Clinical Application of R-ISS Staging System in 412 Newly Diagnosed Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the prognostic value of R-ISS staging system in patients with newly diagnosed multiple myeloma (NDMM).@*METHODS@#The Chinical data of 412 patients with NDMM in our hospital from May 2010 to May 2016 were retrospectively analyzed. All the patients received conventional chemotherapy or thalidomide or bortezomib-based chemotherapy. All the patients with NDMM were divided into R-ISS-Ⅰ, R-ISS-Ⅱ and R-ISS-Ⅲ groups according to R-ISS staging system on the basis of ISS staging system, cytogenetics and LDH level. The progression-free survival (PFS) time and overall survival(OS) of different groups were compared.@*RESULTS@#Among all 412 patients, 76 were rated as R-ISS-Ⅰ, 259 as R-ISS-Ⅱ and 77 as R-ISS-Ⅲ. The median PFS time in 3 groups were 44, 25 and 14 months respectively (P<0.01). The median OS time of the 3 groups were not reached 54 and 25 months respectively (P<0.01). Further analysis also found that statistically different survival associated with different R-ISS groups in the conventional chemotherapy group (P<0.05), bortezomib-based chemotherapy group (P<0.01), thalidomide-based chemotherapy group (P<0.01), transplantation group (P<0.05), different-age stratified group (≤65y P<0.01, 66-75y P<0.01,≥76y P<0.01), damaged renal function group (P<0.01) and extramedullary infiltration group (P<0.01).@*CONCLUSION@#PFS and OS in the patients with multiple myeloma were different among three distrinct R-ISS stages. The R-ISS staging system has important clinical significance for the prognosis evaluation of multiple myeloma.

Chromosomal Abnormalities Associated with Clinical Outcome in Patients with Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the prognostic value of karyotypic abnormalities in evaluation of prognosis of patients with multiple myeloma.</p><p><b>METHODS</b>The clinical and laboratory data of patients with newly diagnosed multiple myeloma (NDMM) were retrospectively analyzed in our hospital from May 2010 to May 2016. Patients who carried t(4; 14), t(14; 16) or 17P (at least one of them) were defined as the patients with high-risk karyotype, whereas patients characterized by the absence of the above-mentioned abnormalities were defined as patients with standard-risk karyotype. PFS (progression-free survival, PFS) and OS (over all survival, OS) time was compared between the 2 groups.</p><p><b>RESULTS</b>There were 110 cases in the high-risk group, and 302 cases in the standard-risk group. The clinical characteristics, such as age, sex, ISS stage and treatment regimen etc were not statistically different between 2 groups. The median OS time of patients in the high-risk and standard-risk groups were 42 months (CI 95%: 34.375-49.625 months) and 53 months (CI 95%: 46.310-59.690 months) (P<0.05). The median PFS time of patients in the high-risk group and standard-risk groups was 21 months (CI95%: 17.198-24.802 months) and 27 months (CI95%: 23.406-30.594 months) (P<0.05).</p><p><b>CONCLUSION</b>Among patients with newly diagnosed MM, the PFS and OS time in the patients with high-risk karyotype is shorter than that in patients with standard-risk karyotyp.</p>

Effect of CP Metronomic Chemotherapy on RPMI 8226 Cell Proli-feration and Notch1/NF-κB Signaling Pathway In Vitro / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of metronomic chemotherapy of low dose phosphoramide combined with prednisolone (CP metronomic chemotherapy) on proliferation and apoptosis of RPMI 8226 cells, and to explore its regulating effect on Notch1/NF-κB signaling pathways.</p><p><b>METHODS</b>Experiment was divided into the DMSO control group, and the phosphoramide mustard (PM) group, the prednisolone group, the phosphoramide mustard plus prednisolone group (the CP group). RPMI 8226 cells were treated with different drugs, CCK-8 method was used to detect cell proliferation, flow cytometry was used to detect the cell cycle and apoptosis, reverse transcription PCR was used to detect Notch1 and NF-κB mRNA expression level.</p><p><b>RESULTS</b>Compared with DMSO control group, RPMI8226 cell proliferation inhibition rate in all the PM, prednisolone and CP groups increased significantly with prolonging of time (r of 0.994,0.996,0.999, respectively, P<0.001). And at the same time, the inhibitory rate of cell proliferation was significantly different; the cell inhibitory rate in PM group was lowest, that in CP group was highgest, that in prednissone group was intermediate (P<0.01). After 48 hours, compared with the DMSO control group, the G/Gcell proportion in treatment group increased significantly, S phase cell proportion decreased significantly, especially in PM and CP groups. The G/M phase cell proportion increased in PM group, while reduced in the prednisolone and the CP groups. After 48 hours, compared with the DMSO control group, RPMI 8226 cell apoptosis rate increased as follow: in PM, pre-dnisolone and CP group(P<0.01). After 48 hours, compared with the DMSO control group, Notch1 and NF-κB mRNA expression in the prednisolone, the PM and the CP group decreased significantly(P<0.001).</p><p><b>CONCLUSION</b>CP metronomic chemotherapy can significantly reduce RPMI 8226 cell proliferation, promote RPMI 8226 cell apoptosis, arrest RPMI 8226 cells mainly in the G/Gphase, and significantly reduce Notch1 and NF-κB expression levels. It is suggested that Notch1/NF-κB signaling pathways is involved in CP metronomic chemotherapy for MM.</p>

Clinical and laboratory features of four cases with IgM multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To improve the understanding of the clinical and laboratory features of the IgM multiple myeloma (MM).</p><p><b>METHODS</b>The clinical data of four cases of IgM MM patients were collected, their clinical and laboratory features were summarized and analyzed.</p><p><b>RESULTS</b>Four patients met the criteria of IgM MM. They were all male. The age at the diagnosis ranged from 54 to 69 years. The primary symptoms included bone pain, hyperviscosity and bleeding. Three cases had κ-chain and only one case had λ-chain. They were all staged ⅢA according to the Durie-Salmon staging system (DSS). One case stagedⅠand three cases staged Ⅱ according to the international staging system (ISS). The average value of IgM, hemoglobin, serum calcium, creatinine and the proportion of bone marrow plasma cells were 83.6 (52.9-111.0) g/L, 79.5 (61.0-105.0) g/L, 3.20(2.11-6.00) mmol/L, 104.3 (56.0-171.0) μmol/L and 0.558 (0.290-0.775), respectively. Bone destruction was found in 3 cases. Immunophenotypes of bone marrow plasma cells were analyzed in 3 patients. Results showed that these cells expressed CD38 and CD138, and did not express CD19, CD20 and CD117. Chromosome and fluorescence in situ hybridization (FISH) analysis were carried out in 4 cases and found that all of them had IgH translocations and 1q21 amplification, 2 cases had 13q and 17p deletion, and 3 cases had t(11;14). Three patients received bortezomib-based regimens as induction therapy and reached partial response (PR) - very good partial response (VGPR). Followed up to November 30, 2012, the median progress-free survival (PFS) and overall survival (OS) of the 4 cases were only 6.0 (2.5-7.0) months and 17.5 (2.5-27.0) months, respectively.</p><p><b>CONCLUSIONS</b>IgM MM is very rare and is no more than 0.5% in all types of MM. IgM MM have frequent t(11;14) and amp(1q21). Bortezomib-based regimens are effective for it, however, the disease progresses rapidly and has poor prognosis.</p>

Anti-angiogenesis effect of metronomic chemotherapy in multiple myeloma patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate effects of low-dose cyclophosphamide and prednisone (CP) metronomic chemotherapy on microvessel density of bone marrow, serum vascular endothelial growth factor (VEGF) and platelet derived growth factor BB (PDGF-BB)in multiple myeloma (MM) patients.</p><p><b>METHODS</b>54 refractory or relapsed MM patients were treated with CP metronomic chemotherapy consisted of oral cyclophosphamide (CTX, 50 mg/d) and prednisone (Pred, 15 mg/d). Bone marrow and peripheral blood of each patient were collected before and 2, 4, 6 months after treatment. Among the 37 assessable patients, 30 cases were responsive with the response rate of 81.08%. Another 17 cases were follow-uped less than 6 months or failure to obtain serum samples or lost to follow-up. Microvessel density of bone marrow was measured by immunohistochemistry and serum VEGF/PDGF-BB expression was analyzed by ELISA in the 37 assessable patients.</p><p><b>RESULTS</b>2, 4, 6 months following CP metronomic chemotherapy, microvessel densities of bone marrow in the responders were 33.1 ± 4.8/HP, 24.8 ± 3.7/HP, 19.7 ± 2.1/HP respectively; the expressions of VEGF were (394 ± 57) ng/L, (268 ± 32) ng/L and (217 ± 20) ng/L respectively; the expressions of PDGF-BB were (304 ± 31) ng/L, (274 ± 31) ng/L and (196 ± 22) ng/L respectively. After CP metronomic chemotherapy, there were significantly lower of microvessel density, VEGF and PDGF-BB levels than pretreatment \[MVD 48.5 ± 5.9/HP, VEGF (517 ± 60) ng/L, PDGF-BB (484 ± 60) ng/L\]in the responders (P < 0.01). While in the non-responders, after treated by CP metronomic chemotherapy for 2 months, microvessel density, the expression of VEGF and the expression of PDGF-BB were 32.5 ± 4.7/HP, 512 ± 39 ng/L and (452 ± 39) ng/L respectively. There were no significant changes of MVD, VEGF and PDGF-BB levels compared with pretreatment \[MVD 33.2 ± 5.6/HP,VEGF (498 ± 55) ng/L, PDGF-BB (488 ± 44) ng/L\] (P > 0.05).</p><p><b>CONCLUSIONS</b>Our findings suggested that continuous low-dose CP metronomic chemotherapy could decrease microvessel density of bone marrow in MM patients. Furthermore, it down-regulated expression of serum VEGF and PDGF-BB to exert its anti-angiogenesis in MM.</p>