Central Nervous System
Bone Marrow Transplant (BMT)
CNS late effects are a significant concern for pediatric HSCT survivors.
Complications are related to multiple factors:
- Total body irradiation
(TBI)
- Includes the brain
- Some patients will have already received prophylactic cranial RT for leukemia and the BMT is salvage therapy for relapse.
- Prior use of high-dose methotrexate and intrathecal (into the CSF) chemotherapy
during treatment for ALL
- Increases the risk of leukoencephalopathy
CNS leukoencephalopathy
- May occur in the white matter of the CNS within days to months of HSCT.
- Characterized by severe neurologic deterioration (lethargy, slurred speech, ataxia, seizures, confusion, coma) sometimes resulting in permanent neurologic disability and death.
- Usually associated with cranial radiation therapy (RT) as part of TBI in conditioning regimen (often with high-dose methotrexate and intrathecal chemotherapy).
Late cognitive effects:
Learning disability are not uncommon in young children treated with TBI prior to BMT. In older children these deficits may be subtle.
Survivors may have difficulties with :
- Visual motor coordination
- Abstract thinking
- Spacial processing
- Behavioral and language processing
Parents often report their children having problems with concentration, memory, and processing complex tasks.
In one study of 38 patients (with hematologic malignancies, all given IT chemotherapy, all had hematopoietic stem cell transplantation (HSCT), neurocognitive function was evaluated before HSCT and then at 1, 3, and 5 years post-HSCT.
- There were significant declines in visual motor skills and memory test scores were noted within the first year post-transplant.
- By 3 years post-transplant, there was an improvement in the visual motor development scores and memory scores, but there were new deficits seen in long-term memory scores.
- By 5 years post transplant, there were progressive declines in verbal skills, performance skills, and new deficits seen in long-term verbal memory scores.
- The greatest decline in neurocognitive function occurred in patients who received cranial irradiation either as part of their initial therapy or as part of their HSCT conditioning.
Secondary Neoplasms:
- Radiation induced meningiomas are a long term risk after low dose cranial RT
- There is a much smaller risk of a RT induced malignant brain tumor
One retrospective analysis and clinical study of survivors after chemotherapy or hematopoietic stem cell transplantation (HSCT) for pediatric cancer showed that there was a wide variety of different CNS late effects, but the group of survivors also had a wide variety of different underlying neoplasms and therapy.
