong>We examined disease characteristics and outcomes of the 1,344 patients on these protocols, 949 with CNS1 (no blasts), 217 with CNS2, and 178 with CNS3, with the latter two receiving additional IT therapy.</p>

<p><strong>RESULTS: </strong>Young age (P = 0.003), hyperleukocytosis (P&nbsp;&lt; 0.001), and the presence of inversion 16 (P&nbsp;&lt; 0.001) were the only factors more prevalent in patients with CNS2 or CNS3 disease. Complete remission at the end of induction (EOI) 2 was achieved less often in patients with CNS involvement (P&nbsp;&lt; 0.001). From diagnosis, event-free survival (EFS) for patients with CNS involvement was significantly worse (P&nbsp;&lt; 0.001), whereas overall survival (OS) was not (P = 0.16). From the EOI1, there was a higher relapse rate (RR) and worse disease-free survival (DFS), but less impact on OS (CNS1:DFS 58.9%, RR 34.1%, OS 69.3%; CNS2:DFS 53.2%, RR 40.9%, OS 74.7%; CNS3:DFS 45.2%, RR 48.8%, OS 60.8%; P = 0.006, P&nbsp;&lt; 0.001, P = 0.045, respectively). Multivariable analysis showed that independently CNS2 and CNS3 status adversely affected RR and DFS. Traumatic diagnostic lumbar puncture was not associated with worse outcome.</p>

<p><strong>CONCLUSIONS: </strong>CNS leukemia confers greater relapse risk despite more aggressive locally directed therapy. Novel approaches need to be investigated in this group of patients.</p>

10.1002/pbc.26612

Pediatr Blood Cancer

28453910

Impact of registration on clinical trials on infection risk in pediatric acute myeloid leukemia.

2016

1785-91

2016 Apr 1

1097-0215

<p>Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged ≤18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy-four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01-1.53; p = 0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08-1.98; p = 0.015). Registration on trials was not associated with Gram-negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML.</p>

10.1002/ijc.29905

Int. J. Cancer

26515793

Single nucleotide polymorphism in IL1B is associated with infection risk in paediatric acute myeloid leukaemia.

2016

2016 Feb 27

1469-0691

<p>We evaluated single nucleotide polymorphisms (SNPs) associated with infection risk in children with newly diagnosed acute myeloid leukaemia (AML). We conducted a multicentre, prospective cohort study that included children aged ≤18&nbsp;years with de novo AML. DNA was isolated from blood lymphocytes or buccal swabs, and candidate gene SNP analysis was conducted. Primary outcome was the occurrence of microbiologically documented sterile site infection during chemotherapy. Secondary outcomes were Gram-positive and -negative infections, viridans group streptococcal infection and proven/probable invasive fungal infection. Interpretation was guided by consistency in risk alleles and microbiologic agent with previous literature. Over the study period 254 children and adolescents with AML were enrolled. Overall, 190 (74.8%) had at least one sterile site microbiologically documented infection. Among the 172 with inferred European ancestry and DNA available, nine significant associations were observed; two were consistent with previous literature. Allele A at IL1B (rs16944) was associated with decreased microbiologically documented infection, and allele G at IL10 (rs1800896) was associated with increased risk of Gram-positive infection. We identified SNPs associated with infection risk in paediatric AML. Genotype may provide insight into mechanisms of infection risk that could be used for supportive-care novel treatments.</p>

10.1016/j.cmi.2016.02.006

Clin. Microbiol. Infect.

26932518

Reasons for non-completion of health related quality of life evaluations in pediatric acute myeloid leukemia: a report from the Children's Oncology Group.

2013

e74549

2013

1932-6203

<p><strong>BACKGROUND: </strong>Health related quality of life (HRQL) assessments during therapy for pediatric cancer are important. The objective of this study was to describe reasons for failure to provide HRQL assessments during a pediatric acute myeloid leukemia (AML) clinical trial.</p>

<p><strong>METHODS: </strong>We focused on HRQL assessments embedded in a multicenter pediatric AML clinical trial. The PedsQL 4.0 Generic Core Scales, PedsQL 3.0 Acute Cancer Module, PedsQL Multidimensional Fatigue Scale, and Pediatric Inventory for Parents were obtained from parent/guardian respondents at a maximum of six time points. Children provided self-report optionally. A central study coordinator contacted sites with delinquent HRQL data. Reasons for failure to submit the HRQL assessments were evaluated by three pediatric oncologists and themes were generated using thematic analysis.</p>

<p><strong>RESULTS: </strong>There were 906 completed and 1091 potential assessments included in this analysis (83%). The median age of included children was 12.9 years (range 2.0 to 18.9). The five themes for non-completion were: patient too ill; passive or active refusal by respondent; developmental delay; logistical challenges; and poor knowledge of study processes from both the respondent and institutional perspective.</p>

<p><strong>CONCLUSIONS: </strong>We identified reasons for non-completion of HRQL assessments during active therapy. This information will facilitate recommendations to improve study processes and future HRQL study designs to maximize response rates.</p>

10.1371/journal.pone.0074549

PLoS ONE

24040278

Children's Oncology Group's 2013 blueprint for research: cancer control and supportive care.

2013

1027-30

2013 Jun

1545-5017

<p>In cancer control research, the objective is to reduce overall morbidity and mortality by decreasing acute and delayed treatment-related toxicities in all children with cancer. To date, the Children's Oncology Group (COG) has focused on infection, neurocognition, quality of life (QoL), and nutrition/antiemetics. COG is conducting randomized controlled trials (RCTs) to determine prophylaxis strategies that will reduce infections in high-risk populations. Two RCTs are determining if modafinil or computerized cognitive training improve cognitive functioning in pediatric brain tumor patients. QoL is being assessed in acute leukemia patients. Improved supportive care outcomes will only occur when the most effective interventions are established.</p>

10.1002/pbc.24426

Pediatr Blood Cancer

23255159

Patient-Reported Outcome Coordinator Did Not Improve Quality of Life Assessment Response Rates: A Report from the Children's Oncology Group.

2015

e0125290

2015

1932-6203

<p><strong>PURPOSE: </strong>Health related quality of life (HRQL) assessments during therapy for pediatric cancer provide valuable information to better understand the patient experience. Our objective was to determine the impact of a patient-reported outcome (PRO) coordinator on HRQL questionnaire completion rates during a pediatric acute myeloid leukemia (AML) trial.</p>

<p><strong>METHODS: </strong>AAML1031 is a multicenter Children's Oncology Group therapeutic trial for de novo AML with a secondary aim to assess HRQL of children and adolescents treated with chemotherapy and hematopoietic stem cell transplantation (HSCT). Parents/guardians are the primary respondents and four questionnaires are administered at eight time points. The questionnaires are the PedsQL 4.0 Generic Core Scales, PedsQL 3.0 Acute Cancer Module, PedsQL Multidimensional Fatigue Scale, and the Pediatric Inventory for Parents. To improve response rates, a central PRO coordinator was instituted and reminded sites about upcoming and delinquent questionnaires. The proportion of HRQL questionnaires completed were compared prior to, and following institution of the PRO coordinator. This analysis evaluated the first five assessment time points.</p>

<p><strong>RESULTS: </strong>There were231 families who consented to participate in the HRQL aim. Overall response rates for all questionnaires were 73-83%. At time point 1, within 14 days of chemotherapy initiation, post-PRO coordinator completion rates were significantly higher for three of four questionnaires. However, the effect was not sustained and at time point 4, one month following last chemotherapy or HSCT, completion rates were significantly lower post-PRO coordinator for all four questionnaires.</p>

<p><strong>CONCLUSION: </strong>Addition of a central PRO coordinator did not result in sustained improvement in HRQL questionnaire completion rates. Efforts to improve response rates must consider other strategies.</p>

10.1371/journal.pone.0125290

PLoS ONE

25915772