ONCAlert | 2017 San Antonio Breast Cancer Symposium
Multicentric Castleman Disease Case Studies

David Fajgenbaum, MD, MBA, MSc: Treatment Options

David Fajgenbaum, MD, MBA, MSc
Published Online:Aug 11, 2015
Mark F. is a 25-year-old law school student from Florida with a 3-week history of severe fatigue, night sweats, and weight loss; he has also reported high fevers for the past week. He did not complain of joint pain.

Guess the Diagnosis: Case 2



What are the potential treatment options?

Dr. David Fajgenbaum, Perelman School of Medicine, University of Pennsylvania, says this patient represents a therapeutic challenge. The patient is very sick, has already failed monotherapy with corticosteroids, and has severe renal impairment. Although neutralization of IL-6 with monoclonal antibodies may be of benefit, it is likely not sufficient to reverse the major hypercytokinemia experienced by this patient. It is important to realize that iMCD can be a severe illness, and the reported 5-year survival rate (65%) is worse than some malignancies, such as multiple myeloma. The decision to give chemotherapy to a severely ill patient with a nonmalignant disorder is a difficult one, but can be lifesaving. Ideally, one should [confer] with a center where there is expertise with this disease. The type of chemotherapy to be given has not been the subject of systematic study and can be individualized. Some use elements of a modified CHOP regimen, while others use chemotherapy used for myeloma. The addition of both rituximab and siltuximab should be considered in these patients.
 
This patient received combination chemotherapy with bortezomib, dexameathasone, thalidomide, adriamycin, etoposide, and cyclophosphamide as well as rituximab and siltuximab. His symptomatology, renal function, and other laboratory parameters rapidly normalized and his lymphadenopathy shrank significantly as well. However, the capillary leak syndrome took 8 to 10 weeks to fully resolve. In view of the fulminant onset and severity of the illness, this patient is at obvious risk for future relapse. The patient was therefore [started] on a maintenance regimen of siltuximab. Some have used immunomodulatory drugs such as cyclosporin, but no data exist with regard to the best approach.

Guess the Diagnosis: Case 2

Mark F. is a 25-year-old law school student from Florida with a 3-week history of severe fatigue, night sweats, and weight loss; he has also reported high fevers for the past week. He did not complain of joint pain.
  • He presents to the emergency department complaining of abdominal pain. His past medical history is notable for enlarged thyroid incidentally found 5 years before; family history relevant for an aunt with rheumatoid arthritis
  • Physical exam was notable for generalized lymphadenopathy (1-2 cm), hepatosplenomegaly, bilateral pleural effusions, ascites, and 4+ peripheral edema. Laboratory findings show anemia (7 gm/dL), elevated CRP (150 mg/L), ESR (120mm/hr), creatinine (3.0 mmol/L), Albumin of 2.1 g/dL and normal immunoglobulin levels (IgG: 1100 mg/dL, IgA: 300 mg/dL, IgM 200 mg/dL), low platelets (50,000/mL), positive ANA 1:160 with a speckled pattern. RhF was negative. Coagulation screen was not suggestive of DIC. LDH was normal
The patient was admitted for further assessment.
  • Regressed germinal centers, scattered hyperplastic follicles, preserved architecture with patent peripheral sinuses and florid interfollicular plasmacytosis with no light chain restriction
  • Rheumatologist diagnosed the patient with SLE and treated with high-dose steroids; this did not result in a major improvement in symptoms, laboratory parameters or lymphadenopathy
Mark’s SLE diagnosis was reviewed and further testing was performed:
  • The patient was believed to be too sick to be taken to the OR to undergo a lymph node biopsy, so a bone marrow biopsy was performed. Bone marrow showed a hypercellular marrow with mild increase in polyclonal plasma cells and moderate reticulin fibrosis
  • Laboratory work: Negative dsDNA, anti-Smith and anti-phopsholipid antibodies with normal complement levels; ANCA and anti-streptolysis O titer are negative. No M protein on protein electrophoresis. 24-hour urine showed mild proteinuria. Monospot negative. TSH, T4, and T3 normal. Normal thyroglobulin and thryoid peroxidase antibodies. Urinary sediment is negative as are urine and blood cultures. IL-6 is 6 pg/mL
  • CT-PET: generalized lymphadenopathy with low-positive FDG uptake
  • Without a clear diagnosis, a lymph node biopsy was performed of the cervical chain: Regressed germinal centers, scattered hyperplastic follicles, preserved architecture with patent peripheral sinuses; florid interfollicular plasmacytosis, prominent vascularization with absence of light chain restriction. Negative LANA-1, IgG4, and EBER stains. Negative PCR for B-cell clonality
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