Technique in allogeneic hematopoietic stem cell transplantation has greatly advanced over the past decades, which has led to an increase in the number of patients receiving transplantation, but the complex procedure places these transplant recipients at high risk of a large spectrum of complications including neurologic involvement. As a common manifestation of neurological disorders, epileptic seizures after transplantation have been of great concern to clinicians because it seriously affects the survival rate and living quality of those recipients. The aim of this review is to elucidate the incidence of seizures after allogeneic hematopoietic stem cell transplantation, and to further summarize in detail its etiologies, possible mechanisms, clinical manifestations, therapeutic schedule, and prognosis, hoping to improve doctors' understandings of concurrent seizures following transplantation, so they can prevent, process, and eventually improve the survival and outlook for patients in a timely manner and correctly.

• allogeneic hematopoietic stem cell transplantation
• complications
• epileptic seizures
• neurotoxicity
• status epilepticus

To evaluate cyclosporine A (CSA)-related neurotoxicity after haploidentical hematopoietic stem cell transplantation (HID-HSCT) in children with hematopathy.

This retrospective case series study included children with hematopathy who underwent HID-HSCT at Fujian Medical University Union Hospital between February 2013 and January 2017.

Fifty-one children (39 males) were included in the study with a median age of 8 (range, 1.1–18) years. Seven patients (13.7%) developed CSA-related neurotoxicity after a median 38 (range, − 3 to 161) days from HID-HSCT. Hypertension (5/7, 71%) was the most common prodrome. Brain magnetic resonance imaging showed posterior reversible encephalopathy syndrome in six patients and atypical abnormalities in one patient. One patient died from grade IV graft-versus-host disease (GvHD) on day + 160, and six patients were alive at the last follow-up. Four patients (71.4%) achieved complete remission, while two patients developed secondary epilepsy and exhibited persistent MRI and electroencephalogram abnormalities at the 5-year follow-up. Hypertension after CSA was more common in patients with CSA-related neurotoxicity than in those without (71% vs. 11%, P = 0.002). Five-year overall survival did not differ significantly between patients with CSA-related neurotoxicity (85.7 ± 13.2%) and those without (65.8 ± 7.2%).

The incidence of CSA-related neurotoxicity in children with hematopathy undergoing HID-HSCT is relatively high.

• Child
• Cyclosporine a
• Hematopathy
• Hematopoietic stem cell transplantation
• Neurotoxicity syndrome

• Clinical character
• Epilepsy
• Immunosuppressant
• Seizure
• Transplantation
• Treatment

Drug-resistant epilepsy (DRE) occurs in 20–30% of all patients who develop epilepsy and can occur from diverse causes. Cyclosporine-A (CSA) is an immunosuppressive drug utilized to prevent graft-versus-host disease (GvHD) in transplant patients and is known to cause neurotoxicity, including seizures. In some cases, however, patients can develop DRE. Only a limited number of cases have been reported in which DRE has developed after CSA exposure — all in children. Here we present a rare case of an adult developing DRE after post-transplant CSA neurotoxicity. In addition, we provide a comprehensive review and analysis of all reported cases in the literature.

A 29-year-old man with Non-Hodgkin's Lymphoma underwent an allogenic hematopoietic stem cell transplant and experienced a CSA-induced seizure at 7.5 months' post-transplant. The patient was discontinued on CSA and began a low dose tacrolimus regimen. At 33 months' post-transplant, he had seizure recurrence and developed DRE. Imaging revealed right mesial temporal sclerosis (MTS) and video EEG localized ictal activity to the right anterior temporal lobe. He was successfully treated with a right anterior temporal lobectomy and amygdalohippocampectomy.

Seven peer-reviewed studies described 15 patients who underwent transplantation with post-transplant CSA administration and subsequently developed DRE following an initial CSA-induced seizure. All 15 patients were children suggesting that young age is a risk factor for DRE after CSA-induced seizures. Initial CSA-induced seizures occurred at an average of 1.6 ± 1.1 months after transplant and seizure recurrence 9.2 ± 8.0 months after transplant. All reported CSA routes of administration (n = 6) were intravenous and 7 of 9 (78%) reported CSA blood levels above the therapeutic range. The incidence of MTS (40%) in these 15 patients was significantly higher than the incidence in the general DRE population (24%) and was most effectively treated via epilepsy surgery.

The use of cyclosporine for GvHD prophylaxis and treatment following transplantation may cause seizures and be associated with DRE. Although discontinuation and dose decrease of CSA often reverse adverse neurological events, initial CSA-induced seizures may be associated with MTS that and subsequent greater risk of DRE development.

• Antiseizure drugs
• Cyclosporine neurotoxicity
• Cyclosporine-A
• Drug-resistant epilepsy
• Medically intractable epilepsy
• Mesial temporal sclerosis
• Seizures
• Transplant

• acute lymphoblastic leukemia (ALL)
• allogeneic hematopoietic stem cell transplantation (allo-HSCT)
• decitabine
• relapse

AIM: To analyze the association between plasma bilirubin levels and veno-occlusive disease (VOD) in non-adult patients undergoing hematopoietic stem cell transplantation (HSCT) during cyclosporine therapy.

METHODS: A total of 123 patients taking cyclosporine were evaluated using an electronic medical system at the Seoul National University Children’s Hospital from the years 2004 through 2011. Patients were grouped by age and analyzed for incidence and type of adverse drug reactions (ADRs) including VOD.

RESULTS: The HSCT patients were divided into three age groups: G#1 ≥ 18; 9 ≤ G#2 ≤ 17; and G#3 ≤ 8 years of age). The majority of transplant donor types were cord blood transplantations. Most prevalent ADRs represented acute graft-vs-host disease (aGVHD) and VOD. Although the incidences of aGVHD did not vary among the groups, the higher frequency ratios of VOD in G#3 suggested that an age of 8 or younger is a risk factor for developing VOD in HSCT patients. After cyclosporine therapy, the trough plasma concentrations of cyclosporine were lower in G#3 than in G#1, indicative of its increased clearance. Moreover, in G#3 only, a maximal total bilirubin level (BILmax) of ≥ 1.4 mg/dL correlated with VOD incidence after cyclosporine therapy.

CONCLUSION: HSCT patients 8 years of age or younger are more at risk for developing VOD, diagnosed as hyperbilirubinemia, tender hepatomegaly, and ascites/weight gain after cyclosporine therapy, which may be represented by a criterion of plasma BILmax being ≥ 1.4 mg/dL, suggestive of more sensitive VOD indication in this age group.

• Hematopoietic stem cell transplantation
• Veno-occlusive disease
• Cyclosporine
• Adverse drug reaction
• Total bilirubin