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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]

Aim: To evaluate the role of postchemotherapy FDG PET and compare it with other predictive factors in paediatric Hodgkin's disease (HD). Materials and methods: In this retrospective study, 98 paediatric patients with HD (enrolled in eight Italian centres) were analysed. Their mean age was 13.8 years (range 5-19 years). A PET scan was performed at the end of chemotherapy and reported as positive or negative on the basis of visual and/or semiquantitative analysis. True outcome was defined as remission or disease on the basis of combined criteria (clinical, instrumental and/or histological) with a mean follow-up period of 25 months. Statistical analyses were performed for the postchemotherapy PET results and other potential predictive factors (age cut-off, stage, presence of bulky masses and therapeutic group) with respect to patient outcome and progression-free survival (PFS). Results: Overall the patients had a mean PFS of 23.5 months (range 4-46 months): 87 achieved remission (88.8%) and 11 showed disease. Of the 98 patients, 17 were positive on postchemotherapy PET . Seven patients (41%) showed disease during follow-up, and relapse occurred in only four out of the 81 patients who were negative on PET ( p = 0.0001). Kaplan-Meier analysis demonstrated significant correlations between PFS and the postchemotherapy PET result ( p = 0.0001) and a cut-off age at diagnosis of 13.3 years ( p = 0.0337), whereas disease stage ( p = 0.7404), therapeutic group ( p = 0.5240) and presence of bulky masses ( p = 0.2208) were not significantly correlated with PFS. Multivariate analysis confirmed a statistically significant correlation with PFS only for the postchemotherapy PET findings ( p = 0.0009). Conclusion: In paediatric HD, age at diagnosis and postchemotherapy PET results are the main predictors of patient outcome and PFS, with FDG PET being the only independent predictive factor for PFS. [ABSTRACT FROM AUTHOR]

Background: Many biological and inflammatory markers have been proposed as having a prognostic value at diagnosis of Hodgkin lymphoma (HL), but very few have been validated in paediatric patients. We explored the significance of these markers in a large population of 769 affected children. Patients and methods: By using the database of patients enrolled in A.I.E.O.P. (Associazione Italiana di Emato-Oncologia Pediatrica) trial LH2004 for paediatric HL, we identified 769 consecutive patients treated with curative intent from 1st June 2004 to 1st April 2014 with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or hybrid COPP/ABV (cyclophosphamide, vincristine, prednisone, procarbazine, doxorubicin, bleomycin and vinblastine) regimens. Results: On multivariate analysis with categorical forms, the 5-year freedom from progression survival was significantly lower in patients with stage IV or elevated value of platelets, eosinophils and ferritin at diagnosis. Furthermore, stage IV and eosinophils seem to maintain their predictive value independently of interim (after IV cycles of chemotherapy) positron emission tomography. Conclusion: Using the combination of four simple markers such as stage IV and elevated levels of platelets, ferritin and eosinophils, it is possible to classify the patients into subgroups with very different outcomes. [ABSTRACT FROM AUTHOR]