The risk of infections in hematologic patients treated with rituximab is not influenced by cumulative rituximab dosage - a single center experience.

BACKGROUND: Rituximab, a monoclonal antibody directed against CD20, is approved for the treatment of CD20-positive B-cell Non-Hodgkin's lymphoma and rheumatologic disorders. Due to its potent activity in depleting CD20-positive lymphocytes, the influence on opportunistic infections is still under discussion. Thus, we analyzed the impact of rituximab either as monotherapy or in combination with other chemotherapeutic regimens to elucidate its role in contributing to infectious complications. METHODS: The records of consecutive patients (n = 125, 141 treatment episodes) treated with rituximab alone or in combination with chemotherapy and corticosteroids were analyzed retrospectively for the incidence, spectrum and outcome of infections during treatment and 6 months after the last course of rituximab. Univariate analysis of cofactors such as steroid medication, antiinfective prophylaxis, underlying disease and remission status were performed. RESULTS: Altogether 80 therapy episodes were associated with infections, the median number of infections per patient being 1 (range 1-7). The number of infectious complications was significantly higher in patients receiving a combination of rituximab and chemotherapy compared to rituximab monotherapy (p < 0.001). There was no statistically significant difference regarding number of rituximab courses or cumulative rituximab dosage between episodes with and without infections, respectively.Mean cumulative prednisone dosage between the cohort with infections and the one without infections showed a trend towards higher dosage of prednisone in the patients with infections (mean difference 441 mg, p > 0.14). CONCLUSIONS: Rituximab in induction treatment, either as monotherapy or combined with chemotherapy by itself does not increase the incidence or change the spectrum of infections in hematologic patients. However the possible influence of higher dosages of concomitant steroid medication on frequency of infections suggests that a heightened awareness of the potential for infectious complications should be applied to patients receiving higher doses of glucocorticoids in combination with other therapeutic regimens.

A rare case of fever of unknown origin: inflammatory myofibroblastic tumor of the liver. Case report and review of the literature.

We present the case of a rare cause of fever of unknown origin (FUO). FUO is challenging for patients as well as for physicians as there are more than 200 differential diagnoses of FUO (1,2). Pointing out a diagnosis often requires numerous noninvasive and invasive procedures that sometimes even fail to explain the fever. Our patient was admitted twice to our hospital due to remitting fever rising up to 40 degrees C without any subjective discomfort. At the first presentation no clinical focus could be identified. This included the examination of multiple blood and urine cultures, serology, autoimmune serology, transesophageal echocardiography, CT-scan of the lung and the abdomen, and bone scintigraphy. Elevated C-reactive protein (268 mg/l) decreased spontaneously and fever disappeared after 4 weeks. However, the patient was re-admitted 4 months later with identical symptoms. Multiple blood and urine cultures, serology, bone marrow examination, CT-scan of the lung and the abdomen, esophago-gastro-duodenoscopy and colonoscopy still showed no pathological findings. MRI-scan of the abdomen identified a liver tumor of 3.3 cm in diameter in segment 6 without typical signs of an adenoma, focal nodular hyperplasia or hepatocellular carcinoma. Biopsy of the suspect liver lesion revealed an inflammatory myofibroblastic tumor (inflammatory pseudotumor). After surgical resection of the tumor elevated inflammation markers as C-reactive protein normalized and fever disappeared. One year after surgery no more episodes of fever re-occurred. An inflammatory myofibroblastic tumor of the liver can be a rare cause of fever of unknown origin. MRI-scan can be an additional imaging tool to identify previously not recognized liver tumors.

Efficacy and safety of capecitabine in combination with docetaxel and mitomycin C in patients with pre-treated pancreatic, gallbladder, and bile duct carcinoma.

PURPOSE: Preclinical data indicate the improvement of the antitumor activity of capecitabine by mitomycin C and docetaxel through upregulation of thymidine phosphorylase activity. Therefore, we have established a combination regimen of these drugs (DocMitoCape), which demonstrated preliminary activity especially in bile duct and pancreatic carcinoma. METHODS: Here we report the safety and efficacy of the DocMitoCape regimen in pre-treated patients with gallbladder, bile duct, or pancreatic carcinoma. Treatment consisted of capecitabine (2,000 mg/m(2) days 1-14) in combination with docetaxel (40 mg/m(2) day 1) and mitomycin C (4 mg/m(2) day 1). Cycles were repeated on day 22. Toxicity was graded according to NCI-CTC criteria, and the antitumor activity was assessed by RECIST criteria. RESULTS: Twenty-eight pre-treated patients with a median age of 59 suffering from pancreatic, gallbladder, intra- (IHCCC) or extrahepatic (EHCCC) bile duct carcinoma were included. Eleven patients had received ≥2 lines of prior chemotherapy. A total of 183 and a median of six cycles were administered (range 1-21). The mean dose intensity was as follows (cycles 1-2/3-4; %): capecitabine 97/92, docetaxel 100/100, mitomycin C 99/100. Main adverse events grades 2/3/4 were (n): leukocytopenia 3/2/2, anemia 13/4/0, thrombocytopenia 3/1/0, nausea/vomiting 2/1/0, diarrhea 5/1/0, hand-foot-skin reaction 7/0/0. Six patients achieved partial and seven patients minor remissions, while six patients had stable disease adding to a tumor control rate of 68%. Median progression-free and overall survival was 4.5 (range 1.0-44.9) and 6.8 months (range 1.5-44.9), respectively, calculated from the start of treatment. CONCLUSION: In all, the DocMitoCape regimen exhibited a favorable safety profile and a high rate of tumor stabilizations in patients with pre-treated gallbladder, bile duct and pancreatic carcinoma. It might be considered after failure of standard regimens in these types of cancer.

Clonal expansions of CD4+ B helper T cells in autoimmune myasthenia gravis.

The weakness in myasthenia gravis (MG) is mediated by T helper cell (Th)-dependent autoantibodies against neuromuscular epitopes. So far, analyzing Th phenotypes or antigen specificities has yielded very few clues to pathogenesis. Here we adopt an alternative antigen-independent approach, analyzing T cell receptor (TCR) Vbeta usage/expansions in blood from 118 MG patients. We found major expansions (>or= five standard deviations above the mean of 118 healthy, individually age- and sex-matched controls) in diverse Vbeta in 21 patients (17.6%, p<0.001) among CD4+ T cells, and in 45 patients (38.1%, p<0.001) among CD8+ T cells. In informative probands, the expanded CD4+ cells consistently showed a Th cell phenotype (CD57+CXCR5+) and expressed Th1 cytokines. Furthermore, their expression of markers for activation, lymphocyte trafficking and B cell-activating ability persisted for >or=3 years. Surprisingly, we noted a selective decline in the expansions/their CD57 positivity while the probands' MG was improving. CDR3 spectratyping suggested mono- or oligoclonal origins, which were confirmed by the prevalent TCR Vbeta CDR3 sequences of Th cells cloned from repeat bleeds. Thus, our data provide evidence for persistent clonally expanded CD4+ B helper T cell populations in the blood of MG patients. These unexpected CD4+ expansions might hold valuable clues to MG immunopathogenesis.