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1.
Sensors (Basel) ; 23(12)2023 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-37420603

RESUMEN

In this paper, based on the information entropy and spatio-temporal correlation of sensing nodes in the Internet of Things (IoT), a Spatio-temporal Scope Information Model (SSIM) is proposed to quantify the scope of the valuable information of sensor data. Specifically, the valuable information of sensor data decays with space and time, which can be used to guide the system to make efficient sensor activation scheduling decisions for regional sensing accuracy. A simple sensing and monitoring system with three sensor nodes is investigated in this paper, and a single-step scheduling decision mechanism is proposed for the optimization problem of maximizing valuable information acquisition and efficient sensor activation scheduling in the sensed region. Regarding the above mechanism, the scheduling results and approximate numerical bounds on the node layout between different scheduling results are obtained through theoretical analyses, which are consistent with simulation. In addition, a long-term decision mechanism is also proposed for the aforementioned optimization issues, where the scheduling results with different node layouts are derived by modeling as a Markov decision process and utilizing the Q-learning algorithm. Concerning the above two mechanisms, the performance of both is verified by conducting experiments using the relative humidity dataset; furthermore, the differences in performance and limitations of the model are discussed and summarized.


Asunto(s)
Algoritmos , Simulación por Computador , Cadenas de Markov
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(3): 693-698, 2023 Jun.
Artículo en Chino | MEDLINE | ID: mdl-37356928

RESUMEN

OBJECTIVE: To investigate the clinical characteristics, therapeutic response and prognosis of patients with plasma cell leukemia (PCL) and improve the understanding of this disease. METHODS: The clinical manifestations, laboratory tests and treatment response of 27 patients with plasma cell leukemia treated in The Second Hospital of Shanxi Medical University from December 2010 to August 2019 were analyzed retrospectively, and their clinical characteristics were summarized. Kaplan-Meier method was used for survival analysis. RESULTS: There were 18 cases of primary plasma cell leukemia (pPCL) and 9 cases of secondary plasma cell leukemia (sPCL). The male to female ratio was 1.7∶1. The median age was 62 years old. The first manifestations were bone pain, fatigue, fever, splenomegaly and bleeding, and a large number of plasma cell infiltration was observed in the morphological examination of peripheral blood and bone marrow cells. 13 cases were detected by immunotyping and all of them expressed CD38/CD138. 8 cases underwent karyotype analysis, and 3 cases were normal, clonal abnormalities occurred in 5 cases. FISH detection was performed in 12 cases, of which 8 cases were abnormal. In 17 cases of bortezomib based chemotherapy, the ovevall response rate was 52.9%, which was higher than that in the non-bortezomib group, but there was no significant difference between the two groups (P =0.242). The overall median survival time of 27 patients was 6.4 months, the median progression-free survival time was 3.5 months, and the median survival time of patients with pPCL and sPCL was 8.2 months and 2.4 months, respectively, the difference between the two groups was statistically significant (P =0.031). CONCLUSION: PCL is highly invasive and has diverse clinical manifestations, and is not sensitive to traditional chemotherapy. The median survival time of patients with pPCL is relatively longer than that of patients with sPCL. The chemotherapy regimen based on bortezomib improves the treatment effectiveness and prolongs the survival time of PCL patients.


Asunto(s)
Leucemia de Células Plasmáticas , Masculino , Femenino , Humanos , Leucemia de Células Plasmáticas/diagnóstico , Estudios Retrospectivos , Bortezomib/uso terapéutico , Pronóstico , Análisis de Supervivencia
4.
Chemosphere ; 326: 138439, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36935057

RESUMEN

The release of highly toxic beryllium in sludge (BCS) produced by physico-chemical treatment of beryllium-containing wastewater from Be smelting production has become a growing concern with the widespread use of Be in the defense industry. This work investigated the potential mobility of Be in BCS. The toxicity characteristic leaching procedure (TCLP) of BCS showed that the amount of leached Be was up to 202 mg L-1, which exceeded the regulated limit by nearly 10,000 times. The chemical fractionation analysis further revealed that the excessive amount of Be leached from BCS was contributed to the high content of acid-soluble fraction and reducible fraction of Be, which accounted for over 70% of the Be content. The results obtained from mineralogical automatic analyzer (MLA) showed that gypsum (23.23%) and epidote (19.55%) were the two major mineralogical phases of BCS. Both were small and loosely structured agglomerated particles with a D50 of 6.61 µm and 3.31 µm. ToF-SIMS results revealed that the Be distribution on the surface of BCS particles was relatively dispersed, with no aggregation or encapsulation. Be co-precipitated with gypsum and chlorite in the form of unstable Be(OH)2, which attached to the surface of these small particles. The unstable state of Be and the small size, loose structure and high liberation of the host material phases are the main reasons for the high leaching mobility of Be. The results of the risk assessment indicated that BCS posed an extremely high potential ecological risk, with Be being the most significant contributor.


Asunto(s)
Metales Pesados , Aguas del Alcantarillado , Aguas del Alcantarillado/química , Aguas Residuales , Metales Pesados/análisis , Berilio , Sulfato de Calcio
6.
Blood Adv ; 6(2): 441-451, 2022 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-34653241

RESUMEN

Single-cell analysis is of significant importance in delineating the exact phylogeny of the subclonal population and in discovering subtle diversification. So far, studies of intratumor heterogeneity and clonal evolution in multiple myeloma (MM) were largely focused on the bulk tumor population level. We performed quantitative multigene fluorescence in situ hybridization (QM-FISH) in 129 longitudinal samples of 57 MM patients. All the patients had newly diagnosed and relapsed paired samples. An expanded cohort of 188 MM patients underwent conventional FISH (cFISH) to validate the cytogenetic evolution in bulk tumor level. Forty-three of 57 patients (75.4%) harbored 3 or 4 cytogenetic clones at diagnosis. We delineated the phylogeny of the subclonal tumor population and derived the evolutionary architecture in each patient. Patients with clonal stabilization had a significantly improved overall survival (OS) than those with other evolutionary patterns (median OS, 71.2 months vs 39.7 months vs 35.2 months vs 25.5 months, for stable, differential, branching, and linear patterns, respectively; P = .001). A high degree of consistency and complementarity across QM-FISH and cFISH was observed in the evaluation of cytogenetic evolution patterns in MM. Survival after relapse was greater influenced by the presence of high-risk aberrations at relapse (hazard ratio = 2.07) rather than present at diagnosis (hazard ratio = 1.55). This study shows that QM-FISH is a valuable tool to elucidate the clonal architecture at the single-cell level. Clonal evolution pattern is of prognostic significance, highlighting the need for repeated cytogenetic evaluation in relapsed MM.


Asunto(s)
Mieloma Múltiple , Aberraciones Cromosómicas , Humanos , Hibridación Fluorescente in Situ , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Recurrencia Local de Neoplasia , Filogenia
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1667-1670, 2021 Oct.
Artículo en Chino | MEDLINE | ID: mdl-34627459

RESUMEN

Autoimmune cytopenia is a general term for all hemocytopenia diseases caused by humoral or cellular immunity abnormalities, and its common immune mechanism determines the importance of immunosuppressive therapy. Sirolimus, as an immunosuppressant against of mTOR, induces immune tolerance by adjusting Treg cells, which has application prospect in the treatment of refractory autoimmune cytopenia. This article reviews the mechanism, application, and possible adverse reactions of sirolimus in the treatment of idiopathic autoimmune cytopenia.


Asunto(s)
Sirolimus , Trombocitopenia , Humanos , Inmunosupresores , Linfocitos T Reguladores
8.
Nat Biomed Eng ; 5(6): 533-545, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34131321

RESUMEN

Regular screening for the early detection of common chronic diseases might benefit from the use of deep-learning approaches, particularly in resource-poor or remote settings. Here we show that deep-learning models can be used to identify chronic kidney disease and type 2 diabetes solely from fundus images or in combination with clinical metadata (age, sex, height, weight, body-mass index and blood pressure) with areas under the receiver operating characteristic curve of 0.85-0.93. The models were trained and validated with a total of 115,344 retinal fundus photographs from 57,672 patients and can also be used to predict estimated glomerulal filtration rates and blood-glucose levels, with mean absolute errors of 11.1-13.4 ml min-1 per 1.73 m2 and 0.65-1.1 mmol l-1, and to stratify patients according to disease-progression risk. We evaluated the generalizability of the models for the identification of chronic kidney disease and type 2 diabetes with population-based external validation cohorts and via a prospective study with fundus images captured with smartphones, and assessed the feasibility of predicting disease progression in a longitudinal cohort.


Asunto(s)
Aprendizaje Profundo , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/estadística & datos numéricos , Fotograbar/estadística & datos numéricos , Insuficiencia Renal Crónica/diagnóstico por imagen , Retina/diagnóstico por imagen , Área Bajo la Curva , Glucemia/metabolismo , Estatura , Índice de Masa Corporal , Peso Corporal , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Progresión de la Enfermedad , Femenino , Fondo de Ojo , Tasa de Filtración Glomerular , Humanos , Masculino , Metadatos/estadística & datos numéricos , Persona de Mediana Edad , Redes Neurales de la Computación , Fotograbar/métodos , Estudios Prospectivos , Curva ROC , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Retina/metabolismo , Retina/patología
9.
Oncogenesis ; 9(3): 31, 2020 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-32139666

RESUMEN

Multiple myeloma (MM) is the second most prevalent hematologic malignancy. Although the use of bortezomib (BTZ) significantly improves MM therapy, intrinsic and acquired drug resistance to BTZ remains a major clinical problem. In this study, we find that Cdc37, a key co-chaperone of Hsp90, is downregulated in relapsed MM patients, especially after BTZ treatment, suggesting a link between Cdc37 and BTZ resistance. Suppression of Cdc37 or inhibition of Cdc37/Hsp90 association induces plasma cell dedifferentiation, quiescence of MM cells, and BTZ resistance in MM. Furthermore, we discover that Cdc37 expression correlates positively with Xbp1s, a critical transcription factor for plasma cell differentiation in MM samples. Depletion/inhibition of Cdc37 downregulates Xbp1s, while overexpression of Xbp1s in MM cell lines partially rescues plasma immaturation and BTZ resistance. It is suggested that Xbp1s may act as a key downstream effector of Cdc37. Experiments with a mouse model also demonstrate that Cdc37 inhibition promotes plasma cell immaturation, confers BTZ resistance, and increases MM progression in vivo. Together, we identify a critical factor and a new signaling mechanism that regulate plasma cell immaturation and BTZ resistance in MM cells. Our findings may constitute a novel strategy that overcomes BTZ resistance in MM therapy.

10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(2): 360-364, 2019 Apr.
Artículo en Chino | MEDLINE | ID: mdl-30998138

RESUMEN

OBJECTIVE: To investigate the safety and efficacy of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) using modified BU/CY conditioning regimen for young AML patients of low and middle risk in the first complete remission (CR1). METHODS: Ten young AML patients of low and middle risk who did not want to accept allogeneic hematopoietic stem cell transplantation(allo-HSCT)and underwent auto-PBHSCT in CR1 during May 2013 to December 2016 were retrospectively analyzed. From 3 months after auto-PBHSCT, the maintenance therapy with interleukin-2 (IL-2) or IL-2 combined with histamine dihydrochloride was performed for these patients in the next 18 months. The side effects of the conditioning regimen, hematopoietic recovery time, transplant-related mortality (TRM) within 100 days and 1 year after auto-PBHSCT, relapse rate, leukemia-free survival (LFS) rate at 2 years and 3 years, overall survival (OS) were evaluated at 3 years and 4 years. RESULTS: Gastrointestinal side effects were the major non-hematologic toxicity reaction, among which, 7 cases relatively mild and 3 cases displayed moderate, just one case suffered from severe reaction. In 4 cases, the mild liver damage occurred, but no hemorrhagic cystitis occurred. All the patients experienced different kinds of infection, including 5 cases of bloodstream infection, 2 cases of gastrointestinal infection, 3 cases of crissum infection and 2 cases of oral infection. The myeloablative effect occurred in all ten patients. The median times for absolute neutrophil count (ANC)<0.5×109/L and for platelet count <20.0×109/L were 1.5 (0-3) days and 3 (2-5) days after transplantation, respectively. The patients achieved ANC>0.5×109/L at 10 to 19 days, median was 13 days after auto-PBHSCT. The patients achieved platelet count >20×109/L at 10 to 72 days; median was 32 days after auto-PBHSCT. The TRM within 100 days and 1 year after transplantation was 0. The relapse occurred in 2 cases at 6 and 14 months after auto-PBHSCT raspectively. The median follow-up time was 48.1 months, and the median survival time was 54.7 months after transplantation. The 2-year and 3-year LFS were 100% (10 cases) and 80% (8 cases), respectively. The 3-year and 4-year OS were 80% (8 cases) and 70% (7 cases), respectively. CONCLUSION: Modified BU/CY as conditioning regimen for auto-PBHSCT can achieve the myeloablative effect without raising TRM and obtain good LFS and OS. As for young AML patients without high risk, it is a valuable therapeutic option, especially for those lacking the chance of allo-HSCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Supervivencia sin Enfermedad , Humanos , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Trasplante Autólogo , Resultado del Tratamiento
11.
Blood Adv ; 3(5): 751-760, 2019 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-30833275

RESUMEN

The treatment of multiple myeloma (MM) with proteasome inhibitor (PI) bortezomib has significantly improved the survival of patients with MM. The 26S proteasome inhibitor targets the unfolded protein response (UPR) by inhibiting proteasome degradation of ubiquitinated paraprotein, subsequently leading to the lethal accumulation of paraprotein within the endoplasmic reticulum. According to secretory status of monoclonal immunoglobulin, newly diagnosed MM (NDMM) is divided into measurable and unmeasurable disease, which includes oligosecretory, nonsecretory, and nonproducer myeloma. The present study analyzed the clinical characteristics of 822 patients with NDMM who had either measurable or unmeasurable diseases and received bortezomib- or thalidomide-based therapies. Our results showed that the median progression-free survival (PFS) and overall survival (OS) of patients with MM was significantly longer in patients with measurable disease than those in oligosecretory, nonsecretory, and nonproducer MM (PFS: 27, 18, 19, and 2.0 months, respectively [P < .001]; OS: 51, 30, 22, and 2.0 months, respectively [P < .001]). Within the unmeasurable group, patients with nonproducer myeloma showed the shortest PFS and OS. Importantly, compared with thalidomide treatment, bortezomib significantly improved the PFS and OS of patients with MM with measurable disease (PFS: 25 and 33 months [P = .022], respectively; OS: 41 and 58 months [P < .001], respectively), but not those with unmeasurable disease (PFS: 18 and 16 months [P = .617], respectively; OS: 22 and 27 months [P = .743], respectively). Our results indicate that bortezomib-based therapy performed no better than thalidomide-based treatment in patients with unmeasurable MM. The results need to be confirmed in other patient cohorts, preferably in the context of a prospective trial.


Asunto(s)
Mieloma Múltiple/diagnóstico , Proteínas de Mieloma/metabolismo , Resultado del Tratamiento , Bortezomib/farmacología , Bortezomib/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Estudios Retrospectivos , Análisis de Supervivencia , Talidomida/farmacología , Talidomida/uso terapéutico
12.
Oncotarget ; 8(12): 18792-18801, 2017 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-27852046

RESUMEN

Elevated inflammatory markers are associated with poor outcomes in various types of cancers; however, their clinical significance in multiple myeloma (MM) have seldom been explored. This study investigated the prognostic relevance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in MM. Totally 559 MM patients were included in this study. NLR, PLR and MLR were calculated from whole blood counts prior to therapy. Kaplan-Meier curves and multivariate Cox proportional models were used for the evaluation of the survival. It has shown that newly diagnosed MM patients were characterized by high NLR and MLR. Elevated NLR and MLR and decreased PLR were associated with unfavorable clinicobiological features. Applying cut-offs of 4 (NLR), 100 (PLR) and 0.3 (MLR), elevated NLR, MLR and decreased PLR showed a negative impact on outcome. Importantly, elevated NLR and decreased PLR were independent prognostic factors for progression-free survival. Thus, elevated NLR and MLR, and decreased PLR predict poor clinical outcome in MM patients and may serve as the cost-effective and readily available prognostic biomarkers.


Asunto(s)
Biomarcadores de Tumor/inmunología , Recuento de Leucocitos , Mieloma Múltiple/inmunología , Adulto , Anciano , Área Bajo la Curva , Plaquetas , Supervivencia sin Enfermedad , Femenino , Humanos , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Linfocitos , Masculino , Persona de Mediana Edad , Monocitos , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Neutrófilos , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Sensibilidad y Especificidad
13.
Zhonghua Xue Ye Xue Za Zhi ; 36(11): 933-6, 2015 Nov.
Artículo en Chino | MEDLINE | ID: mdl-26632466

RESUMEN

OBJECTIVE: To investigate the clinical characteristics and prognosis of very young patients with multiple myeloma (MM). METHODS: We retrospectively analyzed the clinical characteristics and outcome of 35 newly diagnosed MM patients 40 years old or younger during a period of 15 years and compared with published data from western countries. RESULTS: Our study demonstrated that these very young patients were more likely to be in advanced stage of International staging system, IgD isotype, hemoglobin<100 g/L, decreased platelets and deletion of 17p13. With a median follow-up of 17 months (1- 89 months), the median overall survival (OS) of this cohort was 33 months and progression-free survival (PFS) was 13 months, moreover 8 of 17 deaths occurred in the first year after diagnosis. In the univariate analysis, extramedullary infiltration, del (17p13)and renal impairment were associated with reduced PFS (P=0.031, P=0.015, P=000, respectively), while the last two factors also predicted inferior OS (P=0.015, P=0.001), but multivariate analysis showed that only renal impairment independently associated with inferior survival in COX model(PFS: HR=3.953, 95% CI 1.263-12.371, P=0.018; OS: HR=5.769, 95% CI 1.602- 20.771, P=0.007). CONCLUSION: Our research showed for the first time that the clinical characteristics and survival of MM patients ≤ 40 years old in China were different from that in western countries. The special attention should be paid to the patients with their diagnosis and treatment.


Asunto(s)
Mieloma Múltiple/diagnóstico , Adulto , China/epidemiología , Deleción Cromosómica , Supervivencia sin Enfermedad , Humanos , Mieloma Múltiple/epidemiología , Pronóstico , Estudios Retrospectivos
14.
Zhonghua Xue Ye Xue Za Zhi ; 36(8): 682-5, 2015 Aug.
Artículo en Chino | MEDLINE | ID: mdl-26462639

RESUMEN

OBJECTIVE: To study the association between the level of serum DKK1 and disease course of multiple myeloma(MM)as well as myeloma bone disease. METHODS: This study enrolled 145 cases of MM(including 79 newly diagnosed MM, 19 responded MM, 47 relapsed or progressive MM) whose lytic bone disease were evaluated by conventional radiography, ELISA was used to detect the concentration of serum DKK1. RESULTS: Serum DKK-1 elevated in newly diagnosed MM compared with normal donors[2 155(646-35 251)vs 1 487(646-2 577) ng/L, P=0.000], those responded[1 136(431- 3 582) ng/L, P=0.001]and relapsed/progressive MM[1 695(431-3 582) ng/L, P=0.037], and the level of relapsed/progressive MM was marginally higher than the responded ones. Moreover, MM patients without lytic lesions in conventional radiography had significantly lower DKK- 1 levels than those with lytic bone disease[1 910(660-26 925)vs 2 519(646-35 251) ng/L, P=0.005]. Notably serum DKK-1 correlated with the number of bone lesions[0 vs 1-3 vs >3 lesions: 1 910(660-26 925)vs 2 155(1 369-5 974)vs 2 547(646-35 251)ng/L, P=0.018]. CONCLUSION: DKK-1 serum concentration correlated with disease course of MM and myeloma bone disease, indicating that DKK-1 was an important factor for the extent of bone disease, which supporting the hypothesis of DKK-1 as a therapeutic target in myeloma bone disease.


Asunto(s)
Neoplasias Óseas , Mieloma Múltiple , Ensayo de Inmunoadsorción Enzimática , Humanos
15.
Oncotarget ; 6(33): 34276-87, 2015 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-26416457

RESUMEN

Multiple myeloma (MM) is a genetically heterogeneous disease with diverse clinical characteristics and outcomes. Recently, multiplex ligation-dependent probe amplification (MLPA) has emerged as an effective and robust method for the detection of cytogenetic aberrations in MM patients. In the present study, MLPA analysis was applied to analyze cytogenetics of CD138 tumor cells of 59 MM samples, and its result was compared, retrospectively, with the interphase fluorescence in situ hybridization (iFISH) data. We firstly established the normal range of each of the 42 diagnostic probes using healthy donor samples. A total of 151 aberrations were detected in 59 patient samples, and 49/59 cases (83.1%) harbored at least one copy number variation. Overall, 0-7 aberrations were detected per case using MLPA, indicating the heterogeneity and complexity of MM cytogenetics. We showed the high efficiency of MLPA and the high congruency of the two methods to assess cytogenetic aberrations. Considering that MLPA analysis is not reliable when the aberration only exits in a small population of tumor cells, it is essential to use both MLPA and iFISH as complementary techniques for the diagnosis of MM.


Asunto(s)
Hibridación Fluorescente in Situ/métodos , Mieloma Múltiple/genética , Reacción en Cadena de la Polimerasa Multiplex/métodos , Adulto , Anciano , Aberraciones Cromosómicas , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad
16.
Zhonghua Xue Ye Xue Za Zhi ; 36(5): 393-7, 2015 May.
Artículo en Chino | MEDLINE | ID: mdl-26031525

RESUMEN

OBJECTIVE: To investigate the influence of renal function on the level of ß2-microglobulin (ß2-MG) as prognostic factor in newly diagnosed multiple myeloma (MM) patients, and to analyze the overall survival (OS) in different level of ß2-MG with relatively normal or abnormal renal function in MM patients. METHODS: According to the level of ß2-MG, 666 newly diagnosed MM patients were divided into three groups as ß2-MG<3.5, 3.5-<5.5, ≥5.5 mg/L. According to the level of serum creatinine, these patients were divided into two groups:serum creatinine <177 µmol/L as relatively normal group, serum creatinine ≥177 µmol/L as abnormal group. RESULTS: Among 666 patients, there were 416 male and 250 female, the median age was 58 (25-86) years old. Comparison of OS among ß2-MG<3.5, 3.5-<5.5, ≥5.5 mg/L groups indicated that the median OS of the three groups were 85.75 (95% CI 70.99-100.50), 47.25 (95% CI 40.98-53.53) and 35.05 (95% CI 30.75-39.35) months, respectively (P<0.01). Comparison of OS between serum creatinine <177 and ≥177 mmol/L groups, the median OS of the two groups were 64.67 (95% CI 56.57-72.77) and 32.74 (95% CI 27.74-37.73) months, respectively (P<0.01). In ß2-MG≥5.5 mg/L, the median OS of relatively normal and abnormal groups were 37.25 (95% CI 31.45-43.06) and 32.55 (95% CI 26.26-38.83) months, respectively (P=0.142). CONCLUSION: High level of ß2-MG and renal function correlated with shorter survival of MM patients. Higher level of ß2-MG with abnormal renal function can't change the prognostic value of ß2-microglobulin on MM.


Asunto(s)
Mieloma Múltiple , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Riñón , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Microglobulina beta-2
17.
Clin Cancer Res ; 21(9): 2148-56, 2015 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-25652456

RESUMEN

PURPOSE: Accumulating evidence indicates that intratumor heterogeneity is prevalent in multiple myeloma and that a collection of multiple, genetically distinct subclones are present within the myeloma cell population. It is not clear whether the size of clonal myeloma populations harboring unique cytogenetic abnormalities carry any additional prognostic value. EXPERIMENTAL DESIGN: We analyzed the prognostic impact of cytogenetic aberrations by fluorescence in situ hybridization at different cutoff values in a cohort of 333 patients with newly diagnosed myeloma and 92 patients with relapsed myeloma. RESULTS: We found that nearly all IgH-related arrangements were observed in a large majority of the purified plasma cells; however, 13q deletion, 17p deletion, and 1q21 amplification appeared in different percentages within the malignant plasma cell population. Based on the size of subclones carrying these cytogenetic aberrations, the patients were divided into four groups: 0%-10%, 10.5%-20%, 20.5%-50%, and >50%. Receiver-operating characteristics analysis was applied to determine the optimal cutoff value with the greatest differential survival and showed that the most powerful clone sizes were 10% for 13q deletion, 50% for 17p deletion, and 20% for 1q21 gains, which provided the best possible cutoffs for predicting poor outcomes. CONCLUSIONS: Our study indicated that the impact of clone size on prognostic value varies between specific genetic abnormalities. Prognostic value was observed for even a subgroup of plasma cells harboring the cytogenetic aberration of 13q deletion and 1q21 gains; however, 17p deletion displayed the most powerful cutoff for predicting survival only if the predominant clones harbored the abnormality.


Asunto(s)
Mieloma Múltiple/genética , Mieloma Múltiple/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/administración & dosificación , Aberraciones Cromosómicas , Ciclofosfamida/administración & dosificación , Análisis Citogenético , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Humanos , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Pronóstico , Talidomida/administración & dosificación
18.
Ann Hematol ; 94(2): 257-64, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25231928

RESUMEN

The common features shared by primary plasma cell leukemia (pPCL) and multiple myeloma (MM) with circulating plasma cells (CPCs) are peripheral blood invasion and expansion of plasma cells independent of the protective bone marrow (BM) microenvironment niche. However, few studies have addressed the relationship between pPCL and MM with CPCs. Here, we quantitated the number CPCs by conventional morphology in 767 patients with newly diagnosed MM; their clinic features were compared with those of 33 pPCL cases. When the presence of CPCs was defined as more than 2 % plasma cells per 100 nucleated cells on Wright-Giemsa stained peripheral blood smears, the incidence of MM with CPCs was 14.1 % in newly diagnosed MM. Patients with CPCs shared many clinical features with pPCL, especially clinical parameters related to tumor burden. However, no commonalities were found in immunophenotyping and cytogenetics. The prognosis of pPCL was poor, with a median progression free survival (PFS) of 12 months and an overall survival (OS) of 15 months. MM patients with CPCs had a clearly inferior PFS and OS as compared with the control cohort. Most interestingly, although the CPCs were not high enough to meet the diagnostic criteria for pPCL, the survival of MM patients with CPCs was comparable with that of pPCL, with a median PFS of 17 months and an OS of 25 months.


Asunto(s)
Leucemia de Células Plasmáticas/patología , Mieloma Múltiple/patología , Células Plasmáticas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aberraciones Cromosómicas , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/terapia , Células Plasmáticas/metabolismo , Pronóstico , Estudios Retrospectivos , Trasplante Autólogo , Resultado del Tratamiento
19.
Exp Hematol ; 43(3): 168-176.e2, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25462022

RESUMEN

Multiple myeloma (MM) is a heterogeneous disease, and the benefit from bortezomib treatment is not uniform among all patients subgroups. Currently, little information is available to predict patients response to bortezomib treatment. In this study, we aimed to identify patients benefiting minimally from bortezomib as part of first-line therapy and to define high-risk MM in the context of bortezomib treatment. We compared the effect of a bortezomib-based treatment (arm B) with that of a treatment without bortezomib (arm A) on different genetic patient subgroups in a series of 273 cases of newly diagnosed MM. These patients were enrolled in a prospective, non-randomized clinical trial (BDH 2008/02). A subgroup of patients exhibiting little benefit from bortezomib treatment was identified. These patients had at least one of the following characteristics: del(17p13), 1q21 gain, or high lactate dehydrogenase levels. In this subgroup, survival of patients treated with bortezomib was comparable (progression-free survival: 14.0 vs. 15.0 months, p = 0.992; overall survival: 21.0 vs. 14.0 months, p = 0.472) to that of patients undergoing thalidomide-based treatment. We propose that all patients with newly diagnosed MM should be evaluated for these three markers before bortezomib treatment. Other novel drugs and alternative therapeutic strategies are needed for patients with such markers.


Asunto(s)
Ácidos Borónicos/uso terapéutico , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Mutación/genética , Pirazinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Bortezomib , Aberraciones Cromosómicas , Humanos , L-Lactato Deshidrogenasa/sangre , Persona de Mediana Edad , Mieloma Múltiple/enzimología , Mieloma Múltiple/genética , Análisis Multivariante , Valor Predictivo de las Pruebas , Factores de Riesgo , Análisis de Supervivencia , Talidomida/uso terapéutico
20.
Leuk Res ; 38(6): 666-72, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24746293

RESUMEN

Normal plasma cells (PCs) are either undetectable or outnumbered by the myelomatous PC compartment in bone marrow of multiple myeloma (MM). However, residual normal PCs have been detected in a minority of symptomatic MM patients with superior survival. The number of normal PCs is also an important factor to identify monoclonal gammopathy of undetermined significance (MGUS)-like MM. We speculate that the polyclonal serum IgM level in non-IgM myelomas may reflect the number of residual normal PCs. Here we investigated the prognostic relevance of polyclonal serum IgM level in a series of 485 newly diagnosed symptomatic MM (NDMM) patients. Our results showed that symptomatic MM patients with polyclonal IgM more than 0.5g/L displayed a favorable baseline clinical feature, together with a significantly lower frequency of high-risk cytogenetic abnormalities. This group of patients had a significantly prolonged progression-free survival (PFS) and overall survival (OS) regardless of thalidomide or bortezomib therapy. Furthermore, the superior outcome was independent of the depth of response. Our findings suggest that polyclonal IgM level is capable of identifying a group of symptomatic MM patients with distinct clinicobiological characteristics and favorable survival, similar with MGUS-like MM.


Asunto(s)
Inmunoglobulina M/sangre , Mieloma Múltiple/inmunología , Antígenos CD19/sangre , Ácidos Borónicos/uso terapéutico , Bortezomib , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Proteínas Proto-Oncogénicas c-kit/sangre , Pirazinas/uso terapéutico
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