Table 1.
Detailed information of the cases.
| Time of report | Age | Sex | Initial disease | GvHD history | Clinical characteristics, imaging, and biological abnormalities | Histology | Immunosuppressive therapy | Outcome |
|---|---|---|---|---|---|---|---|---|
| 1990 (7) |
32 | m | CML | Chronic GvHD | Clinic: dysphagia, dysarthria; CSF: normal | Perivascular infiltrates of CNS | NA | Deceased |
| 1993 (8) |
9 | f | Posthepatitis aplastic anemia | Chronic GvHD | Onset: 8 mo after HSCT; Clinic: seizure, spasticity, disturbance of consciousness; CSF: pleocytosis, elevated protein; MRI: cortical atrophy, ventricular dilatation | Diffuse infiltration of white matter with CD3 lymphocytes, Inflammatory cell perivascular infiltration, Focal CD68+ microglia proliferation (HLA-DR+) | NA | Deceased 13 mo after neurological symptoms of liver and kidney failure |
| 1993 (8) |
13 | m | ALL | Chronic GvHD | Onset: 100 d after HSCT; Clinic: cognitive deficits; MRI: white matter lesions in cerebellum | Diffuse CD3 lymphocytes infiltration and gliosis, inflammatory cells were mostly confined to perivascular spaces | NA | Deceased 5 mo after neurological symptoms of interstitial pneumonia |
| 1996 (9) |
14 | f | Lymphoblastic lymphoma B | Acute GvHD | Onset: 71 d after HSCT; Clinic: disorientation and myoclonus; CSF: elevated protein (0.9 g/L), elevated CSF Ig; MRI: multiple foci of hyperintense signal on T2-weighted images within the brain stem and deep white matter; EEG: diffuse slowing | No | MP 1g/d | Clinical and MRI PR Deceased 123 d after neurological symptoms of severe sepsis |
| 1999 (10) |
43 | m | CML | Acute and chronic GvHD | Onset: 18 mo after HSCT Clinic: acute vertigo, hemiparesis, aphasia, cortical blindness; MRI: multiple hematoma; CSF: elevated protein Angiography: normal | T cells, B cells, and monohistiocytes vessel wall and perivascular infiltration, sporadic demyelination and micro glia reaction | Corticosteroids (1.5mg/kg) and cyclophosphamide (bolus) | CR Deceased 5 mo after neurological symptoms of pneumonia |
| 1999 (10) |
32 | f | AML | Acute and chronic GvHD | Onset: 28 mo after HSCT; Clinic: aphasia, hemiparesis and seizure; MRI: ischemic areas, white matter lesion; CSF: normal | No | Corticosteroids (1.5mg/kg) and cyclophosphamide (bolus) | Progression with cerebral infarctions Deceased of tentorial herniation |
| 1999 (10) |
19 | m | ALL | Chronic GvHD | Onset: 31 mo after HSCT; Clinic: sub-acute confusion, spastic right hemiparesis Perfusion; MRI: leukoencephalopathy; CSF: normal; Angiography: normal | No | Corticosteroids (1.5mg/kg) | CR |
| 1999 (10) |
32 | m | CLL | Acute and chronic GvHD | Onset: 5 y after HSCT; Clinic: aphasia, apraxia, dementia, tetra paresis; MRI: leukoencephalopathy, hemorrhage; CSF: normal Perfusion; Angiography: normal | No | Corticosteroids (1.5mg/kg) and cyclophosphamide (bolus) | Clinical and MRI stability |
| 1999 (10) |
53 | m | CLL | Acute and chronic GvHD | Onset: 30 mo after HSCT; Clinic: acute aphasia and cognitive deficit; MRI: periventricular white matter lesion, frontoparietal ischemia; CSF: pleocytosis; Angiography: MCA branch occlusion | No | NA | Progression |
| 2000 (11) |
22 | f | ALL | Acute GvHD | Onset: 9 mo after HSCT; Clinic: hemiparesis MRI: white matter lesions in frontal lobe Angiography: multiple stenosis and occlusions in the peripheral branches of the anterior and middle cerebral arteries | No | Corticosteroids | Transient improvement |
| 2001 (12) |
25 | m | T-cells lymphoma | Chronic GvHD | Onset: 380 d after HSCT Clinic: cerebellar and pyramidal syndromes and peripheral neuropathy CSF: oligoclonal bands, pleocytosis MRI: multiple | No | MP 1g/d and plasmapheresis | Clinical PR and MRI stability |
| demyelinating-like, asymmetric, hyperintense areas on T2-weighted images at the brainstem, cerebellar and corona radiata white matter. | ||||||||
| 2002 (13) |
18 | f | AML | Acute GvHD | Onset: 2 mo after HSCT Clinic: seizure, spastic, cognitive dysfunction MRI: diffuse atrophy EEG: bilateral slowing and voltage suppression over the left hemisphere CSF: elevated protein and pleocytosis | Cerebral and meningeal angiitis, granulomatous infiltration, lymphocytic infiltration with microglial proliferation | Corticosteroids | PR |
| 2003 (14) |
51 | f | AML | Acute and chronic GvHD | Onset: 10 mo after HSCT Clinic: diplopia, dysarthria, and gait disturbance MRI: multifocal abnormal high signal intensity mainly in the white matter of both cerebral hemispheres as well as in the cerebellum and brainstem CSF: normal | No | NA | Clinical CR and MR PR Alive 15 mo after |
| 2005 (15) |
55 | f | NHL | Chronic GvHD | Onset: 23 mo after HSCT Clinic: acute cerebellar syndrome CT: acute intra_x005f parenchymal hemorrhage in left cerebellum MRI: white matter lesions peri-ventricular Angiography: aneurysm of the left posterior inferior cerebellar artery and dilated branches of cerebral arteries | No | Tacrolimus | PR |
| 2006 (16) |
48 | m | NHL | Acute GvHD | Onset: 14 mo after HSCT Clinic: headaches, personality change, cognitive dysfunction MRI: diffuse deep white matter changes with periventricular predominance CSF: pleocytosis, elevated protein EEG: slow wave activity consistent with a diffuse encephalopathy | No | MP 2 mg/kg | CR |
| 2007 (17) |
58 | f | ALL | Acute and chronic GvHD | Onset: 178 d after HSCT Clinic: encephalopathy and seizure CSF: elevated protein (0.67 g/L) MRI: patchy areas of white matter lesions | Leptomeningeal perivascular infiltration of CD3+/CD8+ T cells | Corticosteroids | Transient improvement Deceased 123 d after neurological symptoms of multiorgan failure |
| 2007 (17) |
45 | f | T-cells lymphoma | Acute and chronic GvHD | Onset: 18 mo after HSCT; Clinic: right hemiparesis and seizure; CSF: normal; MRI: white matter lesions in fronto-parietal lobe | Perivascular inflammation mainly composed of CD3+/CD4+ T cells of the donor (FISH XY) | MP 1g/d(5d) | Clinical then MRI CR Alive 8y after HSCT |
| 2007 (18) |
41 | m | Follicular lymphoma | Chronic GvHD | Onset: 3 year after; HSCT Clinic: progressive left hemiparesis; CSF: normal; MRI: large mass of right parietal lobe | Focal infiltration of lympho_x005f histiocytic inflammatory cell and noncaseating granuloma with perivascular predominance IHC: CD3+ T cells | Corticosteroids and ciclosporin | Clinical and MRI PR |
| 2009 (19) |
56 | m | NHL | Chronic GvHD | Clinic: dizziness, tinnitus, vertigo, proximal weakness; MRI: large lesion of the corpus callosum | Perivascular inflammation and scattered CD3+/CD8+ T cells associated with microglia activation and macrophages in brain parenchyma | Corticosteroids and MMF | Progression Deceased 2 mo later |
| 2009 (20) |
32 | f | MDS | Chronic GvHD | Onset: 7 mo after HSCT; Clinic: bilateral papillar edema with almost blindness, weakness of lower limbs, urinary retention; CSF: normal; MRI: multiple white matter lesions mainly in internal capsule, thalamus and thorax spine, evocative of multiple sclerosis | No | Corticosteroids (bolus then 0.5 mg/kg) and ciclosporin | Clinical and MRI PR Alive 2y after HSCT |
| 2009 (21) |
40 | f | Follicular lymphoma | Acute GvHD | Onset: 10 d after HSCT; Clinic: encephalitis and seizure; CSF: elevated protein (6.75 g/L), pleocytosis (96.8% of donor cells); MRI: normal | No | Corticosteroids (3 bolus) followed by etoposide (50 mg/m2) because of HLH evidence | Progression Deceased 32 d after HSCT |
| 2010 (22) |
35 | m | CML | Acute and chronic GvHD | Onset: 4 y after HSCT; Clinic: seizure; MRI: cortical/sub cortical acute ischemic lesions in peri-insular region, left frontal and parietal lobe; EEG: temporal slowing without epileptic discharges | Micro-angiopathy | Corticosteroids (3 bolus then 1mg/kg) and cyclophosphamide (bolus) Then methotrexate (10mg/week) | CR |
| 2010 (22) |
28 | f | AML | Acute and chronic GvHD | Onset: 2 y after HSCT; Clinic: progressive depression, cognitive deficits, cortical blindness, seizure, ataxia, tetraparesis; CSF: elevated protein, oligo-clonal bands; MRI: leukoencephalopathy then internal brain atrophy; EEG: generalized slowing and epileptic discharges | Perivascular infiltration of donor CD3+ CD8+ lympho-monuclear cells (FISH XY), loss of myelin and axon preservation | Corticosteroids (5 bolus then 1mg/kg) and cyclophosphamide (1 bolus then 100mg/j) | CR |
| 2010 (22) |
20 | m | SCID | Chronic GvHD | Onset: 20 y after HSCT; Clinic: hemiparesis, ataxia, cortical blindness and deafness; CSF: elevated protein, pleocytosis; MRI: multiple focal ischemic lesions and hemorrhage | Perivascular infiltration of CD3+ CD8+ lympho-monuclear cells, loss of myelin and axon preservation | Corticosteroids and cyclophosphamide (4 bolus) | PR Deceased 1 y after neurological symptoms of severe sepsis |
| 2010 (22) |
33 | m | CLL | Acute and chronic GvHD | Onset: 2 y after HSCT; Clinic: ataxia, cortical blindness, spastic tetraparesis, acute pseudo-bulbar syndrome; CSF: elevated protein, pleocytosis, intrathecal IgG synthesis; MRI: frontally accentuated brain atrophy | Cerebral and meningeal angiitis | Corticosteroids (3 bolus then 1.5mg/kg) and cyclophosphamide (1 bolus) | Small improvement Deceased 4 y after neurological symptoms of acute aspiration |
| 2010 (23) |
57 | m | CMML | No | Onset: 4 w after HSCT Clinic: recurrent myelitis with mild paraparesis, urinary difficulty; CSF: elevated protein; MRI: multiple white matter lesion of spinal cord without cerebral anomalies | No | Corticosteroids (5 bolus then 1mg/kg) then cyclophosphamide (7 bolus) | CR but relapse of myelitis 1,5 y later Treatment by cyclophosphamide with PR |
| 2010 (23) |
65 | m | AML | No | Onset: 3 y after HSCT Clinic: recurrent myelitis with mild paraparesis and lower limb hypoesthesia; CSF: elevated protein and oligoclonal bands; MRI: multiple white matter lesion of spinal cord, T2-hyperintense paraventricular left hemispheric lesion | No | Corticosteroids (5 bolus) | CR but relapse of myelitis 1 mo after Treatment by corticosteroids with CR |
| 2012 (24) |
54 | m | AML | No | Onset: 390 d after HSCT; Clinic: progressive ascending weakness, areflexia and cranial neuropathy; CSF: elevated protein; MRI: multiple | Loss of myelin and axon preservation | Corticosteroids and IV Ig (5 courses) | PR Deceased 5 y later |
| sub-cortical lesions, one with a relatively open ring sign | ||||||||
| 2012 (24) |
59 | m | AML | No | Onset: 240 d after HSCT; Clinic: progressive ascending weakness, areflexia and cranial neuropathy; CSF: elevated protein, oligoclonal bands; MRI: pontine white matter lesion | No | IV Ig (5 courses) | PR Alive 9 y later |
| 2012 (24) |
29 | m | AML | No | Onset: 63 d after HSCT; Clinic: progressive ascending weakness, areflexia and cranial neuropathy; CSF: elevated protein, oligoclonal bands; MRI: multiple white matter lesions of cervical spine and few in brain | Biopsy of spinal cord Loss of myelin and axon preservation | Corticosteroids and IV Ig (5 courses) | PR Deceased 2 y later of severe chronic GvHD |
| 2014 (25) |
63 | m | CLL | Acute GvHD | Onset: 92 d after HSCT; Clinic: cognitive impairment, tremor; CSF: elevated protein; MRI: multifocal subcortical and juxtacortical white matter lesions | No | Prednisolone 0.5 mg/kg/d | CR Alive 1 y after |
| 2015 (26) |
7 | m | Idiopathic aplastic anemia | Chronic GvHD | Onset: 15 mo after HSCT; Clinic: depression and seizure; CSF: normal; MRI: bilateral uncus lesions; EEG: slowing background and one epileptic focus VGKC and ILGI1 antibodies positives | No | Corticosteroids (5 boluses then 1mg/kg) and IV Ig (5 courses) | Clinical PR |
| 2017 (27) |
33 | m | Fanconi disease | Acute and chronic GvHD | Onset: 308 d after HSCT; Clinic: myelitis with motor and sensitive neuronopathy, memory disorders; MRI: Pan-myelitis and posterior lepto-meningitis; EMG: Motor and sensitive neuronopathy and muscular junction damage; CSF: Pleocytosis with majority of T cells, elevated protein, oligoclonal bands | Lymphohistiocytic vasculitis without necrosis, perivascular infiltration with CD3+ CD8+ T cells | Corticosteroids (10 bolus then 1mg/kg), IV Ig (3 courses), plasmapheresis (10 courses), MMF | Clinical stability Alive 37 m after CNS symptoms |
| 2017 (27) |
62 | m | MPN | Acute GvHD | Onset: 152 d after HSCT; Clinic: confusion, coma; MRI: Normal; EEG: diffuse brain suffering and frontal peak-waves discharges; CSF: Pleocytosis and elevated protein | Diffuse lymphocyte T infiltrate with small perivascular predominance and diffuse gliosis | Corticosteroids (1mg/kg) | Progression Deceased 17 d after CNS symptoms |
| 2017 (27) |
68 | f | MPN | Acute GvHD | Onset: 9 d after HSCT; Clinic: encephalitis; MRI: Hyper T2 focal lesion of the left hemisphere; EEG: Encephalitis; CSF: Pleocytosis | No | Corticosteroids (2mg/kg) | Progression Deceased 5 d after CNS symptoms |
| 2017 (27) |
29 | f | Fanconi disease | Chronic GvHD | Onset: 378 d after HSCT; Clinic: cerebellar syndrome, cranial nerves deficits and atypical poly-radiculonevritis; MRI: normal; CSF: elevated protein | No | Corticosteroids (3 bolus then 1mg/kg), plasmapheresis (5 courses), IV Ig (6 courses) | PR Deceased 30 mo after CNS symptoms |
| 2017 (27) |
50 | m | MPN | Chronic GvHD | Onset: 2090 d after HSCT; Clinic: transient and focal deficits (right hemiparesis and paresthesia); MRI: T2 hyper-signals compatible with multiple sclerosis; CSF: normal | No | Ciclosporin A (6mg/kg) | CR Alive 8, 3 mo after CNS symptoms |
| 2017 (27) |
16 | f | AML | Acute GvHD | Onset: 255 d after HSCT; Clinic: encephalitis, extra pyramidal syndrome; MRI: peri-ventricular and posterior leuko-encephalopathy associated with hemispheric cerebellar lesions with contrast enhancement; EEG: Global and diffuse slowing | No | Corticosteroid (1mg/kg) | PR Deceased 4, 2 mo after CNS symptoms |
| 2017 (27) |
36 | m | CML | Acute and chronic GvHD | Onset: 199 d after HSCT; Clinic: cerebellar and vestibular syndromes, left hemiparesis and hypoesthesia, and cranial nerves deficits; MRI: lacunar infarct, cerebral vasculopathy associated with focal lesion Angiography: normal; CSF: Elevated protein with IgG polyclonal | No | Corticosteroids (1mg/kg) | PR then secondary aggravation Deceased 8 mo after CNS symptoms |
| 2017 (28) |
66 | m | AML | Acute GvHD | Onset: 10 mo after HSCT; Clinic: drowsiness, apathy, diffuse cognitive impairment, frontal lobe involvement; MRI: hyperintensities of the centrum ovule and the lateral ventricles without gadolinium enhancement; CSF: normal; EEG: unremarkable | No | Corticosteroids (1mg/kg),fingolimod (0.5 mg/d) | CR but relapse of myelitis 7 mo later Alive 2, 3 y after CNS symptoms |
| 2017 (29) |
46 | f | AML | Acute and chronic GvHD | Onset: 19 mo after HSCT; Clinic: headaches, tremor, memory loss; MRI: areas of confluent and asymmetrical hyperintensity on T2WI and FLAIR in the bilateral cerebral white matter; CSF: pleocytosis, protein elevation, and low glucose Gadolinium-enhanced; MRI: multiple punctate and curvilinear lesions | Perivascular infiltration of CD3+ CD8+ lympho-myonuclear cells, non-caseating granulomas, loss of myelin and axon preservation | Corticosteroids and tacrolimus | CR |
| 2018 (30) |
60 | m | AML | Acute GvHD | Onset: 7 d after HSCT; Clinic: impaired consciousness, psychomotor agitation; CSF: elevated protein; MRI: multiple hyperintense lesions on T2 and fluid-attenuated inversion recovery of the deep white matter in frontal as well on the splenium of the corpus callous | Autopsy after CR showed no lymphocytic infiltration in the central nervous system. | Intrathecal methylprednisolone 40mg/w | CR Deceased 5 mo after neurological symptoms of invasive bronchopulmonary aspergillosis |
| 2018 (31) |
58 | m | ALL | Chronic GvHD | Onset: 1 y after HSCT; Clinic: bradypsychia, cognitive impairment, dyspraxia, ataxia, a pyramidal syndrome, autonomic dysfunction; MRI: infra- and supratentorial leukoencephalopathy, stable in comparison with 1 year before; EEG: diffuse moderate slowing of the dominant rhythm without paroxysmal activity; CSF: elevated protein, oligoclonal bands, elevated IgG; Serum analyses: Caspr2+; PET-CT: diffuse cortical and subcortical hypometabolism | No | MP 1g/d(5d), Cy 500 mg/m2/3w, rituximab 375 mg/m2/w(4 administrations) | CR Alive 13 mo after CNS symptoms |
| 2018 (32) |
59 | f | CLL | Acute and chronic GvHD | Onset: 33 mo after HSCT; Clinic: right upper extremity weakness, dysarthria; MRI: left frontal cortex infarction; MRA: severe stenosis of the left MCA; CSF: mild pleocytosis | Inflammatory cell infiltrations of perivascular areas | Surgical revascularization | Clinical and MR stability Alive 6 mo after CNS symptoms |
| 2019 (33) |
37 | f | MDS | Chronic GvHD | Onset: 2 y after HSCT; Clinic: generalized tonic-clonic type seizures, headache, blurred vision, symmetrical lower leg weakness, increased tendon reflex, hypoesthesia; MRI: multifocal ring enhancement lesions consistent with demyelinating features; multifocal nodular leptomeningeal enhancement and nodular intramedullary enhancing lesions along the spinal cord; CSF: elevated IgG | A loss of myelin fibers, perivascular T-cell infiltration (CD3+), macrophage infiltration associated with reactive gliosis | MP 1g/d(7d), plasmapheresis | CR Alive 1 y after CNS symptoms |
| 2019 (34) |
68 | m | MDS | No | Onset: 742 d after HSCT; Clinic: right-sided pyramidal distribution of weakness and a stimulus sensitive, myoclonus, increased tendon reflexes; MRI: multiple scattered T2 FLAIR hyperintense, cortical and subcortical lesions in both cerebral hemispheres; CSF: elevated protein EEG: diffuse slow wave activity | Perivascular T-cell infiltration (CD3+), microglial proliferation | MP 1g/d(5d), plasmapheresis | PR then secondary aggravation Deceased 195 d after CNS symptoms |
ALL, acute lymphoblastic leukemia; AML, acute myelogenous leukemia; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; CNS, central nervous system; CR, complete response; CSF, cerebrospinal fluid; EEG, electroencephalogram; GvHD, graft versus host disease; HLH, hemophagocytic lymphohistiocytosis; HSCT, hematopoietic stem cell transplantation; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasms; MRI, magnetic resonance imaging; NA, not available; PR, partial response.