New drug treatments still do not improve the prognosis of extramedullary multiple myeloma (EMM) patients. Luckily, high-dose chemotherapy can raise the prognosis, but is intolerant to most patients because of drug cytotoxicity. Nanoparticles (NPs) are used as drug carriers to prolong drug circulation time, control drug release, reduce drug toxicity and bioavailability, and target specific sites. In this work, doxorubicin (DOX) was loaded in polyethylene glycol-modified cadmium telluride quantum dots (PEG-CdTe QDs). PEG-CdTe-DOX facilitated intracellular drug accumulation through polyethylene organizational compatibility and released DOX into the microenvironment in a pH-controlled manner, which enhanced the therapeutic efficacy and the apoptosis rate of myeloma cells (PRMI8226). PEG-CdTe-DOX improved the anti-tumor activity of DOX by regulating the protein expressions of apoptosis-associated genes. In summary, PEG-CdTe-DOX provides a specific and effective clinical treatment for EMM patients.

Multiple myeloma (MM), a bone marrow-resident hematological malignancy of plasma cells, has remained largely incurable despite the recent advancement in novel therapies. The heterogeneity of myelom...

Extramedullary multiple myeloma (EMM) is defined as the presence of plasma cells outside the bone marrow of multiple myeloma patients, and its prognosis is poor. High-dose chemotherapy with autologous stem cell transplantation, as a good option on early lines of therapy, has retained the survival benefit of youny EMM patients, but is intolerant for the majority of old patients because of drug cytotoxicity. To essentially address the intolerance above, we designed a CXCR4-PEG-CdTe-DOX (where CXCR4: chemokine receptor 4; PEG-CdTe: polyethylene glycol-modified cadmium telluride; DOX:doxorubicin) nanoplatform. First, CXCR4 is highly expressed in extramedullary plasma cells. Second, PEG-CdTe a drug carrier that controls drug release, can reduce adverse reactions, prolong drug (e.g, DOX) circulation time in the body, and form a targeting carrier after connecting antibodies. In vitro experiments showed CXCR4-PEG-CdTe-DOX facilitated intracellular drug accumulation through active CXCR4 targeting and released DOX into the microenvironment in a pH-controlled manner, enhancing the therapeutic efficacy and apoptosis rate of myeloma cells (U266). Therefore, targeted chemotherapy mediated by CXCR4-PEG-CdTe-DOX is a promising option for EMM treatment. Graphical

Richter's syndrome, the development of high-grade non-Hodgkin lymphoma in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), may be triggered by viral infections (eg, Epstein-Barr virus infection). Herein, we report an unusual case of CD5-negative CLL/SLL patient with gastrointestinal mantle cell lymphoma (MCL) and hepatitis B virus infection. CLL/SLL was diagnosed based on lymph node immunohistochemistry and bone marrow pathology. This patient was treated with seven cycles of multi-agent chemotherapy. During treatment, the hepatitis B viruses were activated. Then, after 20 months of antiviral treatment with entecavir, he developed abdominal discomfort and abdominal lymphadenopathy and was diagnosed with MCL based on intestinal biopsy. This work indicates that the hepatitis B virus in patients with CLL/SLL may accelerate the progress or transformation to MCL.

Background: Double M-protein multiple myeloma (DMP-MM) is an uncommon phenotype characterized by more than one detectable monoclonal component on serum protein electrophoresis and/or immunofixation electrophoresis. Its clinical significance is uncertain, particularly when a secondary component appears after therapy. Methods: We retrospectively studied 21 patients with DMP-MM treated at Anqing Municipal Hospital. Patients were classified as diagnostic DMP-MM when double M-protein was present at diagnosis (n=10) or treatment-emergent DMP-MM when a secondary component appeared after therapy (n=11). M-protein patterns, treatment response, progression-free survival (PFS), overall survival (OS), and exploratory Cox models were analyzed from double M-protein recognition. In treatment-emergent cases, pre-treatment M-protein and bone-marrow flow-cytometric minimal residual disease (MRD; sensitivity 10^-5) at secondary-component detection were also evaluated. All analyses were exploratory. Results: Median age was 66 years (range, 51-84). At initial diagnosis, M-protein was comparable between diagnostic and later treatment-emergent DMP-MM (34.58 vs 24.67 g/L; P = 0.705). In treatment-emergent cases, M-protein decreased from 24.67 to 5.34 g/L at secondary-component recognition (paired P = 0.002), indicating a treatment- and timing-related effect. The newly appearing component had a median concentration of 1.41 g/L (range, 0.39-23.18). PFS events occurred in 8/10 diagnostic and 5/11 treatment-emergent cases; deaths occurred in 6/10 and 4/11, respectively. Two-year PFS was 40.0% (95% CI, 12.3%-67.0%) versus 62.3% (95% CI, 27.7%-84.0%; log-rank P = 0.297), and 2-year OS was 48.0% (95% CI, 16.1%-74.5%) versus 72.7% (95% CI, 37.1%-90.3%; log-rank P = 0.403). Cox estimates were imprecise for PFS (HR 0.557, 95% CI 0.181-1.712) and OS (HR 0.586, 95% CI 0.165-2.084). Conclusions: Diagnostic and treatment-emergent DMP-MM represent different temporal clinical contexts rather than exchangeable biological groups. Lower M-protein burden at treatment-emergent recognition largely reflects prior therapy and measurement timing. Diagnostic DMP-MM showed a numerically less favorable post-recognition survival trajectory, whereas treatment-emergent secondary M-protein did not show an adverse prognostic signal. Component kinetics, MRD context, and treatment exposure should guide interpretation.

Multiple myeloma (MM), a bone marrow-resident hematological malignancy of plasma cells, has remained largely incurable despite the advancement of novel therapies in recent years. Because of the heterogeneity of myeloma cells, risk stratification of MM is important for making therapeutic regimens. Nevertheless, no immunohistochemical (IHC) predictive and prognostic marker of MM has been constructed yet. Herein, the prognostic value of C-X-C motif chemokine receptor 4 (CXCR4) expression in 48 newly diagnosed MM patients was explored using IHC. Correlations between CXCR4 expression and clinical features of MM were analyzed. CXCR4-positive patients significantly outperformed CXCR4- negative patients in both 3-year estimated overall survival (93.8% vs 45.8%) and progression-free survival (57.1% vs 40.9%). The incidence of extramedullary lesions in CXCR4-negative patients increased significantly compared with CXCR4-positive patients. Plasma cells that reduce CXCR4 expression have poor prognosis and increase the incidence of extramedullary lesions.