Outcome of Children and Adolescents with Recurrent Classical Hodgkin Lymphoma: The Italian Experience
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Alberto Garaventa
1, 
Stefano Parodi
2,
Giulia Guerrini
3,
Piero Farruggia
4,
Alessandra Sala
5,
Marta Pillon
6
,
Salvatore Buffardi
7,
Francesca Rossi
8,
Maurizio Bianchi
9,
Marco Zecca
10,
Luciana Vinti
11,
Elena Facchini
12,
Tommaso Casini
13,
Sayla Bernasconi
14,
Loredana Amoroso
1,
Salvatore D’Amico
15,
Massimo Provenzi
16,
Raffaela De Santis
17,
Antonella Sau
18,
Paola Muggeo
19,
Rosa Maria Mura
20,
Riccardo Haupt
2,
Maurizio Mascarin
21 and
Roberta Burnelli
22,*add
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1
Paediatric Oncology Unit, IRCCS Istituto Giannina Gaslini, L.go G. Gaslini 5, 16147 Genova, Italy
2
Epidemiology and Biostatistics Unit, IRCCS Istituto Giannina Gaslini, L.go G. Gaslini 5, 16147 Genova, Italy
3
UOC Pediatria e Neonatologia, Grosseto USL-Toscana Sud-Est, Via Senese, 58100 Grosseto, Italy
4
Paediatric Haematology and Oncology Unit, A.R.N.A.S. Civic Hospital, Piazza Leotta Nicola 4, 90127 Palermo, Italy
5
Department of Paediatrics, Ospedale San Gerardo, University of Milano-Bicocca, Fondazione MBBM, Via Cadore, 20900 Monza, Italy
6
Dipartimento di Oncoematologia Pediatrica, Università di Padova, Via Gattamelata 5687, 35128 Padova, Italy
7
Paediatric Haemato-Oncology Department, Santobono-Pausilipon Children’s Hospital, Via Mario Fiore 6, 80129 Naples, Italy
8
Dipartimento di Pediatria II Ateneo di Napoli, Servizio di Oncologia Pediatrica, Via Luigi De Crecchio 2, 80138 Naples, Italy
9
Pediatric Onco-Hematology and Stem Cell Transplant Division, City of Health and Science, Regina Margherita Children’s Hospital, Piazza Polonia 94, 10126 Turin, Italy
10
Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, 27100 Pavia, Italy
11
Department of Hematology/Oncology and Stem Cell Transplantation, Bambino Gesù Children’s Hospital, Piazza di Sant’Onofrio 4, 00165 Rome, Italy
12
Pediatric Oncology and Hematology Unit “LallaSeràgnoli”, Department of Pediatrics, University of Bologna, Sant’Orsola Malpighi Hospital, Via Giuseppe Massarenti 9, 40138 Bologna, Italy
13
Division of Pediatric Oncology/Hematology, Meyer University Children’s Hospital, Via Gaetano Pieraccini 24, 50139 Florence, Italy
14
Pediatric Hematology Oncology, Bone Marrow Transplant, S. Chiara University Hospital of Pisa, Via Bonanno Pisano 93, 56126 Pisa, Italy
15
Paediatric Haemato-Oncology Unit, Department of Clinical and Experimental Medicine, University of Catania, Piazza Università 2, 95124 Catania, Italy
16
Department of Pediatrics, Civic Hospital, Piazza OMS 1, 24127 Bergamo, Italy
17
IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Viale Cappuccini, 47156 Foggia, Italy
18
Pediatric Hematology-Oncology Unit, Ospedale Civico, Via Fonte Romana 8, 65124 Pescara, Italy
19
Department of Biomedicine of Developmental Age, University of Bari, Piazza Umberto I 1, 70121 Bari, Italy
20
Department of Paediatric Oncohaematology, Microcitemico Hospital, Via Edward Jenner 18, 09121 Cagliari, Italy
21
AYA Oncology and Pediatric Radiotherapy Unit, CRO-Centro di Riferimento Oncologico di Aviano, IRCCS Aviano, Via Franco Gallini 2, 33081 Aviano, Italy
22
Pediatric Hemato-Oncology Unit, Azienda Ospedaliero Universitaria Sant’Anna di Ferrara, Cona, Via Aldo Moro, 44124 Ferrara, Italy
*
Author to whom correspondence should be addressed.
Cancers 2022, 14(6), 1471; https://doi.org/10.3390/cancers14061471
Submission received: 11 February 2022
/
Revised: 4 March 2022
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Accepted: 11 March 2022
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Published: 13 March 2022
(This article belongs to the Special Issue Childhood and Adolescent Cancer)
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.
Abstract
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.
Keywords:
Hodgkin’s lymphoma; children; adolescents; relapse; survival; prognostic factors
