The origin and underlying driving forces of the SARS-CoV-2 outbreak.

BACKGROUND: SARS-CoV-2 began spreading in December 2019 and has since become a pandemic that has impacted many aspects of human society. Several issues concerning the origin, time of introduction to humans, evolutionary patterns, and underlying force driving the SARS-CoV-2 outbreak remain unclear. METHOD: Genetic variation in 137 SARS-CoV-2 genomes and related coronaviruses as of 2/23/2020 was analyzed. RESULT: After correcting for mutational bias, the excess of low frequency mutations on both synonymous and nonsynonymous sites was revealed which is consistent with the recent outbreak of the virus. In contrast to adaptive evolution previously reported for SARS-CoV during its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation. The sequence similarity in the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression that occurred approximately 40 years ago. The current outbreak of SARS-CoV-2 was estimated to have originated on 12/11/2019 (95% HPD 11/13/2019-12/23/2019). The effective population size of the virus showed an approximately 20-fold increase from the onset of the outbreak to the lockdown of Wuhan (1/23/2020) and ceased to increase afterwards, demonstrating the effectiveness of social distancing in preventing its spread. Two mutations, 84S in orf8 protein and 251 V in orf3 protein, occurred coincidentally with human intervention. The former first appeared on 1/5/2020 and plateaued around 1/23/2020. The latter rapidly increased in frequency after 1/23/2020. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China is two times higher than those derived from the rest of the world. A network analysis found that haplotypes collected from Wuhan were interior and had more mutational connections, both of which are consistent with the observation that the SARS-CoV-2 outbreak originated in China. CONCLUSION: SARS-CoV-2 might have cryptically circulated within humans for years before being discovered. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and determine the critical steps required for effective spreading.

Clinical Analysis of Cardiac Involvement in 53 Patients With Multiple Myeloma Coexistent With Light Chain Amyloidosis.

BACKGROUND: We identified 53 patients with multiple myeloma (MM) who had biopsy evidence of light chain amyloidosis (AL), and studied their cardiac involvement and outcomes. PATIENTS AND METHODS: Our cohort consisted of 53 patients in whom MM and AL were initially diagnosed from July 1, 2006 to June 30, 2016.The diagnosis of MM required > 10% of clonal plasma cells in bone marrow and 1 of the CRAB symptoms, meanwhile, the diagnosis of AL must meet pathologic diagnostic criteria and monoclonal immunoglobulin light chain. Echocardiograms and cardiac biomarker such as N terminal pro B-type natriuretic peptide was used for evaluation of cardiac damage on the baseline and before every cycle of the regimen. RESULTS: There were 36 men and 17 women with a median age of 59 years; their main organ involvement was kidney (72%) and heart (62%). Of these, 22 patients were treated with a bortezomib-based regimen, and the response rate was more effective than the other 21 patients who received non-bortezomib-based regimens (64% vs. 29%). The median overall survival (OS) for the total cohort was 12 months (P < .05). The median OS of the MM cohort with International Staging System stage I and II together was 34 months, which was longer than that of patients with stage III of 8 months. The median OS in Mayo stages I, II, and III was 38, 8, and 1 months, respectively (P < .05). Cardiac involvement significantly adversely affected survival (6 vs. 40 months), as did systolic blood pressure (< 90 mmHg, 3 vs. 8.5 months). CONCLUSIONS: Patients coexistent with MM and AL is rare; AL has a negative impact on survival for the total cohort. Especially, cardiovascular dysfunction caused by AL maybe a major determinant of shortening survival.

Extraction, purification, hypoglycemic and antioxidant activities of red clover (Trifolium pratense L.) polysaccharides.

Hot water extraction was applied to extract red clover (Trifolium pratense L.) polysaccharides (RCP) and the extraction conditions were optimized using the response surface methodology (RSM). An RCP yield of 12.72 ± 0.14% was achieved under the optimum extraction conditions: extracting time of 95 min, extracting temperature of 93 °C, and solvent-material ratio of 21 mL/g. A component named RCP-1.1 with the molecular weight of 7528.81 kDa was purified from RCP. RCP-1.1 was composed of glucose, galacturonic acid, arabinose, and galactose, with molar percentages of 52.54, 1.04, 16.31, and 30.11%, respectively. At the determination concentration of 10 mg/mL, the α-glucosidase inhibition ability of RCP-1.1 reached 86.72% of that of acarbose. The scavenging rates of RCP-1.1 (3.0 mg/mL) for DPPH and ABTS radicals reached 91.82% and 98.95% of that of ascorbic acid (3.0 mg/mL), respectively. Based on these results, RCP-1.1 possesses the potential to be used as a natural hypoglycemic agent or an antioxidant.

Physicochemical properties and activities of comfrey polysaccharides extracted by different techniques.

The effects of extraction techniques on the physicochemical properties, antioxidant activity and antihyperglycemic activity of comfrey polysaccharides (CPs) were evaluated. Four techniques were used to extract CPs: hot water extraction (HW), ultrasonic-assisted extraction (UA), enzyme-assisted extraction (EA) and enzyme-ultrasonic-assisted extraction (EUA). Experimental results indicated that CPs extracted by the UA (UA-CPs) and EUA methods (EUA-CPs) had higher extraction yields. The four CPs showed the same monosaccharide composition but a significant difference in monosaccharide content. CPs showed antioxidant activities and antihyperglycemic activities in a concentration-dependent manner. UA-CPs exhibited better antioxidant capacity, which might have been related to its smaller molecular weight and higher uronic acid content. In addition, UA-CPs showed notable α-glucosidase inhibition activity. These results suggested that ultrasonic-assisted extraction technology was more beneficial to enhance the extraction yields of the polysaccharides, and obtain higher bioactive polysaccharides from comfrey.

Cytogenetic abnormality in patients with multiple myeloma analyzed by fluorescent in situ hybridization.

OBJECTIVE: To analyze the fluorescent in situ hybridization (FISH) data and the association with clinical characteristics, therapy response, and survival time in patients with multiple myeloma. METHOD: We performed a retrospective review of patients with multiple myeloma from November 2010 to April 2014. RESULTS: Cytogenetic abnormalities by FISH were detectable in 66% of patients. One cytogenetic abnormality, two cytogenetic abnormalities, and complex abnormalities were detectable in 21.2%, 51.5%, and 27.3% of cases, respectively. 1q21 amplification, t(4p16.3/14q32), and 17p deletion were observed in 69.7%, 30.3%, and 21.2% of cases, respectively. Total response rates (complete response [CR] + near CR + partial response) were 93.8% and 82.1%, respectively, in cytogenetic normality group and abnormality group. CR rates were 50% and 32.1%, respectively. Median overall survival (OS) time was 51 months and 24 months, respectively, in cytogenetic normality group and abnormality group (P<0.05). Median OS time was not significantly different between 1q21 amplification group and no 1q21 amplification group in patients with FISH abnormalities (P>0.05). Median OS time was not significantly different between t(4;14) group and no t(4;14) group in patients with FISH abnormalities (P>0.05). Seven patients of 17p deletion died in 2 years. CONCLUSION: Multiple myeloma is characterized by a high occurrence of chromosomal aberrations. 1q21 amplification and t(4;14) are the most common abnormalities. Multiple cytogenetic abnormalities are frequently observed in the same one patient. The total response rate, CR rate, and OS time are worse in cytogenetic abnormal patients compared with cytogenetic normal patients. Patients with 17p deletion have a very poor prognosis. Future goals of therapy will be to achieve minimal residual disease, biomarkers, and genomic data, which might provide a better estimate of the depth of response to therapy and OS.

Analysis of clinical features, treatment response, and prognosis among 61 elderly newly diagnosed multiple myeloma patients: a single-center report.

BACKGROUND: We identified the clinical features of 61 cases of multiple myeloma (MM) patients over 65 years and analyzed the treatment and prognosis of the era of new drugs in elderly patients. METHODS: We identified 61 newly diagnosed symptomatic multiple myeloma (NDMM) among elderly Chinese patients more than 65 years old diagnosed from 2006 to 2012. RESULTS: Of the 205 consecutive MM patients whom we reviewed, 61 (29.76%) cases were NDMM patients aged more than 65 years and the others were younger than 65 years old. Among them, 40 (65.6%) cases were in end-stage (ISS stage III); meanwhile, 19 (31.2%) cases of them had MM with extramedullary plasmacytoma (EMP), observed in 42.1% patients at diagnosis, and the top three incidence of position were spinal canal, pleural, and soft tissue. In the whole column, the median follow-up was 38 months and median age was 72.5 years. Patients received bortezomib- or thalidomide-containing regimens as initial therapy. Comparing the two treatment groups, the complete remission (CR)/near-complete remission (nCR) rate was significantly higher in the bortezomib-containing regimens (61.5 vs.18.18%, P=0.001), no difference in progression-free survival (PFS) and overall survival (OS). Patients of age over 75 years had shorter OS than those of age over 65 years (49 vs. 24 months, P=0.001). The patients with EMP had shorter OS than those without EMP in two age groups (32 vs. 42 and 15 vs. 24 months, P=0.017 and 0.024, respectively). CONCLUSIONS: The results highlight that patients over 75 years and MM with EMP have a poorer outcome. While the CR rate is higher in bortezomib-containing regimens, no significant improvement is noted in respect to the survival outcomes; also, it cannot overcome the negative influence on survival of age and MM with EMP in elderly patients.

[Clinical observations of lenalidomide combination chemotherapy for relapsing or refractory multiple myeloma].

OBJECTIVE: To explore the clinical efficacies and toxicities of lenalidomide combination chemotherapy in the treatment of relapsing or refractory multiple myeloma (MM) patients. METHODS: A total of 14 MM patients were recruited to receive lenalidomide combination chemotherapy in Beijing Chaoyang hospital from June 2013 to October 2014. Lenalidomide 25 mg was taken orally daily or every alternate day for 21 days and resting for 7 days. The regimens were RD (lenalidomide and dexamethasone, n = 6), RCD (lenalidomide, ifosfamide and dexamethasone, n = 4), RDD (lenalidomide, liposomal doxorubicinand dexamethasone, n = 1), PRD (lenalidomide, velcade and dexamethasone, n = 1) and R+DECP (lenalidomide, cisplatin, etoposide, ifosfamide and dexamethasone, n = 2). RESULTS: Among them, two patients died during the first cycle of lenalidomide. Ten patients finished 2 cycles of treatment and 2 patients attained near complete remission or complete remission (nCR/CR), 6 partial remission (PR) and 2 stable disease (SD) with an overall response rate (ORR) of 8/10. Ten patients finished 3 cycles of treatment and 3 attained CR, 5 PR and 2 SD. Nine patients finished 4 cycles of treatment and 3 attained CR, 5 PR and 1 progressive disease (PD). Six patients finished 5 cycles of treatment and 1 attained CR, 3 PR and 2 PD. Three patients finished 6 cycles of treatment and 1 attained CR, 1 PR and 1 PD. And the most common adverse reactions were fatigue, loss of appetite and hypocytosis. Six patients died. CONCLUSION: The lenalidomide combination chemotherapy is both efficacious and safe in the treatment of relapsing or refractory MM.

Light chain multiple myeloma, clinic features, responses to therapy and survival in a long-term study.

BACKGROUND: We intended to investigate the long-term clinical characteristics, responses to therapy and survival in patients with lightchain multiple myeloma (MM). METHODS: Ninety-six patients were enrolled into the study. There were 42 κ-chain MM patients and 54 λ-chain MM patients. All the patients werestage III in the Durie-Salmonstaging system. Among them, 66 patients received Velcade (bortezomib) treatment and the other 30 did not. RESULTS: The main symptoms of these patients included bone pain (77.1%), weakness and fatigue (12.5%), foamy urine (8.3%) and extramedullaryplasmocytomas (33.3%). The overall response rate (ORR) was 95.5% in patients treated with Velcade and 60%in the patients without. The median survival times were 23 months in patients treated with Velcade and 12 months in patients without. The median time of progression-free survival (PFS) was nine months in patients treated with Velcade and five months in patients without. The one-year PFS and two-year PFS were 37% and 25%, 27% and 9% for patients treated with Velcade, or without, respectively. The three-year overall survival (OS) and five-year OS were 33% and 24%, 28% and 9% for patients treated with Velcade, or without, respectively. There was no significance in OS between the two groups (P = 0.335). But there was significant difference in PFS between the two groups (P = 0.036). CONCLUSIONS: Our long-term study demonstrated that patients with lightchain myeloma appeared to have more aggressive disease courses and poor outcomes, which could be improved by treatment with Velcade.

[Clinical observation of DECP combination chemotherapy for relapsing and refractory multiple myeloma patients with extramedullary plasmacytomas].

OBJECTIVE: To explore the clinical effect and toxicity of (cisplatin, etoposide, ifosfamide & dexamethasone) DECP combination chemotherapy in the treatment of relapsing and refractory multiple myeloma (MM) with extramedullary plasmacytomas. METHODS: A total of 20 relapsed and refractory MM patients with extramedullary plasmacytomas treated with DECP regimen from May 2005 to May 2013 were analyzed retrospectively. DECP protocols included cisplatin 20 mg/m(2), Day 1-3; etoposide 100 mg/d,Day 1-3; ifosfamide 500 mg·m(-2)·d(-1), Day 1-4; dexamethasone 20 mg/d, Day 1-4. Efficacy was evaluated after 2 therapeutic cycles. RESULTS: After 2 therapeutic cycles, the objective response rate (ORR) was 55% (11/20). After 3 therapeutic cycles, the ORR was 7/12.Seven patients completed 4 cycles with an ORR of 4/7. Two patients had finished 6 cycles and continued to maintain partial remission. The most common adverse events included gastrointestinal reaction and myelosuppression. The median follow-up time was 30 (12-80) months. The median time of overall survival (OS) was 30 (9-121) months. The 1-year OS was 73%, 2-year OS 28% and 3-year OS 21%. CONCLUSION: The DECP chemotherapy is both effective and safe in the treatment of relapsed and refractory MM patients with extramedullary plasmacytomas.

[Clinical analysis of multiple myeloma with extramedullary plasmacytomas].

OBJECTIVE: To explore the clinical features, treatment and prognosis of multiple myeloma (MM) with extramedullary plasmacytomas (EM). METHODS: A total of 43 patients were enrolled and divided into 2 groups. Group-1 had 12 patients of EM occurring after the diagnosis of MM while Group-2 included 31 EM patients at the initial diagnosis of MM. RESULTS: The male-to-female proportion was 23:20 and there was a median age of 53 years. The distribution of different isotypes was IgG (n = 15), IgA (n = 9), IgD (n = 2), κ light chain (n = 6), λ light chain (n = 6), biclonal myeloma (n = 3) and nonsecretory myeloma (n = 2). The sites of complicating plasmacytoma included skin, muscle and spinal canal. Nine patients received bortezomib plus DECP (cisplatin, etoposide, cyclophosphamide and prednisone) and 2 patients underwent traditional chemotherapy in Group-1. The outcomes were as follows: complete remission (CR, n = 2), partial remission (PR, n = 4) and death (n = 5). And 11 patients received traditional chemotherapy in Group-2, 7 attained PR and 4 died. Twenty patients received bortezomib plus other chemotherapeutic drugs in Group-2. The outcomes were as follows: CR (n = 12), PR (n = 7) and death (n = 1). The median overall survival (OS) was 36 months (range: 10 - 120) in Group-1 and 23 months (range: 5 - 52) in Group-2 respectively. In Group-1, the estimated 3- and 5-year OS were 54.21% and 27.10% respectively. And in Group-2, the estimated 3- and 4-year OS were 39.83% and 13.28% respectively. CONCLUSIONS: The EM patients show aggressive, complicated and diverse clinical courses and the unusual manifestation of multiple organ involvement by plasma cells. Traditional chemotherapy has a poor efficacy and the prognosis is unfavorable, especially for EM with concurrent MM. The combined treatment of bortezomib with second-line chemotherapy may achieve curative effects.

[Effects of bortezomib combined with methylprednisolone in treatment of 33 cases of relapsed or refractory multiple myeloma].

The aim of this study was to explore the clinical effect and toxicity of bortezomib combined with methylprednisolone in treatment of relapsed or refractory multiple myeloma (MM). Clinical data of 33 patients (23 male, 10 female; aged from 38 to 85 years old) were analyzed retrospectively. The median diagnosis time was 25 (2 - 120) months. 33 patients received bortezomib (0.9 - 1.1) mg/m(2) on days 1, 4, 8, 11, in combination with methylprednisolone 40 mg/d (4 cases), 80mg/d (13 cases), 120 mg/d (2 cases), 200 mg/d (9 cases), 300 mg/d (5 cases) respectively. The median follow-up time was 10(3-60) months. The used therapy courses were 1 - 8 (mean 4 courses). The results indicated that 24 cases showed the response of different degree, the overall response rate (ORR) was 72.7% (24/33). 32 patients received ≥ 2 therapy courses, and ORR was 71.9% (23/32). 16 patients received 4 therapy courses, and ORR was 93.8% (15/16 cases). 7 patients received 6 therapy courses and the ORR was 100% (7/7 cases). Main side-effects were thrombocytopenia, infection and peripheral neuropathy. The median survival time was 41.5 (2 - 120) months and the 2-year, 3-year and 5-year overall survival rate were 80%, 59.1% and 21.1%, respectively. It is concluded that bortezomib combined with methylprednisolone is an effective therapy with higher response rate, and safe in treatment of relapsed or refractory multiple myeloma.

[The efficacy and safety of bortezomib plus thalidomide in treatment of newly diagnosed multiple myeloma].

OBJECTIVE: The aim of this phase II study was to determine the efficacy and safety of combined bortezomib and thalidomide (VT) regime as initial treatment for newly diagnosed multiple myeloma (MM) in China. METHODS: Thirty-four patients were enrolled in this study and received VT regime up to 21-day cycles. Bortezomib (1.3 mg/m(2)) was administered intravenously on days 1, 4, 8, and 11, while oral thalidomide (100 mg/day) was given from days 1 to 21. The primary end point was clinical response. The secondary end point was safety. RESULTS: Among the 34 patients, 20 were male, 14 were female, with a median age of 59 years, and 15 in international stage system (ISS) III, 18 in ISS II, 1 in ISS I. Among them, 28 completed 2 cycles' treatment and achieved an overall response rate (ORR) of 92.9%; 26 were able to complete the planned 8 cycles of therapy. After 8 cycles, the ORR was 100% (complete response 30.8%, near-complete response 23.1%, partial response 42.3%, minimal response 3.8%). After followed up with a median time of 12 months, the estimated rate without progress of disease was 62%, and the estimated continuous remission rate of 12 months was 62%. The median survival time was not achieved. The most common adverse events were mild to moderate (grades 1, 2). The main toxicities were hematologic (53.3%), gastrointestinal (40.0%), peripheral neuropathy (38.0%), fatigue (36.6%) and fever (32.0%). CONCLUSIONS: VT regime provides a very high ORR and complete response rate in the treatment of newly diagnosed MM patients. No patients experienced deep venous thrombosis. In conclusion, bortezomib in combination with thalidomide is a very effective regimen for newly diagnosed MM patients and the toxicities are manageable.

Bortezomib plus thalidomide for newly diagnosed multiple myeloma in China.

The aim of this Phase II study was to determine the efficacy and safety of combined bortezomib and thalidomide (VT) regime as initial treatment for newly diagnosed patients with multiple myeloma (MM) in China. Thirty-four patients have been enrolled in this study and were planned to receive VT regime up to eight 21-day cycles. Bortezomib (1.3 mg/m(2) ) was given intravenously on days 1, 4, 8, and 11, while oral thalidomide (100 mg/day) was given on days 1 to 21. The primary end point was clinical response; the secondary end point was safety. Among 34 patients enrolled, 26 patients were able to complete the planned eight cycles of therapy. After eight cycles, the overall response rate was 100% (complete response 31%; near-complete response 23%; partial response 42%; minimal response 4%). The best response occurred within the first four cycles in 96% of patients. Adverse events included hematologic (53%), peripheral neuropathy (38%), fatigue (35%), gastrointestinal (45%), and fever (32%). Grade 3 nonhematologic adverse events included four patients (12%) with renal failure associated with tumor lysis syndrome, one patient (3%) with peripheral sensory and motor neuropathy that improved with VT dose reduction, and one patient (3%) with hypotension. One patient (3%) experienced Grade 4 thrombocytopenia. No patient experienced deep venous thrombosis, while 1 patient (3%) died due to acute renal failure. In conclusion, Bortezomib in combination with thalidomide is a very effective regimen for newly diagnosed MM patients and the toxicities are manageable.

[Multiple myeloma complicated with spinal infiltration].

This study was aimed to investigate the clinical features of multiple myeloma (MM) complicated by spinal infiltration (extramedullary plasmacytoma) so as to enhance the understanding of this kind of MM and reduce the missed diagnosis for these MM patients. 10 patients with MM complicated by spinal infiltration were enrolled in this study. Bone marrow, blood, hepatic and renal function, electrolyte, beta2 microglobulin, C-reactive protein and immunoglobulin (M-protein) were detected. The involved spinal sites were examined by using magnetic resonance imaging (MRI) or computerized tomography (CT). 10 patients were staged according to International Stage System (ISS) and Duric-Salmon stage system. The clinical data of patients were analyzed. The results showed that among 10 cases of MM complicated by spinal infiltration, involved pectoral cord was observed in 7 cases, involved lumbar cord in 2 cases and sacral cord in 1 case. The treatment with operation and protocol containing cisplatin, ifosfamide etoposide, prednisone, and bortezomib in combination with other drugs indicated that the total remission rate was 80% (8/10), no serious adverse responses was observed. In conclusion, the patients with MM complicated by spinal infiltration must be diagnosed and treated as early as possible. Once paraplegia happened in patients, the therapeutic efficacy and prognosis would be very poor.

[A clinical analysis of 25 cases of multiple myeloma complicated by extramedullary plasmacytomas].

OBJECTIVE: To investigate the clinical features of multiple myeloma (MM) complicated by extramedullary plasmacytomas (EM). METHODS: Twenty five patients were enrolled into the study. The proportion male to female was 15:10 and the median age 55.2 years. The distribution of different isotypes was IgA ten, IgG nine and light chain lambda five. The sites of complicating plasmacytoma included muscle, bone, skin, rectum, and testicles. The most common site was muscle. RESULTS: Patients with complicated extramedullary plasmacytomas at the time of diagnosis received traditional treatment, including vincristine adriamycin, dexamethasone, medphalan, prednisone, thalidomide and bortezomib. Rates of overall response (ORR) were 80%. Plasmacytomas occurring after the diagnosis of MM received cisplatin, etoposide, cyclophosphamide, prednisone, or bortezomib ORR were 66.7%, 50.0%. CONCLUSION: These results lend support to the efficacy of bortezomib in the treatment of plasmacytoma. MM cases with unconventional disease recurrence are likely to be seen due to sub-clinical seeding of tumour cells suggestive of the presence of an EM clone of plasma cells with a high degree of chemoresistance. Available data in the literature concerning the optimal therapy for patients with EM relapse were reviewed.

[Clinical analysis of 15 patients with Waldenstrom macroglobulinemia].

OBJECTIVE: To explore the clinical characteristics of Waldenstrom macroglobulinemia (WM) and enhance the level of diagnosis and treatment. METHOD: The data of 15 patients with WM in our hospital from November 1995 to October 2007 were retrospectively analyzed. RESULTS: The median age was 68.5 (60 - 79) years, male/female = 2.75/1. Main clinical manifestations were fatigue, loss of weight, splenomegaly and lymphadenopathy. All the patients accepted the treatment of alkylating agents, purine nucleoside analogs, bortezomib or thalidomide respectively. The follow-up period for the patients was 4 months to 10 years and the median follow-up time was 82 months. CONCLUSION: WM may often be seen in old male patients with varied clinical manifestations. The primary treatment is chemotherapy, but the disease is incurable. Bortezomib and thalidomide may improve the therapeutic effect.

[Bortezomib combined with other drugs for treating 60 cases of multiple myeloma].

The aim of this study was to investigate the efficacy and safety of bortezomib-combined with dexamethasone, methylprednisolone and other drugs in the treatment of patients with multiple myeloma (MM). 60 MM patients including 19 de novo patients, out of them 14 patients received the treatment using regimen of bortezomib in combination with thalidomide (BT), 5 patients received bortezomib-methylprednisolone regimen (BMP). Out of 41 patients with refractory or relapsed myeloma 26 cases of MM received the treatment using regimen of bortezomib combined with methylpreamsolone (BMP), 6 cases received the treatment using regimen of bortezomib combined with cyclophosphamide, prednisone and thalidomide (BCPT), 5 cases received the treatment using regimen of bortezomib combined with cis-diaminodichloroplatimm, etoposide, cydophosphomide and dexamethasone (BDECD), 4 cases received the treatment using regimen of bortezomib combined with dexamethasone (BD). Each patient received treatment of 2-8 courses at least. Response was assessed according to the criteria of the Bladè. Adverse events were graded according to the common Toxicity Criteria, version 3.0 (NCI CTCAE, USA). The median follow-up from the start of bortezomib treatment was 9 months. The results showed that out of 19 newly diagnosed patients, 6 cares achieved CR, 6 cases achieved nearly CR, 5 cases achieved PR, 1 case achieved MR, resulting in an ORR of 94.7%. Out of 41 refractory or relapsed patients, 5 cases achieved CR, 10 cases got nearly CR, 14 cases were PR and 5 cases were MR, resulting in an ORR of 82.92%. The main toxicities were fatigue, gastrointestinal disorders, peripheral neuropathy, thrombocytopenia, herpes zoster, skin rash. All adverse events were diminished by using routine ways. In conclusion, bortezomib combined with or the drugs is a very effective regimen, its side effects are predictable and manageable.

[Osteonecrosis of the jaw associated with the use of bisphosphonates in multiple myeloma: report of four cases and literature review].

OBJECTIVE: To summarize the clinical features of osteonecrosis of the jaw (ONJ) in multiple myeloma (MM) patients treated with bisphosphonate. METHODS: The clinical data of 4 patients with bisphosphonate-related (ONJ) in MM were reported and literatures were reviewed. RESULTS: In these patients, 3 males and 1 female, aged 59-73, pamidronate combined with chemotherapy, high dose glucocorticosteroid, and anti-angiogenic drug had been used for 12-44 months before the occurrence of ONJ. In treatment of ONJ conservative debridement of necrotic bone, systematic use of antibiotics, use of chlorhexidine acetate gargle, and withdrawal of bisphosphonates were preferable to aggressive surgical measures. CONCLUSION: Long-term use of bisphosphonates combined with chemotherapy in MM may cause ONJ that involves both mandible and maxilla. No satisfactory therapy is currently available.