Neurological complications of hematopoietic cell transplantation in children and adults

Abstract

Hematopoietic cell transplantation (HCT) is widely performed for neoplastic and non-neoplastic diseases. HCT involves intravenous infusion of hematopoietic progenitor cells from human leukocyte antigen (HLA)-matched donor (allogeneic) or from the patient (autologous). Before HCT, the patient is prepared with high dose chemotherapy and/or radiotherapy to destroy residual malignant cells and to reduce immunologic resistance. After HCT, chemotherapy is used to prevent graft rejection and graft versus host disease (GvHD). Neurological complications are related to the type of HCT, underlying disease, toxicity of the conditioning regimens, immunosuppression caused by conditioning regimens, vascular complications generated by thrombocytopenia and/or coagulopathy, GvHD and inappropriate immune response. In this review, neurological complications are presented according to time of onset after HCT: (1) early complications (in the first month) - related to harvesting of stem cells, during conditioning (drug toxicity, posterior reversible encephalopathy syndrome), related to pancytopenia, (2) intermediate phase complications (second to sixth month) - central nervous system infections caused by prolonged neutropenia and progressive multifocal leukoencephalopathy due to JC virus, (3) late phase complications (after sixth month) - neurological complications of GvHD, second neoplasms and relapses of the original disease.

Keywords: central nervous system infections; drug reaction with eosinophilia and systemic symptoms; graft versus host disease; hematopoietic cell transplantation; immune reconstitution inflammatory syndrome; neurological complications; post-transplant acute limbic encephalitis; posterior reversible encephalopathy syndrome; progressive multifocal leukoencephalopathy; second neoplasm.

Figure 1

Brain MRI of a 32-year-old female with Hodgkin lymphoma treated with allogeneic hematopoietic cell transplantation on March 23, 2018. Posterior reversible encephalopathy syndrome (PRES) typical magnetic resonance imaging (MRI) aspect (black arrows)- symmetrical areas of T2 and Flair hyperintensity in both parieto-occipital lobes. Multiple supratentorial hemosiderotic spots (white arrow).

Figure 2

Brain CT-scan of a 32-year-old female with Hodgkin lymphoma treated with allogeneic hematopoietic cell transplantation on March 23, 2018. Parieto-occipital bilateral hypodensities (black arrows). Small hemorrhagic left parietal and right frontal SAH accumulations (white arrow).

Figure 3

Brain MRI of a 30-year-old male with acute myeloid leukemia who received allogeneic hematopoietic cell transplantation on December 19, 2017. Right frontal cortical parasagital lesion with “acute” pattern (restriction of water on diffusion weighted imaging (DWI))- (white arrow) and leptomeningeal enhancement (black arrows).

Figure 4

Brain MRI of a 12-year-old male with acute lymphoblastic leukemia treated with allogeneic hematopoietic cell transplantation. Cerebral abscesses located into parieto-occipital regions: typical magnetic resonance imaging (MRI) aspects-ring-enhancing lesions, with high signal intensity on T2-weighted images and low signal intensity on T1-weighted images.

Figure 5

Brain MRI of a male treated with allogeneic hematopoietic cell transplantation in 2010. Right orbital cellulitis: magnetic resonance imaging (MRI) and CT aspects: oedema and inflammation of the periorbital and orbital contents (white arrow); right invasive maxillo-ethmoido-frontal sinusitis (head arrows)