Risk of Seizures in Children Receiving Busulphan-Containing Regimens for Stem Cell Transplantation

Abstract

Busulphan (BU) is associated with neurotoxicity and risk of seizures. Hence, seizure prophylaxis is routinely utilized during BU administration for stem cell transplantation (SCT). We collected data on the incidence of seizures among children undergoing SCT in Italy. Fourteen pediatric transplantation centers agreed to report unselected data on children receiving BU as part of the conditioning regimen for SCT between 2005 and 2012. Data on 954 pediatric transplantation procedures were collected; of them, 66% of the patients received BU orally, and the remaining 34%, i.v. All the patients received prophylaxis of seizures, according to local protocols, consisting of different schedules and drugs. A total of 13 patients (1.3%) developed seizures; of them, 3 had a history of epilepsy (or other seizure-related pre-existing condition); 3 had documented brain lesions potentially causing seizures per se; 1 had febrile seizures, 1 severe hypo-osmolality. In the remaining 5 patients, seizures were considered not explained and, thus, potentially related to BU administration. The incidence of seizures in children receiving BU-containing regimen was very low (1.3%); furthermore, most of them had at least 1-either pre-existing or concurrent-associated risk factor for seizures.

Single Daily Busulfan Dosing for Infants with Nonmalignant Diseases Undergoing Reduced-Intensity Conditioning for Allogeneic Hematopoietic Progenitor Cell Transplantation

“…The incidence of mucositis was also very low in our patients, presumably related to the low Bu exposure they received. Similarly, only 1 of our patients developed seizure, likely caused by cyclosporine toxicity, which is in line with the low risk of Bu-induced seizure reported in children [40]. The rate of acute or chronic GVHD development was also very low in our study, in contrast to other studies of infants who underwent HPCT [41].…”

Central Nervous System Complications in Children Receiving Chemotherapy or Hematopoietic Stem Cell Transplantation

“…Despite prophylactic treatment with dexamethasone, chemical meningitis with nausea, fever, vomiting, and back pain may develop in 20% of patients. More severe complications are spinal cord lesions (cauda equina syndrome, paraplegia, or tetraplegia) and papilledema, occurring at a median of 10 days (1–22, 24–59, 62, 63, 70–100) after a variable number of courses. For these, recovery is often incomplete with severe neurologic deficits after many months and no effective therapy available.…”

“…This complication appeared to be dose dependent and related to the high CSF concentrations of this small, lipophilic molecule during systemic administration. Anticonvulsant prophylaxis is now considered the standard of care in pediatrics, although the real utility is not fully understood (62, 75). …”

A survey on hematology‐oncology pediatric AIEOP centres: The challenge of posterior reversible encephalopathy syndrome

“…2,3 In particular, central nervous system complications remain a challenging clinical issue, requiring swift detection and prompt treatment. Posterior reversible encephalopathy syndrome (PRES) is recognized as one of the most common neurological complications in hematology-oncology pediatric patients [2][3][4][5][6] and has emerged as a considerable concern for pediatricians involved in this field. Although PRES is usually reversible, it can lead to life-threatening complications and permanent neurological damage if not promptly recognized and treated.…”