title: Long-term efficacy and safety of cladribine (2-CdA) in adult patients with mastocytosis.
abstract: Mastocytosis (M) is a clonal myeloid-disabling disorder for which no curative therapy is currently available. Cladribine (2-chlorodeoxyadenosine [2-CdA]) is a synthetic purine analog cytoreductive treatment, for which efficacy is mostly reported in advanced M. Here we report, with a long-term follow-up period (>10 years) efficacy and safety in 68 adult patients with M (36 [53%] had indolent M and 32 [47%] had advanced M) treated by 2-CdA (0.14 mg/kg in infusion or subcutaneously, days 1-5; repeated at 4-12 weeks until 1 to 9 courses). Median 2-CdA courses number was 3.7 (1-9). The overall response rate was 72% (complete remission [R]/major/partial R: 0%/47%/25%) and according to indolent/advanced M was 92% (major/partial R: 56%/36%) and 50% (major/partial R: 37.5%/12.5%), respectively. Clinical improvement was observed for 10 of 11 mediator release and 6 of 7 mast cell infiltration-related symptoms including urticaria pigmentosa and organomegaly (P < .02). Serum tryptase levels decreased (P = .01). Median durations of response were 3.71 (0.1-8) and 2.47 (0.5-8.6) years for indolent and aggressive M, respectively. The most frequent grade 3/4 toxicities were lymphopenia (82%), neutropenia (47%), and opportunistic infections (13%). 2-CdA appears to provide a significant efficacy with some toxicity in various M subtypes, mostly in indolent M, refractory to multiple symptomatic therapies.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris VI, Assistance Publique-Hôpitaux de Paris, Département de Dermatologie et Allergologie, Hôpital Tenon, Centre de Référence des Mastocytoses, Paris, France;
authors.forename: Stéphane
authors.identifier: http://orcid.org/0000-0003-1593-9750
authors.initials: S
authors.lastname: Barete
authors.affiliation: Université Sorbonne-Paris-Cité, Paris V, Assistance Publique-Hôpitaux de Paris, Service de Maladies Infectieuses et Tropicales, Centre de Référence des Mastocytoses, Institut Imagine, Hôpital Necker Enfants Malades, Centre d'Infectiologie Necker-Pasteur, Paris, France;
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.affiliation: Service d'Hématologie, Centre Hospitalier Universitaire (CHU) et Faculté de Médecine, Caen, France;
authors.forename: Gandhi
authors.initials: G
authors.lastname: Damaj
authors.affiliation: Centre de Référence des Mastocytoses, Hôpital Necker Enfants Malades, Paris V, IFR Necker, Paris, France;
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hirsch
authors.affiliation: Centre de Référence des Mastocytoses, Hôpital Necker Enfants Malades, Paris V, IFR Necker, Paris, France; Service d'Hématologie, Faculté de Médecine Paris V, Université Sorbonne Paris-Cité et Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France;
authors.forename: Marie Olivia
authors.initials: MO
authors.lastname: Chandesris
authors.affiliation: Unité de Recherche Clinique, Hôpital Necker Paris, France;
authors.forename: Caroline
authors.initials: C
authors.lastname: Elie
authors.affiliation: Service Médecine Interne, CHU de Nantes, France;
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hamidou
authors.affiliation: Service de Médecine Interne, Centre Hospitalier Lyon Sud, Pierre Bénite, France;
authors.forename: Isabelle
authors.initials: I
authors.lastname: Durieu
authors.affiliation: Service d'Hématologie, Faculté de Médecine Paris V, Université Sorbonne Paris-Cité et Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France;
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.affiliation: Service de Médecine Interne, Hôpital Sud, Rennes, France;
authors.forename: Bernard
authors.initials: B
authors.lastname: Grosbois
authors.affiliation: Service de Médecine Interne, CHU Henri Mondor, Créteil, France;
authors.forename: Nicolas
authors.initials: N
authors.lastname: Limal
authors.affiliation: Service d'Hématologie et Thérapie Cellulaire, UMR CNRS 7292, Centre Hospitalier Universitaire, Tours, France;
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Gyan
authors.affiliation: Service de Médecine Interne, CHU Avicenne, Bobigny, France;
authors.forename: Claire
authors.initials: C
authors.lastname: Larroche
authors.affiliation: Service de Dermatologie, CHU de Poitiers, France;
authors.forename: Gérard
authors.initials: G
authors.lastname: Guillet
authors.affiliation: Service de Médecine Interne, Hôpital Foch, Suresnes, France;
authors.forename: Jean Emmanuel
authors.initials: JE
authors.lastname: Kahn
authors.affiliation: Service d'Hématologie, Hôpital Avicenne, Bobigny, France;
authors.forename: Philippe
authors.initials: P
authors.lastname: Casassus
authors.affiliation: Université Sorbonne-Paris-Cité, Paris V, Assistance Publique-Hôpitaux de Paris, Service de Maladies Infectieuses et Tropicales, Centre de Référence des Mastocytoses, Institut Imagine, Hôpital Necker Enfants Malades, Centre d'Infectiologie Necker-Pasteur, Paris, France;
authors.forename: Karima
authors.initials: K
authors.lastname: Amazzough
authors.affiliation: Université Sorbonne-Paris-Cité, Paris V, Assistance Publique-Hôpitaux de Paris, Service de Maladies Infectieuses et Tropicales, Centre de Référence des Mastocytoses, Institut Imagine, Hôpital Necker Enfants Malades, Centre d'Infectiologie Necker-Pasteur, Paris, France;
authors.forename: Hélène
authors.initials: H
authors.lastname: Coignard-Biehler
authors.affiliation: Sorbonne Universités, UPMC Univ Paris VI, Service de Médecine Interne, Hôpital Tenon, Paris France;
authors.forename: Sophie
authors.initials: S
authors.lastname: Georgin-Lavialle
authors.affiliation: Centre de Référence des Mastocytoses, Hôpital Necker Enfants Malades, Paris V, IFR Necker, Paris, France; Université Sorbonne-Paris-Cité, Paris V, Assistance Publique-Hôpitaux de Paris, (INSERM) U1151 Laboratoire d'Onco-Hématologie, Hôpital Necker, Paris, France;
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lhermitte
authors.affiliation: Centre de Référence des Mastocytoses, Hôpital Necker Enfants Malades, Paris V, IFR Necker, Paris, France; Université Sorbonne-Paris-Cité, Paris V, Assistance Publique-Hôpitaux de Paris, Service d'Anatomie-Pathologie, Hôpital Necker, Paris, France;
authors.forename: Sylvie
authors.initials: S
authors.lastname: Fraitag
authors.affiliation: Centre de Référence des Mastocytoses, Hôpital Necker Enfants Malades, Paris V, IFR Necker, Paris, France; Université Sorbonne-Paris-Cité, Paris V, Assistance Publique-Hôpitaux de Paris, Service d'Anatomie-Pathologie, Hôpital Necker, Paris, France;
authors.forename: Danielle
authors.initials: D
authors.lastname: Canioni
authors.affiliation: CRCM, Inserm, U1068, Institut Paoli-Calmettes, Aix-Marseille Université, UM105, CNRS, UMR7258, F-13009, Marseille, France;
authors.forename: Patrice
authors.initials: P
authors.lastname: Dubreuil
authors.affiliation: Centre de Référence des Mastocytoses, Hôpital Necker Enfants Malades, Paris V, IFR Necker, Paris, France; Service d'Hématologie, Faculté de Médecine Paris V, Université Sorbonne Paris-Cité et Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France; Institut Imagine, Université Sorbonne Paris-Cité et Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France; and Laboratoire "Cellular and Molecular Basis of Hematological Disorders and Therapeutic Implications," INSERM U1163, CNRS ERL 8254, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017338:Cladribine / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008415:Mastocytosis / Q000188:drug therapy*; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D017338:Cladribine