How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Francine Garnache-Ottou (1) , Chrystelle Vidal (2) , Sabeha Biichlé (1) , Florian Renosi (1) , Eve Poret (1) , Maïder Pagadoy (2) , Maxime Desmarets (2) , Anne Roggy (2) , Estelle Seilles (2) , Lou Soret (2) , Françoise Schillinger , Sandrine Puyraimond , Tony Petrella , Claude Preudhomme , Christophe Roumier , Elisabeth A. Macintyre (3) , Véronique Harrivel , Yohan Desbrosses , Bérengère Gruson , Franck Geneviève , Sylvain Thepot (4) , Yuriy Drebit , Thibaut Leguay , François-Xavier Gros , Nicolas Lechevalier , Pascale Saussoy , Véronique Salaun , Edouard Cornet , Zehaira Benseddik , Richard Veyrat-Masson , Orianne Wagner-Ballon , Célia Salanoubat , Marc Maynadié , Julien Guy , Denis Caillot , Marie-Christine Jacob , Jean-Yves Cahn , Rémy Gressin , Johann Rose , Bruno Quesnel , Estelle Guerin , Franck Trimoreau , Jean Feuillard , Marie-Pierre Gourin , Adriana Plesa , Lucile Baseggio , Isabelle Arnoux , Norbert Vey , Didier Blaise , Romaric Lacroix (5) , Christine Arnoulet (6) , Blandine Benet , Véronique Dorvaux , Caroline Bret (7, 8) , Bernard Drenou , Agathe Debliquis , Véronique Latger-Cannard , Caroline Bonmati , Marie-Christine Bene , Pierre Peterlin , Michel Ticchioni , Pierre-Simon Rohrlich , Anne Arnaud , Stefan Wickenhauser , Valérie Bardet , Sabine Brechignac , Benjamin Papoular , Victoria Raggueneau , Jacques Vargaftig , Rémi Letestu , Daniel Lusina , Thorsten Braun , Vincent Foissaud , Jérôme Tamburini , Hind Bennani , Nicolas Freynet , Catherine Cordonnier , Magali Le Garff-Tavernier , Nathalie Jacques , Karim Maloum , Damien Roos-Weil , Didier Bouscary , Vahid Asnafi , Ludovic Lhermitte , Felipe Suarez , Etienne Lengline , Frédéric Féger , Giorgia Battipaglia , Mohamad Mohty , Sabrina Bouyer , Ouda Ghoual , Elodie Dindinaud , Caroline Basle , Mathieu Puyade , Carinne Lafon , Thierry Fest (9, 10) , Mikael Roussel (9, 10) , Xavier Cahu , Elsa Bera , Sylvie Daliphard , Fabrice Jardin , Lydia Campos , Françoise Solly , Denis Guyotat , Anne-Cécile Galoisy , Alice Eischen , Caroline Mayeur-Rousse , Blandine Guffroy , Christian Recher (11) , Marie Loosveld , Alice Garnier , Vincent Barlogis , Maria Alessandra Rosenthal , Sophie Brun , Nathalie Contentin , Sébastien Maury , Mary Callanan (12, 13) , Christine Lefebvre (13) , Natacha Maillard , Patricia Okamba , Christophe Ferrand (1) , Olivier Adotevi (1) , Philippe Saas (1) , Fanny Angelot-Delettre (1) , Delphine Binda (1) , Eric Deconinck (1)

1 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
2 Inserm CIC 1431 - Centre d'Investigation Clinique de Besançon
3 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
4 CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
5 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
6 Institut Paoli-Calmettes
7 IGH - Institut de génétique humaine
8 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
9 MICMAC - Microenvironment, Cell Differentiation, Immunology and Cancer
10 CHU Pontchaillou [Rennes]
11 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
12 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
13 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)-like, acute lymphoid leukemia (ALL)-like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])-like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.

Domains: Life Sciences [q-bio]; Cancer

Francine Garnache-Ottou, Chrystelle Vidal, Sabeha Biichlé, Florian Renosi, Eve Poret, et al.. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?. Blood Advances, 2019, 3 (24), pp.4238-4251. ⟨10.1182/bloodadvances.2019000647⟩. ⟨hal-02442440⟩