Neurologic Complications after Allogeneic Hematopoietic Stem Cell Transplantation

Madon, E; Festuccia, Moreno; Brunello, Lucia; Boccadoro, Mario; Giaccone, Luisa; Bruno, Benedetto

doi:10.1016/j.bbmt.2016.12.632

Cited by 83 publications

(56 citation statements)

References 130 publications

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“…37,[41][42][43][44] Our long follow-up period of 5 years allowed us to analyze the temporal profile of NCs after transplant and account for late complications that may not have been detected in prior studies. Consistent with previous studies, 4,43,44,64 we found a decreasing incidence of NC over time from transplant, with the majority of events occurring in the early post-transplant period (up to day +100).…”

Section: Discussionsupporting

confidence: 92%

“…The objectives of the study were to describe the incidence and type of NCs associated with HCT, to determine risk factors associated with CNSC and to 1 Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; 2 Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia; 3 Royal Brisbane and Women's Hospital, Herston, Queensland, Australia; 4 School of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Disease status (AML/ALL only) determine the effect of CNSC on progression-free survival (PFS), overall survival (OS) and non-relapse mortality (NRM). Only CNSCs were included in these analyses as they were considered more likely to affect NRM, PFS and OS than peripheral neuropathy.…”

Section: Discussionmentioning

confidence: 99%

“…1 Neurologic complications (NCs) are a significant cause of morbidity related to HCT. [2][3][4][5] The etiologies of NCs include drug toxicities (for example, due to calcineurin inhibitors (CNIs) [6][7][8][9] ), infections, [10][11][12][13][14][15][16][17][18][19] hemorrhage, [20][21][22] ischemia, 21 metabolic effects, posterior reversal encephalopathy syndrome (PRES), [23][24][25][26][27][28] toxicity due to cryopreserved hematopoietic cell infusion [29][30][31][32][33] and disease infiltration. Both the central and peripheral nervous systems can be affected; clinical syndromes include seizures, encephalopathy, focal neurologic deficits and peripheral neuropathies.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Neurologic complications after allogeneic hematopoietic stem cell transplantation: risk factors and impact

Dowling

Dey

et al. 2017

Bone Marrow Transplant

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Neurologic complications (NCs) may be a significant source of morbidity and mortality after hematopoietic cell transplantation (HCT). We performed a retrospective study of 263 consecutive patients undergoing allogeneic HCT for hematological malignancies to determine the incidence, risk factors and clinical impact of NCs in the first 5 years after HCT. We determined the incidence of central nervous system (CNS) infection, intracranial hemorrhage, ischemic stroke, metabolic encephalopathy, posterior reversal encephalopathy syndrome, seizure and peripheral neuropathy. In all, 50 patients experienced 63 NCs-37 early (⩽day +100), 21 late (day +101 to 2 years) and 5 very late (2 to 5 years). The 1- and 5-year cumulative incidences of all NCs were 15.6% and 19.2%, respectively, and of CNS complication (CNSC; all of the above complications except peripheral neuropathy) were 12.2 and 14.5%. Risk factors for CNSC were age (hazard ratio (HR)=1.06 per year, P=0.0034), development of acute GvHD grade III-IV (HR=2.78, P=0.041), transfusion-dependent thrombocytopenia (HR=3.07, P=0.025) and delayed platelet engraftment (>90th centile; HR=2.77, P=0.043). CNSCs negatively impacted progression-free survival (HR=2.29, P=0.0001), overall survival (HR=2.63, P<0.0001) and non-relapse mortality (HR=8.51, P<0.0001). NCs after HCT are associated with poor outcomes, and usually occur early after HCT.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neurologic complications after allogeneic hematopoietic stem cell transplantation: risk factors and impact

Dowling

Dey

et al. 2017

Bone Marrow Transplant

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“…Described CNS clinical manifestations at TA‐TMA presentation include PRES, confusion, drowsiness, headaches, hallucinations, and seizures. There are no characteristic imaging findings in patients with CNS involvement, and imaging findings consistent with PRES are present in only a minority of patients . To our knowledge, there are no reports of persistent neurologic deficits in survivors of TA‐TMA.…”

Section: Discussionmentioning

confidence: 95%

Severe, persistent neurotoxicity after transplant‐associated thrombotic microangiopathy in a pediatric patient despite treatment with eculizumab

Schoettler

Duncan

Lehmann

2019

Pediatric Transplantation

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Background: TA-TMA is a described complication of aHCT in children with neuro-blastoma. Outcomes are poor with mortality rates approaching 60%. Described late effects in survivors include chronic kidney disease and persistent pulmonary hypertension. Case: We report a case of a 2-year-old with neuroblastoma who developed severe TA-TMA 35 days after high dose chemotherapy and autologous stem cell rescue. He presented with respiratory failure, pericardial and pleural effusions, hemolysis, hy-pertension, and mild altered mental status. He was mechanically ventilated for 3 weeks and after sedation was lifted, he was minimally responsive. He was treated with eculizumab with resolution of hemolysis, kidney injury and polyserositis. Initially he was more responsive; however, after almost a year of intensive therapy he re-mained nonverbal and had persistent irritability and behavioral changes. He had an extensive negative evaluation. On day +345, he presented with severe, refractory epilepsy. Three years after TA-TMA, he continues to have severe neurologic disabilities. Conclusions: To our knowledge, persistent neurologic toxicity has not been reported in TA-TMA. However, deficits and seizures are reported in other TMAs, particularly in children with atypical HUS who present with significant neurologic changes at di-agnosis. Our patient’s persistent neurologic disability despite eculizumab response in all other involved organs may reflect irreversible damage. This case describes a new long-term sequela of TA-TMA and highlights the need for further studies to under-stand both acute and long-term neurologic complications of this disease.

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“…4 Drug toxicity, fungal infections, and immune-mediated disorders prevail among other etiological factors. 5 Furthermore, their severity varies from mild to fatal disorders. 4,6 Those complications need to be recognized first by transplanters-hematologists.…”

Section: Introductionmentioning

confidence: 99%

Neurologic complications after allogeneic transplantation: a meta‐analysis

Gavriilaki

Mainou

Gavriilaki

et al. 2019

Ann Clin Transl Neurol

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ObjectiveNeurologic adverse events remain challenging complications with poor morbidity and mortality post adult allogeneic hematopoietic cell transplantation (allo‐HCT) for hematologic diseases. We conducted a systematic review and meta‐analysis to determine their spectrum, incidence, and impact on survival. MethodsWe searched MEDLINE, COCHRANE, EMBASE through March 2019 for all types of primary studies. Two independent reviewers screened, extracted data, and assessed risk of bias (RoB).ResultsWe identified 552 eligible studies describing 57.972 patients; one randomized controlled trial, two case–control, 17 prospective, 86 retrospective cohort studies, 21 case series, and 425 case reports. RoB ranged from fair to high although case series were low‐risk. The majority of studies traced infectious or drug‐related neurologic manifestations. Infectious complications were present in 2.7% (95% CI 1.9–3.6) and 3.3% (95% CI 0.8–7.1) of patients in retrospective and prospective cohort studies, respectively. In retrospective studies, 3.4% (95% CI 2.1–4.9) of patients suffered from drug‐related neurologic events. In prospective cohorts the equivalent incidence was 13% (95% CI 4.2–24.8). Neurologic complications had a detrimental impact on survival.InterpretationOur study highlights the wide spectrum and significant impact of neurologic complications on survival post allo‐HCT. This systematic review summarizes existing data and provides the necessary background information for every physician involved in the management of these patients.

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Neurologic Complications after Allogeneic Hematopoietic Stem Cell Transplantation

Cited by 83 publications

References 130 publications

Neurologic complications after allogeneic hematopoietic stem cell transplantation: risk factors and impact

Neurologic complications after allogeneic hematopoietic stem cell transplantation: risk factors and impact

Severe, persistent neurotoxicity after transplant‐associated thrombotic microangiopathy in a pediatric patient despite treatment with eculizumab

Neurologic complications after allogeneic transplantation: a meta‐analysis

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