Non-secretory multiple myeloma expressed as multiple extramedullary plasmacytoma with an endobronchial lesion mimicking metastatic cancer:A case report

BACKGROUND Non-secretory multiple myeloma(MM)is a rare condition that accounts for only 3%of MM cases and is defined by normal serum and urine immunofixation and a normal serum free light chain ratio.Non-secretory MM with multiple extramedullary plasmacytomas derived from endobronchial lesions is extremely rare and can be misdiagnosed as metastasis of solid cancer.CASE SUMMARY A 36-year-old man presented with progressive facial swelling and nasal congestion with cough.Various imaging studies revealed an endobronchial mass in the left bronchus and a large left maxillary mass with multiple destructive bone metastatic lesions.He initially presented with lung cancer and multiple metastases.However,pathologic reports showed multiple extramedullary plasmacytomas in the left maxilla and the left bronchus.There was no change in the serum and urine monoclonal protein levels,and no abnormalities were observed in laboratory examinations,including hemoglobin,calcium,and creatinine levels.The bone marrow was hypercellular,with 13.49%plasma cells.The patient was diagnosed with non-secretory MM expressed as multiple extramedullary plasmacytomas with endobronchial lesions in a rare location.Radiation therapy for symptomatic lesions with high-dose dexamethasone was started,and the size of the left maxillary sinus lesion dramatically decreased.In the future,chemotherapy will be administered to control lesions in other areas.CONCLUSION We present a rare case of non-secretory MM with multiple extramedullary plasmacytoma with an endobronchial lesion.

Non-secretory multiple myeloma with lytic bone lesions about a new observation

Non-secretory myeloma is a rare variety of multiple myeloma. Classical techniques of chronic secretion’s research don’t find any immunoglobulin monoclonal peak in the patient’s blood. Lytic bone lesions are rare in this type of myeloma. We report the case of a patient in whom we confirmed multiple myeloma by bone marrow aspiration and we have classified stage III of Durie and Salmon in view of hypercalcemia, anemia, and lytic lesions observed. However, we could not isolate a secretion of monoclonal immunoglobulin in blood but urinary secretion was evident by proteinuria and urinary light chains. The radiographs of our patient found diffuse osteolysis and practice of sternal puncture confirmed multiple myeloma. Our case is original because of rarity on non secretory myeloma particularly with diffuse osteolytic lesion.

Development of a cell adhesion-based prognostic model for multiple myeloma:Insights into chemotherapy response and potential reversal of adhesion effects

Multiple myeloma(MM)is a hematologic malignancy notorious for its high relapse rate and development of drug resistance,in which cell adhesion-mediated drug resistance plays a critical role.This study integrated four RNA sequencing datasets(CoMMpass,GSE136337,GSE9782,and GSE2658)and focused on analyzing 1706 adhesionrelated genes.Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes,including KIF14,TROAP,FLNA,MSN,LGALS1,PECAM1,and ALCAM,which demonstrated the strongest associations with poor overall survival(OS)in MM patients.To comprehensively evaluate the impact of cell adhesion on MM prognosis,an adhesion-related risk score(ARRS)model was constructed using Lasso Cox regression analysis.The ARRS model emerged as an independent prognostic factor for predicting OS.Furthermore,our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs,protein kinase inhibitors,and drugs targeting the PI3K/Akt/mTOR signaling pathway.Nevertheless,we identified promising drug candidates,such as tirofiban,pirenzepine,erlotinib,and bosutinib,which exhibit potential in reversing this resistance.In vitro,experiments employing NCIH929,RPMI8226,and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs.By employing siRNA-mediated knockdown of the key ARRS model gene KIF14,we observed suppressed proliferation of NCIH929 cells,along with decreased adhesion to BMSCs and fibronectin.This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM.Additionally,potential molecular mechanisms underlying adhesion-related resistance are proposed,along with viable strategies to overcome such resistance.These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.

Infection in Multiple Myeloma: Microbiological Profile and Prognosis in Senegalese Patients

Introduction: Infections are additional factors of morbidity and mortality in multiple myeloma (MM), and the current recommendation is antibiotic prophylaxis. In sub-Saharan Africa, few data on infectious complications of MM are available. We aim to describe the microbiological features of infections in MM, and their impact on survival in Senegalese patients. Methods: A retrospective (January 2005-January 2022), analytic, multicenter study on infections in patients followed for MM (IMWG criteria) in Senegalese clinical hematology services. The socio-epidemiological, diagnostic, microbiological, evolutionary and survival aspects were analyzed. Results: The study included 106 patients with multiple myeloma who had an infection at admission or during the treatment. Ten patients have the comorbidity (hypertension, lupus, type 2 diabetes). These patients had 136 infectious events identified at diagnosis (79.2%) or during chemotherapy (20.8%). The sites of infection are lung (42.6%), urinary (29.4%), dermatological (6.6%), digestive (5.2%), osteoarticular (4.4%), ear, nose and throat (3.7%), central nervous system (1.5%), or without site. We recorded 26.4% of patients with multi-site infections. The causal pathogens are bacteria (Gram-negative bacilli: 22.1%;Gram positive bacilli: 9.5%, Mycobacterium tuberculosis: 13.3%), parasitique (plasmodium falciparum 6.6%), viruses (SARS-COV2: 2.9%, VZV: 2.2%) and fungal (2.9%). Survival was reduced in patients who had an infection at the time of multiple myeloma diagnosis (p: 0.189) and those who had multiple infectious foci (p: 0.011). Conclusion: Infections in multiple myeloma are more frequent at diagnosis. The germs are varied and mostly bacteria, particularly gram-negative bacteria, and Kochs bacillus. Our study reveals that multiple infectious foci are a poor prognosis factor. It is necessary to evaluate the infectious risk early, and to adopt an antibiotic prophylaxis based on our tropical environment.

Analysis of the role of dihydromyricetin derived from vine tea(Ampelopsis grossedentata)on multiple myeloma by activating STAT1/RIG-I axis

Multiple myeloma(MM)is a plasma cell malignancy and remains incurable as it lacks effective curative approaches;thus,novel therapeutic strategies are desperately needed.The study aimed to explore the therapeutic role of dihydromyricetin(DHM)in MM and explore its mechanisms.Human MM and normal plasma samples,human MM cell lines,and normal plasma cells were used for in vitro experiments.Cell counting kit-8(CCK-8),flow cytometry,and trans-well assays were performed for the assessment of cell viability,apoptosis,migration,and invasion,respectively.Quantitative real-time polymerase chain reaction(qRT-PCR)was employed to assess the mRNA expression of signal transducer and activator of transcription 1(STAT1)and retinoic acid-inducible gene I(RIG-I).Western blotting was employed to assess E-cadherin,N-cadherin,signal transducer,STAT1,p-STAT1,and RIG-I protein expression.A tumor xenograft model was used for in vivo experiments.Here,dihydromyricetin(DHM)dose-dependently restrained viability,apoptosis,migration,and invasion,and facilitated apoptosis of U266 cells.After DHM treatment,the Ecadherin level was increased and the N-cadherin level was decreased in U266 and RPMI-8226 cells,suggesting the inhibitory effects of DHM on epithelial-mesenchymal transition(EMT)in MM.Besides,the levels of p-STAT1/STAT1 and RIG-I were down-regulated in MM.However,the STAT1 inhibitor fludarabine undid the suppressive effect of DMH on the malignant characteristics of U266 cells.Also,DHM inhibited MM tumor growth and EMT,and activated STAT1/RIG-I pathway in vivo.Collectively,this study first revealed that DHM can restrain EMT and tumor growth in MM by activating STAT1/RIG-I signaling,which provides a novel drug for the treatment of MM.

Enhanced Precision Therapy of Multiple Myeloma Through Engineered Biomimetic Nanoparticles with Dual Targeting

Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@M.The results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in vivo.Additionally,this material demonstrated a capability for drug release triggered by low pH conditions.Moreover,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM cells.Notably,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice.Therefore,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.

Multiple myeloma survival in New South Wales, Australia, by treatment era to 2020

Objective: Australia has relatively high multiple myeloma(MM) incidence and mortality rates. Advancements in MM treatment over recent decades have driven improvements in MM survival in high-income countries;however, reporting in Australia is limited. We investigated temporal trends in population-wide MM survival across 3 periods of treatment advancements in New South Wales(NSW), Australia.Methods: Individuals with an MM diagnosis in the NSW Cancer Registry between 1985 and 2015 with vital follow-up to 2020, were categorized into 3 previously defined treatment eras according to their diagnosis date(1985±1995, chemotherapy only;1996±2007, autologous stem cell transplantation;and 2008±2015, novel agents including proteasome inhibitors and immunomodulatory drugs). Both relative survival and cause-specific survival according to Fine and Gray's competing risks cumulative incidence function were calculated by treatment era and age at diagnosis.Results: Overall, 11,591 individuals were included in the study, with a median age of 70 years at diagnosis. Five-year relative survival improved over the 36-year(1985±2020) study period(31.0% in 1985±1995;41.9% in 1996±2007;and 56.1% in 2008±2015). For individuals diagnosed before 70 years of age, the 5-year relative survival nearly doubled, from 36.5% in 1985±1995 to 68.5% in 2008±2015. Improvements for those > 70 years of age were less pronounced between 1985±1995 and 1996±2007;however, significant improvements were observed for those diagnosed in 2008±2015. Similar overall and age-specific patterns were observed for causespecific survival. After adjustment for gender and age at diagnosis, treatment era was strongly associated with both relative and cause-specific survival(P < 0.0001).Conclusions: Survival of individuals with MM is improving in Australia with treatment advances. However, older age groups continue to experience poor survival outcomes with only modest improvements over time. Given the increasing prevalence of MM in Australia, the effects of MM treatment on quality of life, particularly in older age, warrant further attention.

Identification of TNFRSF1A as a novel regulator of carfilzomib resistance in multiple myeloma

Multiple myeloma(MM)is a hematological tumor with high mortality and recurrence rate.Carfilzomib is a new-generation proteasome inhibitor that is used as the first-line therapy for MM.However,the development of drug resistance is a pervasive obstacle to treating MM.Therefore,elucidating the drug resistance mechanisms is conducive to the formulation of novel therapeutic therapies.To elucidate the mechanisms of carfilzomib resistance,we retrieved the GSE78069 microarray dataset containing carfilzomib-resistant LP-1 MM cells and parental MM cells.Differential gene expression analyses revealed major alterations in the major histocompatibility complex(MHC)and cell adhesion molecules.The upregulation of the tumor necrosis factor(TNF)receptor superfamily member 1A(TNFRSF1A)gene was accompanied by the downregulation of MHC genes and cell adhesion molecules.Furthermore,to investigate the roles of these genes,we established a carfilzomib-resistant cell model and observed that carfilzomib resistance induced TNFRSF1A overexpression and TNFRSF1A silencing reversed carfilzomib resistance and reactivated the expression of cell adhesion molecules.Furthermore,TNFRSF1A silencing suppressed the tumorigenesis of MM cells in immunocompetent mice,indicating that TNFRSF1A may lead to carfilzomib resistance by dampening antitumor immunity.Furthermore,our results indicated that TNFRSF1A overexpression conferred carfilzomib resistance in MM cells and suppressed the expression of MHC genes and cell adhesion molecules.The suppression of MHC genes and cell adhesion molecules may impair the interaction between immune cells and cancer cells to impair antitumor immunity.Future studies are warranted to further investigate the signaling pathway underlying the regulatory role of TNFRSF1A in MM cells.

A genetic variant study of bortezomib-induced peripheral neuropathy in Chinese multiple myeloma patients

Background:Bortezomib results in peripheral neuropathy(PN)in approximately 50%of patients,during multiple myeloma(MM)treatment,a complication known as Bortezomib-induced peripheral neuropathy(BIPN).The drug response varies among individuals.Genetic factor may play an important role in BIPN.Methods:A nextgeneration sequencing(NGS)panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib therapy.mRNA expression of MTHFR and ALDH1A1 in 62 peripheral blood samples was detected by real-time quantitative PCR(RT-qPCR).Serum homocysteine(Hcy)levels were detected in 40 samples by chemiluminescent microparticle immunoassay(CMIA).Results:Compared with the non-BIPN group(n=89),a total of 8 significantly associated single nucleotide polymorphisms(SNPs)were identified in the BIPN group(n=115):MTHFR(rs1801131,rs1801133,rs17421511),EPHX1(rs1051740),MME(rs2016848),ALDH1A1(rs6151031),HTR7(rs1935349)and CYP2A6(rs8192720).The mRNA expression level of MTHFR in newly diagnosed patients with peripheral neuritis after treatment(NP group)was lower than that of newly diagnosed patients without peripheral neuritis after treatment(NnP group)(1.70±0.77 vs.2.81±0.97,p=0.009).Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group(11.66±1.79μmol/L vs.8.52±3.29μmol/L,p=0.016)and healthy controls(11.66±1.79μmol/L vs.8.55±2.13μmol/L,p≤0.001).Conclusion:CYP2A6,EPHX1,MTHFR,ALDH1A1,HTR7,MME and BIPN are linked in Chinese MM patients.BIPN is more likely to occur in patients with lower MTHFR mRNA expression,which might result in higher serum Hcy levels.

Plasmacytosis mimicking multiple myeloma in angioimmunoblastic T-cell lymphoma:A case report and review of literature

BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL)is a common subtype of peripheral T-cell lymphoma.Approximately half of patients with AITL may concurrently present with hypergammaglobulinemia.Increased numbers of plasma cells in the bone marrow are commonly observed at diagnosis.These tumors mimic plasma cell myelomas,hindering a conundrum of clinical diagnoses and potentially delaying appropriate treatment.CASE SUMMARY A 78-year-old woman experienced poor appetite,weight loss of 5 kg,fatigue 2 months before presentation,and shortness of breath 2 d before presentation,but no fever or night sweats.Physical examination revealed splenomegaly and many palpable masses over the bilateral axillary regions,approximately>2 cm in size,with rubbery consistency and no tenderness.Blood tests revealed anemia and thrombocytopenia,lactate dehydrogenase level of 153 U/L,total protein level of 10.9 g/dL,albumin to globulin ratio of 0.2,and immunoglobulin G level more than the upper limit of 3000 mg/dL.The free kappa and lambda light chain concentrations were 451 and 614 mg/L,respectively.A pathological examination confirmed the diagnosis of AITL.The initial treatment was the cyclophosphamide,epirubicin,vincristine,and prednisolone regimen.Following this treatment,pleural effusion was controlled,and the patient was discharged in a stable condition and followed up in our outpatient department.CONCLUSION This report highlights the importance of differentiating reactive plasmacytosis from plasma cell myeloma in patients with hypergammaglobulinemia.A precise diagnosis of AITL requires a comprehensive evaluation,involving clinical,immunophenotypic,and histological findings conducted by a multidisciplinary team to ensure appropriate treatment.

Pleural effusion,ascites,colon ulcers and hematochezia:What we can learn from the diagnostic process of a patient with plasma cell myeloma:A case report

BACKGROUND Plasma cell myeloma(PCM)is characterized by hypercalcemia,renal impairment,anemia,and bone destruction.While pleural effusion,ascites,abdominal pain,and bloody stool are common manifestations of lung disease or gastrointestinal disorders,they are rarely observed in patients with PCM.CASE SUMMARY A 66-year-old woman presented with complaints of recurrent chest tightness,wheezing,and abdominal bloating accompanied by bloody stools.Computed tomography revealed pleural effusion and ascites.Pleural effusion tests showed inflammation,but the T-cell spot test and carcinoembryonic antigen were negative.Endoscopy showed colonic mucosal edema with ulcer formation and local intestinal lumen stenosis.Echocardiography revealed enlarged atria and reduced left ventricular systolic function.The diagnosis remained unclear.Further testing revealed elevated blood light chain lambda and urine immunoglobulin levels.Blood immunofixation electrophoresis was positive for immunoglobulin G lambda type.Smear cytology of the bone marrow showed a high proportion of plasma cells,accounting for about 4.5%.Histopathological examination of the bone marrow suggested PCM.Flow cytometry showed abnormal plasma cells with strong expression of CD38,CD138,cLambda,CD28,CD200,and CD117.Fluorescence in situ hybridization gene testing of the bone marrow suggested 1q21 gene amplification,but cytogenetic testing showed no clonal abnormalities.Colonic mucosa and bone marrow biopsy tissues were negative for Highman Congo red staining.The patient was finally diagnosed with PCM.CONCLUSION A diagnosis of PCM should be considered in older patients with pleural effusion,ascites,and multi-organ injury.

Gene signatures to therapeutics:Assessing the potential of ivermectin against t(4;14)multiple myeloma

BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.

Treatment Efficacy and Safety of Bortezomib Combined with Dexamethasone and Lenalidomide Chemotherapy Regimen for Multiple Myeloma

Objective:To analyze the effect of bortezomib combined with dexamethasone and lenalidomide in the treatment of multiple myeloma.Methods:60 cases of multiple myeloma patients admitted to our hospital from January 2022 to December 2023 were selected randomly,with 30 cases in each group.Bortezomib combined with dexamethasone was administered in the control group,and bortezomib combined with dexamethasone and lenalidomide was given to the observation group,and the treatment effect was analyzed.Results:After treatment,CD^(3+)and CD^(4+)of the observation group were higher than that of the control group,CD^(8+)was lower than that of the control group,and the total treatment efficiency was higher,which was statistically significant(P<0.05),and there was no difference in the total incidence of adverse reactions between the two groups(P>0.05).Conclusion:Bortezomib combined with dexamethasone and lenalidomide is effective in the treatment of multiple myeloma as it regulates the immune function and is safe,thus it can be promoted in clinical practice.

Clinical Features of Renal Insufficiency due to Multiple Myeloma and Related Risk Factors

Objective: To study clinical features of the patients with multiple myeloma(MM) accompanied by renal insufficiency and investigate the related risk factors of renalimpairment. Methods: A control study of clinical characteristics was performed between 91 patientswith renal insufficiency due to MM and 165 patients with normal renal function in MM during the sameperiod. The data were statistically analyzed by chi-square test and logistic regression analysis.Results: Renal insufficiency was the initial presentation in 48 (52.7%) of the 91 patients, and 30(62.5%) of the 48 patients were misdiagnosed. The prognosis of group with renal insufficiency wassignificantly poorer than that of group with normal renal function: mortality in 3 months, 3months-1 year was 26/91 vs 14/165 (P 【 0.0001), 14/91 vs 12/165 (P 【 0.05) respectively, andpatients survived 】 1 year was 18/91 vs 95/165 (P 【 0.0001). The incidence of hypercalcemia,hyperuricemic, severe anemia, high serum M-protein concentration and lytic bone lesions weresignificantly higher in renal insufficiency group than those in control group (P 【 0.05). Logisticregression analysis identified 5 risk factors of renal impairment, including, severe anemia(Exp(β)=13.819, P 【 0.0001), use of nephrotoxic drugs (Exp(β)=6.217, P = 0.001), high serumM-protein concentration (Exp(β) = 5.026, P = 0.001), male (Exp(β)=3.745, P=0.006), andhypercalcemia (Exp(β)=3A72, P=0.006), but age, serum density of uric acid, type of serum M-protein,and Bence Jones proteinuria were not significantly associated with renal insufficiency. Conclusion:Renal insufficiency was a common early complication of MM, which often resulted in misdiagnosis.The status of these patients tended to be very bad, with many other complications, when MM wasdiagnosed, so their prognosis was poor. The occurrence of renal insufficiency in patients with MMand hypercalcemia, severe anemia, high serum M-protein concentration, especially use of nephrotoxicdrugs should be alert.

Extramedullary plasmacytoma with the uvula as first affected site:A case report

BACKGROUND Extramedullary plasmacytoma(EMP)represents one of the rarer forms of plasma cell malignancies,capable of impacting a variety of tissues and organs throughout the body.The majority of EMP cases are predominantly found in the head and neck region,especially within the laryngopharynx,as well as in the gastrointestinal tract.While there have been documented instances of oropharyngeal involvement in EMP cases in the academic literature,it is important to note that EMP specifically affecting the uvula is exceedingly uncommon.Furthermore,it is noteworthy that over 60% of epithelial carcinomas in the upper respiratory tract and oropharynx tend to metastasize to the cervical lymph nodes,indicating a propensity for regional spread in these types of cancers.In this context,we present a rare case of extramedullary plasmacytoma where the uvula served as the initially affected site.This case emphasizes the need for heightened awareness among clinicians regarding such unusual comorbidities,as early recognition and diagnosis can significantly influence patient management and treatment outcomes.In addition,a review of the relevant literature is included to further educate and inform healthcare professionals about this rare presentation,ultimately aiming to enhance clinical understanding and improve patient care in similar situations.CASE SUMMARY A 51-year-old man was admitted to our hospital because of a slowly enlarging neck mass.A physical examination revealed a palpable left lymph node,and magnetic resonance imaging(MRI)of the oropharynx and the neck showed a soft tissue mass in the oropharynx and enlargement of multiple lymph nodes in the neck.The soft tissue mass was diagnosed as plasmacytoma by immunohistochemical analysis.Monoclonal immunoglobulins and bone marrow biopsy showed normal results.Therefore,we diagnosed that as EMP of the uvula.After four cycles of adjuvant chemotherapy dominated by bortezomib,MRI reexamination showed a significant reduction of the mass in the oropharynx and the cervical lymph nodes.Afterwards,the λ light chain returned to normal levels.There was no evidence of evolution to multiple myeloma.CONCLUSION We have reported a rare case of extramedullary plasmacytoma with the uvula as the first affected site and the relevant literature is reviewed to improve clinicians'awareness of such rare comorbidities.

Bortezomib, dexamethasone plus thalidomide for treatment of newly diagnosed multiple myeloma patients with or without renal impairment

Objective： To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma （MM） with or without renal impairment receiving the therapy of bortezomib, dexamethasone plus thalidomide （BTD） regimen in order to analyze the effects of BTD regimen on the prognosis of the MM patients with renal impairment compared with the patients without renal impairment. Methods： Seventy-two newly diagnosed MM patients entered into our study and all the patients belonged to International Stage System （ISS） 3 in which transplantation patients were excluded or the patients refused receiving transplantation therapy. According to the level of serum creatinine （Scr）, the patients were divided into two groups including group 1 （n=42） （Scr 〈2 mg/dL） and group 2 （n=30） （Scr ≥2 mg/dL）. All the patients received the therapy of BTD regimen as induction therapy, and the median treatment time was 5 （range, 2-8） cycles. The outcome was analyzed retrospectively. Results： The overall remission （OR） rates were 81.0% （group 1） and 80.0% （group 2）. There was no statistical difference between the two groups （P〉0.05）. In group 2, 10 patients （33.3%） got renal function reversal, 14 patients （46.7%） got improved renal function and the median time to renal function reversal was 1.4 （range, 0.7-3.0） months. Among 12 patients with hemodialysis at diagnosis, 8 patients got rid of hemodialysis after median 4 cycles of therapy （range, 3-6 cycles）. After a median follow-up period of 16 （range, 2-31） months, 5 patients （11.9%） in group 1 died and 9 patients （30.0%） in group 2 died （P=0.056）. The 2-year estimate of overall survival was 77.3% in group 1 and 63.8% in group 2, respectively （P=0.188）. During a median follow-up time of 13.0 months （range, 2-25 months）, 15 patients （35.7%） in group 1 progressed and 13 patients （43.3%） in group 2 progressed （P=0.513）. The 2-year estimate of response duration was 50.6% in group 1 and 42.1% in group 2, respectively （P=1）. The main toxicities in the two groups included thrombocytopenia, peripheral neuropathy （PN）, infection, herpes zoster and so on. The incidence of grade 3 and 4 adverse events was low. Conclusions： BTD regimen may become the front-line therapy for the newly diagnosed MM patients with renal impairment because BTD regimen can improve the prognosis of the patients with renal impairment as good as the patients without renal impairment.

Multiple myeloma mesenchymal stromal cells: Contribution to myeloma bone disease and therapeutics

Multiple myeloma is a hematological malignancy inwhich clonal plasma cells proliferate and accumulate within the bone marrow. The presence of osteolytic le-sions due to increased osteoclast(OC) activity and sup-pressed osteoblast(OB) function is characteristic of the disease. The bone marrow mesenchymal stromal cells(MSCs) play a critical role in multiple myeloma patho-physiology, greatly promoting the growth, survival, drug resistance and migration of myeloma cells. Here, we specifically discuss on the relative contribution of MSCs to the pathophysiology of osteolytic lesions in light of the current knowledge of the biology of my-eloma bone disease(MBD), together with the reported genomic, functional and gene expression differences between MSCs derived from myeloma patients(pMSCs) and their healthy counterparts(dMSCs). Being MSCs the progenitors of OBs, pMSCs primarily contribute to the pathogenesis of MBD because of their reduced osteogenic potential consequence of multiple OB inhibi-tory factors and direct interactions with myeloma cells in the bone marrow. Importantly, pMSCs also readily contribute to MBD by promoting OC formation and ac-tivity at various levels(i.e., increasing RANKL to OPG expression, augmenting secretion of activin A, uncou-pling ephrinB2-EphB4 signaling, and through augment-ed production of Wnt5a), thus further contributing to OB/OC uncoupling in osteolytic lesions. In this review, we also look over main signaling pathways involved in the osteogenic differentiation of MSCs and/or OB activity, highlighting amenable therapeutic targets; in parallel, the reported activity of bone-anabolic agents(at preclinical or clinical stage) targeting those signaling pathways is commented.

Imaging of multiple myeloma: Current concepts

Medical imaging is of crucial importance for diagnosis and initial staging as well as for differentiation of multiple myeloma(MM)from other monoclonal plasma cell diseases.Conventional radiography represents the reference standard for diagnosis of MM due to its wide availability and low costs despite its known limitations such as low sensitivity,limited specificity and its inability to detect extraosseous lesions.Besides conventional radiography,newer cross-sectional imaging modalities such as whole-body low-dose computed tomography(CT),whole-body magnetic resonance imaging(MRI)and18F-fluorodeoxyglucose(FDG)positron emission tomography(PET)/CT are available for the diagnosis of osseous and extraosseous manifestations of MM.Whole-body low-dose CT is used increasingly,replacing conventional radiography at selected centers,due to its higher sensitivity for the detection of osseous lesions and its ability to diagnose extraosseous lesions.The highest sensitivity for both detection of bone marrow disease and extraosseous lesions can be achieved with whole-body MRI and18F-FDG PET/CT.According to current evidence,MRI is the most sensitive method for initial staging while18F-FDG PET/CT allows monitoring of treatment of MM.There is an evolving role for assessment of treatment response using newer MR imagingtechniques.Future studies are needed to further define the exact role of the different imaging modalities for individual risk stratification and therapy monitoring.

Once-versus Twice-weekly Bortezomib Induction Therapy with Dexamethasone in Newly Diagnosed Multiple Myeloma

In this study,we administered a modified schedule of weekly intravenous Bortezomib at 1.6 mg/m 2 with dexamethasone(BD) and compared it to the standard 1.3 mg/m 2 twice-weekly BD regimen in Chinese patients with newly diagnosed multiple myeloma(MM).We assessed the difference in efficacy,safety profile and survival between the once-weekly and twice-weekly cohorts(13 vs.24 patients).The over response rate was similar with both arms of the study,being 77% in the once-weekly schedule and 74.9% in the twice-weekly schedule(P=0.690).The median overall survival was not reached in either schedule.Also,the median progression-free survival and duration of response of the once-weekly schedule did not significantly differ from those of the twice-weekly schedule(8 months vs.10 months,P=0.545 and 6 months vs.7 months,P=0.467 respectively).Peripheral sensory neuropathy and grade 3/4 hematologic toxic effects were more frequently reported in the twice-weekly schedule than the once-weekly schedule,but there was no statistically significant difference.This preliminary experience in Chinese patients with newly diagnosed MM indicated that once-weekly infusion of Bortezomib plus dexamethasone may improve safety without affecting outcome.

Triptolide Inhibits Cell Growth and Induces G0-G1 Arrest by Regulating P21wap1/cip1 and P27 kip1 in Human Multiple Myeloma RPMI-8226 Cells

Objective： To investigate the effects of triptolide（TPL） on cell growth, cell cycle and the expressions of p21wapl/cipl and p27kipl. Methods： MTT assay was used to determine the cell viability after triptolide treatment in human multiple myeloma RPMI-8226 cells. The effect on cell cycle distribution was determined by flow cytometry. Semi-quantitative reverse transcription-PCR was used to examine the mRNA expressions of p21wapl/cipl and p27kipl. The protein expressions of p21 wapl/cipl and p27kipl were determined by Western blot. Results： Triptolide of varying concentrations induced cell viability inhibition in dose- and time-related fashion and caused Go- G1 phase arrest of cell cycle progression in RPMI-8226 cells. These effects accompanied with up-modulation of the expressions of p21 wapl/cipl and p27kipl. Conclusion： These results suggest that triptolide inhibit cell proliferation and cell cycle progression via up-regulating p21wapl/cipl and p27kipl and triptolide may exert its anti-cancer activity through this pathway.