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2072 Survival Varies By Age and Histology in Classical Hodgkin Lymphoma: A Report from the Children’s Oncology Group

Program: Oral and Poster Abstracts
Session: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: Poster II
Hematology Disease Topics & Pathways:
Diseases, Hodgkin Lymphoma, Pediatric, Young Adult, Lymphoid Malignancies, Study Population, Clinically relevant
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Justine M. Kahn, MD, MSc1, Kara M. Kelly, MD2, Qinglin Pei, PhD3*, Yue Wu, MS4*, Debra L. Friedman, MD5, Tara O. Henderson, MD, MPH6*, David C. Hodgson, MD, MPH, FRCPC7*, Joel A. Kaplan, DO, MPH8*, Frank G. Keller, M.D.9, Smita Bhatia, MD, MPH10, Cindy L. Schwartz, MD11 and Sharon M. Castellino, MD, MSc12

1Division of Pediatric Hematology/Oncology, Columbia University Irving Medical Center, New York, NY
2Department of Pediatric Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY
3Children's Oncology Group, Gainesville, FL
4Department of Biostatistics, Children's Oncology Group Statistics & Data Center, Gainesville, FL
5Vanderbilt University School of Medicine, Nashville, TN
6University of Chicago Comer Children’s Hospital, Chicago, IL
7Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
8Levine Children's Cancer & Blood Disorders, Carolinas Medical Center, Charlotte, NC
9Department of Pediatrics, Emory University School of Medicine, Atlanta, GA
10Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL
11Children’s Hospital of WI, Medical College of Wisconsin, Milwaukee, WI
12Aflac Cancer and Blood Disorders Center, Emory University School of Medicine / Children's Healthcare of Atlanta, Atlanta, GA


While 5-year event-free (EFS) and overall survival (OS) in Hodgkin lymphoma (HL) generally exceed 85% and 95%, respectively, outcomes may not be as favorable in adolescents and young adults (15 – 39 years [y]) compared to children. Small clinical trials have reported better outcomes for pediatric but not adult patients with mixed cellularity (MC) vs. nodular sclerosing (NS) histology, suggesting the possibility of biologic differences across the age-spectrum in HL. We examined survival by age and histology in patients receiving risk-based, response-adapted therapy for de novo HL on contemporary Children’s Oncology Group (COG) trials.


This was a pooled analysis of individual-level data from 1,907 patients enrolled on three Phase 3 COG clinical trials for treatment of low-risk (AHOD0431), intermediate risk (AHOD0031) and high-risk (AHOD0831) HL between 2002 and 2012. Histologic subgroups included MC, NS and classical HL, not-otherwise-specified (cHL, NOS). Five-year cumulative incidence of relapse, EFS and OS were compared by age group (<15 y vs. ≥15 y) in the pooled cohort, and in histologic subgroups (MC and non-MC) using the Kaplan-Meier method. Effect modification was confirmed between age and histology. Cox proportional hazards regression models were used to examine the influence of age on EFS and OS, adjusted for race/ethnicity, Ann Arbor stage, B symptoms, bulky disease, receipt of radiation therapy (RT), and the interaction between age and histology; COG study was also included in the model, given that the criteria for response adaptation differed across the trials.


Between 2002 and 2012, N= 2155 patients 1 – 21 y enrolled on three COG trials, 1,907 (88%) of whom were included in this analysis. Mean age of the cohort was 14.6 y (± 3.5) with N= 871 (46%) <15 y and N= 1,036 (54%) ≥15 y. In total, N= 1,547 patients (81%) had NS histology, N= 108 (6%) had cHL, NOS, and N= 196 (10%) had MC histology; by age, MC histology was present in N= 66 patients (7%) ≥15 y and N= 130 patients (15%) <15 y (p< 0.01). A significantly higher proportion of those ≥15 y vs. younger had B-symptoms at diagnosis (29% vs. 21%, p< 0.01), however the presence of bulky disease did not differ by age. Finally, patients ≥15 y (vs. <15 y) were significantly more likely to receive RT as part of their treatment (72% vs. 63%, p<0.01).

Survival: Median follow up was 6.9 years. In unadjusted analyses, 5-year EFS and OS were 83% and 97%, respectively. The 5-year EFS was lower for patients ≥15 y vs. <15 y (85% vs 89%, p<0.01), as was the 5-year OS (96% vs. 99%, p< 0.01). In multivariable models, age ≥15 y (vs. younger) was associated with a 1.4-fold increased risk of EFS (HR: 1.4, 95% CI: 1.1, 1.8, p< 0.01), and more than a 3-fold increased risk of death (OS: HR: 3.1, 95% CI: 1.5, 6.4, p< 0.01).

The effect of age on EFS varied by histologic subgroup. Among those with non-MC histology, cumulative incidence of relapse did not significantly differ by age in unadjusted models (Figure A), however 5-year EFS was significantly worse in the older group (Figure B). In multivariable analyses, age ≥15 y (vs. younger) was associated with a 1.3-fold increased risk of EFS (HR: 1.3; 1.03 – 1.7, p= 0.03) (Table). Among patients with MC histology, age ≥15 y (vs. younger) was associated with significantly higher relapse rate (22% vs. 5%, p< 0.01) (Figure C) and significantly worse 5-year EFS (75% vs. 94%, p< 0.01) (Figure D). This remained significant in multivariable models: patients with MC histology who were ≥15 y (vs. younger) had a 3.7-fold increased risk of EFS (HR: 3.7, 95% CI: 1.6, 8.9, p< 0.01) (Table).


In patients receiving response-adapted therapy for de novo HL on contemporary COG trials, adolescents ≥15 y had worse EFS and OS compared to younger groups. The magnitude of the effect of age was higher in patients with MC disease. Although recent pediatric trials in HL have indicated better survival for some children with MC histology, alternative approaches or novel therapies should be considered for older adolescents with MC disease, whose outcomes appear more like adults.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH