OBJECTIVETo investigate the value of serum fructosamine (FMN) measurement in clinical typing and staging of multiple myeloma(MM) as well as evaluation of curative efficacy and prognosis of IgA type MM.

METHODSThe levels of FMN were detected by nitro-blue-tetrazolium colorimetric method in 62 IgA type MM patients, 65 IgG type MM patients, 24 IgM type MM patients. The difference between the serum FMN levels and different MM types and its relationship with IgA type MM, patients' stages, efficacy and as well as, the effect of FMN level on overall survival (OS) time of IgA type MM patients were analyzed.

RESULTSFMN level of IgA type patients was obviously higher than that of IgG type and IgM type patients. Patients of DS stage III had higher FMN level than that of stage II, and patients of DS stage II had higher FMN level than that of stage I, the differences were statistical significant(P<0.05). Patients of ISS stage III also had higher FMN level than that of stage II, and patients of ISS stage II also had higher FMN level than that of stage I, the differences were statistical significant(P<0.05). After treatment, FMN level of patients obtained complete remission (CR) or very good partial remission(VGPR) obviously decreased, FMN level of patients obtained partial remission(PR) decreased, FMN level of patients obtained less than PR increased. Patients with normal FMN level had longer OS time, while patients with high FMN level had obviously short OS time.

CONCLUSIONSSerum FMN is obviously elevated in the IgA type MM, there is a certain association between staging and serum FMN level, the IgA type MM patients with FMN normalization after treatment have better prognosis.

OBJECTIVETo explore the effect of CIK cells comined with VAD regimen on prognosis of patients with multiple myeloma(MM).

METHODSForty-six cases of MM were divided into observation group and control group, the control group was treated by VAD and the observation group was treated by CIK cells comined with VAD. The prognosis between 2 groups was compared.

RESULTSThe total efficiency was not significantly different between the 2 groups (P>0.05); the CR in the observation group was significantly higher than that in control group(P<0.05); the levels of osteocytes in observation group were higher than those in control group(P<0.05); the levels of osteoclasts, plasma cells, IgA and IgG in observation group were lower than those in control group(P<0.05); the increasing ranges of albumin and hemoglobin, and the decreasing range of blood sedimentation and β2-MG in observation group were higher than those in control group(P<0.05); the incidences of abnormal electrocardiogram, myocardial enzyme and creatinine in observation group were higher than those in control group(P<0.05).

CONCLUSIONCIK cells comined with VAD regimen can enhance the therapeutic effects on the patients with multiple myeloma, improve the objective index and reduce the risk of adverse reactions, thus may be applicable to clinical practice.

OBJECTIVETo explore the clinical effects of T-VD regimen (bortezomib+dexamethasone+thalidomid) and T-VAD regimen (vincristine+adriamycin+dexamethasone+thalidomide) on the patients with multiple myeloma(MM).

METHODSThirty cases of MM treated by T-VD(T-VD group) and 30 cases of MM treated by T-VAD(T-VAD group) from April 2010 to April 2012 were included in this study. The clinical effects and long-term survival were compared betwwen these 2 groups.

RESULTSBoth the CR and ORR in T-VD group were higher than those in T-VAD group(P<0.05); the ORR of the non-light and light chain type in T-VD group was higher than that in the T-VAD group(P<0.05); the ORR was not different between the no-light chain type and light chain type in T-VD group(P>0.05); the ORR was not different between the non-light and light chain type of T-VAD group(P>0.05); the ORR was not different between the stage I-II of T-VD group and T-VAD group(P>0.05); the ORR for the stages of III T-VD group was higher than that of T-VAD group(P<0.05); the ORR was not different between the I-II and III stages in the T-VD group(P>0.05); The ORR for the I-II stages of control group were higher than that of the III stages(P<0.05); the levels of serum M protein, myeloma cells, β2-MG in the T-VD group were lower than those in T-VAD group(P<0.05). The rate of leukocyteopenia, nausea and vomit, weakness in T-VD group were significantly higher than those in T-VAD group(P<0.05); The incidences of infection and peripheral neuropathy in T-VD group were higher than those in T-VAD group(P<0.05).

CONCLUSIONThe effect of T-VD regimen on the patients with MM is better than that of T-VAD regimen and its effect is not influenced by the clinical classification and stages, but will aggravate some side effects, thus this chemotherapeutic regimen need to be carefully chosen.

OBJECTIVETo evaluate the efficacy and safety of high-dose intravenous mecobalamin (HDIME) for the treatment of bortezomib-induced peripheral neuropathy(BIPN) in the patients with multiple myeloma (MM).

METHODSA total of 65 newly diagonsed patients with multiple myeloma receiving bortezomib in Tianjin Medical University General Hospital were enrolled in this single-centre randomized clinical trial from July 2012 to May 2016. Out of 65 patients 38 in control group received bortezomib-based chemotherapy and 27 patients in HDIME group received the additional high-dose intravenous mecobalamin.

RESULTSThe incidence of BIPN in HDIME group was lower than that in control group(29.63% vs 55.26%, χ=4.197,P<0.05). Whether the BIPN rate of Grade 2 or 3 and above in HDIME group significantly decreased as compared with control group(18.52% vs 47.37%,χ=5.746,P<0.05) (3.71% vs 21.05%, χ=3.983,P<0.05). The BIPN rate of less than 5 cycles of bortezomib was not significantly different between HDIME and control groups(χ=2.714,P>0.05). Overall effective rate of HDIME group and control group was 77.78% and 73.68%(P>0.05) respectively. Neither PFS nor OS was significantly different between HDIME group and control group(P>0.05). Treatment-related toxicity was only mild rash in 1 case. No other side-effects including nausea, abdominal pain, and hypotension occurred.

CONCLUSIONHDIME has a good efficacy for the prophylaxis BIPN and and without serious side effects.

OBJECTIVETo investigate the expression of CC-chemokine receptor 7(CCR7) in patients with multiple myeloma(MM) and its correlation with clinical features of MM.

METHODSThe level of CCR7 expression in bone marrow samples from 53 newly diagnosed MM patients was detected by flow cytometry(FCM). Statistical methods were used to analyze the correlation between CCR7 expression and clinical features, such as sex, age, M protein, peripheral blood cell count, biochemical indicators, plasma cell ratio of bone marrow, immunophenotype, osteopathy and extramedullary disease.

RESULTSThe plasma cells in 24 out of 53 cases(45.28%) expressed CCR7. The rate of extramedullary disease in CCR7 positive group was significantly higher than that in CCR7 negative group (29.17% vs 3.45%)(P<0.05).

CONCLUSIONThe expression of CCR7 in patients with MM is high, moreover this high expression correlates with extramedullary disease, thus CCR7 can be used as an effective indicator for prediction of extramedullary disease.

OBJECTIVETo investigate the diagnostic value of circulating serum miRNA for multiple myeloma.

METHODSForty blood samples from patients with multiple myeloma were collected from July 2013 to June 2014 in Department of Hematology, Zhongshan Hospital Affiliated to Xiamen University. The real-time quantitative PCR was performed to detect the serum expression levels of miRNAs (miR-29a, miR-155, miR-16 and miR-92a) circulating in the different stages of patients with multiple myeloma and evaluate the diagnostic value for patients with multiple myeloma.

RESULTSThe serum level of miR-29a significantly increased in newly diagnosed patients as compared to healthy donor (P<0.01), serum miR-155 levels were significantly lower as compared with healthy donor(P<0.001); The ratio of miR-29a and miR-155 was an effective biomarker for distinguishing multiple myeloma from healthy donor, their sensitivity and specificity were 80.8% and 83.3% respectively for myeloma diagnosis. the change of miR-29a expression was consistent with the changes of bone marrow plasma cells and M protein levels.

CONCLUSIONThese circulating serum microRNA, such as miR-29a, miR-155 and miR-16, may serve as potential diagnostic biomarkers for multiple myeloma, and the ratio of miR-29a/miR-155 may serve as a most useful biomarker for myeloma diagnosis.

OBJECTIVETo study the correlation between the excessive activation of Hedgehog signal and the drug resistance of multiple myeloma.

METHODSThe resistant cell line RPMI 8226/R of multiple myeloma was established by an ascending concentration gradient method. The experiment consisted of 4 groups: RPMI8226/R, RPMI8226/S, GANT61+RPMI8226/R and GANT61+RPMI8226/S. The CCK-8 (cell counting kit-8) assay was used to detect the cell proliferation inhibition rate in 4 groups; the RT-PCR was used to detect the expression of Gli1, Gli2, Shh, Ihh, Smo and Sufu in the RPMI8226/S and RPMI8226/R cells. The Western blot was used to detect the expression of the resistant protein Cyclin D1, P21 and BCL-2 and MDR-related signaling pathways protein p-Akt, p-MAPK and STAT3 in the RPMI8226/S and RPMI8226/R cells. After adding different concentration of GANT61, the Western blot was used to detect the expression of Gli2 in RPMI8226/R and RPMI8226/S cells.

RESULTSThe expression of Shh, Ihh, Smo Gli2 was enhanced significantly in the RPMI8226/R cells, but the expression of Sufu inhibitor was reduced, the expression level of related protein in Hedgehog signaling pathway was significanly higher in RPMI8226/R than that in RPMI8226/S. After theatment of GANT61 in vitro, the expression level of Gli2 in multiple myelom cells obviously decreased, the decreasing effect of GANT61 on Gli2 expression in RPMI8226/R cells was more significant than that in RPMI8226/S cells. The sensitivity of RPMI8226/R cells to DOX after treatment with GANT61 (IC) was risen from 7.11±0.061 µmol/L to 0.99±0.053 µmol/L, the corresponding cell resistance index decreased from 5.51 to 1.69.

CONCLUSIONthe activation of Hedgehog signaling pathway is closely related with the resistance of multiple myeloma cells, and GANT61 can block the Hedgehog signaling pathway, thus Hedgehog signaling may be used as a new target for multiple myeloma treatment.

OBJECTIVETo explore the clinical significance of peripheral blood EB virus detection in NK/T cell lymphoma patients.

METHODSThe positive rate of EB virus and EBV-DNA in 85 cases of NK/T cell lymphoma was assayed; the correlation of positive rate of EB virus with clinical staging, short-term and long-term prognosis was analyzed.

RESULTSThe positive rate of EB virus in NK/T cell lymphoma was high (80.00%). The EBV-DNA copy number in peripheral blood leukocytes was higher than that in peripheral plasma (P<0.05), but there was no significant difference in EBV-DNA level between peripheral leukocytes and serum (P>0.05). The I-II stages ratio of patients in EBVgroup was significantly lower than that in EBVgroup. The CR rate and ORR in EBVgroup was significantly lower than those in EBVgroup, the 3 year OS rate and 3 year DFR in EBVgroup also was significantly lower than those in EBVgroup.

CONCLUSIONThe detection of periphera blood EBV may be used as an reference indicator for anxiliary diagnosis of NK/T cell lymphoma and evaluation of prognosis for patients, thus possessing a certain value for clinical application.

OBJECTIVETo investigate the expression of miR-34a in serum of DLBCL patients, and to analyze its correlation with the expression of BCL-2 protein and clinical prognosis.

METHODSThe clinical data of 65 DLBCL patients and 22 cases of lymphonode reactive hyperplasia (RH) were collected, the serum expressions of miR-34a and BCL-2 were detected by real-time fluorescence quantitative PCR, and the relationship of miR-34a and BCL-2 expression with clinical pathological features and prognosis was analyzed.

RESULTSThe miR-34a lowly expressed in DLBCL and the BCL-2 highly expressed in DLBCL, the miR-34a expression level correlated negatively with BCL-2 expression (P<0.01). The survival time of patients with high expression of miR-34a was significantly longer than that of patients with miR-34a low expression. Multivariate Cox regression analysis revealed that the expression of miR-34a (P<0.01) and BCL-2 (P<0.01) as well as clinical staging (P<0.01) were independent factors influencing the prognosis of patients with DLBCL.

CONCLUSIONThe low expression of miR-34a in DLBCL patients may be involved in the occurrence and development of diffuse large B cell lymphoma, the MiR-34a is correlated with prognosis of diffuse large B cell lymphoma.

OBJECTIVETo investigate the changes of CD4T lymphocytes in peripheral blood of patients with follicular lymphoma and its clinical significance.

METHODSBlood samples were collected for detection of whole blood cells, including absolute monocyte count (AMC), absolute lymphocyte count (ALC), hemoglobin (Hb), platelet count (Plt). Age, sex, pathological grade, number of involved lymph nodes, bone marrow involvement (BMI), Ann Arbor stage, B symptoms, serum lactate dehydrogenase (LDH) and serum β-2 microglobulin (β2-MG) were recorded, the prognostic stratification was performed by using FLIPI and FLIPI-2. The T lymphocyte subsets were analyzed by flow cytometry, including the absolute number of CD4T lymphocytes (ACD4C) and the absolute number of CD8T lymphocytes (ACD8C).

RESULTSPatients were with higher Ann Arbor stage, Hb<120 g/L, LDH greater than the upper limit of normal, the number of lymph nodes were involved> 4, the bone marrow was involvement, β2-MG levels were high FLIPI score and FLIPI-2 score, AMC level was higher (P<0.05). There were no significant differences in ACD4C levels among different groups. Patients with AMC≥0.89×10/L showed a shorter progression-free survival (PFS) and a shorter overall survival time (OS) (P=0.010,0.002) as compared with patients with AMC<0.89×10/L. The patients with ACD4C>0.16×10/L had longer progression-free survival and overall survival time, as compared with patients with ACD4C ≤0.16×10/L (P=0.016,0.012). Low ACD4C and high AMC related with shorter PFS and OS (P=0.013, 0.020). Univariate Cox regression analysis showed that age (P=0.026), bone marrow involvement (P=0.017), elevated LDH (P=0.001), β2-MG (P=0.014), FLIPI and FLIP2 score (P= 0.004 and 0.000) related with a shorter PFS. Multivariable Cox regression analysis showed that Hb (P=0.015), elevated LDH (P=0.003), β2-MG (P=0.045), bone marrow involvement (P=0.016) and FLIPI-2 score(P=0.003) related with short OS. ACD4C ≤0.16×10/L was a factor influencing prognosis of FL patients (PFS and OS) (P<0.05).

CONCLUSIONSLow ACD4C levels relatees with poor prognosis of patients with FL, and the ACD4C levels may be an important predictor for FL disease and prognosis.