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1. Analysis of a cohort of 279 patients with hairy-cell leukemia (HCL): 10 years of follow-up

Author

Xavier Troussard, Agnès Olivrie, Gandhi Damaj, Stephanie Noel, Jean-Claude Eisenmann, Olivier Hermine, Jérémie Riou, Sandrine Vaudaux, Patricia Validire-Charpy, Jean Gutnecht, Alain Devidas, Charlotte Petitdidier-Lionnet, Mohamed Touati, Stephanie Haiat, Vincent Levy, Fabienne Huysman, Eric Lippert, Aline Tanguy-Schmidt, Jehan Dupuis, Olivier Lambotte, Clara Mariette, Marouane Boubaya, Edouard Cornet, Pierre Feugier, Mathilde Hunault-Berger, Bertrand Joly, Stéphane Leprêtre, Jérôme Paillassa, Cécile Tomowiak, Kamel Ghomari, Willy Vaillant, Catherine Thieblemont, Mario Ojeda Uribe, Didier Decaudin, Bernard Drenou, Jean-Michel Karsenti, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor, Centre Hospitalier Sud Francilien [Corbeil-Essonnes] (CH Sud Francilien), Centre Hospitalier Universitaire [Grenoble] (CHU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Limoges, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier d'Auch (CH Auch), Centre Hospitalier Intercommunal Fréjus - St Raphaël (CHI Fréjus - St Raphaël), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CH Beauvais, Hôpital Avicenne [AP-HP], Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Fédération Hospitalo-Universitaire 'Grand Ouest Against Leukemia' (FHU GOAL), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth

Subjects
Adult, Male, medicine.medical_specialty, Disease-free survival, medicine.medical_treatment, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Chemotherapy, Hairy cell leukemia, Risk factor, Adverse effect, Cladribine, Aged, Aged, 80 and over, Hairy cell leukaemia, Leukemia, Hairy Cell, Adverse effects, business.industry, Incidence (epidemiology), Hematology, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, Leukemia, Treatment Outcome, Risk factors, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, business, Pentostatin, Follow-Up Studies, 030215 immunology, medicine.drug
Abstract

In total, 279 patients with hairy-cell leukemia (HCL) were analyzed, with a median follow-up of 10 years. Data were collected up to June 2018. We analyzed responses to treatment, relapses, survival, and the occurrence of second malignancies during follow-up. The median age was 59 years. In total, 208 patients (75%) were treated with purine analogs (PNAs), either cladribine (159) or pentosatin (49), as the first-line therapy. After a median follow-up of 127 months, the median overall survival was 27 years, and the median relapse-free survival (RFS) was 11 years. The cumulative 10-year relapse incidence was 39%. In patients receiving second-line therapy, the median RFS was 7 years. For the second-line therapy, using the same or another PNA was equivalent. We identified 68 second malignancies in 59 patients: 49 solid cancers and 19 hematological malignancies. The 10-year cumulative incidences of cancers, solid tumors, and hematological malignancies were 15%, 11%, and 5.0%, respectively, and the standardized incidence ratios were 2.22, 1.81, and 6.67, respectively. In multivariate analysis, PNA was not a risk factor for second malignancies. HCL patients have a good long-term prognosis. PNAs are the first-line treatment. HCL patients require long-term follow-up because of their relatively increased risk of second malignancies.

Published
2020
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2. Long-term follow-up and second malignancies in 487 patients with hairy cell leukaemia

Author

Jehan Dupuis, Aline Tanguy-Schmidt, Catherine Thieblemont, Loic Ysebaert, Jean-Claude Eisenmann, Xavier Troussard, Edouard Cornet, Stéphane Leprêtre, Patricia Validire-Charpy, Emmanuel Gyan, Clara Mariette, Cécile Tomowiak, Pierre Feugier, Pascale Cony-Makhoul, Alain Devidas, Laurent Sutton, Véronique Leblond, Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Microenvironnement cellulaire et pathologie (MILPAT), Normandie Université (NU)-Normandie Université (NU), Registre des hémopathies malignes de Basse-Normandie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Unité des hémopathies lymphoïdes [CHU Henri Mondor], CHU Henri Mondor, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d’Hématologie - Hôpital Sud Francilien, Clinique Universitaire d'Hématologie [La Tronche, Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie [Institut Curie], Institut Curie [Paris], Service d'Hématologie, Argenteuil, Centre Hospitalier Victor Dupouy, Service d'hématologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service Hématologie, Mulhouse, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre Hospitalier d'Annecy, Centre hospitalier d'Annecy, Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], hairy cell leukaemia, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Pentostatin, Medical history, Cladribine, Aged, Retrospective Studies, Cause of death, Aged, 80 and over, Leukemia, Hairy Cell, Drug Substitution, business.industry, Incidence (epidemiology), Hairy cell leukaemia, second malignancies, Neoplasms, Second Primary, Hematology, Middle Aged, Confidence interval, 3. Good health, Surgery, Treatment Outcome, Standardized mortality ratio, purine nucleoside analogues, Splenectomy, France, business, Follow-Up Studies, medicine.drug
Abstract

International audience; A large, multicentre, retrospective survey of patients with hairy cell leukaemia (HCL) was conducted in France to determine the frequency of second malignancies and to analyse the long-term effects of the established purine nucleoside analogues (PNAs), cladribine and pentostatin. The survey retrospectively reviewed the medical history of patients and their immediate family, clinical and biological presentation at the time of HCL diagnosis, treatment choice, response to treatment, time to relapse and cause of death. Data were collected for 487 patients with HCL. Of the patients included in the survey, 18% (88/487) had a familial history of cancers, 8% (41/487) presented with malignancies before HCL diagnosis and 10% (48/487) developed second malignancies after HCL was diagnosed. An excess incidence of second malignancies was observed, with a standardized incidence ratio (SIR) of 1·86 (95% confidence interval (CI): 1·34-2·51), with no significant difference between PNAs. For second haematological malignancies alone, the SIR was markedly increased at 5·32 (95% CI: 2·90-8·92). This study highlights the high frequency of cancers in HCL patients and their family members. The frequency of second malignancies is notably increased, particularly for haematological malignancies. The respective role of pentostatin and cladribine in the development of second malignancies is debatable.

Published
2014
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3. Hairy Cell Leukemia: Evaluation of Long-Term Outcomes in 487 Patients

Author

Xavier Troussard, Edouard Cornet, Patricia Validire-Charpy, Emmanuel Gyan, Alain Devidas, Stéphane Leprêtre, Jean-Claude Eisenmann, Aline Tanguy-Schmidt, Laurent Sutton, Véronique Leblond, Cécile Tomowiak, Catherine Thieblemont, Clara Mariette, Jehan Dupuis, and Pierre Feugier

Subjects
medicine.medical_specialty, business.industry, Immunology, Follicular lymphoma, Cancer, Cell Biology, Hematology, medicine.disease, Biochemistry, Gastroenterology, Surgery, Regimen, Immunophenotyping, Internal medicine, medicine, Pentostatin, Hairy cell leukemia, Cladribine, business, Monoclonal gammopathy of undetermined significance, medicine.drug
Abstract

Abstract 3921 Introduction: Hairy cell leukemia (HCL) is a rare hematologic disorder, and the place of emerging treatments, such as BRAF inhibitors, remains to be defined. We conducted a large, multi-center, retrospective survey in France to determine the frequency of malignancy in HCL patients (pts) and their families, and to analyze the long-term effects of the established purine nucleotide analogs (PNA) cladribine (C) and pentostatin (P). Methods: Physician members of the Société Française d'Hématologie were surveyed on their management of HCL pts over the past 30 years. Clinicians completed a form that collected data concerning personal and familial medical history of pts, with particular focus on hematologic malignancies, solid tumors, clinical and biological presentation at HCL diagnosis, therapeutic options, response to treatment, time to relapse, secondary malignancies and cause of death. Results: The survey included 36 French clinical centers and 487 HCL cases (mean patient age 59y; range 29–90y). In the centers surveyed, HCL diagnosis was established after examination of peripheral blood and/or bone marrow and by immunophenotyping. Solid tumors and hematologic malignancies were present before HCL diagnosis in 45 cases (9.2%). A further 38 pts (7.8%) with pre-existing cancers were diagnosed with HCL after a median time of 89mo (range 1–529mo). At diagnosis, three HCL pts presented with follicular lymphoma, monoclonal gammopathy of undetermined significance, or large cell B cell lymphoma. Four pts developed HCL within a median time of 33mo (range 30–38mo) after diagnosis of B-cell lymphoproliferative disorders. In 93 pts (19.1%), at least one family member developed neoplasia: solid tumors=75 pts (15.4%); acute or chronic hematologic malignancies=18 pts (3.7%) with one familial HCL case. Twenty-three pts (4.7%) received no treatment for a median follow-up of 32mo (1–293). Three hundred and forty-five pts (70.8%) received just one first-line treatment (C=68.1%, P=23.8%, interferon [IFN]=3.8%, other=4.3%), and 119 pts (16.6%) received two-to-seven lines of therapy. After first-line treatment, complete responses were observed in 365 pts (74.9%; P=85.1%, C=85.0%, IFN=61.1%). Median duration of response was 41 months (1–270; C=40.5mo [1–188; 234 pts], P=43.0mo [1–209; 80 pts], IFN=74mo [24–270; 13 pts], other=21mo [2–186; 15 pts]). After second line treatment, the median duration of response decreased to 33mo (1–261; 80 pts) (C=27mo [1–159; 39 pts], P=38.5mo [0–206; 24 pts]) and also tended to differ according to first-line regimen (Table). After third-line treatment, the median duration of response decreased again to 24mo (2–224; 24 pts) (C=46mo [2–92], P=20mo [2–166], other=22mo [2–224]). After 60 months follow-up (range 1–384mo), overall survival at 5 years was 95%. Twenty-nine pts (6%) had died (11 deaths were HCL-related), and a further 53 pts (10.9%) developed second malignancies (39 solid tumors and 14 hematologic malignancies). Second malignancies occurred 6 months after HCL diagnosis in 50 pts. Conclusions: This study highlights the high frequency of cancers in HCL pts and their family members, suggesting a role for genetic factors in the development of the disease. The survey also confirms the high efficacy of PNA, and we therefore need to be cautious in adopting innovative new therapies treatment such as BRAF inhibitors or immunotoxins into first-line care. Disclosures: No relevant conflicts of interest to declare.

Published
2012
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