The key point of the diagnosis and therapeutic principle of the multiple myeloma (MM) have been well established due to the past decades of research and clinical practice.But the higher heterogeneity of the MM including the extramedullary plasmacytomas,systemic amyloidosis,venous thrombus and osteopathy that have made the disease more complicated and cause a lot of attention.

Plasma cell dyscrasia including multiple myeloma, monoelonal gammopathy of undetermined significance(MGUS), Waldenstrom s macroglobulinemia, amyloidosis and POEMS syndrome is a common malignant disease of hematological system and its incidence is increased by year. Deeply study the clinical process of this kind of disease and make reasonable therapies is an important approach for extending the life span and improving the prognosis of patients.

The incidence of multiple myeloma(MM)has increased each year with the improving medical diagnostic technology and ageing population.The MM is still an incurable disease at present.Following the improving diagnostic technology,serious study of the therapeutic regimen,combination therapy of new drugs with conditional drugs,risk-adapted therapy in MM and individualized treatment,it is an important strategy to prolong the survival,reduce the complication and improve the prognosis.

The breakthrough progress has been made in the treatment of multiple myeloma.Since 1990 s,autologous stem-cell transplantation (ASCT) has resulted in high response rate of MM,and the median overall survival was 5 years.The recent introduction of the novel agents including thalidomide,bortezomib,and lenalidomide further increase the response rate of MM.It is reported that the median overall survival was increased by 50 ％.The latest estimates of the median overall survival was about 10 years in under 65 years old patients,and 5-6 years in the elderly patients.The novel agents under investigation will further prolong the overall survival rate and progression free survival in the near future.

Objective To investigate the clinical features of multiple myeloma (MM) complicated by extramedullary plasmacytomas(EM). Methods Twenty five patients were enrolled into the study. The proportion male to famale was 15:10 and the median age 55. 2 years. The distribution of different isotypes was IgA ten, IgG nine and light chain λ five. The sites of complicating plasmacytoma included muscle, bone, skin, rectum, and testicles. The most common site was muscle. Results Patients with complicated extramedullary plasmacytomas at the time of diagnosis received traditional treatment, including vincristiuum, adriamycin, dexamethasonum, mephalan, presnisone, thalidomide and bortezomib. Rates of overall response (ORR) were 80%. Plasmacytomas occurring after the diagnosis of MM received cisplatin, etoposide, cyclophosphamide, presnisone, or bortezomib ORR were 66. 7% ,50. 0%. Conclusion These results lend support to the efficacy of bortezomib in the treatment of plasmacytoma. MM cases with unconventional disease recurrence are likely to be seen due to sub-clinical seeding of turnout cells suggestive of the presence of an EM clone of plasma cells with a high degree of chemoresistance. Available data in the literature concerning the optimal therapy for patients with EM relapse were reviewed.

Objective Extramedullary plagmocytoma at diagnose or during the course of multiple myeloma is rare.In order to know this entity better and explore new therapy for it,by combining with literature review,we conducted a retrospective study to describe the clinical and laboratory features of this entity and the outcome of these manirestation.Methods From January 2001 to July 2007,123 multiple myeloma patients were treated in our hospital.We analysed the clinical features of patients with extramedullary plagmocytoma at diagnose or during the course of multiple myeloma.The response to therapy was evaluated according to the EBMT criteria.Results 9 eligible patients out of 123 with MM were retrieved from the hematology department of Beijing Chaoyang hospital.The median age was 55(range:48～66)with a female/male ratio of 1/8.One patients was found to have Extramedullary and extraosseous tumor at the time of MM diagnose,and eight patients developed Extramedullary tumor during the course of the disease.Multiple sites were usually involved.Resistance to traditional chemotherapy wag frequent.With a median follow-up of 19 months(range:3～47),2 patients are alive.Median time from progression of disease to diagnose of Extramedullary disease was 4 and a half months.The median interval from diagnosis of Extramedullary disease to death was 2 months and OS was 23 months.Conclusion Extramedullary plasmocytoma is a rare manifestation of MM,with a cumulative incidence of 7.3% of MM in our department.Multiple sites are usually involved.The resistance to the traditional chemotherapy is frequent and the prognosis is very poor.The new therapy is necessarily explored.

Objective To investigate the expression of COX-2 in multiple myeloma(MM)and the relationship between myeloma cells proliferation and apoptosis.To provide a new prognosis factor and therapeutic target.Methods COX-2 from the 22 newly diagnosed MM,14 relapsed MM and PCNA,HSP70 of the newly diagnosed patients were detected by immunohistochemistry method.Results All the newly diagnosed MM exhibited positive COX-2 immunoreactivity.50% had strong COX-2 and 50% showed weak COX-2.Relapsed MM exhibited strong COX-2.COX-2 was related with serum β2 microglobulin,marrow plasma cells,hemoglobin,PCNA,HSP70(P=0.019,0.003,0.048,0.006,0.034).Conclusion COX-2 was overexpressed in MM.Prognosis of patients with strong COX-2 is poorer than those with weak COX-2.COX-2 may promote the proliferation and inhibit the apoptosis of myeloma cells.

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 To explore the relationship of stromal derived factor 1α (SDF-1α) and CD44variant isoforms (CD44v6) with progress of multiple myeloma (MM). Methods Bone marrow mononuclear cells(MNCs) and bone marrow stromal cells (BMSCs) from 24 cases of MM patients (14 cases of untreated and relapsed and 10 cases of stable MM patients) and 15 cases of subjects were investigated as potential SDF-1αand CD44v6 product. The level of SDF-1α and CD44v6 of the conditioned media from MM patients and subjects were analyzed by ELISA. Results The level of SDF-1α and CD44v6 from MNCs in untreated and relapsed MM patients [(7232.41 ± 2644.97) pg/ml and (34.34 ± 13.20) ng/ml] were significantly higher than stable MM patients [(2315.49 ± 748.29) pg/ml and (15.69 ± 5.28) ng/ml] (t =6.25, t= 7.82, P ＜0.05) and 15 subjects [(1149.52 ± 636.06) pg/ml and (4.85 ± 3.62) ng/ml] (t= 4.60, t = 7.61, P＜ 0.05). The level of SDF-1α in stable MM patients was different from healthy subjects (P ＜0.05), but the level of CD44v6 in stable MM patients was not different from controls. The level of SDF-1α and CD44v6 in stable MM patients were significantly higher than health subjects (t = 2.99, t= 4.87, P ＜0.05). The level of SDF-1α was also detected from BMSCs of MM patients. When human MM cell lines U266 were adhered to BMSCs of 9 untreated and relapsed MM patients,and added rhIL-6 to it, there was significant increase of SDF-1α, compared with BMSCs in subjects and MM patients. The expression level of SDF-lα was correlated with the level of CD44v6 (r =0.51, P =0.03). Conclusion The increase of SDF-1α (may be produced by myeloma cells and BMSCs) and CD44v6 (may be produced by myeloma cells) activity is associated with the progress or pathogenesis of MM, and may be involved with tumor invasion. The completion of these processes in vivo may need participation of myeloma cells, BMSCs, IL-6,SDF-lα and CD44v6.