Long-term follow-up of children with risk organ-negative Langerhans cell histiocytosis after 2-chlorodeoxyadenosine treatment

Mohamed Aziz Barkaoui (1, 2) , Emma Queheille (1, 3) , Nathalie Aladjidi (4) , Geneviève Plat , Éric Jeziorski (5, 6) , Despina Moshous (7, 8) , Anne Lambilliotte (9) , Kamila Kebaili (10) , Hélène D. Pacquement (11) , Guy G. Leverger (1) , Ludovic Mansuy (12) , Natacha Entz-Werlé (13) , Damien Bodet (14) , Pascale Schneider (15) , Anne Pagnier (16) , Anne Lutun (17) , Marion Gillibert-Yvert (18) , Frédéric Millot (19) , Fabienne Toutain (20) , Yves Reguerre (21) , Caroline J.C. Thomas (22) , Abdellatif Tazi (23, 24) , Jean François J.F. Emile (25) , Jean Donadieu (2, 1) , Sébastien Héritier (25, 1, 2)

1 CHU Trousseau [APHP]
2 Centre de référence des Histiocytoses [HU Saint-Louis, Lariboisière, Fernand-Widal - APHP]
3 Centre de référence des Histiocytoses
4 CHU de Bordeaux - Centre Hospitalier Universitaire de Bordeaux
5 Hôpital Arnaud de Villeneuve [CHRU Montpellier]
6 Pathogénèse et contrôle des infections chroniques (PCCI)
7 Département d'Immunologie, hématologie et rhumatologie pédiatriques [Hôpital Necker-Enfants malades - APHP]
8 University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris
9 CHU de Lille - Centre Hospitalier Universitaire de Lille
10 Institut d'hématologie et oncologie pédiatriques, 69008 Lyon, France
11 Service de pédiatrie, adolescents, jeunes adultes [Institut Curie]
12 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
13 CHRU de Strasbourg - Centre Hospitalier Régional Universitaire de Strasbourg
14 Department of Hematology, Centre Hospitalier Universitaire (CHU), Faculté de Médecine, University of Normandie Caen
15 Centre Hospitalier Universitaire de Rouen
16 CHU de Grenoble - Centre Hospitalo-Universitaire de Grenoble
17 CHU Amiens-Picardie
18 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
19 CHU de Poitiers - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
20 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
21 CHU La Réunion - Centre Hospitalier Universitaire de La Réunion
22 CHU Nantes - Centre Hospitalier Universitaire de Nantes
23 HIPI (UMR_S_976 / U976) - Immunologie humaine, physiopathologie & immunothérapie
24 AP-HP - Hopital Saint-Louis [AP-HP]
25 BECCOH - Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie

The nucleoside analogue, 2-chlorodeoxyadenosine (2CDA), was reported to be an active treatment for childhood Langerhans cell histiocytosis (LCH) without risk organ (RO−) involvement. However, we lack data on long-term effects of 2CDA treatment, including the disease reactivation rate, permanent sequelae and long-term tolerance. This study included 44 children from the French LCH registry, treated for a RO− LCH with 2CDA monotherapy (median number of six courses). The median age at the beginning of 2CDA was 3·6 years (range, 0·3–19·7 years) and the median follow-up after was 5·4 years (range, 0·6–15·1 years). Objective response to 2CDA was observed in 25 patients (56·8%), while six patients (13·6%) had stable disease and 13 patients (29·5%) exhibited progressive disease. Among patients without progression, only two experienced disease reactivation after 2CDA discontinuation. The five-year cumulative incidence of disease progression or reactivation after 2CDA therapy initiation was 34·3%. The lymphopenia reported in all cases [72% below absolute lymphocyte count (ALC) of 0·5 G/l], was addressed with appropriate prophylactic measures. Other toxicities above grade 2 were uncommon, and no second malignant neoplasm or neuropathy was reported. The five-year overall survival was 97·7%. In conclusion, we could confirm that 2CDA monotherapy was a beneficial long-term therapy for treating patients with RO− LCH. Appropriate management of induced immune deficiency is mandatory.

Mots clés: 2-chlorodeoxyadenosine; children; cladribine; Langerhans cell histiocytosis; long-term follow-up

Domaines: Sciences du Vivant [q-bio]

Mohamed Aziz Barkaoui, Emma Queheille, Nathalie Aladjidi, Geneviève Plat, Éric Jeziorski, et al.. Long-term follow-up of children with risk organ-negative Langerhans cell histiocytosis after 2-chlorodeoxyadenosine treatment. British Journal of Haematology, 2020, 191 (5), pp.825-834. ⟨10.1111/bjh.16944⟩. ⟨hal-03109204⟩