Neurological Complications in Stem Cell Transplantation of Childhood

Stem cell transplantation (SCT) is an effective treatment for hematological diseases and inborn errors of metabolism. Neurological complications in SCT are serious matters, which affect the patients' survival and quality of life. We analyzed the incidence of neurological complications in patients receiving SCT at the Hokkaido University Hospital to evaluate risk factors relating to the onset of these manifestations.

Between February 1988 and May 2012, a total of 236 patients (149 males and 87 females) received SCT; 188 patients received allogenic SCT, 48 patients received autologlous SCT. All of these patients were included in this study. Mean age was 8.1 years (range, 0–31). Indications for transplantation were hematological malignancies such as acute leukemia and lymphoma in 142 patients, bone marrow failure such as aplastic anemia in 30, malignant solid tumor such as neuroblastoma and rhabdomyosarcoma in 36, congenital immunodeficiency in 20, congenital metabolic disorder and brain tumor in 4 each. 213 patients received myeloabelative conditioning (MAC) including total body irradiation (97 patients), 23 patients receiving reduce intensity conditioning (RIC). 116 patients received prophylaxis against graft versus host disease (GVHD) with cyclosporine (CsA) or tacrolimus (Tac) in combination with methotrexate (MTX), 54 patients received CsA or Tac in combination with methylprednisolone, 10 patients received MTX alone, 7 patients received prednisolone or CsA alone. We carefully examined according to the protocol of neurological examination, in Hokkaido university school of medicine department of pediatrics, including (1) mental status including conscious status, orientation emotional reaction, and memory, (2) speech, (3) praxis, (4) gnosia, (5) cranial nerve sign, (6) motor and sensory system, (7) coordination, (8) gait and position, and (9) reflexes. All signs were considered the patients' age.

Among the 236 patients, 57 patients (24.2%) developed neurological symptoms. The neurological events observed in every patient were depicted on the time-course of SCT. The occurrence of the neurological complications seemed to be categorized into 4 on the basis of time of onsets and symptoms: (1) 10 episodes during the conditioning regimen such as convulsion, (2) 17 episodes during hematological recovery such as intracranial hemorrhage, viral encephalitis, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), and posterior reversible encephalopathy syndrome (PRES), (3) 24 episodes around 2–3 months after SCT such as PRES, intracranial hemorrhage, viral encephalitis, and SIADH, (4) 28 episodes beyond 3 months after SCT such as mental retardation, leukoencephalopathy and epilepsy. Neurological complications were seen significantly in the patients receiving allogenic SCT (p=0.013), cord blood transplantation (CBT) (p=0.032), and patients with acute GVHD of over grade II (p=0.048). Moreover, overall survival and event free survival showed significant difference between patients with neurological events and those without the events (59.6±3.8% vs 38.8±7.4% (p=0.015) and 54.7±3.8% vs 39.0±6.6% (p=0.026), respectively). No significant differences were observed between patients with neurological events and those without the events in age, sex, diseases (malignancy or non-malignancy), irradiation during the conditioning regimen, and conditioning regimen (MAC or RIC).

It was thought that allo-immunoreaction such as GVHD, administration of immunosuppressive drugs, vascular disorder related SCT, and virus reactivation participated in development of neurological complications. Particularly, CBT was significant high risk for neurological complications. High frequent virus reactivation such as human herpes virus 6 might induce significantly high incidence of neurological complications in patients receiving CBT.

No relevant conflicts of interest to declare.