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.

2022

2022 Jan 06

1476-5365

<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>

10.1038/s41409-021-01558-6

Bone Marrow Transplant

34992254

Beyond the storm - subacute toxicities and late effects in children receiving CAR T cells.

2021

2021 Jan 25

1759-4782

<p>As clinical advances with chimeric antigen receptor (CAR) T cells are increasingly described and the potential for extending their therapeutic benefit grows, optimizing the implementation of this therapeutic modality is imperative. The recognition and management of cytokine release syndrome (CRS) marked a milestone in this field; however, beyond the understanding gained in treating CRS, a host of additional toxicities and/or potential late effects of CAR T cell therapy warrant further investigation. A multicentre initiative involving experts in paediatric cell therapy, supportive care and/or study of late effects from cancer and haematopoietic stem cell transplantation was convened to facilitate the comprehensive study of extended CAR&nbsp;T cell-mediated toxicities and establish a framework for new systematic investigations of CAR T cell-related adverse events. Together, this group identified six key focus areas: extended monitoring of neurotoxicity and neurocognitive function, psychosocial considerations, infection and immune reconstitution, other end organ toxicities, evaluation of subsequent neoplasms, and strategies to optimize remission durability. Herein, we present the current understanding, gaps in knowledge and future directions of research addressing these CAR T cell-related outcomes. This systematic framework to study extended toxicities and optimization strategies will facilitate the translation of acquired experience and knowledge for optimal application of CAR T cell therapies.</p>

10.1038/s41571-020-00456-y

Nat Rev Clin Oncol

33495553

The impact of donor type on outcomes and cost of allogeneic hematopoietic cell transplant for pediatric leukemia: a merged CIBMTR and PHIS analysis: Pediatric acute leukemia transplant risks and utilization.

2020

2020 May 25

1523-6536

<p><strong>IMPORTANCE: </strong>AlloHCT may be associated with significant morbidity and mortality that result in increased healthcare utilization. To date, no multi-center comparative cost analyses have been performed specifically evaluating alloHCT in children with acute leukemia.</p>

<p><strong>OBJECTIVES: </strong>To describe the relationship between survival and healthcare utilization while investigating the hypothesis that matched sibling donor (MSD) alloHCT has significantly lower inpatient healthcare utilization compared to unrelated donor (URD) and that among URD, umbilical cord blood transplants (UCB) will have higher initial but lower long-term utilization.</p>

<p><strong>DESIGN: </strong>Retrospective cohort study Setting: Clinical and transplant outcomes data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were merged with inpatient cost data from the Pediatric Health Information System (PHIS) database using a probabilistic merge methodology.</p>

<p><strong>PARTICIPANTS: </strong>The merged dataset contained U.S. patients age 1-21 years who received alloHCT for acute leukemia from 2004-2011 with comprehensive CIBMTR data at a PHIS hospital.</p>

<p><strong>EXPOSURE: </strong>AlloHCT analyzed by donor type with specific analysis of utilization and costs using PHIS claims data.</p>

<p><strong>MAIN OUTCOME: </strong>The primary outcomes of overall survival (OS), leukemia free survival (LFS), and inpatient costs were evaluated using Kaplan-Meier curves, Cox, and Poisson models.</p>

<p><strong>RESULTS: </strong>632 patients were identified in both CIBMTR and PHIS. 5-year LFS was 60% for MSD, 47% for well-matched matched unrelated donor bone marrow (MUD), 48% for mismatched unrelated donor, and 45% for UCB (p=0.09). Total adjusted costs were significantly lower for MSD versus MUD by day 100 (adjusted cost ratio (ACR) 0.73, CI 0.62-0.86, p&lt;0.001), and higher for UCB versus MUD (ACR 1.27, CI 1.11-1.45, p&lt;0.001). By 2yrs, total adjusted costs remained significantly lower for MSD when compared to MUD (ACR 0.67, CI 0.56-0.81, p&lt;0.001) and higher for UCB compared to MUD (ACR 1.25, 95% CI 1.02-1.52, p=0.0280).</p>

<p><strong>CONCLUSIONS: </strong>UCB and MUD alloHCT provide similar survival outcomes; however, MUD alloHCT has a significant advantage in cost by day 100 and 2 years. Ongoing research is needed to determine if the cost difference among URD alloHCT remains significant with a larger sample size and/or beyond the 2 years following alloHCT.</p>

10.1016/j.bbmt.2020.05.016

Biol. Blood Marrow Transplant.

32464284

Center-level variation in accuracy of adverse event reporting in a clinical trial for pediatric acute myeloid leukemia: A report from the Children's Oncology Group.

2017

2017 Jun 22

1592-8721

10.3324/haematol.2017.168815

Haematologica

28642300

A comparison of discharge strategies after chemotherapy completion in pediatric patients with acute myeloid leukemia: a report from the Children's Oncology Group.

2016

1-8

2016 Jan 4

1029-2403

<p>While most children receive acute myeloid leukemia (AML) chemotherapy as inpatients, there is variability in timing of discharge after chemotherapy completion. This study compared treatment-related morbidity, mortality and cumulative hospitalization in children with AML who were discharged after chemotherapy completion (early discharge) and those who remained hospitalized. Chart abstraction data for 153 early discharge-eligible patients enrolled on a Children's Oncology Group trial were compared by discharge strategy. Targeted toxicities included viridans group streptococcal (VGS) bacteremia, hypoxia and hypotension. Early discharge occurred in 11% of courses post-Induction I. Re-admission occurred in 80-100%, but median hospital stay was 7 days shorter. Patients discharged early had higher rates of VGS (adjusted risk ratio (aRR) = 1.67, 95% CI = 1.11-2.51), hypoxia (aRR = 1.92, 95% CI = 1.06-3.48) and hypotension (aRR = 4.36, 95% CI = 2.01-9.46), but there was no difference in mortality. As pressure increases to shorten hospitalizations, these results have important implications for determining discharge practices in pediatric AML.</p>

10.3109/10428194.2015.1088652

Leuk. Lymphoma

26727639

Accuracy of Adverse Event Ascertainment in Clinical Trials for Pediatric Acute Myeloid Leukemia.

2016

2016 Feb 16

1527-7755

<p><strong>PURPOSE: </strong>Reporting of adverse events (AEs) in clinical trials is critical to understanding treatment safety, but data on AE accuracy are limited. This study sought to determine the accuracy of AE reporting for pediatric acute myeloid leukemia clinical trials and to test whether an external electronic data source can improve reporting.</p>

<p><strong>METHODS: </strong>Reported AEs were evaluated on two trials, Children's Oncology Group AAML03P1 and AAML0531 arm B, with identical chemotherapy regimens but with different toxicity reporting requirements. Chart review for 12 AEs for patients enrolled in AAML0531 at 14 hospitals was the gold standard. The sensitivity and positive predictive values (PPV) of the AAML0531 AE report and AEs detected by review of Pediatric Health Information System (PHIS) billing and microbiology data were compared with chart data.</p>

<p><strong>RESULTS: </strong>Select AE rates from AAML03P1 and AAML0531 arm B differed significantly and correlated with the targeted toxicities of each trial. Chart abstraction was performed on 204 patients (758 courses) on AAML0531. AE report sensitivity was &lt; 50% for eight AEs, but PPV was &gt; 75% for six AEs. AE reports for viridans group streptococcal bacteremia, a targeted toxicity on AAML0531, had a sensitivity of 78.3% and PPV of 98.1%. PHIS billing data had higher sensitivity (&gt; 50% for nine AEs), but lower PPV (&lt; 75% for 10 AEs). Viridans group streptococcal detection using PHIS microbiology data had high sensitivity (92.3%) and PPV (97.3%).</p>

<p><strong>CONCLUSION: </strong>The current system of AE reporting for cooperative oncology group clinical trials in pediatric acute myeloid leukemia underestimates AE rates. The high sensitivity and PPV of PHIS microbiology data suggest that using external data sources may improve the accuracy of AE reporting.</p>

10.1200/JCO.2015.65.5860

J. Clin. Oncol.

26884558

Effect of body mass in children with hematologic malignancies undergoing allogeneic bone marrow transplantation.

2014

3504-11

2014 May 29

1528-0020

<p>The rising incidence of pediatric obesity may significantly affect bone marrow transplantation (BMT) outcomes. We analyzed outcomes in 3687 children worldwide who received cyclophosphamide-based BMT regimens for leukemias between 1990 and 2007. Recipients were classified according to age-adjusted body mass index (BMI) percentiles as underweight (UW), at risk of UW (RUW), normal, overweight (OW), or obese (OB). Median age and race were similar in all groups. Sixty-one percent of OB children were from the United States/Canada. Three-year relapse-free and overall survival ranged from 48% to 52% (P = .54) and 55% to 58% (P = .81) across BMI groups. Three-year leukemia relapses were 33%, 33%, 29%, 25%, and 21% in the UW, RUW, normal, OW, and OB groups, respectively (P &lt; .001). Corresponding cumulative incidences for transplant-related mortality (TRM) were 18%, 19%, 21%, 22%, and 28% (P &lt; .01). Multivariate analysis demonstrated a decreased risk of relapse compared with normal BMI (relative risk [RR] = 0.73; P &lt; .01) and a trend toward higher TRM (RR = 1.28; P = .014). BMI in children is not significantly associated with different survival after BMT for hematologic malignancies. Obese children experience less relapse posttransplant compared with children with normal BMI; however, this benefit is offset by excess in TRM.</p>

10.1182/blood-2013-03-490334

Blood

24711663