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.

Toxoplasma gondii: How fatal is it in pediatric allogeneic bone marrow transplantation setting?

“…The risk of reactivation is very high during the first months after transplantation, and the risk is even higher if there is a delayed immune reconstitution or GVHD requiring further immunosuppression. Donor seropositive/recipient seronegative (D+/R‐) appear to be at a lower risk than donor seronegative/recipient seropositive (D‐/R+) for toxoplasmosis infection . Our cases confirm the above assumption.…”

“…Unfortunately, diagnosis and treatment are often delayed because of atypical clinical and laboratory findings of toxoplasmosis. It should be highlighted that a negative PCR result cannot rule out the diagnosis of toxoplasma infection and cases of the disease have been reported with negative PCR in the blood …”

“…Pre‐emptive strategy based on the detection of asymptomatic toxoplasma infection may have an impact on disease's nonoccurrence, although in some cases, pre‐emptive therapy does not prevent the development of the disease; however, the interpretation of a positive PCR for toxoplasma in an asymptomatic patient is not very well defined .…”

Identification of disseminated toxoplasmosis by plasma next‐generation sequencing in a teenager with rapidly progressive multiorgan failure following haploidentical stem cell transplantation

“…Toxoplasmosis can cause severe disease in immunocompromised hosts and especially in bone marrow transplant recipients . We describe a case of an 18‐year‐old male after haploidentical alpha/beta T‐cell‐ and B‐cell‐depleted peripheral blood stem cell transplant diagnosed with disseminated toxoplasmosis using plasma next‐generation sequencing (NGS).…”

Reactivation of Multiple Infectious Pathogens after Hematopoietic Stem Cell Transplantation

“…In HSCT, toxoplasma is a devastating complication with attributable mortality up to 43.5% [4]. As many as 87% of the HSCT recipients are seropositive prior to transplant, antibiotics prophylaxis is not always provided against toxoplasmosis after transplant.…”