title: A matched case-control study of toxoplasmosis after allogeneic haematopoietic stem cell transplantation: still a devastating complication.
abstract: Toxoplasmosis (TXP) is a life-threatening complication of allogeneic haematopoietic stem cell transplantation (AHSCT). Little is known about the risk factors and there is no consensus on prophylactic measures. To investigate the risk factors, we conducted a single-centre, retrospective matched case-control study among adults who underwent AHSCT from January 2006 to March 2015 in our hospital. TXP cases were identified from the prospectively maintained hospital's database. The 1:2 control population consisted of the two patients who received an AHSCT immediately before and after each case with similar donor relationship (related, unrelated) but who did not develop TXP. Risk factors were identified by conditional logistic regression. Clinical features and outcome of TXP were examined. Twenty-three (3.9%) cases of TXP (20 diseases, three infections) were identified among 588 AHSCT recipients. Twenty (87%) cases had a positive pre-transplant Toxoplasma gondii serology. In comparison with 46 matched control patients, risk factors were the absence of effective anti-Toxoplasma prophylaxis (odds ratio (OR) 11.95; 95% CI 3.04-46.88; p <0.001), high-grade (III-IV) acute graft-versus-host-disease (OR 3.1; 95% CI 1.04-9.23; p 0.042) and receipt of the tumour necrosis factor-α blocker etanercept (OR 12.02; 95% CI 1.33-108.6; p 0.027). Mortality attributable to TXP was 43.5% (n = 10). Non-relapse mortality rates during the study period of cases and controls were 69.6% (n = 16) and 17.4% (n = 8), respectively. Lung involvement was the dominant clinical feature (n = 14). Two cases were associated with graft failure, one preceded by haemophagocytic syndrome. Given TXP-related morbidity and attributable mortality, anti-Toxoplasma prophylaxis is essential for optimized management of seropositive AHSCT recipients.
authors.affiliation: Département de Maladies Infectieuses et Tropicales, Hospices Civils de Lyon, France; Inserm U1111 Centre International de Recherche en Infectiologie (CIRI), Lyon, France; Université Claude Bernard Lyon I, Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Conrad
authors.affiliation: Université de Lorraine et Paris Descartes, EA 4360 APEMAC, Nancy, France.
authors.forename: M
authors.initials: M
authors.lastname: Le Maréchal
authors.affiliation: Université Claude Bernard Lyon I, Lyon, France; Institut de Parasitologie et de Mycologie Médicale, Hospices Civils de Lyon, Lyon, France; WAKING-Physiologie intégrée du système d'éveil, Centre de Recherche en Neurosciences de Lyon Inserm U1028, CNRS UMR5292, Lyon, France.
authors.forename: D
authors.initials: D
authors.lastname: Dupont
authors.affiliation: Département d'Hématologie, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: S
authors.initials: S
authors.lastname: Ducastelle-Leprêtre
authors.affiliation: Département d'Hématologie, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: M
authors.initials: M
authors.lastname: Balsat
authors.affiliation: Département d'Hématologie, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: H
authors.initials: H
authors.lastname: Labussière-Wallet
authors.affiliation: Département d'Hématologie, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: F
authors.initials: F
authors.lastname: Barraco
authors.affiliation: Département d'Hématologie, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: F-E
authors.initials: FE
authors.lastname: Nicolini
authors.affiliation: Département d'Hématologie, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: X
authors.initials: X
authors.lastname: Thomas
authors.affiliation: Département d'Hématologie, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: L
authors.initials: L
authors.lastname: Gilis
authors.affiliation: Département de Maladies Infectieuses et Tropicales, Hospices Civils de Lyon, France; Université Claude Bernard Lyon I, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Chidiac
authors.affiliation: Département de Maladies Infectieuses et Tropicales, Hospices Civils de Lyon, France; Inserm U1111 Centre International de Recherche en Infectiologie (CIRI), Lyon, France; Université Claude Bernard Lyon I, Lyon, France.
authors.forename: T
authors.initials: T
authors.lastname: Ferry
authors.affiliation: Département d'Anesthésie et de Réanimation du Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, France.
authors.forename: F
authors.initials: F
authors.lastname: Wallet
authors.affiliation: Université Claude Bernard Lyon I, Lyon, France; Institut de Parasitologie et de Mycologie Médicale, Hospices Civils de Lyon, Lyon, France; Emerging Pathogens Laboratory-Fondation Mérieux, CIRI Inserm U1111, CNRS UMR5308, ENS de Lyon, Lyon, France.
authors.forename: M
authors.initials: M
authors.lastname: Rabodonirina
authors.affiliation: Université Claude Bernard Lyon I, Lyon, France; Département d'Hématologie, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: G
authors.initials: G
authors.lastname: Salles
authors.affiliation: Université Claude Bernard Lyon I, Lyon, France; Département d'Hématologie, Hospices Civils de Lyon, Pierre-Bénite, France.
authors.forename: M
authors.initials: M
authors.lastname: Michallet
authors.affiliation: Département de Maladies Infectieuses et Tropicales, Hospices Civils de Lyon, France; Inserm U1111 Centre International de Recherche en Infectiologie (CIRI), Lyon, France; Université Claude Bernard Lyon I, Lyon, France. Electronic address: florence.ader@chu-lyon.fr.
authors.forename: F
authors.initials: F
authors.lastname: Ader
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016019:Survival Analysis; D014122:Toxoplasma / Q000302:isolation & purification; D014123:Toxoplasmosis / Q000453:epidemiology* / Q000473:pathology; D014184:Transplantation, Homologous / Q000009:adverse effects*; D016896:Treatment Outcome
keywords: Allogeneic haematopoietic stem cell transplantation; Anti-Toxoplasma prophylaxis; Graft failure; Haemophagocytic syndrome; Toxoplasma gondii; Toxoplasmosis; Trimethoprim-sulfamethoxazole