[Analysis of the clinical effects and outcome of patients with double-hit high-risk multiple myeloma].

Objective: To compare the clinical features, clinical efficacy, and prognosis of patients with double-hit and non-double-hit high-risk multiple myeloma (MM) and explored the clinical significance of high-risk cell karyotype in MM development. Methods: The clinical data of 73 high-risk MM patients admitted to the Department of Hematology of Fujian Provincial Hospital from January 2011 to February 2019 were retrospectively analyzed. Interphase fluorescence in situ hybridization was used to detect their karyotypes. Based on mSMART 3.0 risk stratification, we divided the patients into a double-hit group (28 cases) and a non-double-hit group (45 cases). Results: Fifteen patients in the double-hit group and 26 in the non-double-hit group received bortezomib-based chemotherapy. The median progression-free survival (PFS) in the double-hit and the non-double-hit groups was 8.0 months and 22.0 months, and the median overall survival (OS) was 10.0 months and not reached, respectively. Ten patients in the double-hit group and 12 in the non-double-hit group received bortezomib combined with lenalidomide (RVD) chemotherapy. The median PFS in the double-hit group and the non-double-hit group was 12.0 months and 24.0 months, and the median OS was 14.0 months and not reached, correspondingly. Both the PFS and OS of the double-hit group were significantly shorter than those of the non-double-hit group (P<0.05). Univariate analysis results indicated that cytogenetic abnormalities, revised-international staging system (R-ISS), ß2 microglobulin, and calcium had significant effects on PFS in high-risk MM patients (P<0.05). The cytogenetic abnormalities, R-ISS, and ß2 microglobulin were associated with OS in high-risk MM patients (P=0.001). Multivariate Cox regression analysis showed that the cytogenetic grouping was an independent prognostic factor for OS and PFS in high-risk MM patients. The risk of disease progression was 3.160 times (95% CI: 1.364-7.318) and the risk of death was 2.966 times higher (95%CI: 1.205-7.306) in the double-hit group than those in the non-double-hit group. Calcium was an independent risk factor for PFS in the high-risk MM patients. Notably, the risk of disease progression in patients with calcium levels≥ 2.75 mmol/L was 2.667 times higher than that in patients with calcium<2.75 mmol/L (95% CI: 1.209-5.883). Conclusions: Double-hit patients are a highly specific group with worse high-risk MM prognosis. In such patients, the relapse is more common, the disease progression is faster, and the survival time is shorter than those in the non-double-hit patients.

[Autologous peripheral blood stem cell transplantation for POEMS syndrome].

Six patients with POEMS syndrome who received autologous peripheral blood stem cell transplantation (auto-PBSCT) were retrospectively analyzed. Conditioning regimen was high dose melphalan. Peripheral blood stem cells were collected after mobilization with cyclophosphamide (CTX) and growth factors. One patient presenting hydrothorax and ascites was treated with 3 cycles of lenalidomide and dexamethasone before mobilization. Auto-PBSCT was fairly tolerable. Hematopoietic reconstitution was successful in all patients without transplantation-related mortality. A decrease or normalization of serum vascular epithelial growth factor (VEGF) was observed in all patients at 3 months after transplantation. The neurological remission was seen in 5/6 patients.

[Efficiency of DA-EPOCH and MA chemotherapy in the mobilization of autologous peripheral blood stem cells in non-Hodgkin's lymphoma].

Objective: To study the effect and safety of the DA-EPOCH chemotherapy combined with G-CSF and the MA chemotherapy combined with G-CSF on mobilizing and collecting the peripheral blood stem cells and the later hematopoietic recovery. Methods: A total of 40 patients accepted mobilization and collection of peripheral blood stem cells(PBSC) after being treated by DA-EPOCH+ G-CSF and MA+ G-CSF therapy respectively, and performed auto-transfusion. The effect of mobilization, the adverse effects and the hematopoietic recovery after autologous transplantation were analyzed retrospectively. Results: Two cases in DA-EPOCH group and 1 case in MA group did not achieve the collection goal and required a G-CSF mobilization therapy again. During the DA-EPOCH mobilization therapy, the lowest median WBC was[0.7(0.5, 0.9)]×10(9)/L and the median lowest platelet (PLT) count was[75.0 (53.0, 107.0)]×10(9)/L.Low-grade fever occurred in 7 cases (37.5-38.3 ℃) and platelet transfusion was required in 2 cases. The collection of MNC number was (5.8±1.8)×10(8)/kg, and the median CD34(+) cell number was[3.7(2.8, 6.7)]×10(6)/kg; for the MA therapy groups, the numbers were[0.4 (0.2, 0.9)]×10(9)/L and[12.0 (6.0, 16.0)]×10(9)/L, respectively. High fever occurred in 8 cases (above 39 ℃). PLT transfusion was required in 15 cases and red blood cell(RBC) transfusion in 4 cases. The collected number of MNC was (6.0±2.9)×10(8)/kg, and CD34(+) median cell number was[8.5(2.6, 11.2)]×10(6)/kg. There are significant differences between the lowest PLT counts and CD34(+) cell numbers in the two groups of patients(P<0.05). A peripheral blood leukocyte increase in 10(9, 11) days and platelet implantation in 12(11, 16) days were observed after ASCT by DA-EPOCH therapy. In MA group, the number were 10(9, 11) and 12(11, 15) days. The hematopoietic recovery in both groups were successful, without any statistically difference(P>0.05). No death occurred during the process of transplantation. Conclusions: DA-EPOCH and MA chemotherapy could effectively mobilize the peripheral blood stem cells in suitable NHL patients.DA-EPOCH chemotherapy was higher in safety and lower in price, and required less transfusion compared with MA therapy.

[Association of miRNA-196b-5p and miRNA-99a-5p with autophagy and apoptosis in multiple myeloma cells].

Objective: To investigate the relationship between miRNA-196b-5p and miRNA-99a-5p expression and autophagy and apoptosis in multiple myeloma cells. Methods: Human myeloma cell line U266 and normal CD138+ plasma cells were selected as the research objects. The subjects were divided into 45 cases of multiple myeloma patients and 40 healthy controls. The expression of miRNA-196b-5p and miRNA-99a-5p was measured by real-time quantitative PCR, and Western blot was used to determine the expression of autophagy related protein LC3-Ⅱ, LC3-Ⅰ, P62, Beclin-1 expression, apoptosis related protein CL caspase3, CL caspase7, Bcl-2, Bax, and TGF-ß/Smad pathway associated proteins TGF-ß1, Smad2/3, p-Smad3 and Smad7. The cell apoptosis rate was determined by flow cytometry. The correlation between miRNA expression level and clinical characteristics of multiple myeloma patients was analyzed. Results: Compared with normal plasma cells, the expression of miRNA-196b-5p in myeloma cells increased significantly (0.43±0.15 vs 2.44±0.63 or 2.02±0.85, all P<0.001), the expression of miRNA-99a-5p was significantly decreased (1.87±0.61 vs 0.62±0.15 or 0.80±0.33, P<0.001), LC3-Ⅱ/LC3-Ⅰ increased significantly (P<0.05), Beclin-1 expression increased significantly (P<0.05), P62 expression decreased significantly (P<0.05). The expression of Bax, CL caspase3 and CL caspase7 decreased significantly (P<0.05), and the expression of Bcl-2 increased significantly (P<0.05) and apoptosis rate significantly decreased (P<0.05). After transfected with miRNA-196b-5p mimic or miRNA-99a-5p inhibitor, the LC3-Ⅱ/LC3-Ⅰ of CD138+ plasma cells increased significantly (P<0.05), the expression of Beclin-1 increased significantly (P<0.05), P62 expression decreased significantly (P<0.05), and the apoptosis rate significantly decreased (P<0.05). However, after autophagy inhibitor of 3-MA was administered, the apoptotic rate of the above reaction system did not change significantly (P>0.05). The expression of miRNA-196b-5p and miRNA-99a-5p was significantly correlated with DS and ISS stage in multiple myeloma patients (P<0.05). Conclusion: miRNA-196b-5p and miRNA-99a-5p are closely related to the clinical characteristics of patients with multiple myeloma. The overexpression of miRNA-196b-5p and down regulation of miRNA-99a-5p could inhibit the apoptosis of myeloma cells by up regulation of autophagy, and the mechanism is related to the activation of the TGF-ß/Smad signaling pathway.