Combined therapy in children and adolescents with classical Hodgkin's lymphoma: A report from the SFCE on MDH-03 national guidelines

ABSTRACT

Hodgkin's lymphoma (HL) in children and adolescents is highly curable, but children are at risk of long-term toxicity. The MDH-03 guidelines were established in order to decrease the burden of treatment in good-responder patients, and this report should be considered a step toward further optimization of treatment within large collaborative trials. We report the therapy and long-term outcomes of 417 children and adolescents treated according to the national guidelines, which were applied between 2003 and 2007 in France. The patients were stratified into three groups according to disease extension. Chemotherapy consisted of four cycles of VBVP (vinblastine, bleomycin, VP16, prednisone) in localized stages (G1/95 pts/23%), four cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, adriamycin, bleomycin, vinblastine) cycles in intermediate stages (G2/184 pts/44%) and three cycles of OPPA (vincristine, procarbazine, prednisone, adriamycin) plus three cycles of COPP in advanced stages (G3/138 pts/33%). Radiation therapy of the involved field was given to 97% of the patients, with the dose limited to 20 Gy in good responders (88%). With a median follow-up of 6.6 years, the 5-year event-free survival (EFS) and overall survival (OS) were 86.7% (83.1–89.7%) and 97% (94.5–98.1%), respectively. EFS and OS for G1, G2, and G3 were 98% and 100%, 81% and 97%, and 87% and 95%, respectively. Low-risk patients treated without alkylating agents and anthracycline had excellent outcomes and a low expected incidence of late effects. Intensification with a third OPPA cycle in high-risk group patients, including stage IV patients, allowed for very good outcomes, without increased toxicity.

KEYWORDS:

• Hodgkin's disease
• lymphoma
• pediatric oncology

Acknowledgments

The authors thank Geneviève Vaudre for help in data collection and registration. They also thank the associations “Recherche Maladies Hématologiques de l'Enfant” for financial support for the database and “Centre de Recherche en Oncologie et Hématologie Pédiatrique” for financial support for the manuscript. They also would like to thank all the investigators for their contribution in the MDH-03 registration:

	Amiens: Dr Catherine Devoldere
	Angers: Pr Philippe Moreau, Dr Isabelle Pellier
	Besançon: Dr Sarah Cohen Beaussant, Dr Emmanuel Plouvier
	Bordeaux: Dr Nathalie Aladjidi, Dr Yves Perel
	Brest: Dr Philippe Lemoine
	Caen: Dr Odile Minckes,
	Clermont-Ferrand: Dr François Demeocq, Dr Justyna Kanold
	Curie: Dr Sylvie Helfre, Dr Jean Michon, Dr Hélène Pacquement
	Dijon: Dr Gérard Couillaud
	Grenoble: Dr Corinne Armari-Alla, Pr Dominique Plantaz
	IGR: Dr Samuel Abbou, Dr Odile Oberlin, Pr Dominique Valteau-Couanet
	La Réunion: Dr Mathilde Jehanne, Dr Yves Reguerre
	Lille: Dr Anne Lambilliotte, Dr Brigitte Nelken
	Limoges: Dr Christophe Piguet
	Lyon CAC (Léon Bérard): Dr Christophe Bergeron, Dr Line Claude, Dr Mathias Schell
	Lyon Hémato: Pr Yves Bertrand, Dr Nathalie Garnier
	Marseille Hémato: Dr Carole Coze, Dr Catherine Curtillet, Pr Gérard Michel
	Nancy: Dr Pascal Chastagner, Dr Claudine Schmitt
	Nantes: Dr Caroline Thomas
	Nice: Dr Anne Deville, Pr Pierre-Simon Rohrlich
	Poitiers: Pr Guillaume Levard, Dr Frédéric Millot
	Reims: Pr Michel Abely, Dr Stéphanie Gorde-Grosjean, Dr Carole Munzer
	Rennes:Virginie Gandemer
	Rouen: Dr Pascale Schneider, Pr Jean-Pierre Vannier
	St Etienne: Pr Jean-Louis Stephan
	St Louis-Debré: Pr André Baruchel, Dr Benoit Brethon, Dr Josette Brière, Pr Eric De Kerviller, Dr Saliha Haouari, Dr Thierry Leblanc, Dr Brigitte Lescoeur, Dr Anne-France Ray-Lunven, Dr Elisa Seror, Dr Bogdana Tilea, Dr Karima Yakouben
	Strasbourg: Dr Patrick Lutz
	Toulouse: Dr Marlène Pasquet, Dr Geneviève Plat, Pr Hervé Rubie
	Tours: Dr Pascale Blouin, Pr Emmanuel Gyan, Dr Odile Lejars
	Trousseau: Dr Sabah Boudjemaa, Dr Aurore Coulomb, Dr Jean Donadieu, Pr Judith Landman-Parker, Pr Guy Leverger, Dr Arnaud Petit, Geneviève Vaudre

Authors' contributions

Dr Coze, Dr Helfre, Pr. Landman-Parker, Dr Lambilliotte, Dr Leblanc, Dr Oberlin, Dr Pacquement, and Dr Schmitt designed the MDH-03 guidelines for the SFCE. All authors contributed to the collection of data. Dr Seror, Dr Donadieu, Dr Clavel, Pr. Landman-Parker and Dr Leblanc contributed to the writing of the manuscript. All authors approved the final version of the manuscript.

Declaration of interests

The authors declare no conflict of interest.