Central nervous system disorders after hematopoietic stem cell transplantation: a prospective study of the Infectious Diseases Working Party of EBMT

• DOI: 10.1007/s00415-019-09578-5
• Publication Date: 2019-10-30T20:53:50Z
• Authors: Martin Schmidt-Hi...; Dan Engelhard; Andrew Ullmann; Per Ljungman; Johan Maertens; Rodrigo Martino; Montserrat Rovira; Peter J. Shaw; Christine Robin; Maura Faraci; Jenny Byrne; Kerstin Schäfer-E...; Hermann Einsele; Edgar Faber; Luigi Rigacci; Riccardo Saccardi; Aitana Balaguer-R...; Cecilia Isaksson; Maximilian Christ...; Gloria Tridello; Junfeng Wang; Nina Knelange; Malgorzata Mikulska; Simone Cesaro; Jan Styczynski
• Keywords: Adult; Male; Adolescent; ENCEPHALITIS; ISAVUCONAZOLE; Hematopoietic Stem Cell Transplantation; Infant; Middle Aged; DIAGNOSIS; 3. Good health; Cerebrovascular Disorders; Young Adult; 03 medical and health sciences; Central Nervous System Infections; 0302 clinical medicine; Adolescent; Adult; Aged; Central Nervous System Infections; Cerebrovascular Disorders; Child; Child, Preschool; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Middle Aged; Prospective Studies; Young Adult; FUNGAL-INFECTIONS; Child, Preschool; NEUROLOGIC COMPLICATIONS; Humans; Female; MARROW-TRANSPLANTATION; Prospective Studies; Child; Aged

We performed a prospective study to evaluate the types and characteristics of central nervous system (CNS) disorders in patients after hematopoietic stem cell transplantation. The study included 163 episodes of CNS disorders of which 58 (36%) were infections. Proven or probable infections were documented in 34 patients and included fungi (n = 10, 29%), viruses (n = 12, 35%), Toxoplasma spp. (n = 9, 27%) and bacteria (n = 3, 9%). Non-infectious neurological disorders (n = 105, 64%) frequently encompassed metabolic/drug-induced abnormalities (n = 28, 27%) or cerebral vascular events (n = 22, 21%). Median onset times were later for infectious (day + 101) vs non-infectious neurological disorders (day + 50, p = 0.009). An unremarkable cranial CT scan was found in 33% of infection episodes. Absence of cerebrospinal fluid pleocytosis despite a normal or increased peripheral blood white blood cell count occurred in 26% of infections. Day-30 mortality rates were significantly higher for fungal (87%) vs non-fungal infections (40%, p < 0.001). Significantly higher mortality rates were also documented for cerebral vascular events than for other non-infectious disorders (86% vs 34%, p < 0.001). Our prospective study shows that diagnostic findings in CNS infections might differ between hematopoietic stem cell transplant recipients and immunocompetent hosts. Special awareness and timely initiation of adequate diagnostics are crucial to improve the prognosis of these patients.