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Simple Summary: Survival of classical Hodgkin's lymphoma (cHL) in Western countries is excellent. However, about 10% of patients with stage I–II disease and 15–30% of those with advanced stages require salvage therapy for resistant or relapsing disease. Many studies have investigated prognostic factors in adult patients, but data on children and adolescents are scarce. We analyzed a cohort of 272 patients aged <18 years with recurrent cHL, enrolled in two Italian subsequent protocols between 1996 and 2016. Overall and event-free survival after 10 years since the first recurrence were 65.3% and 53.3%, respectively. Major prognostic risk factors were progressive disease, advanced stage, ≥5 involved sites, and extra-nodal involvement at the recurrence. Patients with progressive disease, advanced stage, or ≥5 involved sites had a very poor survival and might benefit from more innovative approaches since the first progression. Patients who relapsed later with localized cHL might be considered for a conservative approach. The objective of this study was to identify prognostic factors for children and adolescents with relapsed or progressive classical Hodgkin's lymphoma (cHL) to design salvage therapy tailored to them. We analyzed a homogeneous pediatric population, diagnosed with progressive/relapsed cHL previously enrolled in two subsequent protocols of the Italian Association of Pediatric Hematology and Oncology in the period 1996–2016. There were 272 eligible patients, 17.5% of treated patients with cHL. Overall survival (OS) and event-free survival (EFS) after a 10-year follow-up were 65.3% and 53.3%, respectively. Patients with progressive disease (PD), advanced stage at recurrence, and ≥5 involved sites showed a significantly worse OS. PD, advanced stage, and extra-nodal involvement at recurrence were significantly associated with a poorer EFS. Multivariable analysis identified three categories for OS based on the type of recurrence and number of localizations: PD and ≥5 sites: OS 34%; PD and <5 sites: OS 56.5%; relapses: OS 73.6%. Four categories were obtained for EFS based on the type of recurrence and stage: PD and stage 3–4: EFS 25.5%; PD and stage 1–2: EFS 43%; relapse and stage 3–4: EFS 55.4%; relapse and stage 1–2: EFS 72.1%. Patients with PD, in advanced stage, or with ≥5 involved sites had a very poor survival and they should be considered refractory to first- and second-line standard chemotherapy. Probably, they should be considered for more innovative approaches since the first progression. Conversely, patients who relapsed later with localized disease had a better prognosis, and they could be considered for a conservative approach. [ABSTRACT FROM AUTHOR]

Many studies have reported a more favorable outcome in younger patients with Hodgkin lymphoma (HL). The aims of this study were to find an appropriate age cutoff able to identify low-risk children and to describe the natural history of 135 very young patients affected by classic HL (cHL). The best age cutoff was identified at 7 years of age. EFS (p =.0451) and PFS (p =.00921) were significantly better in the group of younger patients. The OS rate at 10 years was 97.0% in the younger group and 92.5% in the older one (p =.0448). However, age was not found to be an independent prognostic factor in multivariate analysis and the better prognosis in younger patients seems to be related to more favorable disease characteristics at presentation. [ABSTRACT FROM AUTHOR]