Episode 5: Dr. Fajgenbaum’s Commentary

• In midst of remission, an interesting finding appears on PET scan
  • Hot mass based on PET scan in liver, which when biopsied, was found to be inflammatory myofibroblastic tumor
    • These tumors often associated with autoimmune diseases, but also with other lymphoproliferative disorders like Multicentric Castleman Disease
  • Tumor resected and patient does not have recurrence of tumor
• When treating Multicentric Castleman Disease, there are number of other disorders that can also occur concurrently
• Following tumor resection and 1½-year remission, patient has recurrence of same symptoms
  • This time, patient tracked weekly with labs leading up to remission, offering significant insights into changes leading to patient’s relapse
    • About 3 months before relapse, there were increases in first cytokine
    • Vascular endothelial growth factor was first cytokine that began to rise leading up to episode
    • Following rise of VEGF, patient was still healthy
    • Weekly decrease in platelet counts by about 10 to 15 thousand each week
    • Rise in soluble interleukin-2 receptor
    • All 3 changes occurred before significant changes in fatigue, patient’s clinical features, and CRP, before began to rise
    • After 3 months of changes in cytokines, patient had full-blown relapse of increasing CRP and symptoms associated with disease, while on bortezomib, dexamethasone, thalidomide, and siltuximab
• Patient given IV Ig empirically because of low immunoglobulins from treatment, as well as suspicion that IV Ig could help
• Patient had a 2-week-long response where symptoms and laboratory values improved with dose of IV Ig
  • Remission was fleeting, and disease got out of control, with CRP climbing over 100, platelets crashing, albumin falling, and symptoms becoming very intense/li>
• Used cytotoxic chemotherapy, adriamycin, cyclophosphamide, etoposide, bortezomib, dexamethasone, thalidomide, and rituximab, to try to obtain remission
• Patient responded very well to chemotherapy once again
• Patient very sick before chemotherapy; needs another month-long hospitalization to recover
• Once patient brought into remission, physicians think about new therapy
  • Sirolimus used in kidney transplantation, was tried off label
  • Not approved for Multicentric Castleman Disease, but used to both prevent VEGF expression and suppress activated T cells
• Patient started on sirolimus daily and IV Ig monthly
• Doing well at 18 months post last chemotherapy, while on sirolimus and IV Ig

Read through the episodes of one patient’s journey toward an accurate diagnosis and listen to an expert’s analysis on each episode.