[Bendamustine combined with pomalidomide and dexamethasone in relapsed multiple myeloma with extramedullary disease: a multicenter study].

Objective: To evaluate the efficacy and safety of bendamustine combined with pomalidomide and dexamethasone (BPD regimen) in the treatment of relapsed multiple myeloma (MM) with extramedullary disease. Methods: This open, single-arm, multicenter prospective cohort study included 30 relapsed MM patients with extramedullary disease diagnosed in seven hospitals including Qingdao Municipal Hospital. The patients were treated with BPD regimen from February 2021 to November 2022. This study analyzed the efficacy and adverse reactions of the BPD regimen. Results: The median age of the 30 patients was 62 (47-72) years, of which 18 (60% ) had first-time recurrence. The overall response rate (ORR) of the 18 patients with first-time recurrence was 100%, of which three (16.7% ) achieved complete remission, 10 (55.5% ) achieved very good partial remission (VGPR), and five (27.8% ) achieved partial remission (PR). The ORR of 12 patients with recurrence after second-line or above treatment was 50%, including zero patients with ≥VGPR and six patients (50% ) with PR. Three cases (25% ) had stable disease, and three cases (25% ) had disease progression. The one-year progression free survival rate of all patients was 65.2% (95% CI 37.2% -83.1% ), and the 1-year overall survival rate was 90.0% (95% CI 76.2% -95.4% ). The common grade 3-4 hematology adverse reactions included two cases (6.7% ) of neutropenia and one case (3.3% ) of thrombocytopenia. The overall adverse reactions are controllable. Conclusions: The BPD regimen has good efficacy and tolerance in relapsed MM patients with extramedullary disease.

[Efficacy and safety of bendamustine-rituximab combination therapy for newly diagnosed indolent B-cell non-Hodgkin's lymphoma and elderly mantle cell lymphoma: a multi-center prospective phase II clinical trial in China].

Objectives: This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) . Methods: From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy. Results: The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients. Conclusion: Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.

[Fungal peritoneal dialysis catheter-related exit-site infection combined with tunnel infection: A case report].

Peritoneal dialysis (PD) catheter-related infection (i.e. exit-site infection and tunnel infection) is one of the main causes of PD-related peritonitis. If it cannot be controlled effectively, it could lead to PD technique failure. Therefore, timely and effective diagnosis and treatment and active prevention so as to reduce PD catheter-related infection is an important treatment goal in PD patients. PD catheter exit-site infection (ESI) and tunnel infection can be caused by a variety of microorganisms, mainly bacteria, while fungi are very rare. Few public data can be used to guide treatment of PD catheter-related fungal infection, and there is no related report in China till now. Once fungal peritonitis occurred, the patient can only withdraw from PD treatment. Here, we report a case of fungal PD catheter ESI combined with tunnel infection which was successfully diagnosed and treated in our PD center. A 71-year-old woman came to clinic because of "PD for 5 years, secretions from exit site for 8 days and aggravation for 1 day". The patient suffered from peritonitis, ESI and tunnel infection for many times in the past 5 years, involving a variety of pathogens. Eight days before, she found white viscous discharge from exit site. The subcutaneous cuff completely came out of it and rubbed its skin. The Schaefer exit-site score was 3 points. Due to the suspected ESI 2 months before, the discharge swab for bacterial culture was positive for Pseudomonas aeruginosa, so the exit site swab for bacterial culture was done again, and gentamicin injection was applied topically once a day for empirical treatment. The exit site was evaluated one day before: The subcutaneous tunnel was significantly swollen and slightly tender at 2.5 cm away from the exit site, and with white medium amount of viscous secretions. The exit-site score increased to 4 points. Routine test of dialysis effluent was (-). The bacterial culture of the exit-site discharge was rechecked twice, and Candida parapsilosis was positive for two times, so the diagnosis of fungal PD catheter ESI combined with tunnel infection was clear. Immediately we searched for the causes of ESI and tunnel infection. We found that the patient had a suspicious history of gray toenail on the foot. The toenail smear was positive for fungi and visible hyphae. She washed feet with hands every day, and washed clothes on a low bench every day, which made the exit-site and tunnel squeezed for a long time. Based on the above causes, we gave her comprehensive treatment as follows: For ESI and tunnel fungal infections, fluco-nazole was used systemically according to the drug sensitivity results, and miconazole cream was applied to the exit-site locally. For the subcutaneous cuff that came out completely, daily iodophor disinfection was given locally. At the same time, local antifungal treatment was given to the foot. We followed up closely during treatment, evaluated the exit-site every 2-3 days, and took photos of the exit-site to dynamically observe the effect. After 14 days of treatment, the exit-site score continued to be 0-1, the bacterial culture of the exit-site was negative, the cuff culture was negative, and the tunnel B-ultrasound was normal. The patient had been followed up regularly once a month for 60 months, no ESI and tunnel infection occurred. Fungal PD catheter ESI and tunnel infection are rare complications of PD. When the standard anti-infection treatment is ineffective, the possibility of fungal infection should be considered, so as to avoid prolonged use of antibiotics, aggravating fungal infection, and even progressing to fungal peritonitis, leading to withdrawal from PD. Accurate exit-site evaluation is helpful for timely diagnosis and early treatment of ESI and tunnel infection. The exit-site discharge culture and drug sensitivity test before treatment are helpful to identify the pathogen and adjust subsequent treatment. At the same time, repeated discharge culture is required in order to exclude positive fungal culture results caused by contamination. Once fungal catheter-related infection is diagnosed, we should search for possible causes actively, subsequent targeted and comprehensive treatment plays a decisive role for the prognosis of patients.

[Tryptophan metabolism in patients with primary immune thrombocytopenia with high dose of dexamethasone].

Objective: To test whether the tryptophan metabolism was abnormal in newly diagnosed ITP patients as well as in these patients after treatment with dexamethasone. Methods: Newly diagnosed patients with ITP between Jan 2014 and May 2015 were enrolled, including 14 females and 11 males, with a median age of 57 years and a median PLT count of 16 (0-32) ×10(9)/L. All patients were treated with oral dexamethasone. The expression levels of IDO mRNA and TTS mRNA in peripheral blood mononuclear cells (PBMC) were analyzed by real-time quantitative polymerase chain reaction. ELISA was used to test the concentrations of IDO and TTS in serum. The concentrations of plasma kynurenine and tryptophan were detected by high-pressure liquid chromatography. Samples from healthy individuals were tested as controls. Results: ①After dexamethasone treatment, 17 patients resulted in persistent remission, 2 cases were ineffective, and relapse occurred in 6 cases at a median follow-up of 11 (6-18) months. ②Before and after dexamethasone treatment, the relative expression of indoleamine2,3-dioxygenase (IDO) mRNA and tryptophanyl t-RNA synthetase (TTS) mRNA showed that there were significant decline in persistent remission group (2.54±0.86 vs 19.85±5.36, t=3.188, P=0.003; 0.68±0.19 vs 45.39±15.83, t=2.842, P=0.008) , compared with the normal control group, the difference was not statistically significant (t=2.313, P=0.027; t=1.127, P=0.268) . After treatment, the IDO concentration decreased [ (19.34±0.42) U/ml] and the TTS concentration was markedly increased [ (13.37±0.54) µg/L] in sustained remission group compared with that before treatment [ (21.91±0.37) U/ml] as well as that in normal controls. In particularly, abnormal tryptophan catabolism could be recovered in these 17 patients with persistent remission [Try: (19.85±5.36) µmol/L vs (19.65±4.55) µmol/L, t=1.027, P=0.311; Kyn: (0.56±0.26) µmol/L vs (0.58±0.23) µmol/L, t=2.075, P=0.448]. ③There was no obviously difference in the relative expression of IDO mRNA and TTS mRNA, the concentration of IDO and TTS and the abnormal tryptophan catabolism between before and after treatment of dexamethasone in patients without response and relapsed patients (all P>0.01) . Conclusion: The tryptophan catabolism was abnormal in ITP patients, and it could be recovered in patients with persistent remission.

Modulation of immune response with cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin-induced anergic T cells in chronic idiopathic thrombocytopenic purpura.

BACKGROUND: Platelet glycoprotein (GP)-reactive CD4+ T cells are essential for the stimulation and maintenance of antiplatelet autoantibody production in chronic idiopathic thrombocytopenic purpura (ITP). Blocking costimulatory signals could result in platelet-specific T-cell anergy. METHODS: GP-specific CD4+ T cells from patients with ITP were made anergic using cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin (CTLA4-Ig). The CTLA4-Ig-induced GP-specific anergic T cells were investigated for their inhibitory function on GP-reactive T-cell proliferation and antibody production with in vitro culture systems. To further analyze their tolerizing mechanisms, we cocultured GP-anergic T cells with dendritic cells (DCs) from patients with ITP. RESULTS: Our studies demonstrated that the anergized GP-specific T cells have profound effects on both GP-specific T-cell proliferation and antibody production. These anergic T cells exerted their suppressive effects mainly in a cell contact-dependent manner, and they were not constitutively suppressive but required specific antigen stimulation to make DCs tolerogenic. The anergic T-cell-modulated DCs could induce the autoreactive T cells to be tolerant, and this effect was not restricted to T cells of the same specificity. CONCLUSION: Our studies demonstrate the efficacy of CTLA4-Ig in suppressing the pathologic autoimmune responses in ITP. These findings provide new insights into the underlying mechanisms of anergy induction in chronic ITP.