A Score for Predicting Freedom from Progression of Children and Adolescents with Hodgkin Lymphoma

Valli De Re,Maurizio Mascarin,Mariangela De Zorzi,With The A.i.e.o.p Consortium ,Alessandra Sala,Ombretta Repetto,Lara Mussolin,Roberta Burnelli,Marta Pillon,Caterina Elia,Maurizio Bianchi,Emanuele D’Amore,Luciana Vinti,Elena Facchini,Piero Farruggia,Paola Muggeo,Salvatore Buffardi,Egesta Lopci,Laura Caggiari

doi:10.3390/hemato2020016

Abstract

Several studies have examined the prognostic performance of therapeutic groups (TG) and early responses to therapy on positron emission tomography/computed tomography (PET/CT) in children and adolescents with classical Hodgkin lymphoma (cHL); less research has been performed on molecular parameters at diagnosis. The aim of the present study was to devise a scoring system based on the TG criteria for predicting freedom from progression (FFP) in 133 patients: 63.2% males; 14 years median age (interquartile range (IQR) 11.9–15.1); with cHL (108 nodular sclerosis (NS) subtype) treated according to the AIEOP LH-2004 protocol; and median 5.55 (IQR 4.09–7.93) years of follow-up. CHL progressed or relapsed in 37 patients (27.8%), the median FFP was 0.89 years (IQR = 0.59–1.54), and 14 patients (10.5%) died. The FPR (final prognostic rank) model associates the biological HLA-G SNP 3027C/A (numerical point assigned (pt) = 1) and absolute neutrophil count (>8 × 109/L, pt = 2) as variables with the TG (TG3, pt = 3). Results of FPR score analyses for FFP suggested that FPR model (Kaplan–Meier curves, log-rank test for trends) was better than the TG model. At diagnosis, high-risk patients classified at FPR rank 4 and 5 identified 18/22 patients who relapse during the follow-up.

Highlights

In the AIEOP LH-2004 protocol’s de-escalation of chemoradiotherapy for pediatric and adolescent Hodgkin lymphoma, risk stratification for patients at higher risk of disease progression or relapse became fundamental to identify candidates for less intensive treatment
Most patients of the classical Hodgkin lymphoma (cHL) set were in TG3 (76.7%) and had the NS histological tumor type (81.2%)
The results showed that TG3, HLA-G C/A, and neutrophils (>8 × 109 /L) were independent factors negatively affecting the freedom from progression (FFP) survival curves of patients (p = 0.0037); the model excluded the TG2 variable considered not crucial to the prediction of FFP survival (Table 4)

Summary

Introduction

In the AIEOP LH-2004 protocol’s de-escalation of chemoradiotherapy for pediatric and adolescent Hodgkin lymphoma (cHL), risk stratification for patients at higher risk of disease progression or relapse became fundamental to identify candidates for less intensive treatment. Using the current standard of care for pediatric/adolescent cHL, patients allocated to three treatment groups (TG) with both the number of cycles and the addition of radiotherapy depending on the stage, and the computed tomography and positron emission tomography (PET)-guided response assessments [1,2]. TG1 included stage IA or IIA without bulky mediastinal disease or pulmonary hilar lymph node involvement and less than four positive lymph node regions. TG3 included patients considered to be at Ann Arbor stage IIIB or stage IV, or bulky mediastinal disease, whatever the stage. Patients assigned to TG1 received three courses of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)

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