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1. Systemic antifungal strategies in allogeneic hematopoietic stem cell recipients hospitalized in french hematology units: a post-hoc analysis of the cross-sectional observational AFHEM study

Author

Mauricette Michallet, Jean el Cheikh, Raoul Herbrecht, Ibrahim Yakoub-Agha, Denis Caillot, Jean-Pierre Gangneux, Centre Léon Bérard [Lyon], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), American University of Beirut Medical Center [Beyrouth, Liban] (AUBMC), American University of Beirut [Beyrouth] (AUB), Les Hôpitaux Universitaires de Strasbourg (HUS), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pontchaillou [Rennes], and Malbec, Odile

Subjects
Adult, Antifungal Agents, Prophylaxis, [SDV]Life Sciences [q-bio], Hematopoietic Stem Cell Transplantation, Hematology, Hematopoietic Stem Cells, [SDV] Life Sciences [q-bio], Invasive fungal diseases, Prospective, Cross-Sectional Studies, Infectious Diseases, Allogeneic hematopoietic stem cell transplantation, Humans, Transplantation, Homologous, Antifungal stewardship, observational study
Abstract

Background Invasive fungal diseases (IFD) remain a major complication of allogeneic hematopoietic stem cell transplantation (alloHSCT) and are associated with high mortality rates in patients receiving alloHSCT. Antifungal prophylaxis is increasingly being used in the management of IFDs in patients receiving alloHSCT. Methods A post-hoc analysis of the cross-sectional observational AFHEM study was carried out to describe the use of antifungal drugs in real-life clinical practice in alloHSCT recipients hospitalized in French hematological units. Results A total of 147 alloHSCT recipients were enrolled; most were adults (n = 135; 92%) and had received alloHSCT n = 123; 84%). Overall, 119 (81%) patients received a systemic antifungal therapy; of these, 95 (80%) patients received antifungal prophylaxis. Rates of patients receiving systemic antifungal treatment were similar irrespective of transplant time, neutropenic, and graft-versus-host disease status. Among patients on systemic antifungal treatment, 83 (70%) received an azole, 22 (18%) received an echinocandin, and 16 (13%) received a polyene. Conclusions This work provides evidence of the antifungal strategies used in alloHSCT recipients hospitalized in French hematological units. Unlike earlier studies, the AFHEM study showed that prophylaxis appears to be the leading antifungal strategy used in alloHSCT recipients in France.

Published
2022
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2. Comparable outcomes of haploidentical transplant with TBF conditioning versus matched unrelated donor with fludarabine/busulfan conditioning for acute myeloid leukemia

Author

Nicolaus Kröger, Alexandros Spyridonidis, Bipin N. Savani, Ana Berceanu, Emanuele Angelucci, Arnon Nagler, Mohamad Mohty, Ibrahim Yakoub-Agha, Claude Eric Bulabois, Patrice Ceballos, Alessandro Rambaldi, Jean El Cheikh, Didier Blaise, Ali Bazarbachi, Stephan Mielke, Gérard Socié, Edouard Forcade, Myriam Labopin, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)

Subjects
Oncology, medicine.medical_specialty, Transplantation Conditioning, Cyclophosphamide, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, ThioTEPA, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Busulfan, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Transplantation, business.industry, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, Matched Unrelated Donor, 3. Good health, Fludarabine, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Transplantation, Haploidentical, [SDV.IMM]Life Sciences [q-bio]/Immunology, Unrelated Donors, business, Thiotepa, Vidarabine, 030215 immunology, medicine.drug
Abstract

We compared transplant outcomes of 708 acute myeloid leukemia (AML) patients receiving haploidentical allogeneic hematopoietic-cell transplantation using thiotepa/busulfan/fludarabine (TBF) conditioning with posttransplant cyclophosphamide (ptCy), to 2083 patients receiving matched unrelated donor (MUD) transplantation using fludarabine/busulfan (FB) conditioning and in vivo T-cell depletion. For intermediate cytogenetic risk AML transplanted in first complete remission (CR1), multivariate analysis revealed that haplo-TBF significantly increased nonrelapse mortality (NRM) (HR 2.1; p = 0.0006) but did not affect relapse incidence (RI), leukemia-free survival (LFS), overall survival (OS), or graft-versus-host disease-free, relapse-free survival (GRFS). For high cytogenetic risk AML transplanted in CR1, haplo-TBF significantly increased NRM (HR = 2.7; p = 0.02), decreased RI (HR = 0.45; p = 0.03) but had no influence on LFS, OS, or GRFS. For AML transplanted in CR2, haplo-TBF significantly increased NRM (HR = 2.36; p = 0.008), decreased RI (HR = 0.38; p = 0.005), but had no influence on LFS, OS, or GRFS. Finally, for AML patients transplanted with active disease, haplo-TBF had no influence on transplant outcomes. In conclusion, compared to MUD-FB, haplo-TBF increased NRM, reduced RI in high-risk AML in CR, resulting in similar LFS, OS, and GRFS. These results comparing two different approaches support the use of a haploidentical family donor for high-risk AML patients lacking a matched sibling donor.

Published
2021
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3. Donor Lymphocyte Infusions (DLI): Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)

Author

Thierry Guillaume, John De Vos, Xavier Poiré, Audrey Cras, Marie-Agnès Guerout-Verite, Anne-Lise Ménard, Sylvain Lamure, Jean El Cheikh, Marie-Noëlle Lacassagne, Ibrahim Yakoub-Agha, Catherine Letellier, Etienne Baudoux, Boris Calmels, Etienne Daguindau, Jacques-Olivier Bay, CHADEYRON, DOMINIQUE, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Liège (CHU-Liège), CHU Clermont-Ferrand, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), American University of Beirut Faculty of Medicine and Medical Center (AUB), Etablissement français du sang [Rennes] (EFS Bretagne), CHU Amiens-Picardie, Etablissement Français du Sang Nouvelle Aquitaine [Bordeaux] (EFS Bordeaux Nouvelle Aquitaine), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Cliniques Universitaires Saint-Luc [Bruxelles], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Faculté de Médecine Henri Warembourg - Université de Lille, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Nantes (CHU Nantes), CCSD, Accord Elsevier, UCL - (SLuc) Centre du cancer, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, and UCL - (SLuc) Service d'hématologie

Subjects
0301 basic medicine, Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Injection de lymphocytes du donneur, Cancer Research, medicine.medical_specialty, T-Lymphocytes, Graft vs Leukemia Effect, Context (language use), Donor lymphocyte infusion, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, Secondary Prevention, medicine, Humans, Transplantation, Homologous, Radiology, Nuclear Medicine and imaging, Allogreffe de cellules souches hématopoïétiques, ComputingMilieux_MISCELLANEOUS, Bone Marrow Transplantation, Cryopreservation, Acute leukemia, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Cellular immunotherapy, business.industry, Myelodysplastic syndromes, Hematopoietic Stem Cell Transplantation, Immunothérapie cellulaire, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, General Medicine, medicine.disease, Tissue Donors, Allogeneic stem cell transplantation, 3. Good health, Transplantation, 030104 developmental biology, Hematologic Neoplasms, 030220 oncology & carcinogenesis, Stem cell, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Donor lymphocyte infusion (DLI) can be proposed to treat or prevent the relapse of malignant hemopathies following allogeneic stem cell transplantation. The efficiency has been mainly reported in the treatment of CML and low-grade lymphomas while the anti-tumoral activity is less in forms of acute leukemia and myelodysplastic syndromes. The GVL benefit should always be compared to the possible toxic effects of GVHD. This article updates the initial SFGM-TC recommendations, proposed in 2013, that were focused on the use of DLI. Doses of DLI in the context of haplo-identical stem cell transplantation are now indicated. We confirm that remaining mobilized stem cells may be used as classical DLI. The definition and the place of preemptive and prophylactic DLI are precisely given. Recommendations regarding the quality of thawed DLI as well as necessary clinical and biological follow-up are also described in detail., Les injections de lymphocytes du donneur (DLI) peuvent être proposées pour traiter ou prévenir la rechute d’une hémopathie maligne après allogreffe de cellules souches hématopoïétiques. L’efficacité est principalement rapportée dans le traitement de la leucémie myéloïde chronique et les lymphomes à caractère indolent. L’activité antitumorale est moindre pour les leucémies aiguës et les syndromes myélodysplasiques. L’effet bénéfique « greffon versus leucémie » (GVL) doit toujours être évalué par rapport à la morbi-mortalité possible liée à la réaction du greffon contre l’hôte (GVHD). Les premières recommandations de la SFGM-TC de 2013 concernant l’utilisation des DLI sont mises à jour. Les doses de DLI dans le cadre des greffes haplo-identiques sont indiquées. L’excédent de cellules souches périphériques mobilisées par rhG-CSF peut être utilisé comme DLI. La définition et la place des DLI préemptives et prophylactiques sont précisées. Des recommandations sont également proposées concernant l’évaluation de la qualité des DLI décongelées et le suivi clinique et biologique après DLI.

Published
2019
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4. Systemic Antifungal Prophylaxis in Patients Hospitalized in Hematology Units in France: The AFHEM Cross-Sectional Observational Study

Author

Raoul Herbrecht, Denis Caillot, Jean-Pierre Gangneux, Jean-Baptiste Quiniou, Ibrahim Yakoub-Agha, Mauricette Michallet, Jean El Cheikh, Service de Parasitologie-Mycologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Astellas Pharma France, Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d’Hématologie Clinique [CHU de Lyon], CHU de Lyon, and Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Acute myeloblastic leukemia, Echinocandin, 030106 microbiology, Context (language use), Disease, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Amphotericin B, Systemic antifungal treatment, medicine, Medical prescription, Original Research, Hematology, business.industry, medicine.disease, 3. Good health, Infectious Diseases, Observational study, Antifungal prophylaxis, Invasive fungal disease, business, medicine.drug
Abstract

International audience; IntroductionThe frequency of invasive fungal diseases (IFDs) has increased in recent years. Within a context where both treatments and guidelines are fast evolving, we aim to shed new light on IFD management in hematologic departments in France.MethodsA multicenter cross-sectional observational study was prospectively conducted in 24 French centers in September and October 2013.ResultsFour hundred ninety-four hospitalized children and adult patients suffering from hematologic malignancy were enrolled: 147 (30%) were allogeneic hematopoietic stem cell transplant (HSCT) recipients, 131 (27%) were patients with acute myeloblastic leukemia or myelodysplastic syndrome (MDS), 71 (14%) were patients with acute lymphoblastic leukemia who did not undergo allogeneic HSCT, and the 145 (29%) remaining patients did not belong to the three above groups. Two hundred forty-six patients (50%) received antifungal treatment, which was prophylactic in 187 (76%) treated patients. These rates were similar across all groups (63–80%). Patients received prophylaxis with an azole (79%), intravenous amphotericin B formulation (10%), echinocandin (9%), or two combination drugs (2%).ConclusionResults indicate that prophylaxis is the leading antifungal strategy in French hematology units, regardless of the disease condition, representing 76% of prescriptions for antifungal therapy.FundingAstellas Pharma France.

Published
2018
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5. Tandem autologous-haploidentical transplantation is a feasible and effective program for refractory Hodgkin lymphoma

Author

Lucio Morabito, Samia Harbi, Didier Blaise, Stefania Bramanti, Jamel Mokart, Christian Chabannon, Raynier Devillier, Jacopo Mariotti, Angela Granata, Catherine Faucher, Armando Santoro, Carmelo Carlo-Stella, Jean El Cheikh, Luca Castagna, Barbara Sarina, Rossana Mineri, Pierre Jean Weiller, Sabine Furst, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Treatment outcome, MEDLINE, Transplantation, Autologous, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Refractory Hodgkin Lymphoma, Humans, Retrospective Studies, Salvage Therapy, Transplantation, Haploidentical transplantation, business.industry, Retrospective cohort study, Hematology, Hodgkin Disease, Treatment Outcome, 030220 oncology & carcinogenesis, Transplantation, Haploidentical, business, 030215 immunology
Published
2018
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6. Reduced-toxicity conditioning prior to allogeneic stem cell transplantation improves outcome in patients with myeloid malignancies

Author

Christian Chabannon, Benjamin Esterni, Patrice Chevallier, Catherine Faucher, Luca Castagna, Raynier Devillier, Mohamad Mohty, Angela Granata, Sabine Furst, Jean El Cheikh, Jacques Delaunay, Claire Oudin, Thierry Guillaume, Norbert Vey, Didier Blaise, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Aix Marseille Université (AMU), Service d'Hématologie Clinique [Nantes], Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique en cancérologie (CI2C), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), HAL UPMC, Gestionnaire, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)

Subjects
Adult, Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Transplantation Conditioning, Adolescent, medicine.medical_treatment, Karyotype, Graft vs Host Disease, Comorbidity, Hematopoietic stem cell transplantation, Gastroenterology, Young Adult, Recurrence, Internal medicine, medicine, Humans, Transplantation, Homologous, Cumulative incidence, Survival rate, Aged, Neoplasm Staging, business.industry, Myelodysplastic syndromes, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Articles, Hematology, Middle Aged, medicine.disease, 3. Good health, Surgery, Fludarabine, Transplantation, Leukemia, Myeloid, Acute, Treatment Outcome, Myelodysplastic Syndromes, Toxicity, Female, business, medicine.drug
Abstract

International audience; The introduction of reduced intensity/toxicity conditioning regimens has allowed allogeneic hematopoietic cell transplantation to be performed in patients who were previously considered too old or otherwise unfit. Although it led to a reduction in non-relapse mortality, disease control remains a major challenge. We studied the outcome of 165 patients with acute myeloid leukemia (n=124) or myelodysplastic syndrome (n=41) transplanted after conditioning with fludarabine (30 mg/m2/day for 5 days), intravenous busulfan (either 260 mg/m2: reduced intensity conditioning, or 390–520 mg/m2: reduced toxicity conditioning), and rabbit anti-thymoglobulin (2.5 mg/kg/day for 2 days). The median age of the patients at transplantation was 56.8 years. The 2-year relapse incidence was 29% (23% versus 39% for patients transplanted in first complete remission and those transplanted beyond first complete remission, respectively; P=0.008). The 2-year progression-free survival rate was 57% (95% CI: 49.9–65). It was higher in the groups with favorable or intermediate cytogenetics than in the group with unfavorable cytogenetics (72.7%, 60.5%, and 45.7%, respectively; P=0.03). The cumulative incidence of grades 2–4 and 3–4 acute graft-versus-host disease at day 100 was 19.3% and 7.9%, respectively. The cumulative incidence of chronic graft-versus-host disease at 1 year was 21.6% (severe forms: 7.8%). Non-relapse mortality at 1 year reached 11%. The 2-year overall survival rate was 61.8% (95% CI: 54.8–69.7). Unfavorable karyotype and disease status beyond first complete remission were associated with a poorer survival. This well-tolerated conditioning platform can lead to long-term disease control and offers possibilities of modulation according to disease stage or further development.

Published
2014
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7. Impact of azacitidine before allogeneic stem-cell transplantation for myelodysplastic syndromes: a study by the Société Française de Greffe de Moelle et de Thérapie-Cellulaire and the Groupe-Francophone des Myélodysplasies

Author

Laurence Clement, Yves Beguin, Alain Duhamel, Pierre Fenaux, Eric Deconinck, Marie-Thérèse Rubio, Ibrahim Yakoub-Agha, Aline Schmidt-Tanguy, Claude-Eric Bulabois, Pierre Bories, Jean-Pierre Marolleau, Gandhi Damaj, Jean El Cheikh, Mohamad Mohty, Lionel Ades, Stephane Vigouroux, Zora Marjanovic, Faeyzeh Legrand, Natacha Maillard, Charles Dauriac, Anne Huynh, Jérôme Cornillon, Jacques-Olivier Bay, Gaelle Guillerm, Sophie Park, Nathalie Fegueux, Mauricette Michallet, Marie Robin, Alice Garnier, Federico Garnier, Saas, Philippe, CHU Amiens-Picardie, Centre d'Etude et Recherche en Informatique Médicale, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie, Université de Liège, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Bordeaux [Bordeaux], Service Hématologie, CHU Strasbourg, 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), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Unité de transplantation médullaire et laboratoire d'oncologie moléculaire, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Hôpital Jean Bernard, Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Agence de la biomédecine [Saint-Denis la Plaine], Hôpital Avicenne [AP-HP], UAM Allogreffes de CSH, Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], CRLCC Jean Perrin, CHU Nice, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -hopital Jean Minjoz, Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ) -Hôpital Jean Bernard, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], CHU Cochin [AP-HP], Hôpital avicenne, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne-Université Paris 13 ( UP13 ), 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), Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), and Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest]

Subjects
Male, Oncology, Cancer Research, MESH: Combined Modality Therapy, MESH : Retrospective Studies, MESH : Induction Chemotherapy, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, MESH: Treatment Outcome, MESH: Antimetabolites, Antineoplastic, MESH: Middle Aged, MESH : Antimetabolites, Antineoplastic, Hematopoietic Stem Cell Transplantation, Induction Chemotherapy, Middle Aged, Combined Modality Therapy, MESH: Induction Chemotherapy, 3. Good health, Treatment Outcome, International Prognostic Scoring System, 030220 oncology & carcinogenesis, Azacitidine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Stem cell, MESH: Myelodysplastic Syndromes, medicine.drug, Antimetabolites, Antineoplastic, medicine.medical_specialty, MESH : Azacitidine, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Transplantation, Homologous, MESH : Male, MESH: Azacitidine, MESH : Myelodysplastic Syndromes, MESH : Treatment Outcome, 03 medical and health sciences, MESH : Hematopoietic Stem Cell Transplantation, Internal medicine, parasitic diseases, medicine, Overall survival, MESH: Transplantation, Homologous, Humans, Transplantation, Homologous, MESH : Middle Aged, MESH: Hematopoietic Stem Cell Transplantation, Retrospective Studies, MESH: Humans, business.industry, Myelodysplastic syndromes, MESH : Humans, Induction chemotherapy, Retrospective cohort study, MESH: Retrospective Studies, medicine.disease, MESH: Male, Transplantation, Myelodysplastic Syndromes, MESH : Combined Modality Therapy, business, MESH: Female, 030215 immunology
Abstract

Purpose To investigate the impact of prior-to-transplantation azacitidine (AZA) on patient outcome after allogeneic stem-cell transplantation (alloSCT) for myelodysplastic syndrome (MDS). Patients and Methods Of the 265 consecutive patients who underwent alloSCT for MDS between October 2005 and December 2009, 163 had received cytoreductive treatment prior to transplantation, including induction chemotherapy (ICT) alone (ICT group; n = 98), AZA alone (AZA group; n = 48), or AZA preceded or followed by ICT (AZA-ICT group; n = 17). At diagnosis, 126 patients (77%) had an excess of marrow blasts, and 95 patients (58%) had intermediate-2 or high-risk MDS according to the International Prognostic Scoring System (IPSS). Progression to more advanced disease before alloSCT was recorded in 67 patients. Donors were sibling (n = 75) or HLA-matched unrelated (10/10; n = 88). They received blood (n = 142) or marrow (n = 21) grafts following either myeloablative (n = 33) or reduced intensity (n = 130) conditioning. Results With a median follow-up of 38.7 months, 3-year outcomes in the AZA, ICT, and AZA-ICT groups were 55%, 48%, and 32% (P = .07) for overall survival (OS); 42%, 44%, and 29% (P = .14) for event-free survival (EFS); 40%, 37%, and 36% (P = .86) for relapse; and 19%, 20%, and 35% (P = .24) for nonrelapse mortality (NRM), respectively. Multivariate analysis confirmed the absence of statistical differences between the AZA and the ICT groups in terms of OS, EFS, relapse, and NRM. Conclusion With the goal of downstaging underlying disease before alloSCT, AZA alone led to outcomes similar to those for standard ICT.

Published
2012
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