The overall goal of this Program Project is to identify methods of reducing symptoms in multiplemyeloma (MM) in order to deliver the best available therapy to the largest number of patientswith this incurable disease. This Program Project focuses on the reduction of disease-related andtreatment-related inflammation as a potential cause of many of these symptoms. In this project (Project 4),we propose clincial trials that will directly test whether modulation of inflammation will ease thesymptomatic insult of therapy during inducton therapy and during stem cell treatment.
Specific Aim i tests the efficacy of either targeted (anti-TNF) or broad cytokine blockade to preventtreatment-induced neuropathy from thalidomide or bortezomib, an incapacitating toxicity of 2 of the mostpotent antimyeloma agents used as front-line therapy. We will also examine the effects of these therapieson other treatment-related symptoms.
Specific Aim 2 seeks to determine whether patients at the highest risk of developing severe transplantrelatedsymptoms (patients who are older, have comorbid conditions, or have amyloidosis) who receive alarge dose of hematopoietic stem cells (HSCs) after high-dose melphalan will have less-severe symptomsthan patients who receive a standard dose of HSCs.
This aim capitalizes on exciting new data that largenumbers of HSCs dramatically decrease the most severe symptoms experienced by patients followingAuSCT.
Specific Aim 3 tests the efficacy of IL-6 cytokine blockade in minimizing the most severe symptomsexperienced by patients after high-dose melphalan with autologous stem cell support (AuSCT).In addition, the direct effect of each of these interventions on inflammation will be assessed by themeasurement of specific inflammatory markers.These findings may directly benefit patients in terms of ameliorating symptom severity duringtreatment for MM and will further understanding of the mechanisms behind the development ofsymptoms. Reducing the symptom severity associated with AuSCT for at-risk patients will increase thenumber of patients who can undergo this strenuous but effective therapy. Finally, we expect to be able touse our results to validate, in humans, some potential pathogenetic mechanisms of treatment-inducedneuropathy and post-AuSCT symptoms. Such findings will be extremely valuable in extending the relativelyyoung science of symptom research. Successful completion of these 3 aims will allow us to determine theefficacy of a variety of strategies to reduce treatment-induced symptoms and will suggest avenues todecrease symptoms related to other diseases where aggressive therapies are employed.
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