The prognostic value of biological markers in paediatric Hodgkin lymphoma

Farruggia, Piero; Puccio, Giuseppe; Sala, Alessandra; Todesco, Alessandra; Buffardi, Salvatore; Garaventa, Alberto; Bottigliero, Gaetano; Bianchi, Maurizio; Zecca, Marco; Locatelli, Franco; Pession, Andrea; Pillon, Marta; Favre, Claudio; D’Amico, Salvatore; Provenzi, Massimo; Trizzino, Angela; Zanazzo, Giulio Andrea; Sau, Antonella; Santoro, Nicola; Murgia, G; Casini, Tommaso; Mascarin, Maurizio; Burnelli, Roberta; Cesaro, Simone; Zaccaron, Ada; Bertolini, Patrizia; Consarino, Caterina; Iaria, Grazia; Pericoli, Roberta; Pierani, Paolo; Fedeli, Fausto; Cellini, Monica; Santis, R. De; Porta, Fulvio; Caini, Mauro; Cosmi, Carlo; Mirra, Nadia; Civino, Adele; Sperlì, Domenico; Nespoli, Luigi; Caniglia, Maurizio; Perruccio, Katia; D’Angelo, Paolo; Passone, E; Caruso, Roberta; Scarzello, Giovanni; Rondelli, Roberto

doi:10.1016/j.ejca.2015.09.003

Cited by 15 publications

(23 citation statements)

References 27 publications

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“…According to the AIEOP LH-2004 criteria, patients were stratified into 3 therapeutic groups (GR) based on increased radiation dosage and aggressive chemotherapy (both length and intensity) to reduce long-term toxicities in younger patients [ 4 ]. The groups according to AIEOP LH-2004 risk score criteria were (1) GR1: stage IA or IIA without mediastinal bulky disease or involvement of lung hilum lymph nodes, and less than four lymph nodal regions; (2) GR2: negative for GR1 or GR3 criteria; (3) GR3: stage IIIB or stage IV or mediastinal bulky disease.…”

Section: Resultsmentioning

confidence: 99%

“…A substantial number of HL cases are linked to Epstein-Barr virus (EBV) [ 3 ]. A follow-up clinical study of the Italian Association of Pediatric Hematology-Oncology (AIEOP) trial LH-2004 for pediatric HL showed that 108 out of 769 (14%) enrolled children showed disease progression or relapse (37 progression and 71 relapses), in general 2 years after diagnosis [ 4 ]. Therefore, it is important to identify markers that predict relapse in HL patients in order to obtain better responses with less aggressive therapy, particularly considering the long term adverse effects of HL therapy such as secondary cancer, infertility and neurological toxicity [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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HLA-G+3027 polymorphism is associated with tumor relapse in pediatric Hodgkin's lymphoma

Caggiari

Mussolin

et al. 2017

Oncotarget

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In this study, we tested whether polymorphisms in human leukocyte antigen G (HLA-G) were associated with event-free survival (EFS) in pediatric Hodgkin's lymphoma (HL). We evaluated the association of HLA-G 3′-UTR polymorphisms with EFS in 113 pediatric HL patients treated using the AIEOP LH-2004 protocol. Patients with the +3027-C/A genotype (rs17179101, UTR-7 haplotype) showed lower EFS than those with the +3027-C/C genotype (HR= 3.23, 95%CI: 0.99-10.54, P=0.012). Female patients and systemic B symptomatic patients with the HLA-G +3027 polymorphism showed lower EFS. Multivariate analysis showed that the +3027-A polymorphism (HR 3.17, 95%CI 1.16-8.66, P=0.025) was an independent prognostic factor. Immunohistochemical analysis showed that HL cells from patients with the +3027-C/A genotype did not express HLA-G. Moreover, HLA-G +3027 polymorphism improved EFS prediction when added to the algorithm for therapeutic group classification of pediatric HL patients. Our findings suggest HLA-G +3027 polymorphism is a prognostic marker in pediatric HL patients undergoing treatment according to LH-2004 protocol.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HLA-G+3027 polymorphism is associated with tumor relapse in pediatric Hodgkin's lymphoma

Caggiari

Mussolin

et al. 2017

Oncotarget

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“…This study used plasma samples from 12 pediatric HL patients enrolled in LH2004 [43]. These patients were selected for having had either a favorable (e.g., non-relapsing, n = 6) or unfavorable (relapsing, n = 6) response to treatment over a five-year period in the trial.…”

Section: Patients and Plasma Samplesmentioning

confidence: 99%

Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma

Repetto

Mussolin

et al. 2020

IJMS

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The identification of circulating proteins associated with relapse in pediatric Hodgkin lymphoma (HL) may help develop predictive biomarkers. We previously identified a set of predictive biomarkers by difference gel electrophoresis. Here we used label-free quantitative liquid chromatography-mass spectrometry (LC-MS/MS) on plasma collected at diagnosis from 12 children (age 12–16 years) with nodular sclerosis HL, including six in whom the disease relapsed within 5 years of treatment in the LH2004 trial. Plasma proteins were pooled in groups of three, separately for non-relapsing and relapsing HL, and differentially abundant proteins between the two disease states were identified by LC-MS/MS in an explorative and validation design. Proteins with a fold change in abundance >1.2 or ≤0.8 were considered “differentially abundant”. LC-MS/MS identified 60 and 32 proteins that were more abundant in non-relapsing and relapsing HL plasma, respectively, in the explorative phase; these numbers were 39 and 34 in the validation phase. In both analyses, 11 proteins were more abundant in non-relapsing HL (e.g., angiotensinogen, serum paraoxonase/arylesterase 1, transthyretin), including two previously identified by difference gel electrophoresis (antithrombin III and α-1-antitrypsin); seven proteins were more abundant in relapsing HL (e.g., fibronectin and thrombospondin-1), including two previously identified proteins (fibrinogen β and γ chains). The differentially abundant proteins participated in numerous biological processes, which were manually grouped into 10 biological classes and 11 biological regulatory subclasses. The biological class Lipid metabolism, and its regulatory subclass, included angiotensinogen and serum paraoxonase/arylesterase 1 (more abundant in non-relapsing HL). The biological classes Immune system and Cell and extracellular matrix architecture included fibronectin and thrombospondin-1 (more abundant in relapsing HL). These findings deepen our understanding of the molecular scenario underlying responses to therapy and provide new evidence about these proteins as possible biomarkers of relapse in pediatric HL.

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“…The treatment of pediatric cHL is based on combined‐modality therapies, relying on patient stratification into classes of risk. The latter are calculated by integrating clinical‐radiological parameters, including disease stage and site, the number of affected nodal regions, the presence of bulky disease and B symptoms 4 . Recent studies have also suggested a prognostic role for serologic and molecular markers, such as platelet and white blood cell counts, ferritin and albumin levels, 4‐6 erythrocyte sedimentation rate (ESR), 7 tumor‐associated mutations and polymorphisms, 8,9 and features of the tumor microenvironment 10,11 .…”

Section: Introductionmentioning

confidence: 99%

Histology of pediatric classic Hodgkin lymphoma: From diagnosis to prognostic stratification

Pizzi

Tazzoli

Carraro

et al. 2020

Pediatric Blood & Cancer

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Aims Classic Hodgkin lymphoma (cHL) is a common malignancy of the pediatric age. Although clinical‐radiological features are routinely used for disease risk stratification, the role of tumor histology has yet to be defined. This study aimed to characterize the clinical‐pathological features of a large cohort of pediatric cHL specifically investigating the relevance of tumor histology for the prognostic stratification of patients. Methods and results The study considered 96 clinically annotated cases of pediatric cHL treated according to the AIEOP‐LH2004 protocol. The following histological parameters were considered: (i) cHL variant; (ii) grade of nodular sclerosis (NS); (iii) staining for Bcl2 and p53, and expression of B‐cell (BCA) and T‐cell antigens (TCA) by Hodgkin/Reed‐Sternberg cells. The study population consisted of 51 males and 45 females (median age: 13.6 years) with five‐year overall and progression‐free survival of 94% and 81%, respectively. Most cases featured NS morphology (96%) with a prevalence of NS1 over NS2 grades. Two NS2 variants were recognized (sarcomatous/syncytial and fibrohistiocytic). A consistent subset of cases disclosed positivity for BCA (34%), TCA (26%), p53 (13%), and Bcl2 (19%). Clinical‐pathological correlations showed a more aggressive clinical course for NS2 over NS1 cases. The NS2 fibrohistiocytic variant was associated with the worst outcome. No other histological features correlated with prognosis. Conclusions Pediatric cHL is a clinically and histologically heterogeneous neoplasm. The majority of cases disclose NS morphology and aberrant phenotypes are frequently encountered. In the pediatric population, NS grading and NS2 subtyping bear significant prognostic impact.

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The prognostic value of biological markers in paediatric Hodgkin lymphoma

Cited by 15 publications

References 27 publications

HLA-G+3027 polymorphism is associated with tumor relapse in pediatric Hodgkin's lymphoma

HLA-G+3027 polymorphism is associated with tumor relapse in pediatric Hodgkin's lymphoma

Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma

Histology of pediatric classic Hodgkin lymphoma: From diagnosis to prognostic stratification

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