Neurologic Sequealae of Hematopoietic Stem Cell Transplantation (HSCT)

Hematopoietic stem cell transplantation (HSCT) has been used to cure many pediatric patients with both malignant and non-malignant diseases in whom conventional therapy has failed. HSCT is generally performed after the administration of high sublethal doses of chemotherapy or chemoradiotherapy to achieve myeloablation, immunosuppression and eradication of abnormal cells. The use of high dose cytotoxic therapy before HSCT places children at risk for acute and long-term side effects which may differ or be more severe than those seen in children who did not receive HSCT. One important organ that may be damaged from cytotoxic therapies used to treat recipients of HSCT has been the brain. Survival rates for childhood ALL improved after the introduction of treatments to prevent the development of central nervous system (CNS) leukemia. During the past 25 years, CNS prophylaxis for leukemia has consisted of either intrathecal chemotherapy alone or a combination of both chemotherapy and cranial irradiation. There is a wide range of deficits associated with this CNS prophylaxis. Neurological sequelae include severe leukoencephalopathy to more subtle and mild dysfunction, such as learning disorders and abnormalities that can be seen on CT scan or MRI (Packer R 1986, Brouwers P 1985). In contrast, patients with malignant brain tumors often present with neurological symptoms of their primary disease such as a) increased intracranial pressure b) problems with balance and cranial nerve findings, which are associated with infratentorial tumors and c) seizures, which are often seen in those with supratentorial tumors. The treatment of malignant brain tumors involves chemoradiotherpay in addition to neurosurgery. The cranial irradiation that these children receive is often more than double that received by patients with acute leukemias. Therefore, the neurological sequelae of patients with this particular malignancy are greater than that seen for patients with a hematological malignancy. The neurocognitive sequelae following cranial irradiation and chemotherapy for childhood acute leukemia and brain tumors have been well documented (Fletcher et al 1988, Smibert et al 1996, Anderson et al 1997, Stehbens et al 1991, Butler and Copeland 1993, Moleski 2000, Ris and Noll 1994, Mulhern and Butler 2004). However, information regarding the