Bone marrow transplantation (BMT) has become the standard treatment lor a variety of hematological malignancies. With this intensive treatment, a substantial percentage of patients can be cured. In most long-term survivors, performance status and overall quality of life are reported as rather good. However, a significant percentage of patients continues to experience lingering late complications, such as cognitive deficits, psychological distress and fatigue, which have a great impact on patient's daily living and rehabilitation. Both cranial irradiation and high-dose chemotherapy are known causes of delayed encephalopathies. In BMT, high dose chemotherapy is combined with total body irradiation (TBI). The effects of this combination of potentially neurotoxic treatments on the central nervous system (CNS) are unclear. In addition to this, some BMT patients receive intrathecal chemotherapy, and in the first three months after BMT several types of acute CNS complications (e.g. encephalopathies) are quite frequent. Both factors may enhance delayed CNS toxicity. No well-designed study has investigated the frequency and severity of delayed cognitive deficits after BMT, and their impact on quality of life in long-term survivors. Preliminary studies at our institute show serious acute neurological complications and late cognitive dysfunction in a considerable number of BMT patients. This emphasises the importance of research on cognitive dysfunctioning and its effect on quality of life in long-term survivors of BMT.
The present study will prospectively and longitudinally investigate the cognitive sequelae in patients treated with high-dose chemotherapy in conjunction with TBI. It will analyse the relation between cognitive functioning, psychosocial status and quality of life with specific treatment-related complications, as graft versus host disease and previous treatment for CNS disease. The outcome will be compared to patients with hematological malignancies treated with chemotherapy in a conventional dosage, and a group of healthy controls in the same age range.
Plan of investigation: the cognitive functions over time of 50 patients treated for a hematological malignancy with a combination of high-dose chemotherapy with total body irradiation followed by allogeneic or autologous stem cell or bone marrow transplant, will be compared to the cognitive functions of 50 patients treated with conventional dose chemotherapy and/or involved field irradiation lor low or intermediate grade NHL or lor Hodgkin's disease. Anticipating a drop out ratio of 50-60%, 100-120 consecutive patients will be included in both patient groups. A control group of 50 healthy subjects in the same age range will be added to control for a normal level of cognitive performance over time. The BMT patients will have their first assessment before the BMT conditioning regimen at which time they will be in complete response (CR) to the induction regimen. Follow-up will be obtained 8 months and 20 months after BMT. The patient control group will have the first assessment once they are in CR or have residual disease only. Further examinations will be done 8 and 20 months after the first assessment. Evaluation will be done with standardised neuropsychological tests and with questionnaires for psychosocial functioning and quality of life.
The study will result in detailed documentation of cognitive and psychosocial functioning in BMT patients and its impact on quality of life. lt will lead to a clearer understanding of acute and long-term neurobehavioral effects of the BMT procedure, and will investigate the disease and/or treatment related factors enhancing neurotoxicity. The relative risks of cognitive dysfunction after BMT in comparison to conventional treatment will be determined. We expect that the results will have implications for the development and modification of intervention strategies aimed at preventing or reducing cognitive, behavioral and social disabilities. |
