Real-world Outcomes With Rituximab-based Therapy for Posttransplant Lymphoproliferative Disease Arising After Solid Organ Transplant.

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.

Post-transplant Monoclonal Gammopathy of Renal Significance: A Case Series.

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.

Successful Renal Outcome in Membranoproliferative Glomerulonephritis Following Treatment of the Underlying Subtle Clone: A Case Report.

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.

Rapidly progressive intravascular primary effusion lymphoma in an HIV-positive renal transplant recipient.

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.

The Spectrum of Renal Allograft Failure.

BACKGROUND: Causes of "true" late kidney allograft failure remain unclear as study selection bias and limited follow-up risk incomplete representation of the spectrum. METHODS: We evaluated all unselected graft failures from 2008-2014 (n = 171; 0-36 years post-transplantation) by contemporary classification of indication biopsies "proximate" to failure, DSA assessment, clinical and biochemical data. RESULTS: The spectrum of graft failure changed markedly depending on the timing of allograft failure. Failures within the first year were most commonly attributed to technical failure, acute rejection (with T-cell mediated rejection [TCMR] dominating antibody-mediated rejection [ABMR]). Failures beyond a year were increasingly dominated by ABMR and 'interstitial fibrosis with tubular atrophy' without rejection, infection or recurrent disease ("IFTA"). Cases of IFTA associated with inflammation in non-scarred areas (compared with no inflammation or inflammation solely within scarred regions) were more commonly associated with episodes of prior rejection, late rejection and nonadherence, pointing to an alloimmune aetiology. Nonadherence and late rejection were common in ABMR and TCMR, particularly Acute Active ABMR. Acute Active ABMR and nonadherence were associated with younger age, faster functional decline, and less hyalinosis on biopsy. Chronic and Chronic Active ABMR were more commonly associated with Class II DSA. C1q-binding DSA, detected in 33% of ABMR episodes, were associated with shorter time to graft failure. Most non-biopsied patients were DSA-negative (16/21; 76.1%). Finally, twelve losses to recurrent disease were seen (16%). CONCLUSION: This data from an unselected population identifies IFTA alongside ABMR as a very important cause of true late graft failure, with nonadherence-associated TCMR as a phenomenon in some patients. It highlights clinical and immunological characteristics of ABMR subgroups, and should inform clinical practice and individualised patient care.

Kikuchi-Fujimoto disease: a rare but important differential diagnosis for lymphadenopathy.

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.