Clinicopathological Characteristics and Prognosis Analysis of the Patients with Plasmablastic Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the clinicopathological characteristics, treatment and prognosis of the patients with plasmablastic lymphoma(PBL).</p><p><b>METHODS</b>The clinical and pathological data of 21 patients with PBL diagnosed and treated in our center between January 2009 and September 2017 were retrospectively analyzed. The clinical and pathological features, treatment and therapentic outcome were summarized and the high risk factors affecting the prognosis of patients were investigated.</p><p><b>RESULTS</b>The 21 PBL patients included 12 males and 9 females, and their median age was 52 years old. The human immunodeficiency virus (HIV) was negative in all patients. The primary involved sites of 16 patients were extranodal, and the patients staged in III-IV accounted for 81%; 18 patients receved first-line chemotherapy with standard CHOP(E) (cyclophosphamide +epirubicin +vincristine +prednisone±etoposide). After treatment, only 1 patient achieved complete response (CR), and 8 patients achieved partial response (PR). The median overall survival time was 6.3 months. Multivariate analysis showed the America Eastern Cooperative Oncology Group (ECOG) physical score and bone marrow infiltration were significant prognostic factors (P<0.01).</p><p><b>CONCLUSION</b>Plasmablastic lymphoma frequently occurrs in the middle-old aged persons with all HIV negative. Primary extranodal lesions are frequent. Most patients were in advanced stage with poor treatment response. ECOG score≥2 and bone marrow infiltration are independent prognostic factors related with worse prognosis.</p>

Valproic Acid Represses Autophagy and Enhances the Anti-myeloma Activity of DNA-damaging Drugs / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of valproic acid(VPA) on anti-myeloma activity of Doxorubicin(DOX) or Melphalan(MEL) and its related mechanism.</p><p><b>METHODS</b>Human multiple myeloma(MM) cells were treated with VPA of non-toxic dose in absence and presence of DOX or MEL at different concentrations (ie. IC10, IC20, IC40). The cell proliferation was detected by MTT method. Western blot was used to detect the expression levels of autophagy-related proteins (LC3, ATG5, ATG7) and acetylated histone H4K16ac.</p><p><b>RESULTS</b>Cell proliferation inhibition markedly increased in VPA plus DOX or MEL as compared with DOX or MEL alone (P<0.05). Both LC3 and H4K16ac expression levels in co-treatment were between VPA and DOX or MEL treated alone. Importantly, VPA of non-toxic dose not only augmented the anti-myeloma activity of DOX or MEL, but also down-regulated the autophagy-related protein expression and increases H4K16ac protein levels.</p><p><b>CONCLUSION</b>H4K16ac can inhibit the transcription of autophagy-related genes, The VPA enhance the anti-myeloma activity of DNA-damaging drugs, at least in part, via H4K16ac-mediated suppression of cytoprotective autophagy.</p>

Influence of CD117 Expression on Response of Multiple Myeloma Patients to Chemotherapy / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the influence of CD117 expression on response of multiple myeloma patients to chemo-therapy.</p><p><b>METHODS</b>A total of 65 cases of newly diagnosed multiple myeloma in our hospital from 2011 to 2013 were enrolled in this study. Cytogenetic abnormalities and immunophenotype were detected by using fluorescence in situ hybridization and flow cytometry before chemotherapy. The therapeutic efficacy of patients was evaluated after 4 cycles of PAD or TAD regimen.</p><p><b>RESULTS</b>The positive rates of 1q21 amplification, RB1: 13q14 deletion, D13S319: 13q14.3 deletion, IgH: 14q32 rearrangement and p53: 17p13 deletion were 32.2%, 40%, 40%, 20% and 3.1% respectively; the positive rates of CD38, CD138, CD56, CD117, CD20 were respectively 100%, 100%, 60%, 20%, 10.8%; the positive rates of CD19 and CD10 were 4.6% and 4.6% respectively; the positive CD22, CD7, CD5, CD103 did not found in any patients. The therapeutic efficacy of CD117⁻ patients was better than that of CD117⁺ patients (P < 0.05), there was no correlation of the remaining indicators with efficacy; the proportion of CD117⁺ patients with β2-microglobulin ≥ 5.5 mg/L was significantly higher than that of CD117⁻ patients (P < 0.05); the rest of baseline data had no significant difference (P > 0.05).</p><p><b>CONCLUSION</b>CD117 can be used as an indicator for evaluating efficacy of patients with newly diagnosed multiple myeloma.</p>

Inducing effect of chidamide on apoptosis of multiple myeloma cells and its relerance to DNA damage response / 中国实验血液学杂志

<p><b>OBJECTIVE</b>This study was aimed to explore the effect of a novel histone deacetylase inhibitor Chidamide on apoptosis of human multiple myeloma(MM) cells and its relevance to DNA damage response(DDR).</p><p><b>METHODS</b>The cell proliferation was detected by MTT method, apoptosis and cell cycle distribution were analyzed by flow cytometry, the expression levels of targeted proteins were detected by Western blot, the DNA damage response was blocked by ATM kinase inhibitor KU-55933.</p><p><b>RESULTS</b>Chidamide inhibited RPMI 8226 cell proliferation in dose- and time-dependent manner and its IC50 values of 24,48,72 h were 9.6, 6 and 2.8 µmol/L respectively. Chidamide induced cell cycle arrest of RPMI 8226 cells in G0/G1 phase by upregulating the expression of P21. Chidamide triggered caspase-3 dependent apoptosis and upregulated expression of DDR-related proteins including γH2AX, pATM in RPMI 8226 cells. Pretreatment with ATM kinase inhibitor KU-55933 down-regulated expression of DDR related proteins induced by chidamide, thereby inhibiting DNA damage response and finally resulting in suppression of apoptotic cell death.</p><p><b>CONCLUSION</b>Proliferative inhibtion, cell cycle arrest and apoptosis of multiple myeloma cells induced by chidamide involve DDR.</p>

Efficacy comparison between standard and reduced doses of bortezomib combined with adriamycin and dexamethasone in the treatment of patients with multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the efficacy and safety of standard or reduced doses of bortezomib combined with adriamycin and dexamethasone (PAD) in patients with multiple myeloma (MM).</p><p><b>METHODS</b>Eighty-two newly diagnosed or refractory/relapsed patients received bortezomib [either 1.2-1.3 mg/m(2) (standard dose) or 1.0-1.1 mg/m(2) (reduced dose) on day 1, 4, 8 and 11], and adriamycin (10 mg/m(2)) plus dexamethasone (40 mg/m(2)) on day 1-4 at 3-week intervals for 1 to 6 courses. The International Myeloma Working Group Criteria were used to evaluate the response. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (Version 3.0).</p><p><b>RESULTS</b>Two courses of standard dose of PAD resulted in a similar response rate of partial and very good partial complete remissions (PR) compared with reduced dose (80.0% vs 80.8%, P=0.728). Grade III- Ⅳ neutropenia and thrombocytopenia were higher with standard dose than that with reduced doses of PAD (21.1% vs11.1%, P=0.270; 10.5% vs 6.3%, P=0.619, respectively). Grade III-Ⅳ bortezomib-induced peripheral neuropathy, herpes zoster, fatigue or abdominal distention were significantly higher with standard dose than that with reduced dose of PAD (15.8% vs 1.6%, P=0.037; 26.3% vs 6.3%, P=0.028; 36.8% vs 14.3%, P=0.046; 15.8% vs 1.6%, P=0.037, respectively).</p><p><b>CONCLUSION</b>Reduced dose of PAD appears to result in a similar overall response rate, but a better tolerance and safety compared with standard dose.</p>

Clinical analysis on 28 patients with hemophagocytic lymphohistiocytosis syndrome / 中国实验血液学杂志

In order to profoundly understand the clinical and laboratorial characteristics and inducing factors of hemophagocytic lymphohistiocytosis syndrome (HLH), 28 HLH patients received from 2004 to 2009 years in our hospital were analyzed retrospectively. The results indicated that all of the patients had a history with prolonged fever (more than 1 week), pancytopenia, hepatosplenomegaly, elevated ferritin level, hypofibrinogen, and hemophagocytosis in bone marrow. HLH was the first characteristic sign of malignant lymphoma in 9 patients; 1 patient had a clinical manifestation similar to fulminant hepatic failure; severe psycho-abnormality occurred in 1 HLH patient and pronounced hemophagocytosis were detected in his cerebrospinal fluid; 1 patient was eventually diagnosed as having HLH by the findings in a lymph node biopsy showing obvious hemophagocytosis. Additionally, the analysis of underlying factors in 28 patients with HLH indicated 11 patients with EB virus-associated HLH, 11 with lymphoma-associated HLH, 2 with Leishmania-associated HLH, and 3 with autoimmune disease-associated HLH. It is concluded that HLH disease is characterised with high heterogenicity in both clinical features and inducing factors; in addition, the patients from a pasturing area should be paid attention to parasite infection such as leishmania.

Effects of xbp-1 gene silencing on bortezomib-induced apoptosis in human multiple myeloma cells / 中国实验血液学杂志

This study was purposed to investigate the effect of xbp-1 gene silencing on bortezomib-induced apoptosis in multiple myeloma cell line NCI-H929 (H929). After xbp-1 gene expression was interfered by small hairpin RNA, the cell apoptosis was assayed by flow cytometry with Annexin V-FITC/PI staining, and the expression level of XBP-1 protein was detected by Western blot. The results showed that XBP-1 protein level of H929 cells was inhibited effectively by the PLL3.7 lentiviral vector mediated expression xbp-1 shRNA. The apoptosis rate was significantly higher in xbp-1 shRNA-expressing cells than in untreated control group [(10.13±0.61)% vs (2.5±0.2)%, p<0.05]. After treatment with bortezomib, the apoptosis rate of XBP-1 protein functionally deficient H929 cells was significantly higher than those in vector control group [(45.07±1)% vs (19.53±0.8)%, p<0.05]. It is concluded that xbp-1 gene silencing can significantly enhance the pro-apoptotic activity of bortezomib in multiple myeloma cells.

PAD regimen for relapsed or refractory patients with multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of PAD [bortezomib (PS-341), doxorubicin and dexamethasone] regimen for relapsed or refractory multiple myeloma (MM).</p><p><b>METHODS</b>Seventeen patients with relapsed or refractory MM received two to four 21-day cycles of PAD: an intravenous bolus of bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11; doxorubicin 10 mg per day on days 1 to 4, and dexamethasone 40 mg on days 1-4. Response was evaluated according to International Myeloma Working Group Criteria (IMWG 2006), toxicity was graded according to NCI CTCAE (common terminology criteria for adverse events) v 3.0.</p><p><b>RESULTS</b>After 2-4 courses of PAD, 14 patients (82.4%) response, including complete response (CR) in 4 (23.5%), very good partial response (VGPR) in 4 (23.5%), partial response (PR) in 6 (35.3%) and stable disease (SD) in 3 (17.6%). Median time to progression was 9.5 months. The median course to response was 1.6 (1-3). All of 5 patients with extramedullary plasmacytoma achieved at least PR after the first cycle therapy; the plasmacytoma disappeared after 1-2 cycles of PAD. The efficacy was independent of other prognostic factors such as beta2-MG. Adverse events included thrombocytopenia in 9 patients (52.9%), leukopenia in 4 (23.5%), peripheral neuropathy in 4 (23.5%), varicella herpes zoster in 3 (17.6%), fatigue in 6 (35.3%) and diarrhea in 2 (11.7%). All of these adverse reactions could be controlled with routine supportive treatment, only one patient died from respiratory failure during his fifth PAD cycle.</p><p><b>CONCLUSIONS</b>PAD regimen should be considered as an appropriate treatment for relapsed or refractory MM, especially for MM with extramedullary plasmacytoma. Its efficacy is independent of traditional prognostic factors. The side effects are usually manageable.</p>

Role of CD4(+) CD25(high) T cells in the pathogenesis of idiopathic thrombocytopenic purpura / 中国实验血液学杂志

This study was aimed to investigate the expression level of CD4(+) CD25(high) T cells in peripheral blood of patients with idiopathic thrombocytopenic purpura (ITP) before and after treatment and to explore its significance in pathogenesis of ITP. The expressions of CD4(+) CD25(high) T cells in peripheral blood of 20 ITP patients before treatment, 20 ITP patients after treatment and 14 normal individuals (control) were detected by immunofluorescence and flow cytometry. The result showed that the expression of CD4(+) CD25(high) in ITP group before treatment was evidently lower than that in treated ITP group and control (p < 0.01), but there was no remarkable difference between the treated ITP group and the control group p > 0.05). In conclusion, the expression of CD4(+) CD25(high) T cells in the ITP group before treatment was evidently lower than that in the control group, which becomes higher than before when the patients showed effective response to the treatment. Correlation of CD4(+) CD25(high) T cell expression rate in peripheral blood with platelet level was positive. Therefore the expression level of CD4(+) CD25(high) T cells can be used as an effective index to judge the ITP prognosis. Further study of CD4(+) CD25(high) T cells regarded as an immune target is needed.