Background: Toxoplasmosis is a rare but highly lethal opportunistic infection after allogeneic haematopoietic cell transplantation (HCT). Successful management depends on screening, early recognition and effective treatment. Objectives: To review the current epidemiology and approaches to diagnosis, prevention and treatment of toxoplasmosis in adult and paediatric allogeneic HCT recipients. Source: Search of the English literature published in MEDLINE up to 30 June 2020 using combinations of broad search terms including toxoplasmosis, transplantation, diagnosis, epidemiology, prevention and treatment. Selection of articles for review and synthesis on the basis of perceived quality and relevance of content. Content: Toxoplasmosis continues to be a major challenge in the management of allogeneic HCT recipients. Here we provide a summary of published case series of toxoplasmosis in adult and paediatric patients post allogeneic HCT. We review and discuss the pathogenesis, epidemiology, clinical presentation, diagnosis and current recommendations for prevention and treatment. We also discuss impacts of toxoplasmosis in this setting and factors affecting outcome, emphasizing attention to neurological, neuropsychological and neurocognitive late effects in survivors. Implications: Apart from careful adherence to established strategies of disease prevention through avoidance of primary infection, identification of seropositive patients and implementation of molecular monitoring, future perspectives to improve the control of toxoplasmosis in allogeneic HCT recipients may include the systematic investigation of pre-emptive treatment, development of immunomodulatory approaches, antimicrobial agents with activity against the cyst form and vaccines to prevent chronic infection.

Summary The low‐density lipoprotein receptor (LDLR) is a membrane receptor that mediates the endocytosis of low‐density lipoprotein (LDL). Uptake of LDL has been proposed to contribute to chemotherapy resistance of acute myeloid leukaemia (AML) cell lines in vitro. In the present study, we analysed LDLR expression and survival using bone marrow biopsies from 187 intensively treated patients with AML. Here, increasing LDLR expression was associated with decreasing overall (58·4%, 44·2%, and 24·4%; P = 0·0018), as well as event‐free survival (41·7%, 18·1%, and 14·3%; P = 0·0077), and an increasing cumulative incidence of relapse (33·9%, 55·1%, and 71·4%; P = 0·0011). Associations of LDLR expression with survival were confirmed in 557 intensively treated patients from two international validation cohorts. In the analytic and validation cohorts, LDLR expression remained associated with outcome in multivariable regression analyses including the European LeukemiaNet genetic risk classification. Thus, LDLR predicts outcome of patients with AML beyond existing risk factors. Furthermore, we found low expression levels of LDLR in most healthy tissues, suggesting it as a promising target for antibody‐based pharmacodelivery approaches in AML.

No abstract

No abstract