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Monoclonal gammopathy of renal significance (MGRS) is a new concept with evolving evidence for treatment. MGRS in the transplant kidney is a rare cause of renal transplant dysfunction that can lead to graft loss. Most cases of post-transplant MGRS are due to recurrent disease. Clone-specific chemotherapy is required to target the underlying clone, and this may improve graft survival; however, this can be challenging, as most patients are elderly with age-related comorbidities and may have complications associated with increasing immunosuppression. Here, we report 3 cases of renal allograft MGRS, and each case highlights different challenges in the diagnosis and management of this condition.

Background Optimal upfront therapy for posttransplant lymphoproliferative disease (PTLD) arising after solid organ transplant remains contentious. Rituximab monotherapy (R-Mono) in unselected patients has shown a lack of durable remissions. Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-based chemotherapy confers improved response rates, although concerns exist about toxicity. Methods This multicenter retrospective study reports outcomes for adults with biopsy-proven B-cell PTLD treated initially with R-Mono or Rituximab plus CHOP (R-CHOP). Selection of therapy was made according to physician preference. Results Among 101 patients, 41 received R-Mono and 60 had R-CHOP. Most (93%) had undergone renal or liver transplantation. R-CHOP showed a trend toward improved complete (53% versus 71%; P = 0.066) and overall (75% versus 90%; P = 0.054) response rates. In the R-Mono group, 13 of 41 (32%) subsequently received chemotherapy, while 25 of 41 (61%) remained progression-free without further therapy. With median follow-up of 47 months, overall survival (OS) was similar for R-Mono and R-CHOP, with 3-year OS of 71% and 63%, respectively (P = 0.722). Non-PTLD mortality was 3 of 41 (7%) and 4 of 60 (7%) within 12 months of R-Mono or R-CHOP, respectively. The International Prognostic Index was statistically significant, with low- (0-2 points) and high-risk (≥3 points) groups exhibiting 3-year OS of 78% and 54%, respectively (P = 0.0003). In low-risk PTLD, outcomes were similar between therapies. However, in high-risk disease R-Mono conferred an inferior complete response rate (21% versus 68%; P = 0.006), albeit with no impact on survival. Conclusions Our data support R-Mono as initial therapy for PTLD arising after renal or liver transplantation. However, upfront R-CHOP may benefit selected high-risk cases in whom rapid attainment of response is desirable.

Membranoproliferative glomerulonephritis (MPGN) secondary to a monoclonal gammopathy is a rare glomerular disease and is defined as a monoclonal gammopathy of renal significance. The disease is characterized by glomerular monotypic immunoglobulin deposits and specific changes on light microscopy and electron microscopy. Immunochemistry is required to establish monoclonality, and electron microscopy helps to characterize the deposits ultrastructurally. Investigation for the underlying monoclonal protein should be done. We report a case of MPGN secondary to monoclonal gammopathy of renal significance that responded to treatment of the underlying clone with chemotherapy, resulting in improvement in renal function. Patients with MPGN and immunoglobulin deposition should be evaluated for a monoclonal protein to guide the management strategy.

We describe the clinical and post-mortem findings of a case of rapidly progressive, ultimately fatal primary effusion lymphoma (PEL) arising in an HIV-positive man 2 years after renal transplantation. Disseminated multi-organ involvement associated with a peculiar intravascular pattern of growth, as seen in this case, has only been reported once previously. This is also, to our knowledge, the first detailed description of a lymphoma arising post-transplant in an HIV-positive patient.

A 23-year-old man presented with a 6-week history of fevers, cervical lymphadenopathy and fatigue. A CT of the neck, chest, abdomen and pelvis showed left cervical lymphadenopathy, enlarged lymph nodes in the axilla and groin and hepatomegaly. A left cervical excisional lymph node biopsy was undertaken and the histopathological findings were consistent with Kikuchi-Fujimoto disease. He was treated with high-dose prednisolone for 1 week, which was then tapered. Generalised arthralgia and daily episodes of malaise were experienced for a subsequent 2 months following the cessation of corticosteroids. The condition lasted 4 months from the onset of symptoms. This case report highlights the importance of including Kikuchi-Fujimoto disease as a differential diagnosis for lymphadenopathy. Kikuchi-Fujimoto disease has commonly been mistaken for tuberculosis and lymphoma, and unnecessary exposure to agents used to treat these conditions can be avoided by prompt histological diagnosis.

Background Treatment of transformed follicular lymphoma (TFL) remains undefined and there is no consensus on the role of consolidation after induction chemotherapy. Outcomes for TFL in the pre-rituximab era were poor with a reported median overall survival (OS) of only 1.7 years1. This study investigates whether R-CHOP is an effective therapy for patients with TFL and which patient factors present at transformation help to predict outcome. Methods 1900 lymphoma diagnoses from January 2000 - June 2012 were retrospectively screened and identified 60 patients with transformed indolent lymphoma. 40 eligible patients with histologically confirmed TFL were identified for this study. Overall survival (OS) and progression-free survival (PFS) were the primary study end-points. Results The median follow up time for the cohort was 66 months (interquartile range (IQR) - 25-92 months) and the median age at diagnosis of TFL was 60 years (52-68 years). The majority (60%) of the cohort had high-grade (HG) transformation subsequent to diagnosis of follicular lymphoma (asynchronous TFL) with a median time to transformation of 48 months (24-78 mo). 32.5% of patients were simultaneously diagnosed with follicular lymphoma (FL) and HG disease (synchronous TFL). In a minority (3%), FL was diagnosed after HG disease. Univariate analysis revealed no significant relationship between outcome and patient age, sex or disease stage. However, patients with an elevated LDH (defined as >1.5x the upper limit of normal) at the time of diagnosis had a significantly reduced OS (5 mo vs 86 mo; p=0.003) and PFS (2.25 mo vs 56 mo; p=0.02). When compared with synchronous TFL, patients with asynchronous TFL had a reduced median survival (9 mo vs 67 mo; p=0.03) and PFS (7 mo vs 67 mo; p=0.003). When multivariate analysis is performed, elevated LDH and asynchronous TFL remain significant factors in determining PFS (p=0.021 and p=0.008 respectively). However, only elevated LDH remains a significant factor in determining OS (p=0.002). 25/40 patients were treated with R-CHOP for TFL, with the remaining 15 either treated palliatively: steroids and etoposide (n=8), radiotherapy (n=1); with CHOP (n=4) or another R-chemo (n=2; R-ESCHAP; R-CVP). All R-CHOP treated patients were rituximab naïve. Of the 25 patients treated with R-CHOP: 20 were treated with R-CHOP alone, 2 received R-CHOP and another chemotherapy, 1 had R-CHOP and autograft and 2 received R-CHOP and allograft. In our cohort, R-CHOP treated patients had a 5-year OS of 62%, a median OS of 86 months (31-120 months) and PFS of 56 months (14-86 months). This represents a marked improvement in outcome compared to historic data, which showed a 5-year OS of 33% for TFL patients treated with CHOP alone2. The patients treated with R-CHOP alone (without further chemotherapy, autograft or allograft) had a similar outcome with a median OS of 86 months (37-120 months) and median PFS of 56 months (11-86 months). Conclusion Our results demonstrate the excellent outcomes achieved with R-CHOP alone in rituximab naïve patients with transformed follicular lymphoma. Patients with TFL presenting with synchronous disease and non-elevated LDH have significantly improved outcomes. In such patients, we may consider reserving consolidation with autograft or allograft for the future. 1. Al-Tourah, A. J. et al. Population-based analysis of incidence and outcome of transformed non-Hodgkin’s lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology26,5165–9 (2008). 2. Al-Tourah, A. J. et al. Addition of Rituximab to CHOP Chemotherapy Significantly Improves Survival of Patients with Transformed Lymphoma. Blood (ASH Annual Meeting Abstracts)110, (2007). Disclosures: Chaganti: Roche: Membership on an entity’s Board of Directors or advisory committees, Receipt of travel grant Other.

Pruritic papular eruption of HIV (PPE) represents an intensely pruritic papular rash with greatest severity on the extensor surfaces of extremities. It is one of the most common cutaneous manifestations in HIV-infected individuals, in whom prevalence ranges between 11% and 46% depending on geographic location.1, 2, 3, 4, 5 Persistent or recurrent PPE despite effective antiretroviral therapy (ART) may be associated with higher viral load at ART initiation.6 Although pathogenesis is uncertain, an exaggerated immunologic reaction to arthropod bites has been suggested because of geographical restriction to the tropics, localization to the extremities, similarity in histology, and increased peripheral eosinophil counts.1 The optimum treatment pathway is poorly defined because of lack of evidence for different treatment modalities. We report a case of recurrent PPE responding well to oral thalidomide during a 3-month treatment period.