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BACKGROUND: Chromosomal 1q gains and amplifications (+1q21) are frequently observed in patients with newly diagnosed multiple myeloma (NDMM). However, the interpretation of the high-risk (HR) prognostic implications stemming from 1q21 abnormalities remain challenging to implement effectively. METHODS: In a comprehensive analysis of 367 consecutive patients with symptomatic MM, we assessed the prognostic significance of +1q21 using FISH with a threshold of 7.4%. The patient cohort was randomly divided into a training set (66.5%, n = 244) and a validation set (33.5%, n = 133). A multivariate Cox regression analysis was conducted to identify significant prognostic factors associated with PFS. Weight scores were assigned to each risk factor based on the ß-value of the corresponding regression coefficient. A predictive risk-scoring model involving +1q21 was then developed, utilizing the total score derived from these weight scores. The model's discriminative ability was evaluated using the AUC in both the training and validation sets. Finally, we compared the performance of the +1q21-involved risk with the established R-ISS and R2-ISS models. RESULTS: Upon initial diagnosis, 159 patients (43.32%) exhibited +1q21, with 94 (59.11%) having three copies, referred to as Gain(1q21), and 65 (40.89%) possessing four or more copies, referred to as Amp (1q21). Both were significantly linked to a reduced PFS in myeloma (p < 0.05), which could be effectively mitigated by ASCT. The +1q21-involved risk model, with an AUC of 0.697 in the training set and 0.725 in the validation set, was constructed including Gain(1q21), Amp(1q21), no-ASCT, and TP53 deletion. This model, termed the ultra-high-risk (UHR) model, demonstrated superior performance in predicting shorter PFS compared to the R-ISS stage 3 and R2-ISS stage 4. CONCLUSION: The UHR model, which integrates the presence of +1q21 with no-ASCT and TP53 deletion, is designed to identify the early relapse subgroup among patients with +1q21 in NDMM.
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Cromosomas Humanos Par 1 , Mieloma Múltiple , Centros de Atención Terciaria , Mieloma Múltiple/mortalidad , Mieloma Múltiple/genética , Mieloma Múltiple/diagnóstico , Humanos , Femenino , Masculino , Cromosomas Humanos Par 1/genética , Persona de Mediana Edad , China/epidemiología , Pronóstico , Anciano , Medición de Riesgo/métodos , Factores de Riesgo , Adulto , Anciano de 80 o más AñosRESUMEN
Although the significant strides in novel therapeutic approaches have prolonged the survival of multiple myeloma (MM) patients, the unfavorable prognosis of cytogenetically high-risk newly diagnosed MM (NDMM) remains intractable with the lack of consensus regarding the choice of maintenance regimens. Therefore, this study was initiated with the aim of examining the effectiveness of various maintenance treatments for this group of patients in jeopardy. Overall, 17 studies with 1937 high-risk NDMM patients were included in the network meta-analysis. Combination therapies involving novel drugs presented encouraging prospects in the maintenance phase, while the patients and circumstances for the application of different regimens still needed to be further distinguished and clarified. To investigate the current status of maintenance therapy of high-risk NDMM patients in clinical practice, a real-world cohort of high-risk NDMM was retrospectively incorporated 80 patients with lenalidomide maintenance and 53 patients with bortezomib maintenance, presenting the median PFS of 31.7 months and 30.4 months, respectively (p = 0.874, HR = 0.966, 95% CI: 0.628-1.486). Collectively, this study illuminated the present constraints of conventional approaches during the maintenance phase for high-risk NDMM patients while highlighting the future potential associated with enhanced regimens integrating novel medications.
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Lenalidomida , Quimioterapia de Mantención , Mieloma Múltiple , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Humanos , Lenalidomida/uso terapéutico , Bortezomib/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Antineoplásicos/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: TQB3602 is a novel orally bioavailable proteasome inhibitor. This study is the first-in-human phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of TQB3602 in relapsed/refractory multiple myeloma (RRMM). METHODS: This is a multicenter phase I clinical trial consisting of the 3+3 dose-escalation phase and dose expansion phase. Patients with MM who have received ≥2 prior antimyeloma therapies were enrolled. TQB3602 is administered at a dose of 0.5~7mg on days 1, 8, 15 in 28-day cycle. RESULTS: Twenty-five RRMM patients who relapsed or failed ≥2 lines of therapies were enrolled in the dose escalation phase. Two patients in the 7.0 mg dose group developed dose-limiting toxicity events (one with grade 2 peripheral neuropathy [PN] complicated by pain and one with diarrhea and abdominal pain), leading to a maximum tolerated dose of 6.0 mg. Any-grade adverse events (AEs) occurred in 24 (96.0%) patients, while grade ≥3 AEs occurred in 13 (52.0%). The most common grade ≥3 AEs was anemia (6, 24.0%). The incidence rate of PN was 16% with no grade ≥3 PN occurred. TQB3602 was rapidly absorbed, resulting in a time-to-plasma peak concentration of 0.8-1.5 h. The mean half-life was approximately 82 h. The AUClast and Cmax were approximately 1.9 times higher on day 15 than on day 1. Among 22 response-evaluable patients, 63.7% achieved stable disease or better. CONCLUSIONS: TQB3602 is well tolerated, with a favorable neurotoxicity profile, and has shown preliminary efficacy in patients with RRMM. The anticipated therapeutic dose was 6 mg and was adopted for an ongoing dose-expansion phase.
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Mieloma Múltiple , Inhibidores de Proteasoma , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Masculino , Persona de Mediana Edad , Femenino , Anciano , Inhibidores de Proteasoma/uso terapéutico , Inhibidores de Proteasoma/farmacocinética , Inhibidores de Proteasoma/efectos adversos , Inhibidores de Proteasoma/administración & dosificación , Administración Oral , Dosis Máxima Tolerada , Resultado del Tratamiento , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Relación Dosis-Respuesta a Droga , Resistencia a AntineoplásicosRESUMEN
Background: Since no randomized controlled trials have directly compared the efficacy and safety of immunotherapy with daratumumab versus lenalidomide/bortezomib/dexamethasone (RVD) in the frontline treatment of transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM), this study systematically reviewed the clinical studies regarding immunotherapy with daratumumab and RVD regimen in the treatment of TIE-NDMM to explore the optimization direction of the best first-line therapy. Methods: The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to collect studies on regimens containing daratumumab or RVD/RVD-lite for TIE-NDMM. Pooled and meta-analysis was then performed to compare the overall response rate (ORR), stringent complete remission (sCR) and CR rate, progression-free survival (PFS), overall survival (OS) and treatment-related discontinuation rate between daratumumab-containing immunotherapy regimen and RVD/RVD-lite regimen by using R 4.3.1 software. Results: Nine prospective clinical trials were included, including 1795 TIE-NDMM or NDMM without intent for immediate ASCT. Among them, 938 patients were treated with daratumumab-based immunotherapy and 857 with RVD/RVD-lite regimens. Meta-analysis results showed that The daratumumab-based regimen showed a significantly higher CR/sCR rate than RVD/RVD-lite for TIE-NDMM (47% vs. 24%, P<0.01). The median PFS of the daratumumab-based and RVD/RVD-lite groups were 52.6 months and 35.1 months respectively (HR 0.77, 95%CI, 0.66-0.90). The median OS of both groups was not reached, and there were no significant differences in OS between the two groups (HR 1.03, 95%CI, 0.86-1.23). The therapy discontinuation rate led by adverse events was significantly higher in the RVD/RVD-lite group than in the daratumumab-based regimen group for the TIE-NDMM (16% vs. 7%, P=0.03). Conclusion: This meta-analysis suggests that daratumumab-containing immunotherapy is superior to RVD in the depth of treatment efficacy, progression-free survival, and lower treatment-related discontinuation rates. Limited by the lack of head-to-head clinical trials, this conclusion needs to be verified by concurrent cohort studies.
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Molecular and clinical stratification of patients with angioimmunoblastic T-cell lymphoma (AITL) is unsatisfactory, which hinders the development of personalized therapies. This study aimed to identify molecular biomarkers for AITL based on peripheral cell-free DNA (cfDNA) that could be used to predict prognosis and guide treatment non-invasively. A customized panel containing 46 genes was used to study pretreatment cfDNA and paired tumour tissues in 64 Chinese AITL patients from three clinical centres, and gene mutations in cfDNA and tumour tissue were assessed for concordance (34 paired samples). Then, the association of gene mutations and prognosis was analysed, and a functional enrichment analysis was performed. The sequencing results showed good consistency between cfDNA samples and paired tissue samples. KDM5A, STAT1, FANCM, ERBB4, PIK3R5 and NSD1 were identified as novel recurrent mutations. Mutations in FANCM or combinations of RHOA, KDM5A and FAT1 were associated with poor prognosis. Additionally, functional analysis revealed that RHOAG17 might serve as a predictive biomarker of PD-1 blockade respondence. Our findings confirmed the role of cfDNA as a liquid biopsy in AITL, and revealed novel molecular determinants that can stratify patients and guide treatment options.
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Ácidos Nucleicos Libres de Células , Linfadenopatía Inmunoblástica , Linfoma de Células T Periférico , Linfoma de Células T , Humanos , Linfoma de Células T/genética , Pronóstico , Dermatoglifia del ADN , Linfadenopatía Inmunoblástica/diagnóstico , Linfadenopatía Inmunoblástica/genética , Linfadenopatía Inmunoblástica/patología , Mutación , Linfoma de Células T Periférico/genética , Proteína 2 de Unión a Retinoblastoma/genética , ADN Helicasas/genéticaRESUMEN
Multiple myeloma(MM)is a systemic malignancy of plasma cells.Nowadays,the basic research on MM is flourishing with the continuous optimization and innovation of mouse models of MM.Heterologous mouse models of MM established with human-derived cells and immunodeficient mice have been applied in assessing drug efficacy,exploring drug resistance mechanisms,and observing tumor-bone marrow microenvironment interactions.In the last decades,the homologous mouse models of MM established with murine-derived cells or gene-editing technologies have been widely used in the research on the pathogenesis and drug development.Additionally,the stable modeling of targeted organ injury will be a key problem to be tackled in this field.This review summarizes the characteristics and application progress of mouse models of MM.
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Mieloma Múltiple , Humanos , Animales , Ratones , Mieloma Múltiple/patología , Médula Ósea/patología , Modelos Animales de Enfermedad , Resistencia a Medicamentos , Microambiente TumoralRESUMEN
Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.
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Although the development of novel drugs has significantly improved the survival of patients with multiple myeloma (MM) over the past decades,the lack of effective therapeutic options for relapsed and refractory MM results in poor prognosis.The chimeric antigen receptor (CAR) T-cell therapy has achieved considerable progress in relapsed and refractory MM.Nevertheless,this therapy still has limitations such as cytokine release syndrome,neurotoxicity,and off-target effects.Natural killer (NK) cells,as a critical component of the innate immune system,play an essential role in tumor immunosurveillance.Therefore,CAR-modified NK (CAR-NK) cells are put forward as a therapeutic option for MM.The available studies have suggested that multiple targets can be used as specific therapeutic targets for CAR-NK cell therapy and confirmed their antitumor effects in MM cell lines and animal models.This review summarizes the anti-tumor mechanisms,biological characteristics,and dysfunction of NK cells in the MM tumor microenvironment,as well as the basic and clinical research progress of CAR-NK cells in treating MM.
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Mieloma Múltiple , Receptores Quiméricos de Antígenos , Animales , Receptores Quiméricos de Antígenos/metabolismo , Mieloma Múltiple/terapia , Mieloma Múltiple/metabolismo , Células Asesinas Naturales/metabolismo , Inmunoterapia Adoptiva/métodos , Microambiente TumoralRESUMEN
Multiple myeloma (MM) is the second most common hematological malignancy; however, it remains incurable, and the underlying pathogenesis and mechanisms of drug resistance remain unclear. It is widely recognized that the bone marrow microenvironment plays a crucial role in regulating the immune response, inducing drug resistance, and promoting tumor proliferation and invasion in MM, and thus serves as a potential therapeutic target. Among the various signaling loops between myeloma cells and components of the microenvironment, noncoding RNAs are emerging as crucial regulators of intercellular communication within the microenvironment. Noncoding RNAs, such as microRNAs, long noncoding RNAs, circular RNAs, and PIWI-interacting RNAs, have been associated with numerous biological processes involved in myeloma cell growth, survival, migration, invasion, and drug resistance. This review summarizes recent advances in the regulatory mechanisms of noncoding RNAs involved in the interaction between the MM bone marrow microenvironment and discusses the therapeutic potential of noncoding RNAs in MM.
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MicroARNs , Mieloma Múltiple , Humanos , Médula Ósea/patología , Mieloma Múltiple/tratamiento farmacológico , MicroARNs/genética , MicroARNs/uso terapéutico , Resistencia a Medicamentos , Transducción de Señal , Microambiente TumoralRESUMEN
BACKGROUND: Multiple myeloma (MM) is the second most common hematological malignancy without cure, and Chimeric Antigen Receptor T Cell (CAR-T) therapy has been shown great promising in MM. Unlike previous published studies mainly focusing on efficacy and safety, this study aims to summarize time points in the process of CAR-T therapy in MM and establish a standardized time-related CAR-T therapy platform to provide a reference for CAR-T treatment in MM. METHODS: All the literatures were retrieved from PubMed, Web of Science, Embase, American Society of Hematology (ASH), American Society of Clinical Oncology (ASCO) and European Hematology Association (EHA). Relevant median detection time of efficacy and safety-related indicators of CAR-T therapy in MM were extracted from included literatures, and median values were applied to represent detection time points of indicators. Notably, the median values were not the certain and optimal detection time points, while the significance is that indicators could be detected more frequently around the median values to obtain the ideal results. RESULTS: This review presented the median detection time points of efficacy and safety-related indicators of CAR-T therapy in MM according to the chronological order. For short-term effects on inflammation status within 1 month after CAR-T initiation, the median time points of cytokine release syndrome onset, immune effector cell-associated neurotoxicity syndrome onset, neutrophils recovery and CAR-T expansion peak were 4.5, 8, 10 and 12 days, respectively. For medium-term effects on clinical response in MM beyond 1 month and up to 3 months following CAR-T infusion, the median time points of minimal residual disease negativity, the reduction of serum light chain to minimum, platelet recovery and the reduction of M protein to minimum were 30, 30, 44 and 90 days, respectively. CONCLUSIONS: This systematic review summarized the median detection time points of efficacy and safety-related indicators of CAR-T therapy in MM and constructed the time-related CAR-T therapy platform, providing an evidence-based standard for establishment of CAR-T treatment regimen in MM.
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Mieloma Múltiple , Receptores Quiméricos de Antígenos , Humanos , Mieloma Múltiple/tratamiento farmacológico , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Inmunoterapia , Linfocitos TRESUMEN
Background: For multiple myeloma (MM), the proportions of patients reaching the subsequent line of therapy (LOT) decline gradually and real-world data describing the attrition rates of LOT in Chinese MM were limited. Herein, we investigated the attrition rates by subsequent LOTs and their relevant risk factors in MM patients in China. Methods: MM patients who had been hospitalized and received at least one LOT from January 2008 to August 2019 in West China Hospital Sichuan University were retrospectively recruited. Demographic and clinical characteristic data were obtained from the "HemaTank" Chinese Multiple Myeloma Database. The Cox proportional hazards regression model was applied to analyze the risk factors of frontline treatment attrition. Results: A total of 1,255 newly diagnosed MM were enrolled, with 573 (45.7%) patients receiving only one LOT and 682 (54.3%) patients receiving more than one LOT. Thalidomide with dexamethasone/prednisone was the most common frontline treatment before 2017, while bortezomib-based regimens constituted the majority of frontline treatment in 2017 and beyond. The attrition rates from the first to the fifth LOT exhibited a gradual upward trend (45.7%, 48.7%, 58.9% and 62.5%, respectively). Meanwhile, 54.3%, 27.9%, 11.5%, and 4.3% of all the enrolled MM patients received a second, third, fourth and fifth LOT. MM who underwent autologous stem cell transplantation (ASCT) showed lower attrition rates across all LOTs (range 12%-56.8%) than MM without ASCT (range 49.1%-64.5%). The multivariate Cox regression model revealed that ISS stage III (HR 2.07, p < .001), elevated LDH (HR 1.47, p = .006), and comorbidities such as amyloidosis (HR 1.63, p = 0 .01), hepatic disease (HR 1.36, p = .022), pulmonary disease (HR 1.38, p = .022), and cardiac disease (HR 1.62, p = .004) were independent risk factors for MM patients attritted from the frontline treatment. Conclusion: In this study, the attrition rates were generally high and increased gradually across all LOTs. Nearly half of MM patients received only one LOT, and higher tumor burden and more comorbidities may be associated with fewer subsequent LOTs. The high attrition rates highlight the importance of applying the most optimal frontline treatment regimen rather than salvaging subsequent LOTs.
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OBJECTIVE: Despite the availability of new agents, elderly patients with multiple myeloma (MM) usually present with poor outcomes due to the heterogeneity of disease conditions, especially immune deficiency. Regulatory B cells (Bregs) can be involved in immune defects by exerting immune regulatory functions in MM. In order to provide more evidence-based practice for the elderly MM, the study established and assessed a stratified therapeutic model with studies on Bregs for Chinese Elderly Multiple Myeloma in 2021 (CEMM2021). METHODS: In this open-label, non-interventional, prospective study in the real world, 159 newly diagnosed MM (NDMM) patients over 65 years old were sequentially recruited and bone marrow aspirates prior to treatment were obtained to detect the ratios of Bregs by flow cytometry. RESULTS: Based on the CEMM2021 model, 147 patients had received at least one cycle of induction therapy, including bortezomib/dexamethasone (Bd) (n = 80), lenalidomide/dexamethasone (Rd) (n = 27), Bd with a third agent X (Bd + X) (n = 27), and other regimens (n = 13). The proportions of patients achieving very good partial response or better were comparable among Bd, Bd + X, and Rd groups (41.9% vs. 54.5% vs. 44.0%, p = 0.472). Besides, the progression-free survival (PFS) and overall survival (OS) were not significantly different among Rd, Bd, and Bd + X groups. Multivariable analysis showed that induction efficacy less than partial response (PR) were poor prognostic factors for PFS, while Revised-International Staging System (R-ISS) III and efficacy less than PR were poor prognostic factors for OS. This study also found that the ratios of bone marrow Bregs <10% (p = 0.036) and SUVmax of PET-CT scan >4.2 (p = 0.000) were closely correlated with OS in the elderly MM. CONCLUSIONS: For the elderly NDMM, the CEMM2021 algorithm in our center might provide a valuable reference for the guidance of therapeutic strategies, with the combination of Bregs resulting in an effective and clinically meaningful prediction in contemporary treatment.
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Linfocitos B Reguladores , Mieloma Múltiple , Anciano , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib , Dexametasona , Supervivencia sin Enfermedad , Lenalidomida , Mieloma Múltiple/tratamiento farmacológico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios ProspectivosRESUMEN
[This corrects the article DOI: 10.7150/jca.53209.].
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Multiple myeloma is a hematologic tumor characterized by clonal proliferation of plasma cells.The development of novel agents and immunotherapy have substantially improved the prognosis of multiple myeloma,with an expectable median survival beyond ten years.Therefore,there is an urgent need to improve the management of this disease.Health management is effective in controlling chronic diseases and full-cycle management should be implemented from the early to the end stage of the disease.Implanting the full-cycle concept into the health management of multiple myeloma will guide and standardize the advances in this field.This review focuses on the full-cycle concept of multiple myeloma and the corresponding application of health management at each stage of the cycle.
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Mieloma Múltiple , Humanos , Inmunoterapia , Mieloma Múltiple/terapia , PronósticoRESUMEN
Multiple myeloma is an incurable malignant disease characterized by proliferation of clonal plasma cells in the bone marrow.About 90% of the patients with multiple myeloma develop myeloma bone disease(MBD),which seriously affects the quality of life and prognosis of the patients.Traditional therapies for MBD include bisphosphonates,radiotherapy,and surgery.The recent studies have confirmed that the receptor activator of nuclear factor κB ligand (RANKL)-receptor activator of nuclear factor κB(RANK) signaling pathway plays a key role in MBD,providing a new therapeutic target for MBD.This review summarized the role of RANKL-RANK signaling pathway in the pathogenesis of MBD and the advance in the targeted therapy.
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Enfermedades Óseas , Mieloma Múltiple , Enfermedades Óseas/tratamiento farmacológico , Enfermedades Óseas/etiología , Enfermedades Óseas/metabolismo , Humanos , Ligandos , Mieloma Múltiple/metabolismo , FN-kappa B/metabolismo , Calidad de Vida , Ligando RANK/metabolismo , Receptor Activador del Factor Nuclear kappa-B , Transducción de SeñalRESUMEN
The dinoflagellate genus Alexandrium comprises most of the toxic bloom-forming species producing paralytic shellfish toxins (PSTs) in the sea. Recently, repeated paralytic shellfish poisoning episodes have been recorded in Qinhuangdao located at the west coast of the Bohai Sea. To elucidate the relationship between toxic Alexandrium blooms and the poisoning episodes, a year-round investigation was carried out in this region from July 2020 to July 2021. Two qPCR assays were used to detect A. catenella and A. pacificum, and LC-MS/MS was applied to analyze PSTs in phytoplankton and shellfish samples. The blooms of A. catenella and A. pacificum were found in April and July, respectively, and PST content in three bivalves exhibited notable increase following the bloom of A. catenella. The results revealed bloom dynamics of the two toxic Alexandrium species in the Bohai Sea for the first time, and further confirmed A. catenella as the causative agent of poisoning episodes.
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Dinoflagelados , Intoxicación por Mariscos , Toxinas Biológicas , Cromatografía Liquida , Humanos , Mariscos , Espectrometría de Masas en TándemRESUMEN
Protein S deficiency is associated with an increased risk of thromboembolism, which may be caused by hereditary deficiency and several physiological and pathologic conditions, such as pregnancy, contraceptive use, liver diseases, inflammatory disease, and certain viruses infections. However, monoclonal immunoglobulin-mediated Protein S deficiency is rarely reported. Here we described a 49-year-old woman with a history of recurrent painful swelling in both lower extremities due to venous thrombosis for 7 years, accompanied by recurrent gross hematuria and multiple painful necrotic purpuras for 5 years, who was then diagnosed with acquired Protein S deficiency induced by the monoclonal immunoglobulin. Then she was successfully treated with rituximab combined with anticoagulation therapy. This case highlights the rare manifestations of Protein S deficiency and the influence of the monoclonal immunoglobulin produced by monoclonal B lymphocytes and monoclonal plasma cells on the activity of Protein S, which can be treated effectively with rituximab combined with anticoagulation therapy.
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Deficiencia de Proteína S , Púrpura , Anticoagulantes/uso terapéutico , Femenino , Hematuria , Humanos , Persona de Mediana Edad , Necrosis/complicaciones , Embarazo , Deficiencia de Proteína S/complicaciones , Púrpura/complicaciones , Rituximab/uso terapéuticoRESUMEN
To assess patients with multiple myeloma (MM), the whole-body positron-emission tomography/computed tomography (PET/CT) occupies a pivotal position for diagnostic stratification, response evaluation, and survival prediction, while important limitations are recognized as incapable of representing tumor microenvironment. Regulatory B cells (Bregs) have been reported to have an inhibitory immune function, contributing to bone marrow (BM)-immunosuppressive microenvironment for MM. Therefore, to investigate the role of PET/CT in combination with Bregs' ratios to predict therapeutic response and survival, we sequentially enrolled 120 patients with newly diagnosed MM (NDMM) who were treated with novel agents in our center, while conventional PET/CT parameters including maximum standard uptake value (SUVmax), ratios of BM-derived Bregs within CD19+ B cells, and patients' clinical characteristics were collected. After a median follow-up of 28.20 months (range 7.00-46.93 months), SUVmax > 4.2 at onset, accounting for 53.2% of NDMM, was uncovered to predict inferior progression-free survival (PFS) as well as overall survival (OS). With regard to the ratios of BM-derived Bregs within CD19+ B cells, the cohort with the Bregs' proportions lower than 10%, accounting for 46.2%, exerted poorer OS. Additionally, the patients with both SUVmax > 4.2 and Bregs' ratios < 10%, accounting for 31.7%, yielded compromised therapeutic response and long-term survival. Collectively, this study may draw attention on the prognostic value of combination of PET/CT and Bregs' ratios when clinical decisions are made for MM in the era of novel agents.
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Linfocitos B Reguladores/inmunología , Mieloma Múltiple/diagnóstico por imagen , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/inmunología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Adulto , Anciano , Antineoplásicos/uso terapéutico , Dexametasona/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
An outbreak of paralytic shellfish poisoning, recorded in April 2016 in Qinhuangdao China, was suspected to be caused by a toxic species in genus Alexandrium. Shortly after the poisoning outbreak, shellfish and net-concentrated phytoplankton samples were collected from the Bohai Sea, and analysed using high performance liquid chromatography coupled with fluorescence detection. Paralytic shellfish toxins (PSTs) were detected in both phytoplankton and shellfish samples, with similar toxin profiles dominated by carbamate toxins. High throughput sequencing data for phytoplankton samples collected previously in the coastal waters of Qinhuangdao were then analysed, and 8 operational taxonomic units (OTUs) were assigned to Alexandrium affine, A. andersonii/A. ostenfeldii, A. catenella, A. fraterculus, A. hiranoi/A. pseudogonyaulax, A. margalefii, A. pacificum and A. pohangense, among which A. catenella, A. pacificum and A. ostenfeldii could be potential producers of PSTs. During a cruise in 2019, three isolates of Alexandrium were established by cyst germination, and identified as A. catenella based on the sequences of the 28S ribosomal RNA gene (28S rDNA) D1-D2 region. Interestingly, all the three strains had the same toxin profile consisting of gonyautoxins 1, 3, 4 (GTX1, 3, 4) and neosaxitoxin (NEO). The toxin profile is similar to those of phytoplankton samples collected previously in the coastal waters of Qinhuangdao, but remarkably different from the general toxin profile of A. catenella dominated by N-sulfocarbamoyl toxins C1-2 in the Bohai Sea and the Yellow Sea. The results suggest that A. catenella is most likely to be the causative species of the poisoning outbreak in Qinhuangdao. As far as we know, this is the first report of A. catenella in the Bohai Sea producing PSTs dominated by high potent gonyautoxins GTX1-4. Occurrence of the highly toxic A. catenella will increase the risk of paralytic shellfish poisoning, which necessitates in-depth mechanism studies and increasing monitoring efforts.
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Dinoflagelados , Intoxicación por Mariscos , Carbamatos , China , Alimentos MarinosRESUMEN
Multiple myeloma (MM) is a heterogeneous disease that remains incurable with significant interpatient variability in outcomes. Regulatory B cells (Bregs) were observed to be involved into specific defects in MM. Here, we provide our risk-adapted approach to newly diagnosed MM (NDMM), combining with the fundamental dysfunction of Bregs. We reported one hundred consecutive patients with NDMM from South-Western China, primarily treated with bortezomib plus dexamethasone with or without a 3rd agent, were enrolled from 2017. Bone marrow aspirates were obtained and flow cytometry (FCM) was used to quantify the percentage of Bregs from the bone marrow. The correlation between Bregs and clinical characters were further analyzed. This study found using bortezomib plus dexamethasone as backbone showed promising efficacy with acceptable tolerability in NDMM. The relatively compromised progression free survival (PFS) points to the essential synergy of bortezomib and lenalidomide here. This study also found that altered proportions of Bregs were closely correlated with treatment efficacy and prognosis in MM. Further understanding of Bregs biology might provide new opportunities to develop immunotherapy, which could prove beneficial in treating MM.