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1. Prophylactic, preemptive, and curative treatment for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients : a position statement from an international expert group

Author

Mohty, M., Malard, F., Abecasis, M., Aerts, E., Alaskar, A.S., Aljurf, M., Arat, M., Bader, P., Baron, F., Basak, G., Bazarbachi, A., Blaise, D., Ciceri, F., Corbacioglu, S., Dalle, J.H., Dignan, F., Fukuda, T., Huynh, A., Kuball, J., Lachance, S., Lazarus, H., Masszi, T., Michallet, M., Nagler, A., NiChonghaile, M., Okamoto, S., Pagliuca, A., Peters, C., Petersen, F.B., Richardson, P.G., Ruutu, T., Saber, W., Savani, B.N., Soiffer, R., Styczynski, J., Wallhult, E., Yakoub-Agha, I., Duarte, R.F., Carreras, Enric, Universitat Autònoma de Barcelona, HUS Comprehensive Cancer Center, Clinicum, Hematologian yksikkö, Mohty, M., Malard, F., Abecasis, M., Aerts, E., Alaskar, A. S., Aljurf, M., Arat, M., Bader, P., Baron, F., Basak, G., Bazarbachi, A., Blaise, D., Ciceri, F., Corbacioglu, S., Dalle, J. -H., Dignan, F., Fukuda, T., Huynh, A., Kuball, J., Lachance, S., Lazarus, H., Masszi, T., Michallet, M., Nagler, A., Nichonghaile, M., Okamoto, S., Pagliuca, A., Peters, C., Petersen, F. B., Richardson, P. G., Ruutu, T., Saber, W., Savani, B. N., Soiffer, R., Styczynski, J., Wallhult, E., Yakoub-Agha, I., Duarte, R. F., Carreras, E., and UAM. Departamento de Medicina

Subjects
Feature, Adult, medicine.medical_specialty, HEPATIC VENOOCCLUSIVE DISEASE, HAPLOIDENTICAL DONOR TRANSPLANTATION, Medicina, 3122 Cancers, Hepatic Veno-Occlusive Disease, Disease, Hematopoietic cell transplantation (HCT), Therapeutics, PERIPHERAL-BLOOD, law.invention, 03 medical and health sciences, 0302 clinical medicine, Polydeoxyribonucleotides, Randomized controlled trial, law, medicine, Humans, Vascular Diseases, Intensive care medicine, Transplantation, Adult patients, business.industry, Mortality rate, Consensus guideline, Hematopoietic Stem Cell Transplantation, REGIMEN-RELATED TOXICITIES, STEM-CELL TRANSPLANTATION, Hematology, Expert group, BONE-MARROW-TRANSPLANTATION, PD-1 BLOCKADE, EUROPEAN-SOCIETY, RANDOMIZED-TRIAL, 3. Good health, URSODEOXYCHOLIC ACID, 030220 oncology & carcinogenesis, Veno-occlusive disease (SOS/VOD, Veno-Occlusive Disease, Complication, business, Haematological diseases, 030215 immunology
Abstract

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life-threatening complication that can develop after hematopoietic cell transplantation (HCT). While SOS/VOD may resolve within a few weeks in the majority of patients with mild-to-moderate disease, the most severe forms result in multiorgan dysfunction and are associated with a high mortality rate (>80%). Therefore, careful surveillance may allow early detection of SOS/VOD, particularly as the licensed available drug is proven to be effective and reduce mortality. The aim of this work is to propose an international consensus guideline for the treatment and prevention of SOS/VOD in adult patients, on behalf of an international expert group, This work was made possible thanks to the support of the Association for Training, Education, Research, in Hematology, Immunology and Transplantation (ATHERIT), which received an unrestricted educational grant from JAZZ pharmaceuticals

Published
2021

2. Beneficial role of CD8+T-cell reconstitution after HLA-haploidentical stem cell transplantation for high-risk acute leukaemias

Author

Bondanza, A., Ruggeri, L., Noviello, M., Eikema, D.J., Bonini, C., Chabannon, C., Werf, S. van der, Biezen, A. van, Wreede, L.C. de, Crucitti, L., Vago, L., Merluzzi, M., Massei, M.S., Veelken, H., Koc, Y., Bader, P., Gruhn, B., Locatelli, F., Ciceri, F., Toubert, A., Velardi, A., Bernardo, M.E., Dazzi, F., Ellard, R., Fleischhauer, K., Greco, R., Hudecek, M., Kohl, U., Kuball, J., Malard, F., Pedrazzoli, P., Rocha, V., Ruggeri, A., Urbano-Ispizua, A., Wang, J.F., Wieten, L., EBMT Cell Therapy Immunobiol Worki, Bondanza, Attilio, Ruggeri, Loredana, Noviello, Maddalena, Eikema, Dirk-Jan, Bonini, Chiara, Chabannon, Christian, van der Werf, Steffie, van Biezen, Anja, de Wreede, Liesbeth C., Crucitti, Lara, Vago, Luca, Merluzzi, Mara, Massei, Maria Speranza, Veelken, Hendrik, Koc, Yener, Bader, Peter, Gruhn, Bernd, Locatelli, Franco, Ciceri, Fabio, Toubert, Antoine, Velardi, Andrea, MUMC+: DA TI Laboratorium (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and MUMC+: DA TI Staf (9)

Subjects
Male, Oncology, BLOOD, COUNT, Medizin, CHILDREN, CD8-Positive T-Lymphocytes, DISEASE, 0302 clinical medicine, Risk Factors, hemic and lymphatic diseases, Cytotoxic T cell, Registries, Child, INDEX, Leukemia, Hematology, Middle Aged, RECOVERY, Haematopoiesis, surgical procedures, operative, medicine.anatomical_structure, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Transplantation, Child, Preschool, 030220 oncology & carcinogenesis, HSCT, Female, Stem cell, Adult, medicine.medical_specialty, Adolescent, T cell, Human leukocyte antigen, Young Adult, 03 medical and health sciences, CD8-positive T-lymphocytes, haematopoietic stem cell transplantation, risk factors, Internal medicine, SCORE, medicine, Humans, IMMUNOTHERAPY, Aged, business.industry, ADULTS, BONE-MARROW-TRANSPLANTATION, Transplantation, Haploidentical, business, CD8, Stem Cell Transplantation, 030215 immunology, RESPONSES
Abstract

HLA-haploidentical haematopoietic stem cell transplantation (haplo-HSCT) is increasingly offered to patients with high-risk acute leukaemia. Unfortunately, haplo-HSCT is followed by a delayed immunoreconstitution. The aim of this EBMT registry study was to explore the clinical impact of lymphocyte subset counts after haplo-HSCT. We considered 144 leukaemic patients transplanted in the period 2001-2012. Pre-transplantation clinical variables and differential immune-cell counts (CD3, CD4, CD8 T cells, NK and B cells) measured before day 100 were evaluated for their capacity to predict overall survival, relapse mortality or non-relapse mortality (NRM). Negative prognostic factors for overall survival were advanced disease state at transplantation, host age and CMV seropositivity. Higher CD3, CD4 and CD8 counts were associated with a better overall survival and a lower NRM. Strikingly, when tested in multivariable analysis, higher CD3 and CD8 counts were still significantly associated with a lower NRM. These results indicate that an accelerated T-cell reconstitution correlates with less transplantation mortality, likely due to the protective role of T cells against viral infections. This observation suggests that CD8+ T-cell counts should be investigated as surrogate biomarkers of outcome in prospective haplo-HSCT trials.

Published
2019
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3. Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders : current practice in Europe, 2019

Author

Duarte, R.F., Labopin, M., Bader, P., Basak, G.W., Bonini, C., Chabannon, C., Corbacioglu, S., Dreger, P., Dufour, C., Genneryl, A.R., Kuball, J., Lankester, A.C., Lanza, F., Montoto, S., Nagler, A., Latour, R.P. de, Snowden, J.A., Styczynski, J., Yakoub-Agha, I., Kroger, N., Mohty, M., Albert, M., Alexander, T., Averbuch, D., Baron, F., Bazarbachi, E., Beksac, M., Brissot, E., Bug, G., Cesaro, S., Chalandon, Y., Ciceri, F., Czerw, T., Dazzi, F., Esteve, J., Fleischhauer, K., Garderet, L., Giebel, S., Gil, L., Gilleece, M., Gorin, N.C., Hayden, P., Halter, J., Boluda, J.C.H., Hudecek, M., Kleinschmidt, K., Kenyon, M., Koenecke, C., Locatelli, F., Malard, F., McLornan, D., Mikulska, M., Murray, J., Onida, F., Pedrazzoli, P., Penack, O., Peric, Z., Risitano, A., Robin, M., Robinson, S., Ruggeri, A., Sanz, J., Savani, B., Schetelig, J., Schied, C., Schmid, C., Schoemans, H., Schonland, S., Sharrack, B., Shouval, R., Spyridonidis, A., Toubert, A., Tourniac, O., Urbano-Ispizua, A., Vago, L., Gelder, M. van, Verhoeven, B., Versluis, J., Wietten, L., Willasch, A., European Soc Blood Marrow Transpla, Duarte, R. F., Labopin, M., Bader, P., Basak, G. W., Bonini, C., Chabannon, C., Corbacioglu, S., Dreger, P., Dufour, C., Gennery, A. R., Kuball, J., Lankester, A. C., Lanza, F., Montoto, S., Nagler, A., Peffault de Latour, R., Snowden, J. A., Styczynski, J., Yakoub-Agha, I., Kroger, N., Mohty, M, and on behalf of the European Society forBlood and Marrow Transplantation, (EBMT)

Subjects
medicine.medical_specialty, Transplantation Conditioning, medicine.medical_treatment, MEDLINE, Disease, Hematopoietic stem cell transplantation, History, 21st Century, NO, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, medicine, Humans, Intensive care medicine, Multiple myeloma, Accreditation, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, medicine.disease, Hematologic Diseases, Europe, Immune System Diseases, Hematologic disease, 030220 oncology & carcinogenesis, business, 030215 immunology
Abstract

This is the seventh special EBMT report on the indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders. Our aim is to provide general guidance on transplant indications according to prevailing clinical practice in EBMT countries and centres. In order to inform patient decisions, these recommendations must be considered together with the risk of the disease, the risk of the transplant procedure and the results of non-transplant strategies. In over two decades since the first report, the EBMT indications manuscripts have incorporated changes in transplant practice coming from scientific and technical developments in the field. In this same period, the establishment of JACIE accreditation has promoted high quality and led to improved outcomes of patient and donor care and laboratory performance in transplantation and cellular therapy. An updated report with operating definitions, revised indications and an additional set of data with overall survival at 1 year and non-relapse mortality at day 100 after transplant in the commonest standard-of-care indications is presented. Additional efforts are currently underway to enable EBMT member centres to benchmark their risk-adapted outcomes as part of the Registry upgrade Project 2020 against national and/or international outcome data.

Published
2019
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4. Features of Toxoplasma gondii reactivation after allogeneic hematopoietic stem-cell transplantation in a high seroprevalence setting

Author

Christophe Hennequin, Olivier Paccoud, Mohamad Mohty, Florent Malard, Laure Surgers, Giorgia Battipaglia, Eolia Brissot, Remy Dulery, Myriam Labopin, Juliette Guitard, Paccoud, O., Guitard, J., Labopin, M., Surgers, L., Malard, F., Battipaglia, G., Dulery, R., Hennequin, C., Mohty, M., and Brissot, E.

Subjects
medicine.medical_specialty, medicine.medical_treatment, Hematopoietic stem cell transplantation, 03 medical and health sciences, 0302 clinical medicine, Seroepidemiologic Studies, Internal medicine, parasitic diseases, medicine, Humans, Seroprevalence, Retrospective Studies, Transplantation, Cytopenia, biology, business.industry, Hematopoietic Stem Cell Transplantation, Toxoplasma gondii, Retrospective cohort study, Hematology, medicine.disease, biology.organism_classification, Toxoplasmosis, 030220 oncology & carcinogenesis, business, Toxoplasma, Atovaquone, 030215 immunology, medicine.drug
Abstract

We performed a single-centre retrospective study to evaluate the effectiveness of Toxoplasma gondii prevention strategies after allogeneic stem-cell transplantation. The charts of 138 allogeneic stem-cell recipients over a 4-year period were reviewed. Forty-nine percent of patients were not receiving optimal trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis at day +30, mainly due to persistent cytopenia. Six months after transplantation, the rate of toxoplasmosis reactivation was 11.6%, including nine cases of Toxoplasma infection and seven cases of Toxoplasma disease. Fifty-six percent of cases of reactivation occurred before day +30. Thirty-eight percent occurred in patients receiving atovaquone prophylaxis. In 57% of patients presenting with Toxoplasma disease, signs of disease were present at first evidence of Toxoplasma DNA in peripheral blood samples. This study illustrates the limitations inherent to currently used toxoplasmosis prevention strategies and argues for the use of a combined prophylactic and preemptive approach. After performing the initial study, we limited the use of atovaquone in favour of TMP-SMZ when possible, and implemented an early prevention strategy consisting of the introduction of prophylaxis starting on day of engraftment. Over the following 16 months, 88.9% of eligible Toxoplasma-seropositive patients were receiving TMP-SMZ at day +30, and the rate of early Toxoplasma reactivation was 1.5%.

Published
2019
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5. Mucoepidermoid carcinoma of salivary glands: A French Network of Rare Head and Neck Tumors (REFCOR) prospective study of 292 cases

Author

A. Varoquaux, L. Castillo, M. Tassart, R. Jankowski, Emmanuelle Uro-Coste, F. Massip, L. Brugel, S Testelin, René-Jean Bensadoun, Olivier Mauvais, C. Bach, P. Herman, Christian-Adrien Righini, Laurent Gilain, Xavier Dufour, T. Mom, L. Laccoureye, E. Baudin, Justin Michel, Ludovic Le Taillandier de Gabory, G. Moulin, D. de Raucourt, C. Ferron, Juliette Thariat, R. Breheret, J.-M. Badet, V. Darrouzet, Bruno Devauchelle, T. Radulesco, Bertrand Baujat, V. Strunski, G. Poissonnet, Thomas Radulesco, Jean-Claude Merol, Renaud Garrel, C. Borel, A. Cosmidis, Odile Casiraghi, Dominique Chevalier, E. Serrano, Caroline Even, J.-C. Merol, P. Demez, L. Geoffrois, N. Fakhry, J.-P. Lavieille, A. Banal, J. Lacau St Guily, S. Duflo, J.-P. Bessède, B. Baujat, Marie Christine Kaminsky, F. Chabolle, Sebastien Albert, Roch Giorgi, O. Sterkers, N. Sarroul, Vianney Bastit, D. Blanchard, P. Lang, E. de Monès, P. Breton, G. Dolivet, R. Garrel, Sébastien Vergez, B. Toussaint, Anne Sudaka, A. Giovanni, G. Noel, P. Hofman, A. Bozorg-Grayeli, O. Malard, M. Housset, E. Lartigau, P. Ceruse, Valérie Costes-Martineau, C. Bertolus, Cécile Badoual, G. Andry, T. Van den Abbeele, F. Kolb, S. Faivre, F. Floret, P. Dessi, M. Juliéron, Nicolas Fakhry, J. Michel, Louis Crampette, Francois Mouawad, O. Choussy, Philippe Schultz, S. Hans, Marine Lefevre, L. Gilain, Emile Reyt, Sylvain Morinière, Philippe Herman, G. Valette, Béatrix Barry, A. Timochenko, Gilles Poissonnet, Antoine Moya-Plana, F. Veillon, S. Vergez, A. Coste, Franck Jegoux, E. Cassagnau, Christine Bach, Y. Marie Robin, B. Guerrier, E. Uro Coste, X. Leroy, Valérie Costes, Olivier Malard, F. Rolland, F. Dubrulle, A.C. Baglin, L. de Gabory, B. Ruhin, A. Girod, G. Calais, Laurie Saloner Dahan, Emmanuel Babin, J.C. Chobaut, Michel Wassef, Benjamin Lallemant, Jean-Michel Prades, C.-A. Righini, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Aix Marseille Université (AMU), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Toulouse [Toulouse], CHU Bordeaux [Bordeaux], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Universitaire de la Face et du Cou [Nice], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), 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), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Foch [Suresnes], CHU Lille, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), CHU Clermont-Ferrand, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut Gustave Roussy (IGR), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), REFCOR members: S Albert, G Andry, E Babin, C Bach, J-M Badet, C Badoual, A C Baglin, A Banal, B Barry, E Baudin, B Baujat, R J Bensadoun, C Bertolus, J-P Bessède, D Blanchard, C Borel, A Bozorg-Grayeli, R Breheret, P Breton, L Brugel, G Calais, O Casiraghi, E Cassagnau, L Castillo, P Ceruse, F Chabolle, D Chevalier, J C Chobaut, O Choussy, A Cosmidis, A Coste, V Costes, L Crampette, V Darrouzet, P Demez, P Dessi, B Devauchelle, G Dolivet, F Dubrulle, S Duflo, X Dufour, S Faivre, N Fakhry, C Ferron, F Floret, L de Gabory, R Garrel, L Geoffrois, L Gilain, A Giovanni, A Girod, B Guerrier, S Hans, P Herman, P Hofman, M Housset, R Jankowski, F Jegoux, M Juliéron, M-C Kaminsky, F Kolb, J Lacau St Guily, L Laccoureye, B Lallemant, P Lang, E Lartigau, J-P Lavieille, M Lefevre, X Leroy, O Malard, F Massip, O Mauvais, J-C Merol, J Michel, T Mom, S Morinière, E de Monès, G Moulin, G Noel, G Poissonnet, J-M Prades, T Radulesco, D de Raucourt, E Reyt, C Righini, Y Marie Robin, F Rolland, B Ruhin, N Sarroul, P Schultz, E Serrano, O Sterkers, V Strunski, A Sudaka, M Tassart, S Testelin, J Thariat, A Timochenko, B Toussaint, E Uro Coste, G Valette, T Van den Abbeele, A Varoquaux, F Veillon, S Vergez, M Wassef, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), Université de Bourgogne (UB)-Université de Bourgogne (UB), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), dormoy, valerian, Pathogénèse et contrôle des infections chroniques (PCCI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )

Subjects
medicine.medical_specialty, Multivariate analysis, [SDV]Life Sciences [q-bio], Salivary glands, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Mucoepidermoid carcinoma, Internal medicine, Diabetes mellitus, Medicine, Stage (cooking), Intermediate Grade, 030223 otorhinolaryngology, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Cancer, [PHYS]Physics [physics], business.industry, General Medicine, medicine.disease, 3. Good health, Parotid gland, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Surgery, business
Abstract

International audience; Background: To describe the characteristics of the largest European study of MEC of salivary glands and to determine the prognostic factors for overall and disease free survival.Patients and methods: Patients with MEC were prospectively included in the Réseau d'Expertise Français sur les Cancers ORL Rares (REFCOR, French Network of Rare Head and Neck Tumors) database between 2009 and 2015.Results: A total of 292 patients were included. Tumors were classified as low grade in 175 cases (60%), intermediate in 39 (13%) and high grade in 78 (27%). Median follow-up was 26 months. The 5-year OS and DFS rates were respectively 83% and 69%. In multivariate analysis, age (p = 0.004), diabetes (p = 0.02) and advanced stage (p = 0.03) were found to have a significant negative impact on OS. Diabetes (p = 0.001), alcohol consumption (p = 0.003) and advanced stage (p = 0.001) were found to have a significant negative impact on DFS. Compare to low grade, high grade tended to have a negative impact on OS (p = 0.05) and had a significant effect on DFS (0.002) while intermediate grade had no significant influence on survival. The surgical treatment had a positive impact on both OS (p = 0.00005) and DFS (p = 0.0005). Postoperative radiotherapy had no impact in multivariate analysis.Conclusion: Advanced clinical stage, high grade tumor, high age, the impossibility of carrying out a complete surgical resection, and diabetes are the main prognostic factors in this prospective series of patients with MEC. Such findings open new research perspectives on the influence of these components on initial patient care.

Published
2020
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6. Extracorporeal photopheresis as first line strategy in the treatment of acute graftversus-host disease after haematopoietic stem cell transplantation: a single centre experience

Author

Giorgia Battipaglia, Remy Dulery, Clemence Mediavilla, Zoé Van de Wyngaert, Tounes Ledraa, Florent Malard, Annalisa Paviglianiti, Anne Banet, Eolia Brissot, Mohamad Mohty, Sandra Eder, Simona Sestili, Ramdane Belhocine, Agnes Bonin, 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), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [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), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Gestionnaire, HAL Sorbonne Université 5, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sestili, S., Eder, S., Belhocine, R., Dulery, R., Battipaglia, G., Brissot, E., Mediavilla, C., Banet, A., van de Wyngaert, Z., Paviglianiti, A., Ledraa, T., Bonin, A., Mohty, M., and Malard, F.

Subjects
0301 basic medicine, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Cancer Research, medicine.medical_treatment, Graft vs Host Disease, Hematopoietic stem cell transplantation, Single Center, Gastroenterology, Graft-versus-host disease, 0302 clinical medicine, Photopheresis, Prednisone, Extracorporeal Photopheresis, Immunology and Allergy, Genetics (clinical), Remission Induction, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, 3. Good health, Treatment Outcome, photopheresis, Oncology, 030220 oncology & carcinogenesis, Acute Disease, hematopoietic stem cell transplantation, Female, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Immunology, acute GVHD, 03 medical and health sciences, Young Adult, Internal medicine, Acute graft versus host disease, medicine, Humans, Transplantation, Homologous, Aged, Retrospective Studies, Transplantation, business.industry, Retrospective cohort study, Cell Biology, medicine.disease, Survival Analysis, 030104 developmental biology, Chronic Disease, business
Abstract

International audience; Background aims: Corticosteroids are the standard first-line treatment for acute graft-versus-host disease (aGVHD), but they are associated with many complications, and less than half of patients have a sustained response.Methods: To improve outcomes, we performed a retrospective study to analyze the efficacy of the addition of extracorporeal photopheresis (ECP) to low-dose corticosteroids in 37 adult patients (median age, 57 years) with skin-predominant aGVHD (grade I, n = 17; grade II, n = 18; and grade III, n = 2). All patients received ECP in combination with 1 mg/kg prednisone (n = 26) or topical steroids (n = 11).Results: Overall response rate was 81% after a median of three ECP procedures (range, 2–8), including 22 complete responses (CR, 59%) and eight very good partial responses (VGPR, 22%). The 11 patients treated with topical corticosteroids achieved CR. Furthermore, 16 (62%) patients reached prednisone withdrawal at a median of 100 days (range, 42–174 days) after its initiation. Eighteen patients developed chronic GVHD (cGVHD); 11 of them (who were in CR of aGVHD) had a new-onset cGVHD, and seven experienced progressive cGVHD (five non-responding and two VGPR patients). A second-line immunosuppressive treatment was initiated in only five (14%) non-responding patients. With a median follow-up of 31 months (range, 6–57 months) 2-year overall survival and non-relapse mortality were 74% and 11%, respectively.Conclusions: Overall, the combination of low-dose corticosteroids and ECP appear to be safe and effective for first-line treatment of skin predominant aGVHD.

Published
2020
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7. Thiotepa and antithymocyte globulin-based conditioning prior to haploidentical transplantation with posttransplant cyclophosphamide in high-risk hematological malignancies

Author

Giorgia Battipaglia, Marie-Thérèse Rubio, Eolia Brissot, Myriam Labopin, Tounes Ledraa, Remy Dulery, Françoise Isnard, Anne Vekhoff, Juliana Bastos, Ollivier Legrand, Mohamad Mohty, Simona Sestili, Federica Giannotti, Zinaida Peric, Ramdane Belhocine, Razan Mohty, Annalisa Ruggeri, Simona Lapusan, Clemence Mediavilla, Agnès Bonnin, Florent Malard, 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), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [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)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [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), Peric, Z., Mohty, R., Bastos, J., Brissot, E., Battipaglia, G., Belhocine, R., Sestili, S., Giannotti, F., Vekhoff, A., Ledraa, T., Legrand, O., Lapusan, S., Isnard, F., Labopin, M., Bonnin, A., Mediavilla, C., Rubio, M. -T., Ruggeri, A., Dulery, R., Malard, F., and Mohty, M.

Subjects
medicine.medical_specialty, Transplantation Conditioning, Cyclophosphamide, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, ThioTEPA, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Refractory, Internal medicine, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Antilymphocyte Serum, Transplantation, Neutrophil Engraftment, Hematologic Neoplasms / therapy, business.industry, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, 3. Good health, Regimen, surgical procedures, operative, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Transplantation, Haploidentical, [SDV.IMM]Life Sciences [q-bio]/Immunology, Stem cell, Neoplasm Recurrence, Local, business, Graft vs Host Disease / prevention & control, Thiotepa, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, medicine.drug
Abstract

We report results of a thiotepa-based conditioning in haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-CY) and antithymocyte globulin (ATG), for unmanipulated peripheral blood stem cell (PBSC) transplants, in 80 patients with hematological malignancies. Patients in complete remission (CR) received a thiotepa-busulfan-fludarabine (TBF) regimen, while patients with relapsed/refractory (R/R) malignancies received a sequential regimen consisting of thiotepa-etoposide-cyclophosphamide (TEC) and reduced-intensity conditioning (RIC). The median age was 52 (range, 17-72) years, 44% patients had R/R disease at transplant, and the median follow-up was 417 (range, 180-1595) days. The median days to neutrophil engraftment was 17 (range, 12-34). The cumulative incidences (CI) of acute graft-versus-host disease (GVHD) grade III to IV, severe chronic GVHD, nonrelapse mortality (NRM), and relapse were 16%, 16%, 26, and 26%, respectively. The 2-year overall survival (OS) and disease-free survival (DFS) were 53% and 47%, respectively. There were no significant differences between the patients in CR and R/R patients in terms of engraftment, GVHD, NRM, relapse, OS, or DFS. We conclude that thiotepa-based regimen with PT-CY can be modified with PBSC and ATG, still providing low toxicity, protection against GVHD, and low relapse incidence. Particularly encouraging are the results with the modification to sequential regimen in R/R patients.

Published
2020
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8. Rhino-orbital Mucormycosis presenting as facial cellulitis in a patient with high-risk acute myeloid leukemia in relapse

Author

Remy Dulery, Florent Malard, Bertrand Baujat, Olivier Paccoud, Eolia Brissot, Giorgia Battipaglia, Mohamad Mohty, Federica Giannotti, Juliette Guitard, Annalisa Ruggeri, Pierre-Edouard Debureaux, Debureaux, P. -E., Paccoud, O., Guitard, J., Baujat, B., Ruggeri, A., Battipaglia, G., Dulery, R., Giannotti, F., Malard, F., Mohty, M., and Brissot, E.

Subjects
Male, medicine.medical_specialty, Eye Infections, Fungal/complications/diagnosis, Leukemia, Myeloid, Acute/complications/immunology/pathology, MEDLINE, General Biochemistry, Genetics and Molecular Biology, Mucormycosis/complications/diagnosis, Diagnosis, Differential, Immunocompromised Host, Text mining, Recurrence, Risk Factors, medicine, Humans, Cellulitis/complications/diagnosis, business.industry, Myeloid leukemia, General Medicine, Middle Aged, medicine.disease, Dermatology, Facial Dermatoses/complications/diagnosis, Cellulitis, Opportunistic Infections/complications/diagnosis, Rhinitis/complications/diagnosis, business, Orbital mucormycosis, Orbital Diseases/complications/diagnosis/microbiology
Published
2019
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9. Pre-emptive rituximab treatment for Epstein-Barr virus reactivation after allogeneic hematopoietic stem cell transplantation is a worthwhile strategy in high-risk recipients: a comparative study for immune recovery and clinical outcomes

Author

Corinne Amiel, Myriam Labopin, Federica Giannotti, Béatrice Gaugler, Joël Gozlan, Florent Malard, Nicolas Stocker, Olivier Paccoud, Giorgia Battipaglia, Annalisa Ruggeri, Eolia Brissot, Remy Dulery, Inès Boussen, Mohamad Mohty, Agnès Bonnin, Stocker, N., Labopin, M., Boussen, I., Paccoud, O., Bonnin, A., Malard, F., Amiel, C., Gozlan, J., Battipaglia, G., Dulery, R., Giannotti, F., Ruggeri, A., Gaugler, B., Mohty, M., and Brissot, E.

Subjects
Oncology, Epstein-Barr Virus Infections, medicine.medical_specialty, Herpesvirus 4, Human, medicine.medical_treatment, Hematopoietic stem cell transplantation, Neutropenia, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Medicine, Humans, Cumulative incidence, Epstein-Barr Virus Infections / drug therapy, Retrospective Studies, Transplantation, business.industry, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, Bone marrow failure, Hematopoietic Stem Cell Transplantation / adverse effects, Retrospective cohort study, Hematology, Rituximab / therapeutic use, medicine.disease, Lymphoproliferative Disorders, 030220 oncology & carcinogenesis, Rituximab, Neoplasm Recurrence, Local, business, 030215 immunology, medicine.drug
Abstract

This retrospective study evaluated the impact of a pre-emptive rituximab (RTX) strategy for Epstein-Barr virus (EBV) reactivation on immune recovery and outcomes of 219 high-risk recipients undergoing allogeneic stem cell transplantation (allo-SCT) for hematological malignancies or bone marrow failure. One-hundred and seven patients received pre-emptive RTX for EBV reactivation (RTX group) and 112 did not (control group). The median onset time of EBV reactivation was 49 days (range, 14-561), including five patients who developed post-transplant lymphoproliferative disorder (EBV-PTLD). RTX and control groups were pair-matched to assess the impact of RTX on all endpoints. In RTX patients, CD19 + B cells were significantly decreased until 1-year post-transplant, so were immunoglobulin levels. Twenty-one patients (17%) developed RTX-related neutropenia. There was, in the RTX group, a trend towards a lower cumulative incidence of chronic GvHD (P = 0.059). Overall survival, progression-free survival, non-relapse mortality, relapse incidence, and incidence of overall infections at 2 years following allo-SCT were comparable in the two groups. We conclude that pre-emptive RTX, despite inducing a delayed B-cell reconstitution and a high risk of RTX-related neutropenia, may be considered as a worthwhile treatment, given the absence of negative impact on post allo-SCT outcomes and a low incidence of EBV-PTLD.

Published
2020

10. Fractionated gemtuzumab ozogamicin in association with high dose chemotherapy: a bridge to allogeneic stem cell transplantation in refractory and relapsed acute myeloid leukemia

Author

Florent Malard, Ollivier Legrand, François Delhommeau, Anne Vekhoff, Giorgia Battipaglia, Rosa Adaeva, Pierre Hirsch, Eolia Brissot, Myriam Labopin, Françoise Isnard, Anne-Claire Mamez, Mohamad Mohty, Pierre-Edouard Debureaux, Simona Lapusan, Agnès Bonnin, Remy Dulery, Debureaux, P. -E., Labopin, M., Mamez, A. -C., Lapusan, S., Isnard, F., Adaeva, R., Bonnin, A., Hirsch, P., Delhommeau, F., Battipaglia, G., Dulery, R., Malard, F., Vekhoff, A., Mohty, M., Legrand, O., Brissot, E., 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), Sorbonne Université (SU), Service d'immunologie et hématologies biologiques [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Oncology, medicine.medical_specialty, Gemtuzumab ozogamicin, Salvage therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Salvage Therapy, Transplantation, Mitoxantrone, business.industry, Cytarabine, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Gemtuzumab, 3. Good health, Regimen, Leukemia, Myeloid, Acute, Aminoglycosides, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, 030215 immunology, medicine.drug
Abstract

International audience; Optimization of the salvage regimen is required to improve prognosis in primary refractory or relapsed acute myeloid leukemia (AML). In fit patients, a bridge to allogeneic transplant is the primary purpose of salvage. We tested the combination of fractionated gemtuzumab ozogamicin with cytarabine and mitoxantrone (MYLODAM schema) with primary endpoint of efficacy and safety. We also attempted to define predictive factors for survival and response after salvage. We included 58 patients with a median age at salvage of 56 years. The overall response rate was 67%. Leukemia-free survival (LFS) and overall survival (OS) at 2 years was 36% (95% CI: 23–49) and 54% (95% CI: 39–68), respectively. Treatment-related mortality was 7%. Three veno-occlusive diseases (SOS/VOD) occurred during salvage. In the allogeneic group of 28 patients (48%), LFS and OS at 2 years was 57 % (95% CI: 36.3–77.5) and 69 % (95% CI: 49.3–88.7), respectively. Incidences of nonrelapse mortality, grade II–IV acute graft-versus-host disease (GVHD) and chronic GVHD were 16%, 40%, and 45%, respectively. A GO-based intensive regimen is a viable option for salvage therapy and a feasible schedule as a bridge to allogeneic transplant.

Published
2019
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11. Tolerability and Efficacy of Treatment With Azacytidine as Prophylactic or Preemptive Therapy for Myeloid Neoplasms After Allogeneic Stem Cell Transplantation

Author

Zoé van de Wiegert, Clemence Mediavilla, Mohamad Mohty, Tounes Ledraa, Giorgia Battipaglia, Anne Vekhoff, Eolia Brissot, Agnès Bonnin, Remy Dulery, Abdulhamid Bazarbachi, Simona Lapusan, Annalisa Paviglianiti, Ollivier Legrand, Annalisa Ruggeri, Françoise Isnard, Anne Bannet, Florent Malard, Simona Sestili, Ramdane Belhocine, Carolina Marini, Rosa Adaeva, Myriam Labopin, Marini, C., Brissot, E., Bazarbachi, A., Dulery, R., Sestili, S., Battipaglia, G., Mediavilla, C., Paviglianiti, A., Belhocine, R., Isnard, F., Lapusan, S., Adaeva, R., Bannet, A., van de Wiegert, Z., Vekhoff, A., Ledraa, T., Legrand, O., Labopin, M., Bonnin, A., Ruggeri, A., Malard, F., and Mohty, M.

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Myeloid, Allogeneic transplantation, Adolescent, Lymphocyte, Posttransplantation, Disease, Prophylaxy, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, medicine, Humans, Aged, Retrospective Studies, Acute myeloid leukemia, Myeloproliferative Disorders, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Allografts, Discontinuation, Transplantation, Low burden disease, medicine.anatomical_structure, Oncology, Tolerability, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Azacitidine, Female, Stem cell, business, Myelodysplastic syndrome, 030215 immunology, Follow-Up Studies
Abstract

Introduction/Background Azacytidine (AZA) has been used as a promising treatment for relapse after allogeneic transplantation. A clear benefit has been demonstrated when treating patients with a reduced disease burden, thus a prophylactic and preemptive approach to these patients has emerged. Materials and Methods We retrospectively analyzed patients with myeloid malignancies treated with azacytidine in the posttransplantation setting between September 2013 and April 2018 in a single tertiary care hospital. Of 32 patients analyzed, 21 were treated for prophylactic use and 11 preemptively, with a median follow-up of 20 months. Prophylactic treatment consisted of AZA at 32 mg/m2 for 5 days every 28 days, and preemptive treatment of AZA 75 mg/m2 for 5 or 7 days per cycle. In addition, 10 patients received one or more donor lymphocyte infusions (DLIs). Two patients presented with infectious complications demanding hospitalization, and 13 patients (10 in the prophylactic group and 3 in the preemptive group) presented graft-versus-host disease (GvHD). Of patients who had GvHD, 3 needed treatment discontinuation. Overall, 12 patients suspended treatment, 8 for disease progression and 1 due to patient request. Results In the prophylactic group, all patients are alive at 1 year with an event-free survival (EFS) of 95%, as only 1 patient relapsed. In the preemptive group, 1-year EFS was 54% and 1-year overall survival was 82%. Conclusion Low-dose AZA in posttransplantation patients with myeloid neoplasms is a well-tolerated therapy with the potential to prevent relapse and maintain stable remissions. Randomized prospective trials are needed to determine patient selection and dosage, timing, and duration of treatment.

Published
2019

12. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation

Author

Mauricette Michallet, Takahiro Fukuda, Peter Bader, Ahmed Alaskar, Paul G. Richardson, C Peters, Mutlu Arat, Bipin N. Savani, Finn Bo Petersen, Erik Aerts, Tapani Ruutu, J.-H. Dalle, Fiona L Dignan, Fabio Ciceri, M. Abecassis, Mairead NiChonghaile, M. Mohty, Selim Corbacioglu, Arnon Nagler, E. Wallhult, S. Okamoto, Tamás Masszi, Didier Blaise, Florent Malard, R. F. Duarte, Anne Huynh, M Aljurf, Ali Bazarbachi, Enric Carreras, Ibrahim Yakoub-Agha, Frédéric Baron, A Pagliuca, Department of Medicine, Clinicum, Department of Oncology, Mohty, M, Malard, F., Abecassis, M., Aerts, E., Alaskar, A. S., Aljurf, M., Arat, M., Bader, P., Baron, F., Bazarbachi, A., Blaise, D., Ciceri, Fabio, Corbacioglu, S., Dalle, J. H., Dignan, F., Fukuda, T., Huynh, A., Masszi, T., Michallet, M., Nagler, A., Nichonghaile, M., Okamoto, S., Pagliuca, A., Peters, C., Petersen, F. B., Richardson, P. G., Ruutu, T., Savani, B. N., Wallhult, E., Yakoub Agha, I., Duarte, R. F., Carreras, E., and UAM. Departamento de Medicina

Subjects
Pediatrics, Veno-occlusive disease, medicine.medical_treatment, Hepatic Veno-Occlusive Disease, Hematopoietic stem cell transplantation, Disease, Defibrotide, Severity of Illness Index, 0302 clinical medicine, Risk Factors, Diagnosis, VERSUS-HOST-DISEASE, Medicine, HIGH-RISK POPULATION, MR-IMAGING FINDINGS, Sinusoidal obstruction syndrome, Mortality rate, Hematopoietic Stem Cell Transplantation, Hematology, 3. Good health, 030220 oncology & carcinogenesis, medicine.drug, Adult, medicine.medical_specialty, Hepatic veno-occlusive disease, Patients, Medicina, 3122 Cancers, Sensitivity and Specificity, 03 medical and health sciences, CONDITIONING REGIMEN, VENOCCLUSIVE DISEASE, Severity of illness, Humans, Special Report, TISSUE-PLASMINOGEN ACTIVATOR, Transplantation, HEPATIC VENOOCCLUSIVE-DISEASE, business.industry, STEM-CELL TRANSPLANTATION, medicine.disease, Surgery, Early Diagnosis, MULTIORGAN FAILURE, bacteria, Complication, business, SIGNIFICANT TOXICITY, Biomarkers, 030215 immunology
Abstract

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate ( > 80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation., FM was supported by educational grants from the 'Association for Training, Education and Research in Hematology, Immunology and Transplantation' (ATERHIT, Nantes, France)

Published
2016
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13. Thiotepa, Busulfan, and Fludarabine Conditioning Regimen in T Cell-Replete HLA-Haploidentical Hematopoietic Stem Cell Transplantation

Author

Anne Banet, Eolia Brissot, Tounes Ledraa, Florent Malard, Simona Lapusan, Giorgia Battipaglia, Annalisa Ruggeri, Zoé Van de Wyngaert, Rosa Adaeva, Ollivier Legrand, Annalisa Paviglianiti, Marie-Thérèse Rubio, Anne Vekhoff, Federica Giannotti, Juliana Bastos, Françoise Isnard, Mohamad Mohty, Clémence Médiavilla, Simona Sestili, Ramdane Belhocine, Remy Dulery, Dulery, R., Bastos, J., Paviglianiti, A., Malard, F., Brissot, E., Battipaglia, G., Mediavilla, C., Giannotti, F., Banet, A., de Wyngaert, Z. V., Ledraa, T., Belhocine, R., Sestili, S., Adaeva, R., Lapusan, S., Isnard, F., Legrand, O., Vekhoff, A., Rubio, M. -T., Ruggeri, A., Mohty, M., 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), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [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)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [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), Hospital de São João [Porto], and Sorbonne Université (SU)

Subjects
Male, Transplantation Conditioning, Haploidentical transplantation, medicine.medical_treatment, T-Lymphocytes, Graft vs Host Disease, Hematopoietic stem cell transplantation, Gastroenterology, Graft-versus-host disease, 0302 clinical medicine, Thiotepa/administration & dosage, HLA Antigens, Medicine, Cumulative incidence, ComputingMilieux_MISCELLANEOUS, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, 3. Good health, Fludarabine, Survival Rate, surgical procedures, operative, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Cyclosporine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Vidarabine/administration & dosage/analogs & derivatives, Vidarabine, medicine.drug, Graft vs Host Disease/metabolism/mortality/pathology/prevention & control, Busulfan/administration & dosage, Adult, medicine.medical_specialty, Adolescent, Hematologic Neoplasms/metabolism/mortality/pathology/therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, ThioTEPA, Cyclosporine/administration & dosage, Disease-Free Survival, Mycophenolic Acid/administration & dosage, 03 medical and health sciences, Internal medicine, Humans, Busulfan, Aged, Retrospective Studies, Transplantation, Neutrophil Engraftment, business.industry, Myelodysplastic syndromes, Mycophenolic Acid, medicine.disease, T-Lymphocytes/metabolism/pathology, Antithymocyte globulin, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Thiotepa, 030215 immunology, Conditioning
Abstract

We report the outcomes of 51 patients who underwent unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide (PT-Cy) and antithymocyte globulin (ATG), from peripheral blood stem cells (PBSCs) or bone marrow, after receipt of a TBF (thiotepa, busulfan, and fludarabine) conditioning regimen. Their median age was 55 years (range, 16 to 72 years). Hematologic diagnoses included acute leukemias (n = 31), lymphoid neoplasm (n = 12), myeloproliferative neoplasm (n = 5), and myelodysplastic syndromes (n = 3). Thirty-seven patients (73%) were in complete remission. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate for all patients, associated with ATG in 39 patients (76.5%). The median time to neutrophil engraftment was 17 days (range, 12 to 34 days). The cumulative incidences of grade II-IV and grade III-IV acute GVHD were 27.5% and 14%, respectively. In patients receiving a PBSC graft and ATG prophylaxis, grade II-IV aGVHD occurred in 16% of patients. The use of ATG and a lower thiotepa dose (5 mg/kg versus 10 mg/kg) were associated with a reduced cumulative incidence of grade II-IV acute GVHD (P = .03 and .005, respectively). The 2-year cumulative incidence of chronic GVHD was 29% and was significantly reduced to 13% with the lower thiotepa dose (P = .002). After a median follow-up of 25 months (range, 12 to 62 months), the cumulative incidences of nonrelapse mortality, relapse, overall survival (OS), disease-free survival (DFS), and GVHD-free, relapse-free survival (GFRFS) were 20%, 22.5%, 67%, 58%, and 51%, respectively. Pretransplantation disease status (complete remission versus others) was the main factor associated with OS, DFS, and GFRFS. In conclusion, the TBF conditioning regimen is an appealing platform in the haplo-HSCT setting with PT-Cy in terms of engraftment rate, toxicity, and disease control. We found no benefit of a thiotepa dose of 10 mg/kg compared with a dose of 5 mg/kg. ATG reduced the risk of acute GVHD without comprising outcomes.

Published
2019
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14. CD34+-selected stem cell 'Boost' for poor graft function after allogeneic hematopoietic stem cell transplantation

Author

Annalisa Ruggeri, Florent Malard, Mohamad Mohty, Remy Dulery, R Mohty, Giorgia Battipaglia, Eolia Brissot, Simona Sestili, R. Belhocine, C Mediavilla, Mohty, R., Brissot, E., Battipaglia, G., Ruggeri, A., Sestili, S., Mediavilla, C., Belhocine, R., Dulery, R., Mohty, M., and Malard, F.

Subjects
business.industry, medicine.medical_treatment, CD34, CD34+ selected stem cell, General Medicine, Hematopoietic stem cell transplantation, Graft function, General Biochemistry, Genetics and Molecular Biology, Allogeneic hematopoietic stem cell transplantation, medicine, Cancer research, Poor graft function, Stem cell, business, Boost
Published
2019

15. Fecal microbiota transplantation before or after allogeneic hematopoietic transplantation in patients with hematologic malignancies carrying multidrug-resistance bacteria

Author

Rubio, Marie-Thérèse, Battipaglia, Giorgia, Malard, Florent, Rubio, Marie Therèse, Ruggeri, Annalisa, Mamez, Anne Claire, Brissot, Eolia, Giannotti, Federica, Dulery, Remy, Joly, Anne Christine, Baylatry, Minh Tam, Kossmann, Marie Jeanne, Tankovic, Jacques, Beaugerie, Laurent, Sokol, Harry, Mohty, Mohamad, University of Naples Federico II, 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), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [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), Sorbonne Universités (COMUE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Pharmacie [CHU Saint Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Laboratoire des biomolécules (LBM UMR 7203), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL), This study was supported by educational grants from the 'Association for Training, Education and Research in Hematology, Immunology and Transplantation' (ATERHIT, Nantes, France)., Service d'Hématologie [CHRU Nancy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Université de Lorraine (UL), CHU Saint-Antoine [APHP], Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), PSL Research University (PSL), University of Naples Federico II = Università degli studi di Napoli Federico II, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Gestionnaire, Hal Sorbonne Université, Battipaglia, G., Malard, F., Rubio, M. T., Ruggeri, A., Mamez, A. C., Brissot, E., Giannotti, F., Dulery, R., Joly, A. C., Baylatry, M. T., Kossmann, M. J., Tankovic, J., Beaugerie, L., Sokol, H., and Mohty, M.

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Constipation, medicine.medical_treatment, Hematopoietic stem cell transplantation, Drug resistance, Gastroenterology, [SHS]Humanities and Social Sciences, Perioperative Care/methods, 0302 clinical medicine, fluids and secretions, Hematologic Neoplasms/complications/diagnosis/therapy, Retrospective Studie, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Resistance, Multiple, Bacterial, Transplantation, Homologou, ComputingMilieux_MISCELLANEOUS, allogeneic, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Enema, Fecal Microbiota Transplantation, Clostridium difficile, Middle Aged, 3. Good health, Diarrhea, Treatment Outcome, Hematologic Neoplasms, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, medicine.symptom, Human, Adult, medicine.medical_specialty, Article, Perioperative Care, 03 medical and health sciences, Internal medicine, medicine, Humans, Transplantation, Homologous, hematologic, Hematologic Neoplasm, hematopoietic, Feces, Aged, Retrospective Studies, business.industry, Fecal Microbiota Transplantation/methods, Dysbiosis/etiology/therapy, Dysbiosi, Transplantation, malignancies, Dysbiosis, business, Stem Cell Transplantation, 030215 immunology, transplantation
Abstract

International audience; Fecal microbiota transplantation is an effective treatment in recurrent Clostridium difficile infection. Promising results to eradicate multidrug-resistant bacteria have also been reported with this procedure, but there are safety concerns in immunocompromised patients. We report results in ten adult patients colonized with multidrug-resistant bacteria, undergoing fecal microbiota transplantation before (n=4) or after (n=6) allogeneic hematopoietic stem cell transplantation for hematologic malignancies. were obtained from healthy related or unrelated donors. Fecal material was delivered either by enema or via nasogastric tube. Patients were colonized or had infections from either carbapenemase-producing bacteria (n=8) or vancomycin-resistant enterococci (n=2). Median age at fecal microbiota transplantation was 48 (range, 16-64) years. Three patients needed a second transplant from the same donor due to initial failure of the procedure. With a median follow up of 13 (range, 4-40) months, decolonization was achieved in seven of ten patients. In all patients, fecal micro-biota transplantation was safe: one patient presented with constipation during the first five days after FMT and two patients had grade I diarrhea. One case of gut grade III acute graft-versus-host disease occurred after fecal microbiota transplantation. In patients carrying or infected by multidrug-resistant bacteria, fecal microbiota transplantation is an effective and safe decolonization strategy, even in those with hematologic malignancies undergoing hematopoietic stem cell transplantation.

Published
2019
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16. Defibrotide for Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease Prophylaxis in High-Risk Adult Patients: A Single-Center Experience Study

Author

Annalisa Ruggeri, Anne Vekhoff, Mor Seny Gueye, Ramdane Belhocine, Florent Malard, Clémence Médiavilla, Minh-Tam Baylatry, Adrien Picod, Rosa Adaeva, Françoise Isnard, Federica Giannotti, Anne-Christine Joly, Myriam Labopin, Ollivier Legrand, Remy Dulery, Eolia Brissot, Giorgia Battipaglia, Mohamad Mohty, Agnès Bonnin, Simona Lapusan, Picod, A., Bonnin, A., Battipaglia, G., Giannotti, F., Ruggeri, A., Brissot, E., Malard, F., Mediavilla, C., Belhocine, R., Vekhoff, A., Gueye, M. S., Lapusan, S., Adaeva, R., Isnard, F., Legrand, O., Baylatry, M. -T., Joly, A. -C., Labopin, M., Dulery, R., and Mohty, M.

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Thrombotic microangiopathy, Hepatic veno-occlusive disease, Adolescent, Defibrotide, medicine.medical_treatment, Hepatic Veno-Occlusive Disease, Hematopoietic stem cell transplantation, Endothelial cell activation syndrome, Single Center, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Polydeoxyribonucleotides, medicine, Humans, Cumulative incidence, Aged, Transplantation, business.industry, Sinusoidal obstruction syndrome, Incidence (epidemiology), Hematology, Middle Aged, medicine.disease, Polydeoxyribonucleotide, 030220 oncology & carcinogenesis, Female, Complication, business, 030215 immunology, medicine.drug, Human
Abstract

Sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a serious complication after hematopoietic stem cell transplantation (HSCT). SOS/VOD usually occurs within 3 weeks of HSCT, but the 2016 European Society for Blood and Marrow Transplantation diagnosis criteria have been revised to include late forms. Prophylactic use of defibrotide is recommended in the pediatric setting, but its value remains uncertain in the adult population. We report here a single-center series of 63 adult patients considered at high risk for SOS/VOD who received defibrotide prophylaxis in combination with ursodeoxycholic acid between May 2012 and August 2016. The median duration of defibrotide therapy was 23 days. Bleeding occurred in 14 patients (21.5%). Defibrotide prophylaxis was discontinued in 7 patients (10.8%): 4 cases (6.3%) due to bleeding and 3 cases (4.6%) because of the need for antithrombotic therapy. Overall, SOS/VOD occurred in 4 cases (6.3%) within 21 days after HSCT (days 13 and 14) in 2 cases and late-onset SOS/VOD (days 57 and 58) in the other 2 cases. SOS/VOD was moderate in 1 case, very severe in 3 cases, with 2 deaths related to SOS/VOD. Cumulative incidence of grades II to IV acute graft-versus-host disease and transplant-associated thrombotic microangiopathy were 22.2% and 3.2%, respectively. With a median follow-up of 31 months (range, 10.7 to 60.3), the rates of 2-year overall survival, progression-free survival, incidence of relapse, and nonrelapse mortality were 56.5%, 49%, 28.7%, and 22.3%, respectively. In our experience defibrotide prophylaxis is associated with a low incidence of SOS/VOD after allogeneic HSCT in a high-risk adult population with an acceptable safety profile.

Published
2018

17. Sinusoidal obstruction syndrome/veno-occlusive disease: current situation and perspectives—a position statement from the European Society for Blood and Marrow Transplantation (EBMT)

Author

Fabio Ciceri, Tapani Ruutu, Mairead NiChonghaile, Anne Huynh, Enric Carreras, Ibrahim Yakoub-Agha, P. G. Richardson, As. Alaskar, C Peters, M. Abecassis, B.N. Savani, M. Mohty, Selim Corbacioglu, Tamás Masszi, J.-H. Dalle, Mutlu Arat, Takahiro Fukuda, Peter Bader, Frédéric Baron, M Aljurf, Ali Bazarbachi, Florent Malard, Arnon Nagler, Fb. Petersen, Elisabeth Wallhult, Didier Blaise, R. F. Duarte, T. Pagluica, Erik Aerts, Mauricette Michallet, Mohty, M, Malard, F, Abecassis, M, Aerts, E, Alaskar, A, Aljurf, M, Arat, M, Bader, P, Baron, F, Bazarbachi, A, Blaise, D, Ciceri, Fabio, Corbacioglu, S, Dalle, Jh, Duarte, Rf, Fukuda, T, Huynh, A, Masszi, T, Michallet, M, Nagler, A, Nichonghaile, M, Pagluica, T, Peters, C, Petersen, Fb, Richardson, Pg, Ruutu, T, Savani, Bn, Wallhult, E, Yakoub Agha, I, and Carreras, E.

Subjects
Position statement, Adult, medicine.medical_specialty, medicine.medical_treatment, genetic processes, Hematopoietic stem cell transplantation, Disease, Defibrotide, Postoperative Complications, Risk Factors, medicine, Humans, Vascular Diseases, Prospective cohort study, Intensive care medicine, Special Report, Transplantation, Marrow transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, biochemical phenomena, metabolism, and nutrition, enzymes and coenzymes (carbohydrates), surgical procedures, operative, bacteria, Veno-Occlusive Disease, Complication, business, Biomarkers, medicine.drug
Abstract

Sinusoidal obstruction syndrome or veno-occlusive disease (SOS/VOD) is a potentially life-threatening complication of hematopoietic SCT (HSCT). This review aims to highlight, on behalf of the European Society for Blood and Marrow Transplantation, the current knowledge on SOS/VOD pathophysiology, risk factors, diagnosis and treatments. Our perspectives on SOS/VOD are (i) to accurately identify its risk factors; (ii) to define new criteria for its diagnosis; (iii) to search for SOS/VOD biomarkers and (iv) to propose prospective studies evaluating SOS/ VOD prevention and treatment in adults and children.

Published
2015

18. Safety and feasibility of romiplostim treatment for patients with persistent thrombocytopenia after allogeneic stem cell transplantation

Author

Federica Giannotti, M. Labopin, M.-T. Rubio, Giorgia Battipaglia, Annalisa Ruggeri, Florent Malard, Ramdane Belhocine, Anne Vekhoff, Eolia Brissot, M. Mohty, Tounes Ledraa, Anne-Claire Mamez, Battipaglia, G., Ruggeri, A., Brissot, E., Mamez, A. -C., Malard, F., Belhocine, R., Vekhoff, A., Giannotti, F., Ledraa, T., Labopin, M., Rubio, M. -T., and Mohty, M.

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Recombinant Fusion Proteins, Hematopoietic stem cell transplantation, Receptors, Fc, Allograft, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Thrombopoietin, Aged, Transplantation, Romiplostim, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Allografts, Thrombocytopenia, surgical procedures, operative, Immunology, Female, Stem cell, business, medicine.drug, Human, Recombinant Fusion Protein
Abstract

Safety and feasibility of romiplostim treatment for patients with persistent thrombocytopenia after allogeneic stem cell transplantation

Published
2015

19. Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients

Author

A.-C. Mamez, Françoise Isnard, T. Ledraa, Alejandro Palomar Gómez, Ollivier Legrand, M.-T. Rubio, Ramdane Belhocine, Annalisa Ruggeri, Mohamad Mohty, M. Labopin, J. Gozlan, Giorgia Battipaglia, Gabrielle Roth-Guepin, D. Boutolleau, Anne Vekhoff, Eolia Brissot, Florent Malard, Simona Lapusan, Ruggeri, A., Roth-Guepin, G., Battipaglia, G., Mamez, A. -C., Malard, F., Gomez, A., Brissot, E., Belhocine, R., Vekhoff, A., Lapusan, S., Isnard, F., Legrand, O., Gozlan, J., Boutolleau, D., Ledraa, T., Labopin, M., Rubio, M. -T., and Mohty, M.

Subjects
Adult, medicine.medical_specialty, Cyclophosphamide, Adolescent, Cystiti, Graft vs Host Disease, Hemorrhage, medicine.disease_cause, Gastroenterology, Immunosuppressive Agent, Young Adult, Immune system, Risk Factors, Internal medicine, Cystitis, Haplotype, Medicine, Humans, Cumulative incidence, Hemorrhagic cystiti, Aged, Transplantation, business.industry, Incidence (epidemiology), Risk Factor, Incidence, BK viru, Hematopoietic Stem Cell Transplantation, Middle Aged, medicine.disease, BK virus, Surgery, surgical procedures, operative, Infectious Diseases, Haplotypes, business, Complication, Post-transplant cyclophosphamide, Immunosuppressive Agents, Hemorrhagic cystitis, medicine.drug, Unmanipulated haploidentical transplant, Human
Abstract

Background Hemorrhagic cystitis (HC) is a common complication after hematopoietic allogeneic stem cell transplantation (HSCT) associated with intensity of the conditioning regimen, cyclophosphamide (Cy) therapy, and BK polyomavirus (BKPyV) infection. Methods We analyzed 33 consecutive haploidentical (haplo) HSCT recipients transplanted for hematologic diseases. Eleven patients had a previous transplant. Median follow-up was 11 months. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine + mycophenolate mofetil and post-HSCT Cy. Results Thirty-two of 33 patients achieved neutrophil recovery. Cumulative incidence (CI) of platelet recovery was 65%. CI grade II–IV acute GVHD was 44%. Twenty patients developed HC in a median time of 38 days. CI of HC at day 180 was 62%. BKPyV was positive in blood and urine of 91% of patients at HC onset. HC resolved in 18/20 patients. Factors associated with HC were previous transplant (P = 0.01) and occurrence of cytomegalovirus reactivation before HC (P = 0.05). Grade II–IV acute GVHD was not associated with HC (P = 0.62). CI of day 180 viral infections was 73%. Two-year overall survival (OS) was 50%; HC did not impact OS (P = 0.29). Conclusion The incidence of HC after haplo with post-HSCT Cy is high and is associated with morbidity, especially in high-risk patients such as those with a previous transplant history and with impaired immune reconstitution.

Published
2015

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