Major central nervous system complications after allogeneic stem cell transplantation: A large retrospective study on 888 consecutive adult patients

Mannina, Daniele; Berneking, Laura; Both, Anna; Timm, Wiebke; Urbanowicz, Tatiana; Wolschke, Christine; Ayuk, Francis; Fischer, Nicole; Fiehler, Jens; Grzyska, Ulrich; Rösner, Sabine; Choe, Chi Un; Christopeit, Maximilian

doi:10.1111/ejh.13489

Cited by 6 publications

(5 citation statements)

References 22 publications

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“…The incidence of abnormal findings in autopsies is up to 90% (24). A recent Chinese study assessing 196 children (8) found the incidence to be 17%, comparable with our results (and similar to the 14.8% incidence in a recent study on 888 adult allotransplanted patients) (17). The incidence of NCs after HSCT is higher than in children treated with chemotherapy only (10).…”

Section: Neurological Complications 107supporting

confidence: 91%

“…GVHD was found to be correlated with NCs (9,12); a recent retrospective analysis revealed statistically significant correlations between noninfectious NCs and GVHD, specifically between PRES or seizures, and acute GVHD, as well as seizures or stroke, and chronic GVHD; but causal relationships could not be established (4). The abovementioned large adult study found increased age as the only significant risk factor (17).…”

Section: Neurological Complications 107mentioning

confidence: 96%

“…The survival rates of patients who develop NCs, both children and adults, are reduced (8,9,12,17); mortality could be attributed to the NCs in more than half of the cases (8,11); and 27%-43% (5,7,18) suffer from long-term neurological sequelae. NCs are often accompanied by neuroimaging changes such as brain edema, intracranial hemorrhage, ring-enhancing lesions or abscess, and cortical dysplasia (19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

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Neurological complications following pediatric allogeneic hematopoietic stem cell transplantation: Risk factors and outcome

et al. 2022

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BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is an efficient treatment for numerous malignant and nonmalignant conditions affecting children. This procedure can result in infectious and noninfectious neurological complications (NCs).ObjectiveThe objective of the study is to examine the incidence, risk factors, and outcomes of NCs in pediatric patients following allogeneic HSCT.MethodsWe performed a retrospective study of 746 children who underwent 943 allogeneic HSCTs in two large pediatric hospitals in Israel from January 2000 to December 2019.ResultsOf the pediatric patients 107 (14.3%) experienced 150 NCs. The median follow-up was 55 months. Noninfectious NCs were more common than infectious NCs (81.3% vs. 18.7%). Factors significantly associated with type of NC (infectious vs. noninfectious) were underlying disease (immunodeficiency vs. malignant and metabolic/hematologic disease) (p-value = 0.000), and use of immunosuppressive agent, either Campath or ATG (p-value = 0.041). Factors with a significant impact on developing neurological sequelae post-NC were number of HSCT >1 (p-value = 0.028), the use of alemtuzumab as an immunosuppressive agent (p-value = 0.003), and infectious type of NC (p-value = 0.046). The overall survival rate of whole NC-cohort was 44%; one-third of all mortality cases were attributed to the NC. The strongest prognostic factors associated with mortality were older age at HSCT (p-value = 0.000), the use of alemtuzumab as an immunosuppressive agent (p-value = 0.004), and the existence of neurological sequelae (p-value = 0.000). Abnormal central nervous system imaging (p-value = 0.013), the use of alemtuzumab as an immunosuppressive agent (p-value = 0.019), and neurological sequelae (p-value = 0.000) had statistically significant effects on neurological cause of death.ConclusionInfectious and noninfectious NCs are a significant cause of morbidity and mortality following allogeneic HSCT in children. Further research is required to better understand the risk factors for different NCs and their outcomes regarding sequelae and survival.

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Section: Neurological Complications 107supporting

confidence: 91%

Section: Neurological Complications 107mentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Neurological complications following pediatric allogeneic hematopoietic stem cell transplantation: Risk factors and outcome

et al. 2022

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“…Although the presence of CNS dysfunction is essential for the diagnosis of HHV-6 encephalitis, allo-HSCT recipients may develop CNS dysfunction due to many other factors than HHV-6 encephalitis. 32,33 In our study, only 14 out of 41 patients with CNS dysfunction after allo-HSCT were caused by HHV-6 encephalitis. The sensitivity, speci city, PPV, NPV, LR+, and LR-of CNS dysfunction for the diagnosis of HHV-6 encephalitis were 100%, 77.5%, 34.1%, 100.0%, 4.444, and 0.000, respectively (Table 3).…”

Section: Timing Of Hyponatremia Hhv-6 Encephalitismentioning

confidence: 66%

The preceding hyponatremia is a useful hallmark for the diagnosis of HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation

Ara

Yoshida

Okada

et al. 2022

Preprint

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Human herpes virus-6 (HHV-6) encephalitis is one of the life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early diagnosis and intervention are important for the prevention of poor prognosis and sequelae. Although hyponatremia is known to be associated with HHV-6 encephalitis, it is unclear whether the preceding hyponatremia is a useful hallmark for the diagnosis of HHV-6 encephalitis. We retrospectively reviewed 134 consecutive patients who underwent allo-HSCT at our institution and evaluated the relationship between HHV-6 encephalitis and hyponatremia. Interestingly, 7 (50%) of 14 patients who developed HHV-6 encephalitis presented hyponatremia within a week before the onset of HHV-6 encephalitis. On the other hand, only 14 (11.7%) out of 120 patients without HHV-6 encephalitis developed hyponatremia. Hyponatremia, treating as a time-dependent covariate, was significantly correlated with the incidence of HHV-6 encephalitis. Moreover, the diagnostic accuracy analysis showed that the coexistence of hyponatremia and central nerve system (CNS) dysfunction strongly suggests HHV-6 encephalitis. In conclusion, our study suggests the likelihood of HHV-6 encephalitis significantly increases in the patients with CNS dysfunction following hyponatremia after allo-HSCT and this combination may help in early diagnosis and intervention of HHV-6 encephalitis after allo-HSCT.

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“…1d ). Allo-HSCT recipients may develop CNS dysfunction due to many other factors than HHV-6 encephalitis [ 11 ]. In fact, 27 (65.9%) of 41 patients with CNS dysfunction had other causes than HHV-6 encephalitis in this study.…”

Section: To the Editormentioning

confidence: 99%

The preceding hyponatremia is a useful hallmark for the diagnosis of HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation

Yoshida

Ara

Okada

et al. 2022

Bone Marrow Transplant

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Major central nervous system complications after allogeneic stem cell transplantation: A large retrospective study on 888 consecutive adult patients

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 6 publications

References 22 publications

Neurological complications following pediatric allogeneic hematopoietic stem cell transplantation: Risk factors and outcome

Neurological complications following pediatric allogeneic hematopoietic stem cell transplantation: Risk factors and outcome

The preceding hyponatremia is a useful hallmark for the diagnosis of HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation

The preceding hyponatremia is a useful hallmark for the diagnosis of HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation

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