A unique case of rituximab-related posterior reversible encephalopathy syndrome in a heart transplant recipient with posttransplant lymphoproliferative disorder.

Rituximab is commonly used as a first line therapy to treat posttransplant lymphoproliferative disorders (PTLDs). It has also proved useful in the management of refractory antibody mediated graft rejection. We report an unusual case in which a heart transplant recipient being treated with rituximab for PTLD developed altered mental status, hallucinations and visual symptoms and magnetic resonance imaging (MRI) findings of symmetrical enhancement suggestive of posterior reversible leukoencephalopathy syndrome (PRES). Resolution of these clinical symptoms and radiological findings after discontinuation of therapy confirmed the diagnosis. This is the first case of PRES seen due to rituximab in a heart transplant recipient. Another unique feature of the case is the development of PRES after second cycle of rituximab as compared to prior reports in nonheart transplant patients in which the syndrome developed after first dose administration. The objective of this case report is to increase the awareness of this rare entity amongst immunocompromised transplant patients.

A novel therapeutic approach to the treatment of scleroderma-associated pulmonary complications: safety and efficacy of combination therapy with imatinib and cyclophosphamide.

OBJECTIVE: Scleroderma-related interstitial lung disease (SSc-ILD) has limited therapeutic options due to unclear pathogenesis. Recently, PDGF receptor (PDGFR) amplification has been postulated to cause fibrosis. We hypothesized that a combination of immunosuppressive agents, e.g. cyclophosphamide (CYC) and imatinib (PDGFR inhibitor), might be useful for treating SSc-related ILD. Our objective was to evaluate the safety and efficacy of this combination therapy in scleroderma-related pulmonary disease. METHODS: Five patients with advanced SSc-ILD underwent comprehensive cardiopulmonary evaluation, followed by administration of oral imatinib (200 mg/day) and intravenous CYC (500 mg every 3 weeks). Safety was assessed by close monitoring of complete blood count, liver and cardiac functions. Efficacy was evaluated by measuring pulmonary functions at 6 and 12 months. RESULTS: Of the five patients in the study, four had severe and one had mild restrictive lung disease. All patients tolerated the combination treatment without myelosuppression, deterioration of liver functions or cardiac status. Only one patient had mild fluid overload requiring diuretics. Two patients completed 1 yr of treatment. Only the patient with mild restrictive lung disease showed improvement in pulmonary function. CONCLUSION: The combination of intravenous CYC and oral imatinib was well-tolerated without major side effects. Clinical improvement was seen in only the patient with mild restrictive disease. To our knowledge, this is the first study examining the safety, tolerability and efficacy of imatinib in combination with CYC in scleroderma-related pulmonary disease. Large prospective trials are needed to further determine optimal timing, dose and duration of this regimen.

Clonal T-large granular lymphocyte proliferation in solid organ transplant recipients.

Large granular lymphocytic (LGL) leukemia is a rare disorder, usually caused by clonal proliferation of CD3+ CD57+ T-LGL cells. T-cell clonality is confirmed by rearrangements of the T-cell receptor (TCR) gene. Characteristic features of T-LGL leukemia include neutropenia, anemia, and constitutional symptoms such as fatigue. Many solid organ transplant recipients experience similar symptoms and have neutropenia and anemia often attributed to immunosuppressive therapy. The purpose of this study was to determine the prevalence of T-LGL proliferation in solid organ transplant recipients and demonstrate its association with leukopenia and anemia. Twenty-three cardiac and renal transplant patients were evaluated by peripheral smear examination, flow cytometry, and TCR gene rearrangement study by polymerase chain reaction. Ten of 14 (71%) cardiac transplant patients and 4 of 9 (44%) renal transplant patients, without evidence of either allograft rejection or a viral syndrome, were found to have clonal expansion of T-LGL cells. Constitutional symptoms were present in 30% of these patients. Anemia of <10 g/dL was seen in 75% of renal transplant and 10% of cardiac transplant patients. None of these patients had significant neutropenia defined as absolute neutrophil count of 1500 mu/L. Most of the patients did not require any specific therapeutic intervention. Although TCR gene rearrangement is considered a hallmark of T-LGL leukemia, we believe that this monoclonality is not a true form of posttransplant lymphoproliferative disorder. Constant antigenic stimulus from the allograft may be the underlying etiology of clonal expansion and may contribute to cytopenias and fatigue seen in transplant patients.

The environment and cancer in New Jersey.

Tumorigenesis involves a complex series of steps. These steps are influenced by genetic predisposition and by lifestyle, tobacco and alcohol use, diet, and occupation. The way a person chooses to or is forced to live will influence the risk of developing cancer.