Role of 18F-FDG PET/CT in the Management of Patients Affected by HHV-8-Associated Multicentric Castleman’s Disease

Our aim was to investigate the usefulness of 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the diagnosis, treatment response evaluation, and follow-up of human herpesvirus-8 (HHV-8)-associated multicentric Castleman’s disease (MCD). Fifteen patients with histologically diagnosis of HHV-8-associated MCD were retrospectively included. For all patients, a 18F-FDG PET/CT scan was performed before any treatment for diagnosis and PET/CT scans after Rituximab (4 cycles) for the evaluation of treatment response; moreover, 22 PET/CT were performed during the follow-up to check disease status. To evaluate treatment response, we applied Deauville criteria. PET/CT findings were compared with other conventional imaging (CI) findings. At diagnosis, 18F-FDG PET/CT showed an increased FDG-uptake in all cases corresponding to lymph nodes and confirming the MCD. The average SUVmax of the FDG avid lesions were 8.75, average lesion-to-liver SUVmax ratio was 3.6, and average lesion-to-blood pool SUVmax ratio was 3.9. After first-line therapy, 18F-FDG PET/CT resulted negative (Deauville score < 4) in seven patients and positive in the remaining eight (Deauville score 4–5). A negative restaging PET/CT was associated with a lower risk of relapse. During follow-up, PET/CT detected the presence of relapse or progression in 5 (23%) cases with an accuracy higher than CI. 18F-FDG PET/CT seems to be an useful tool in studying HHV-8-associated MCD both at diagnosis and during follow-up.

Membranous nephropathy associated with multicentric Castleman’s disease that was successfully treated with tocilizumab: a case report and review of the literature

Background Multicentric Castleman’s disease is a life-threatening disorder involving a systemic inflammatory response and multiple organ failure caused by the overproduction of interleukin-6. Although renal complications of Castleman’s disease include AA amyloidosis, thrombotic microangiopathy, and membranoproliferative glomerulonephritis, membranous nephropathy is relatively rare. We experienced a case of secondary membranous nephropathy associated with Castleman’s disease. Case presentation The patient was a 43-year-old Japanese man who had shown a high zinc sulfate value in turbidity test, polyclonal hypergammaglobulinemia, anemia, and proteinuria. A physical examination revealed diffuse lymphadenopathy, an enlarged spleen and papulae of the body trunk. A skin biopsy of a papule on the patient’s back showed plasma cells in the perivascular area and he was diagnosed with multicentric Castleman’s disease, plasma cell variant. Kidney biopsy showed the appearance of bubbling in the glomerular basement membranes in Periodic acid methenamine silver stain and electron microscopy revealed electron dense deposits within and outside the glomerular basement membranes. Since immunofluorescence study showed predominant granular deposition of IgG1 and IgG2, he was diagnosed with secondary membranous nephropathy associated with Castleman’s disease. He was initially treated with prednisolone alone, however his biochemical abnormalities did not improve. After intravenous tocilizumab (700 mg every 2 weeks) was started, his C-reactive protein elevation, anemia, and polyclonal gammopathy improved. Furthermore, his urinary protein level declined from 1.58 g/gCr to 0.13 g/gCr. The prednisolone dose was gradually tapered, then discontinued. He has been stable without a recurrence of proteinuria for more than 6 months. Conclusions Tocilizumab might be a treatment option for secondary membranous nephropathy associated with Castleman’s disease.

A Prospective, Multicenter Study of Bortezomib, Cyclophosphamide and Dexamethasone in Relapsed/Refractory Idiopathic Multicentric Castleman's Disease

【Introduction】Relapsed and refractory idiopathic Multicentric Castleman's disease (R/R iMCD) is a challenge for hematologists with poor prognosis. In the current study, we aimed to investigate the efficacy and safety of BCD regimen (bortezomib, cyclophosphamide, dexamethasone) in R/R iMCD patients. 【Methods】From 2017 to 2020, R/R iMCD patients who met the diagnostic criteria (Blood. 2017;129(12):1646-1657) were enrolled from Peking Union Medical College Hospital and Peking University First Hospital. BCD regimen (botezomib 1.3mg/m2 weekly, cyclophosphamide 300mg/m2 weekly, dexamethasone 40mg weekly out of a 28-day cycle) was administered for 9 cycles; after 9 cycles of BCD treatment, BD regimen (botezomib 1.3mg/m2 twice a week, dexamethasone 20mg twice a week) was used as maintenance for the next 1 year. Treatment was discontinued after 1 year of maintenance or until treatment failure which was defined as death or progression of disease. Treatment responses were evaluated according to the treatment guidelines published recently (Blood. 2018;132(20):2115-2124). Biochemical, lymph node and symptomatic responses were evaluated which all contributed to the assessment of overall response. An overall CR (complete response) requires a complete biochemical, lymph node, and symptomatic response. An overall PR (partial response) requires nothing less than a PR across all categories, but not meeting criteria for CR. Overall SD (stable disease) requires no PD in any of the categories and not meeting the criteria for CR or PR. An overall PD (progression of disease) occurs when any category has a PD. 【Results】Data from 20 patients who were followed for at least 6 months were analyzed. The median age was 42 years (range 22-65 years), with a male: female ratio of 1.5:1. Six patients were defined as 'refractory' and fourteen patients were classified as 'relapsed'. ALL patients (n=20) received BCD regimen and was followed every three months. As for biochemical response, 75.0% (n=15) achieved PR; 15.0% (n=3) were assessed as SD; 10% (n=2) were evaluated as PD. As for lymph node response, 5% (n=1) achieved CR and 75.0% (n=15) achieved PR; 10% (n=2) had SD while 10% (n=2) suffered from PD. As for symptomatic response, 85% (n=17) had PR (45%) or CR (40%); 15% (n=3) experienced PD. After incorporation of all the above evaluation results, 75.0% (n=15) patients achieved overall treatment responses (all were overall PR); 10% (n=2) patients were evaluated as overall SD; 15% (n=3) patients suffered from overall PD and were evaluated as treatment failure. As for safety issues, no patient suffered from Grade 3 or above adverse events and no patient died from treatment-related toxicity. With a median follow-up of 22 months (range 8-38), 40.0% (n=8) patients experienced disease of progression and two of them died from progression of iMCD. The estimated 1-year progression-free survival (PFS) and overall survival (OS) were 85.0% and 90.0% respectively (Fig 1). 【Conclusions】BCD regimen is an effective and safe treatment option for relapsed/refractory iMCD patients. Fig 1. Kaplan-Meier survival analyses of relapsed/refractory iMCD patients receiving BCD regimen showing the overall survival and progression-free survival. Figure 1 Disclosures No relevant conflicts of interest to declare.