Risk and Response Adapted Treatment Guidelines for Managing First Relapsed and Refractory Classical Hodgkin Lymphoma in Children and Young People. Recommendations from the EuroNet Pediatric Hodgkin Lymphoma Group

Abstract

The objective of this guideline is to aid clinicians in making individual salvage treatment plans for pediatric and adolescent patients with first relapse or refractory (R/R) classical Hodgkin lymphoma (cHL). While salvage with standard dose chemotherapy followed by high dose chemotherapy and autologous stem cell transplant is often considered the standard of care in adult practice, pediatric practice adopts a more individualized risk stratified and response adapted approach to salvage treatment with greater use of non-transplant salvage. Here, we present on behalf of the EuroNet Pediatric Hodgkin Lymphoma group, evidence and consensus-based guidelines for standardized diagnostic, prognostic and response procedures to allocate children and adolescents with R/R cHL to stratified salvage treatments.

Comparison of Interim PET Response to Second-Line Versus First-Line Treatment in Classic Hodgkin Lymphoma: Contribution to the Development of Response Criteria for Relapsed or Progressive Disease

“…Our results influenced the recently published risk-and responseadapted treatment guidelines of the EuroNet-PHL group for managing a first relapse of classic HL in children and young adults (9). These guidelines recommend defining CMR in a first relapse as DS 1-3 or a qPET value of less than 1.3-similarly to first-line treatment.…”

“…PET is also used to guide treatment after relapse: patients with residual PET positivity after first-line salvage chemotherapy were switched to second-line salvage chemotherapy, and if they achieved CMR, they had a posttransplant outcome similar to that of patients achieving CMR with first-line salvage treatment (7). In the EuroNet-PHL-R1 trial, medium-risk children and adolescents achieving CMR after 2 cycles of secondline chemotherapy were deescalated to standard chemotherapy plus radiotherapy only, whereas inadequate responders received highdose chemotherapy and autologous stem cell transplantation (9).…”

“…However, no special response criteria for second-line treatment have been established. To date, published studies have used the transition between Deauville score (DS) 2 and DS 3 as the cutoff between inadequate and adequate response, corresponding to the criteria in first-line treatment at that time (7,9,16). Would it be justifiable for second-line treatment to adopt the new response criteria used in first-line treatment?…”

Pediatric Hodgkin Lymphoma, Version 3.2021

“…55 Relapsed or Refractory CHL Although the outcomes for pediatric HL are excellent, approximately 10% of patients with early-stage disease and up to 25% of patients with advanced-stage disease experience relapse. 8,56,57 For patients with relapsed or refractory disease, treatment options include standarddose chemotherapy (reinduction therapy), high-dose chemotherapy with ASCR, or novel approaches. 56 Reinduction regimens (see PHL-E 2 of 3, page 747) can be divided into 4 major categories.…”

Proteomic Exploration of Plasma Exosomes and Other Small Extracellular Vesicles in Pediatric Hodgkin Lymphoma: A Potential Source of Biomarkers for Relapse Occurrence

“…It is considered as a curable pediatric cancer, since most patients are cured with first-line treatment and the 5-year survival rate is 90–95% [ 3 ]. Relapses occur in about 10–20% of patients, depending on disease stage [ 4 , 5 ]. Great attention is currently given to these subgroups of pediatric HL patients at risk of relapse, and several studies have reported candidate biomarkers predictive of relapse [ 6 , 7 , 8 , 9 ].…”