Pathophysiology of myeloma bone disease is unclear and complex.At early stage,osteoclastic bone resorption is increasing,myeloma cells are dependent upon the cells of bone for growth and survival.With the increase in tumor burden,osteoblast suppression is maintained.Based on the diagnosis of multiple myeloma (MM),conventional morphology,M proteins and skeletal survey are effective approach for diagnosis and monitoring of MM.However,the multiparameter flow cytometry (MFC) has advantage in distinguishing clonal from normal plasma cells.If the patient has significant paraprotein relapse in 2 consecutive measurements separated by no more than two months,the experts of International Myeloma Working Group (IMWG) consider that myeloma therpy should be re-started,even if the symptoms or evidences of new end-organ damage has not yet appeared.For newly diagnosed MM patients who are ineligible for autologous stem cell transplantation,the combination of melphalan,prednisone and with either thalidomide (MPT) or bortezomib (VMP) is the standard treatment option,and then given with lenalidomide and low-dose dexamethasone is gradually developing a new standard continuous therapy.For elderly patients,especially over 75 years old,always have a poor clinic outcome.It should be fully aware that frailty is an independent prognostic factor which carries a greater impact on overall survival than the renal function or cytogenetic abnormalities.Therefore,it must be under consideration in developing individualized treatment programs.

Multiple myeloma (MM) is a unique cancer paradigm for investigating the mechanisms involved in the transformation from a premalignant condition (unknown monoclonal gamma globulin,MGUS) into a malignant disease (MM).In its pathogenesis,genotype characteristics of tumor clones which are highly complex and heterogeneous,as well as the dialogue between plasma cells and their microenvironment are equally important and both play a key role in the outcome of the disease.MM will soon no longer be considered as a single disease.A large number of new drug emergence and applications will increase the need for monitoring minimal residual disease (MRD) in prognosis and treatment of MM.New drugs and high-dose chemotherapy with autologous stem cell transplantation applications have been significantly improving the prognosis of MM in the past 20 years.Re-examining the early MM diagnostic criteria and the possibility of early intervention will open up a new therapeutic approach.It is important to find a balance of efficacy,toxicity and cost in order to achieve a cure for this disease.

As understanding the biology of multiple myeloma (MM) and application of new drugs, regimens containing new drugs deepened therapeutic response and prolonged the survival of MM patients. This article updates the therapeutic response of regimens reported in the 57th American Society of Hematology annual meeting, containing immunomodulatory agents, proteasome inhibitors, histone deacetylase inhibitors and other new drugs including monoclonal antibodies and the others. In the same time, minimal residual disease (MRD) is also used to evaluate the remission depth of MM. In order to achieve durable long-term remission and higher quality of life, new drug combination regimens have been recommended, especially for the relapsed or the high risk MM patients.

Objective To investigate the efficacy and outcome in newly diagnosed multiple myeloma (MM) patients with renal insufficiency using bortezomib-or thalidomide-based regimens as front line treatment.Method Sixty-nine newly diagnosed MM patients with renal insufficiency were retrospectively analyzed from August 2006 to August 2014.Results ① Among thirty-nine patients with bortezomib based regimens (the bortezomib group),the overall response rate (ORR) was 89.7％ and complete response (CR) plus near CR(nCR) rate was 41.0％.By contrast,among thirty patients with thalidomide based regimens (the thalidomide group),the ORR was 83.3％ and CR + nCR rate was 26.7％.There was no significant difference of either ORR or CR + nCR rate between bortezomib and thalidomide groups.② The improvement rate of renal function in bortezomib group and thalidomide group were 87.2％ and 60.0％respectively (P =0.012).The median duration time of renal injury was 45 days in 52 patients with renal function improved,which was significantly shorter compared with 222 days in 17 patients without improvement (P ＜ 0.05).There was no difference of median serum creatinine and creatinine clearance rate between the two groups.③ The median progression-free survival (PFS) and the overall survival (OS) were 18 and 33.5 months,respectively in all patients.The three-year and five-year OS rates were 57％ and 17％,respectively.The median PFS was 19 months in bortezomib group,while it was only 12 months in thalidomide group (P =0.023).The median OS were 36.5 months and 25.5 months respectively,which was no difference (P =0.285).Conclusions The newly diagnosed MM patients with renal insufficiency could get higher ORR and the longer PFS using bortezomib-containing regimens as initial therapy.Meanwhile the improvement rate of renal function and the living quality in patients with bortezomib are better compared with those with thalidomide based treatment.

Objective:This study investigated the clinical characteristics of multiple myeloma with early death in the era of novel drugs. Methods:Medical records from 188 patients diagnosed from January 2009 to December 2015 were retrospectively reviewed, showing that early death occurred in 19 patients. Early death was defined as death by any cause within the first year after diagnosis. Results:(1) Early mortality was 10.1%, and the median age was 67 years old (range:40-84 years). Eight cases presented IgG type, and 11 cases were non-IgG type. All 19 patients were diagnosed to be at stageⅢin accordance with the Durie–Salmon staging system, and renal insufficiency occurred in 10 patients. In accordance with the International Staging System (ISS), four patients were diagnosed to be at stageⅡ, whereas 15 other patients were at stageⅢ. Extramedullary plasmacytoma (EMP) occurred in six cases, whereas 10 cases pre-sented high-risk patients with cytogenetic abnormalities. Elevated lactate dehydrogenase (LDH) was found in five cases, amyloidosis was detected in three patients, and secondary plasma cell leukemia was observed in two cases. The median score of performance sta-tus (KPS) was 70 (range: 20-80). A total of 16 patients were treated with bortezomib, and 3 patients were treated with CADT. (2) Among the 13 patients who were evaluated, the overall response rate was 46.2%(6/13), and the complete response (CR) and near-CR rate was 7.7%(1/13). (3) The median overall survival was 3 (1-11.5) months, although the two patients with secondary plasma cell leu-kemia survived for less than 2 months. (4) Eight patients died of disease progression (42.1%), eight patients died of severe infections (42.1%), and three patients died of thrombotic events. Conclusion:The important causes of early death include the following:high-risk cytogenetics, elevated LDH, EMP, amyloidosis, advanced age, poor performance status, and serious complications during treat-ment. In the era of novel drugs, we should improve early diagnosis rates and explore individualized treatment for high-risk multiple my-eloma for the benefit of a wide range of patients.

Objective Toexplore the application value of diffusion tensor imaging (DTI) in evaluating evaluation offunctional changes of the in patients with primary trigeminal neuralgia caused (PTN) by neurovascular compression. Methods 40 unilateral PTN patients and 40 healthy volunteers were enrolled in ourstudy.They allAll patients underwent the general sequences and DTI ,and then to measured the ADC and FA values of the trigeminal nerves. Results (1) Compared with contralateral side (0.408 ± 0.054)and bilateral sides in control group(0.423 ± 0.057), FA value of the ipsilateral side in PTN group(0.330 ± 0.056) was significant lower (P< 0.05)compared with the contralateral side (0.408 ± 0.054) and bilateral sides in control group (0.423 ± 0.057).The ADC value of ipsilateralside (2.052 ± 0.473)× 10-3 mm2/s was significantly higher (P < 0.05) thancompared withthe contralateral side (1.541 ± 0.266) ×10-3 mm2/s and bilateral sides in control group(1.431 ± 0.308) ×10-3 mm2/s. (2) An There's a nnegative correlation was found (r = -0.613,P < 0.001) between the loss of FA and the increase of ADC (r = -0.613,P < 0.001). Conclusion DTI could be used to evaluate the changes of neuratrophy and demyelination ,so it canmight be used of in diagnosis and treatment of PTNin further way.

Purpose To explore CT manifestations of thyroid carcinoma and its correlation with neck lymph node metastasis. Materials and Methods CT findings of 165 patients with thyroid carcinoma confirmed by surgical pathology were studied, including number, shape, size, calcium, necrosis, surrounding invasion and enhancement of substantial part, and its correlation with neck lymph node metastasis was also analyzed. Results 107 out of 165 patients (64.85%) suffered from neck lymph node metastasis. Different tumor number, calcium and necrosis were not associated with the rate of neck lymph node metastasis (χ2=0.009, 2.606, 1.522;P>0.05);tumor shape, size, surrounding invasion and enhancement were significantly different from the rate (χ2=26.510, 75.995, 68.922, 20.819;P<0.05). Patients age, tumor shape, size, enhancement and surrounding invasion were positively correlated with lymph node metastasis (r=0.124, 0.243, 0.276, 0.287, 0.395;P<0.05);the sequence of correlation was as follows:surrounding invasion>enh ancement>shape>size>age. However, patients gender, tumor number, calcium and necrosis showed on correlation (r=0.074, 0.126, 0.005, 0.121;P>0.05). Conclusion Lymph node metastasis is mainly associated with factors like age, tumor shape, size, enhancement and surrounding invasion. It is advisable that patients with high risk rate may consider selective cervical lymph node dissection.

Objective To investigate the value of 1q21 amplification in newly diagnosed myeloma patients.Methods Fifty-two cases of newly diagnosed multiple myeloma from June 2008 to June 2010 were enrolled.Fluorescence in situ hybridization (FISH) was used to detect the 1q21 amplification,and the clinical characteristics and treatment response were analyzed.Results 1q21 amplification was discovered in 30 of 52 patients (57.7 ％),Clinical characteristics such as gender,malignant pleural effusion,extramedullary plasmacytoma,bone destruction,β2 microglobulin,ALB,hemoglobin,blood calcium,plasma cell proportion,clinical stage seemed to have no correlation with 1q21 amplification.The 52 patients all received bortezomibbased regimens.The response rates were not significant difference between patients with and without 1q21 amplification,the OS was also not significant difference [26 months (6-30 months) vs 30 months (12-85 months),P =0.409],but the patients with presence of 1q21 gain resulted in significantly shorter PFS [8 months (1-30 months) vs 20 months (3--48 months),P=0.019].Multivariate analysis showed 1q21 with more than two additional genetic abnormalities was an independent prognostic predictor (P =0.031).Conclusion 1q21 amplification is one of the adverse prognostic predictors,the response rate is not significant difference between patients with and without 1q21 amplification in bortezomib-based group,but the 1q21 amplification could result in significantly shortened PFS.

Objective:To investigate the expression of serum human phosphatidylethanolamine-binding protein 4 (hPEBP4) in patients with multiple myeloma (MM) and its clinical significance.Methods:A total of 59 symptomatic MM patients admitted to West Branch of Beijing Chaoyang Hospital from September 2016 to September 2018 were selected as the research objects. According to the CRAB symptoms [elevated serum calcium (C), kidney injury (R), anemia (A), bone lesions (B)], all patients were divided into 2 groups, including the active group of 44 patients with CRAB symptoms, and the response group of 15 patients who achieved at least partial remission after chemotherapy and symptom relief of CRAB. According to the degree of bone lesions (BL), 30 patients with severe bone-related events were grouped as the severe bone lesions (SBL) group, and 14 patients were grouped as the non-severe bone lesions (NSBL) group. According to the revised international prognostic staging system (R-ISS), patients in the active group were divided into three subgroups: stage Ⅰ, stage Ⅱ, and stage Ⅲ, including 26, 11 and 7 patients, respectively. A total of 15 healthy examination people whose gender and age matched those of the patients were treated as the healthy control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of hPEBP4, tumor necrosis factor ligand superfamily member 14 (LIGHT/TNFSF14) and activin A of patients in different groups. Pearson was used to analyze the relationship of the expressions of multiple factors in the active group. The optimal cut-off value of multiple factors diagnosing MM was determined by using receiver operating characteristic (ROC) curve, and according to the cut-off value, the differences in overall survival (OS) of patients with different stratification were compared.Results:In the active group, the respond group, the healthy control group, the level of hPEBP4 was (1.48±0.64) μg/L, (1.49±0.75) μg/L, (0.31±0.10) μg/L, respectively; the level of LIGHT/TNFSF14 was (169±112) ng/L, (256±132) ng/L, (44±27) ng/L,respectively; the level of activin A was (383±266) ng/L, (223±79) ng/L, (234±85) ng/L, respectively; and the differences were statistically significant (all P<0.05). In the active group, the level of hPEBP4 was (1.06±0.60) μg/L, (1.15±0.50) μg/L, (1.73±0.68) μg/L, respectively in patients with stage R-ISSⅠ, R-ISSⅡ and R-ISS Ⅲ, and the difference was statistically significant ( F=3.287, P=0.032). The level of activin A was (219±55) ng/L, (247±117) ng/L, (450±215) ng/L, respectively among patients in stage R-ISSⅠ, R-ISSⅡ, R-ISS Ⅲ, and the level of activin A in stage R-ISS Ⅲ was higher than that in stage R-ISSⅠand R-ISSⅡ (all P < 0.05). The levels of LIGHT/TNFSF14 and activin A of SBL patients were higher than those of NSBL patients [(174±101) ng/L vs. (98±53) ng/L; (467±238) ng/L vs. (189±71) ng/L, all P < 0.05]. The level of hPEBP4 was positively correlated with the levels of M protein ( r=0.694, P < 0.01) and activin A ( r=0.252, P < 0.01) of IgG patients in the active group. ROC curve analysis showed that the optimal cut-off value of hPEBP4, LIGHT/TNFSF14, activin A diagnosing MM was 1.04 μg/L, 97.0 μg/L, 156.2 ng/L. The median overall survival (OS) time of patients with hPEBP4 >1.04 μg/L and hPEBP4 ≤ 1.04 μg/L was 57 months (95% CI 22-92 months) and not reached, respectively, and the difference was statistically significant ( P < 0.05); while the median OS time of patients with activin A ≥ 156.2 ng/L and activin A < 156.2 ng/L was 61 months (95% CI 24-98 months) and not reached, respectively, and the difference was statistically significant ( P < 0.05). Conclusions:High expression level of hPEBP4 is related with the progression of MM. It is positively related with the level of M protein and negatively with the OS of MM patients. It is suggested that hPEBP4 may be used as an important marker to judge disease progression and tumor burden in MM. LIGHT/TNFSF14 and activin A cooperate with hPEBP4 to participate in the pathological processes of tumor microenvironment of MM.

OBJECTIVETo explore the expression of WT1 gene in leukemia patients and its clinical implications.

METHODSExpression of WT1 mRNA was detected in two leukemia cell lines (K562 and HL-60), 49 acute leukemia (AL) patients, 33 chronic myeloid leukemia (CML) patients and 25 healthy subjects by reverse trans-criptase-nested polymerase chain reaction (RT-Nested PCR).

RESULTSWT1 gene was expressed in all subtype of AL including K562 and HL-60 cell lines, 21/29 newly diagnosed and relapsed AL patients, 1/20 complete remission (CR) AL patients, 15/18 CML blastic crisis patients, 1/5 CML patients in accelerated phase, and 1/10 CML patients in chronic phase. WT1 gene was undetectable in 25 healthy subjects. The expression level of WT1 gene was related to the prognosis of AL, patients with relative level >/= 1.0 had lower CR rates and disease-free survival. For CML patients, WT1 gene expression was associated with the clinical phase, it increased with disease progressed.

CONCLUSIONWT1 gene expression is associated with pathogenesis of leukemia. It is a prognostic factor and a marker for the detection of minimal residual disease in AL and may used as an indicator for diagnosing CML blastic crisis.

Disease-Free Survival ; Gene Expression ; HL-60 Cells ; Humans ; Neoplasm, Residual ; diagnosis ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; WT1 Proteins ; genetics