The efficacy and safety analysis of bortezomib retreatment in 76 patients with relapsed/refractory multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of bortezomib retreatment in 76 patients with relapsed/refractory multiple myeloma (MM), who previously responded to bortezomib.</p><p><b>METHODS</b>Retrospective analysis of 76 MM patients, who had achieved at least a partial response (PR) on initial bortezomib therapy in our hospital from May 2006 to August 2011, received bortezomib retreatment when they relapsed or progressed.</p><p><b>RESULTS</b>The overall response rate (ORR) was 60.5%, among them 6.5% patients achieved CR, 5.8% patients achieved very good partial response (VGPR), 38.2% patients achieved PR. Then we further stratified all patients into 3 groups according to the response of initial bortezomib therapy, including CR group, VGPR group and PR group. After bortezomib retreatment, the ORR of the 3 groups was 84.6%, 73.1% and 43.2%, respectively. According to the response of bortezomib retreatment, the patients were divided into 2 groups: group 1 who at least achieved PR, group 2 who showed no response. The median progression-free survival (PFS) after bortezomib retreatment for group 1 and 2 was 7(1-39) and 5(1-14) months, respectively (P>0.05), while the median overall survival (OS) after bortezomib retreatment was 16(2-64) and 8(1-28) months, respectively (P<0.05). Adverse events (AE) were identified in 88% patients during bortezomib retreatment, including neutropenia, diarrhea and thrombocytopenia, only 9.2%(7 patients) reached Ⅲ-Ⅳ grade of AE. Severe peripheral neuropathy occurred in only one patient.</p><p><b>CONCLUSION</b>Bortezomib retreatment regimen is demonstrated a higher response rate in patients who achieved deeper response in initial treatment, with no more adverse events.</p>

Busulfan, cyclophosphamide and etoposide as conditioning for autologous stem cell transplantation in multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of dose-reduced intravenous busulfan, cyclophosphamide and etoposide (BCV) as conditioning for autologous stem cell transplantation (ASCT) in multiple myeloma (MM).</p><p><b>METHODS</b>From September 2007 to September 2010, thirty-two ASCT-eligible patients with MM received high dose melphalan (HDM) as conditioning in our center. Median age was 53.5 (30-63) years. From October 2010 to October 2012, thirty-eight patients conditioned by BCV regimen (intravenous busulfan, total doses 9.6 mg/kg), whose median age was 54(35-64) years.</p><p><b>RESULTS</b>There were no statistical differences in clinical characteristics between the two groups, including myeloma isotype, Durie-Salmon staging, international staging system(ISS), and patients received the first line, second line or more than third line therapy. The median time to neutrophil and platelet engraftment were 10.5 vs 11 days (P=0.057) and 11 vs 12 days (P=0.100) in the BCV and HDM groups, respectively. The toxicity of two conditioning regimens had no significant difference. None of hepatic veno-occlusive disease and early transplant related mortality was observed. Although overall response rates showed no significant difference between two groups (P>0.05), the CR rates increased from 44.74% pre-ASCT to 63.18% post-ASCT in the BCV group, while 37.50% to 59.38% in the HDM group. During the median follow-up of 16 months (range 2-27) in BCV group, ten patients (26.32%) developed progressive disease and PFS at 12 months were 71.37%.</p><p><b>CONCLUSIONS</b>In this study, the dose-reduced intravenous busulfan, cyclophosphamide and etoposide (BCV) conditioning was demonstrated an effective and safety regimen for ASCT-eligible patients with MM. However, the long term observation is needed.</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>

Protective effect of intracerebral transplantation of human mesenchymal stem cells on hypoxic-ischemic brain damage in rats / 第二军医大学学报

Objective: To explore the migration,differentiation and the therapeutic effect of intracerebral transplantation of human mesenchymal stem cells (hMSCs) after hypoxic-ischemic brain damage in rats, and to test whether three anti-hMSCs monoclonal antibodies prepared by our group can detect hMSCs in rat brains. Methods: hMSCs were isolated and purified by density gradient centrifugation and adherence to culture flask. Cells of passage 3-5 were prelabeled with bromodeoxyuridine (BrdU) for 72 h before transplantation. Animal models of hypoxic-ischemic brain damage (HIBD) were built with 1 month old Wistar rats. Three days after hypoxia-ischemia, HIBD rats in hMSCs-treated group (n=18) received intracerebral transplantation of 5×105 hMSCs. In control group (n=18) HIBD rats received phosphate buffered saline of the same volume. In sham-operated group (n=6) and HIBD group (n=6), rats did not receive any transplantation. Rats in hMSCs-treated group and control group were allowed to survive for 0 day,3 days, 1 weeks,2 weeks (all n=3) and 4 weeks (n=6, after transplantation). Rats in sham-operated group and HIBD group were allowed to survive for 31 days (4 weeks after transplantation). Rats of all the 4 groups received behavior test (alternative electro-stimulus Y-maze) 4 weeks after transplantation before sacrificed; their brains were sectioned for H-E staining. The brains from all rats were also prepared for immunohistochemistry analysis to detect the distribution of hMSCs. Results: Immunohistochemistry results showed that hMSCs migrated mainly along the ventricular system 1 week later,and a few hMSCs migrated along the corpus callosum to the opposite side. Four weeks after transplantaion, hMSCs migrated to the parenchyma and distributed throughout the cerebra. Behavior test showed that the total errors (TE) in hMSCs-treated group (TE= 5.00±2.82) were significantly less than those in the control group (TE = 12.67±3.72, P < 0.05). H-E staining showed that the brain damage in the hMSCs-treated group was slighter than that of the control group and HIBD group. Conclusion: After transplanted in the brain of rats,hMSCs can survive and migrate in the central nervous system (CNS). hMSCs can promote tissue repair and functional recovery of rat brain, suggesting that hMSCs might be a possible treatment for hypoxic-ischemic brain damage.

Improved laparoscopic Vechitti procedure for constructing a functioning vagina / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical effect of improved laparoscopic Vechitti procedure for constructing a functioning vagina.</p><p><b>METHODS</b>By using the method of raising vestibular mucosa, 18 patients with congenital absence of vagina and uterus underwent surgery in our hospital. No cave was made between bladder and rectum. The procedure involved puncturing the vulvar vestibulum pit with an epidural paracentetic needle or specially-made needle into abdominal cavity through rectovesical interspace, two drag-lines was introduced through anterior abdominal wall, using the line to tie a clothes button of 2.0-2.5 cm diameter to the vulva, rasing the lines day by day, the vestibule go upward along with the button, then the vagina was formed.</p><p><b>RESULTS</b>After the procedures, the artificial vagina of all 18 patients could hold a speculum and the mucosa appeared soft and smooth with normal lubrication. The vulvar tissues appeared uninjured and normal in all cases. The married patients were satisfactory to the intercourse. One case of vagino-rectal fistula was observed in a patient after she rode a bicycle with the vaginal mould.</p><p><b>CONCLUSION</b>The improved laparoscopic Vechitti procedure for constructing a functioning vagina has less trauma than conventional operation and is easy to operate. Therefore, the new improved procedure is a preferred way in constructing vagina for treating those patients.</p>