Evaluation of Infectious Complications after Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide Following Reduced-Intensity and Myeloablative Conditioning: A Study on Behalf of the Francophone Society of Stem Cell

Amandine Fayard 1, Fabien Tinquaut 2, Didier Blaise 3, Patrice Chevallier 4, Mauricette Michallet 5, Ana Berceanu 6, Ibrahim Yakoub-Agha 7, Gérard Socié 8, Amandine Charbonnier 9, Felipe Suarez 10, Anne Huynh 11, Mélanie Mercier 12, Claude-Eric Bulabois 13, Bruno Lioure 14, Sylvain Chantepie 15, Yves Beguin 16, Jean Henri Bourhis 17, Jean Valere Malfuson 18, Laurence Clément 19 and Jerome Cornillon 20

Author address: 

1Hematolgy Department, Institut de Cancérologie Lucien Neuwirth, Saint-Etienne, France 2Centre Hygée, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France 3Programme de Transplantation &Therapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France 4Department of Hematology, Nantes University Hospital, Nantes, France 5Department of Hematology, Centre Hospitalier Lyon-Sud, Lyon, France 6Hematology, Besançon University Hospital, Besançon, France 7Service des Maladies du Sang, Hopital Claude Huriez, CHRU Lille, Lille, France 8Hematology / Transplantation, Saint Louis Hospital, Paris, France 9Department of Hematology, University Hospital, Amiens, France 10Hôpital Universitaire Necker-Enfants Malades, Paris, France 11Institut Universitaire du Cancer, Oncopole IUCT, Toulouse, France 12Hematology Department, CHU, Angers, France 13Hematology, CHU Grenoble, Grenoble, France 14Hematology and Oncology, Hopital Hautepierre, Strasbourg, France 15Institut d'Hématologie, Caen University Hospital, Caen, France 16Hematology, University and CHU of Liege, Liege, Belgium 17Gustave Roussy Cancer Center, Villejuif, France 18Hôpital d'instruction des armées Percy, Paris Cedex 10, FRA 19Department of Hematology, Bodreaux University Hospital, Bordeaux, France 20Hematology department, Institut de Cancerologie Lucien Neuwirth, Saint-Priest-en-Jarez, France

Abstract: 

Introduction: Hematopoietic stem cell transplantation (HSCT) is a major treatment for many hematological disorders. However, this treatment comes with significant risks linked to toxicity and infectious complications which may lead to death. Recently haploidentical transplants without ex vivo T-depletion have been developed through the use of post-transplant cyclophosphamide, thus reducing the risk of lethal GVHD. Toxicity data are still limited and few studies have evaluated infectious complications following haploidentical transplants without ex vivo T-cell depletion. In this study, we evaluated the incidence of infectious complications in patients who received haploidentical HSCT with post-transplant cyclophosphamide.

Patients and methods: Data from 21 French centers and one Belgian center were retrospectively collected. Between January 2013 and December 2014, 159 patients all older than 18 years, affected with hematological malignancy and having undergone a haploidentical HSCT were included. Informed consent was obtained in accordance with the Declaration of Helsinki. Clinical data were obtained through ProMISe (Project Manager Internet Server), the internet-based system shared by all Francophone transplantation centers. Results: In total, 159 patients were included (Table 1). The median age at transplantation was 51.2 years (20-72 years). All patients were treated with post-transplant cyclophosphamide combined with an anticalcineurin and mycophenolate mofetil as GVHD prophylaxis. The median follow-up of the cohort was 14 months. Meanwhile, 49 patients (13%) developed acute GVHD (grade 2-4). Forty-three patients (27%) developed chronic GVHD. Median overall survival wasn't reached and the median progression-free survival was 571 days. At the end of the study, 69 patients had died, 29 were in relapse and 36 presented treatment related toxicity. TRM was of 14% and 22% at day 100 and 365 respectively. At least one infectious complication occurred in 135 patients. These were mostly clinically or microbiologically documented. Median time from transplant to the first occurrence of infectious complication was 12 days. Twenty five percent of patients presented between 3 and 5 infectious complications. The average number of infectious complications per patient was 2.9 (0-12). Sixty-two percent of early infectious complications occurred throughout conditioning or within 20 days post- transplant. Fifty-two percent of those infections were bacterial, 33% viral (39% of which related to CMV and 28% to BK virus), and 4.5% were parasitic or fungal (50% of which related to aspergillosis). Overall 436 infectious episodes were reported: bloodstream infections (62%) (bacteremia, viremia, fungemia or parasitaemia), respiratory (10%), urinary tract (8%), digestive tract (6%), skin (3%), septic shock and multi organ failure (6%), others (5%). Among those complications, 46% were bacteria related, 36% were virus related (17% of which due to BK virus and 39% to CMV), 7% were parasitic or fungal related (in these cases, 61% aspergillosis related). In total, 26 cases (6%) of BK virus infections were observed. Conclusion: In conclusion, in these preliminary results, except for maybe in the case of BK infections, incidence of infectious disease after haploidentical HSCT seem not to differ to related or unrelated HSCT. Further prospective studies are necessary to confirm these results, especially by evaluating infectious viremia with BK virus after HSCT haploidentical with post-transplant cyclophosphamide following reduced-intensity and myeloablative conditioning for this patient population. Table 1: Patient disease and treatment characteristics

2016

Poster: 

AttachmentSize
Image icon Figure 149.3 KB

abstract No: 

5758

Full conference title: 

58th American Society of Hematology Meeting
    • ASH 58th (2016)