Low Grade Fibromyxoid Sarcomas and Multiple Myeloma in the Same Patient: One Case Report and Literature Review

Introduction Multiple myeloma (MM) is a neoplastic plasma cell dyscrasia char-acterized by anemia; a monoclonal protein(M-protein) in the serum and/or urine; abnormal bone radiographs and bone pain;hypercal-cemia; and renal insuf.ciency or failure.According to the results of immunoelectrophoresis, patients are separated to Ig type (IgG, IgA, IgD, IgE and IgM); light chain; nonsecretory[1].     

IgE Myeloma： the First Report of Chinese Case and a Review of the Literature

To report a case of IgE myeloma and to compare its clinical features with those reported in the literature. Methods: M-component in serum and urine was determined using celluloseacetate membrane electrophoresis, immunofixation electrophoresis and quantification of immunoglobulins. Immunohistochemistry was performed to detect the expression of IgE and its light chain. Results: A monoclonal peak was detected by cellulose-acetate membrane electrophoresis. The monoclonal band showed on immunofixation electrophoresis the following reactive patterns: positive for A antisera and negative for κ, IgG, IgA, IgM and IgD antisera. The serum immunoglobulin concentrations were: IgG 21.6 g/L, IgA1.2 g/L, IgM 2.64 g/L, κ 7.49 g/L, λ 16.0 g/L, κ/A 0.47. The results of immunohistochemistry showed cytoplasmic expression of IgE immunoglobulin and A light chain in the tumor tissue. Conclusion: This is the first case of IgE multiple myeloma reported in China.     

Primary gastric signet ring cell carcinoma presenting as cardiac tamponade

Primary gastric signet ring cell carcinoma presenting as cardiac tamponade is difficult to diagnosis early.Patients are generally asymptomatic until the disease is advanced.General practitioners usually focus on the initial symptoms related to pericarditis and pericardial effusion.We report a case of signet-ring cell carcinoma of the stomach presenting as cardiac tamponade with pericarditis and pericardial effusion but without any gastrointestinal symptoms.A 49-year old woman was admitted because of progressive dyspnea and cough.Chest X-ray revealed an increased cardiothoracic ratio and a small amount of bilateral pleural effusion.Two dimensional ultrasonographic echocardiography pericardial effusions with atrial and right ventricular early diastolic collapse were found,establishing the diagnosis of cardiac tamponade.Pericardiocentesis was performed and 420 mL of bloody fluid was taken.The patient died of respiratory failure and cardiac arrest on October 28,2009.Post-mortem examination revealed diffuse gastric mucosa erosion and edema with stomach mucosa incrassation in the greater curvature.The primary lesion was histopathologically diagnosed as signet-ring cell carcinoma of the stomach.     

Why bortezomib cannot go with ＂green＇？

Eat more ＇green＇ or eat ＇five a day＇ is one of the most important healthy lifestyle behaviours in the 21 century. Aiming to fight cancer effectively, more than half patients use vitamins or herbs concurrently with conventional anticancer treatment. Flavonoids or polyphenols existing in vegetables, fruits and green tea are common plant pigments with antioxidant properties and considered acting as cancer preventing or anti-cancer agents. Recently it was found that some flavonoids and vitamin C in diet or supplements have antagonistic effect with the anti-cancer drug bortezomib. Bortezomib is a specific inhibitor for proteasome and is currently used for treatment of relapsed and refractory multiple myeloma. Despite its successful rates in treating multiple myeloma and other solid tumors, it is unable to kill leukemic cells in the blood. It was recently revealed that some flavonoids and vitamin C present in green leaves and green teas in the blood can neutralize bortezomib by directly interaction between two chemicals. Here we summarize why dietary flavonoids should be avoided in patients who take bortezomib as chemotherapeutic drug.     

A case report of tracheal extramedullary plasmacytoma

Introduction Extramedullary plasmacytoma (EMP) is an uncommon tumor that often develops outside the bone and arises from clonal proliferation of atypical plasma cells before EMP is diagnosed. Multiple myeloma(MM) must be excluded by performing laboratory tests such as serum protein electrophoresis, bone marrow biopsy and skeletal imaging ex-aminations. A bone marrow biopsy should show no evidence of mul-tiple myeloma, and less than 3% of plasma cells. Monoclonal bands of serum protein and Bence-Jones protein in the urine can sometimes be detected. EMP can involve any extraosseous organs, but it pre-dominantly affects the head and neck areas. Any extra-osseous organ may also be involved[1,2]. Tracheal involvement is a rare finding. Only a few cases of primary tracheal extramedullary plasmcytoma have been reported[2-4], Here we present a rare case of truly localized tra-cheal extram edullary plasmacytoma without evidence of myelomaelsewhere.     

Efficacy of Recombinant Adenoviral Human p53Gene in Treatment of Malignant Pleural or Peritoneal Effusions

Background and objective Once the malignant pleural or peritoneal effusion is developed it is difficult to control.This report presents a new method for controlling the malignant effusions.Methods Forty-eight patients,29 males and 19 females with an average age of 61.2 years old,who were satisfied with the study inclusion criteria,were recruited in this study.Twenty-seven and 21 patients had a malignant pleural and peritoneal effusion,respectively.After draining most of fluids,these patients received intra-cavity infusion of rAd-p53 once per week for 4 weeks,at dose of 2×1012 viral particles(VP) diluted into 200 mL of saline solution for pleural effusions,and 4×1012 VP diluted into 500 mL of saline solution for peritoneal effusions.Results Participants were followed up for a median time of 13.6 month.A total of 11 cases,7 with pleural effusions and 4 with peritoneal effusions achieved a complete response(CR),and 20 cases(12 pleural effusions and 8 peritoneal effusions) had a partial response(PR).The overall response rate is 64.6%.Patients’ quality of life,assessed by using Karnofsky performance scale(KPS) scores,was improved by an average of 26.4.The one-year of overall survival rate was 54.2% with a median survival time of 12.5 months.There were no serious side effects observed except for self-limited fever found in 79.8% of the cases.Conclusions Intra-cavity infusion of rAd-p53 is an effective and safe treatment for the patients with malignant pleural or peritoneal effusions,especially for those patients who can’t tolerate the standard treatments.     

胰脾胸腔易位在残胃食管吻合术中的应用

Objective： To investigate the value of spleen and pancreatic tail thorax translocation on the residual stomach esophagus anastomosis. Methods： 10 patients with esophageal carcinoma after gastrectomy were enrolled in this study. Lesions were removed through left thoracotomy and residual stomach was fully mobilized, with short gastric artery being reserved. Spleen and pancreatic tail were dissected from the back of peritoneum and transposed into thorax. Residual stomach esophagus anastomosis was performed. Results： All the operation went favorably. Patients were recovered rapidly and a relatively good prognosis was acquired. Late leakage and pleural effusion happened in one case respectively, but these com- plications were cured through conservative management without operation death. Conclusion： Residual stomach is an ideal candidate for the replacement of esophagus and residual stomach esophagus anastomosis is a simple operative alternative with few trauma and good results for the treatment of esophageal carcinoma after gastrectomy.     

多发性骨髓瘤终末期患者84例临床资料总结

Objective To analyze the characteristics of multiple myeloma(MM)patients at end-stage in order to introduce optimal therapeutic strategies for MM.Methods The clinical features of 84 end-stage multiple myeloma patients were analyzed and related literatures were reviewed.Results The pain in bone was the main complaint in 61.9%patients and bisphosphonates could treat bone disease effectively.Drug resistance including primary and secondary displayed in all patients.The primary drug resistance had a poor prognosis with median survival of only 11 months(range 7～14 months)and the secondary of 46 months(range 12-87 months)(P＜0.01).The main abnormal characteristics were infection.hematocytopenia,hypoproteinemia,renal inadequacy,electrolyte disturbances,cardiac inadequacy and abnormity of hemostasis and thrombosis.But hypoproteinemia was a rare event(4.8%).The patients who suffered from secondary plasmacytic leukemia,extramedullary tumor(intracal,canalis spinalis and serous cavity et al) and secondary tumor had a poor response to treatment and a shorter survival duration.Conclusion MM at end-stage has a poor prognosis and effective supportive therapies are very important for those patients.New strategies should be applied to those patients.     

Megakaryocyte aplastic thrombocytopeniaafter CAR T-cell therapy in a patient withmultiple myeloma:A case report

Chimeric antigen receptor(CAR)T-cell therapy is an effective new treatment strategy for hematologic malignancies.The success of CAR T-cell therapy in treating leukemia and lymphoma has promoted its development for multiple myeloma(MM),and the initial results of CAR T cell therapy have been encouraging.CAR T-cell therapy target antigens that have been clinically evaluated in MM;these antigens include CD19,B cell maturation antigen(BCMA),CD38,and CD138.A barrier to the widespread use of CAR T-cell therapy is its toxicity,primarily cytokine release syndrome(CRS),and neurologic toxicity.This study reports a patient with refractory MM who also developed megakaryocyte aplastic thrombocytopenia after receiving CAR T-cell therapy;such a case or the unusual side effects involving medications are yet unreported.There are risks in using cyclosporine and other immunosuppressants that may lead to MM recurrence as the use of such substances is contradictory to previous treatments;therefore,we temporarily administered platelet infusion as supportive care.Thus far,the condition of the patient has been steady and the patient regularly takes blood test in the hospital.     

心包腔内注入重组改构人肿瘤坏死因子治疗恶性心包积液的疗效分析

Objective: To evaluate the therapeutic efficacy of injecting recombinant mutant human tumor necrosis factor (rmhTNF) into pericardial cavity of carcinoma patients with malignant pericardial effusion. Methods: In 20 cases of malignant pericardial effusion, the intrapericardial catheter was inserted into pericardial cavity, and then rmhTNF of 1.5 × 107 U was infused. The infusion was repeated every 5-7 days with the total 4-6 times. If the effusion disappeared, rmhTNF was then used 2 more times and then the intrapericardial catheter was pulled out. Results: Of 20 patients, 14 were complete response (CR), 4 were partial response (PR) and 2 no change (NC). The disappearance of effusion in 6 cases lasted for more than 6 months. Conclusion: Injecting rmhTNF into pericardial cavity may be a better way to control malignant pericardial effusion and has mild side effects.     

Nonsecretory myeloma, immunoglobulin D myeloma, and plasma cell leukemia

Nonsecretory myeloma, which accounts for 1% to 5% of all myelomas, is characterized by the absence of detectable M-protein in serum and urine. The presenting features of nonsecretory myeloma are similar to those in patients with a detectable M-protein, except for the absence of renal function impairment. The response to therapy and survival of patients with nonsecretory myeloma are similar to those of patients with measurable M-protein. Immunoglobulin D myeloma represents 2% of all myelomas. Patients with IgD myeloma usually present with a small band or no evident M-spike on serum electrophoresis and heavy light-chain proteinuria. Thus, IgD myeloma can be considered a variant of Bence Jones myeloma; the presence of the IgD M-protein and the predominance of the lambda light chain are the only distinctive features. The median survival of patients with IgD myeloma is almost 2 years, with one fifth of them surviving for more than 5 years. Plasma cell leukemia is also a rare form of plasma cell dyscrasia (2% to 4% of all myelomas). The primary form accounts for 60% of the cases. In primary PCL, the constellation of adverse biologic prognostic factors in patients with advanced aggressive myeloma is already present at diagnosis. In fact, primary PCL has a more aggressive clinical presentation than MM, with a higher frequency of extramedullary involvement, anemia, thrombocytopenia, hypercalcemia, and renal failure. Treatment with a single alkylating agent plus prednisone is not appropriate. Combination chemotherapy with VAD, cyclophosphamide and etoposide, or VCMP/VBAP is a better initial option. Given the poor prognosis of primary PCL, intensification with high-dose therapy followed by stem cell rescue should be offered to affected patients.     

Immunoglobulin D myeloma--problems with diagnosing and staging (own experience and literature review)

Immunoglobulin D (IgD) myeloma is a rare disease accounting for about 2% of all myelomas. The distinctive features are the predominant occurrence in males and young patients, short survival time, uncertain appearance of M-component in serum electrophoresis, predominance of lambda light chains, frequent renal impairment, hypercalcemia and amyloidosis. The aim of the present study was to show diagnostic difficulties resulting from a variety of non-specific initial symptoms and laboratory findings as well as to compare the staging system proposed by Durie and Salmon with the new risk grouping by Shimamoto. Case histories of 7 patients were analyzed retrospectively. Five of them were diagnosed as IgD multiple myeloma (IgD MM), 1 as non-secretory IgD myeloma and 1 as solitary bone IgD plasmocytoma that evolved to an IgD MM. All patients were staged according to the Durie and Salmon classification and the new risk grouping by Shimamoto. We report diagnostic problems with IgD myeloma in our patients, with special emphasis on non-specific rheumatoidal and neurological symptoms in 1 case. There was a very good correlation of the Japanese classification with the severity of the disease and the risk of death. In conclusion, the initial symptoms of IgD myeloma can be very misleading. Wide differential diagnosis, including autoimmunological disorders of the connective tissue, is necessary. The new Japanese risk grouping seems to be of greater prognostic significance for IgD myeloma than the Durie and Salmon staging system.     

IgD Subtype But Not IgM or Non-Secretory Is a Prognostic Marker for Poor Survival Following Autologous Hematopoietic Cell Transplantation in Multiple Myeloma. Results From the EBMT CALM (Collaboration to Collect Autologous Transplant Outcomes in Lymphomas and Myeloma) Study

BackgroundThe Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study has provided an opportunity to evaluate the real-world outcomes of patients with myeloma. The aim of this study was to compare the outcome according to the different subtypes of myeloma using CALM data.PatientsThis study compared overall survival (OS), progression-free survival (PFS), and complete remission (CR) and the impact of novel versus non-novel drug containing induction regimens prior to autologous hematopoietic cell transplantation (HCT) of 2802 patients with “usual” and “rare” myelomas.ResultsOur data suggest that IgM and non-secretory myeloma have superior PFS and OS compared with IgD myeloma and outcomes comparable to those for usual myeloma. Patients who received novel agent induction had higher rates of CR prior to transplant. Non-novel induction regimens were associated with inferior PFS but no difference in OS. Although not the primary focus of this study, we show that poor mobilization status is associated with reduced PFS and OS, but these differences disappear in multivariate analysis suggesting that poor mobilization status is a surrogate for other indicators of poor prognosis.ConclusionWe confirm that IgD myeloma is associated with the worst prognosis and inferior outcomes compared with the other isotypes.     

Biased Iglambda expression in hypermutated IgD multiple myelomas does not result from receptor revision.

Normal IgM(-)IgD(+) CD38(+) B cells and IgM(-)IgD(+) multiple myelomas (MM) are characterized by Cmu deletion, biased Iglambda expression and hypermutated IgV regions. The predominant Iglambda usage has been proposed as resulting from secondary Ig gene rearrangements during extensive clonal expansion in the germinal center environment. Here, four cases of IgDlambda MM were studied to address the question of light chain receptor revision in a 'single cell' model. Detailed analyses of both IGK and IGL alleles of each case were performed by Southern blotting, (RT-) PCR, and sequencing. The expressed IgV genes were extensively mutated and Cmu deletion was confirmed in two cases. In addition, in the four MM a total of six non-functional deletional IGK rearrangements were identified, which proved to be unmutated. We conclude that IgD myelomas indeed originate from (post) germinal center B cells in which, in spite of the fact that they are hypermutated, there is no evidence of receptor revision.     

Fas Antigen/APO-1 (CD95) Expression on Myeloma Cells

Many factors involved in the proliferation of myelomas have been reported, and the relationship between these factors and the pathogenesis of multiple myeloma has been discussed. We found that most myeloma cells express Fas antigen/APO-1 (CD95), a cell surface antigen that mediates apoptosis. However only some cells are sensitive to anti-Fas antibody and undergo apoptosis. These data indicate that some multiple myelomas are generated not only by cell proliferation but also by cell immortalization. The mechanism by which myelomas are immortalized is still unclear, but Bcl-2, Bcl-x_L, adult T cell leukemia derived factor (ADF), soluble Fas are all candidate factors for this mechanism. The possibility also exists that inducers of apoptosis, e.g. tumor necrosis factor(TNF), interleukin-lβ-converting enzyme(lCE), Bcl-x_S, or Bax, do not have a lethal effect. In this review, we focus on the system that immortalizes myeloma cells, and suggest the possibility that multiple myeloma constitutes one group of cells which cannot undergo apoptosis in the bone marrow.     

IgD型多发性骨髓瘤的诊治现状及展望

IgD型多发性骨髓瘤（IgD multiple myeloma，IgD MM）是多发性骨髓瘤（multiple myeloma，MM）中一种罕见类型，以年轻男性患者居多。主要表现为高钙血症、肾衰竭、贫血、骨损害、髓外浸润和系统性淀粉样变性等，具有侵袭性高，预后较差的特点。近年来，随着免疫调节剂（沙利度胺、来那度胺）、蛋白酶抑制剂（硼替佐米）等药物以及自体造血干细胞移植（autologous stem cell transplantation，ASCT）的应用，IgD型MM的预后得到明显改善。新一代蛋白酶体抑制剂、CD38单克隆抗体、组蛋白去乙酰化酶抑制剂（histone deacetylase inhibitor,HDACI）、新型免疫治疗技术等治疗方法也为IgD型MM 的治疗提供了新的方向。目前关于IgD型MM的相关报道较少，本文就IgD型MM的临床特点、诊断、治疗、预后及新药研究现状进行如下综述。     

Outcome of patients with IgD and IgM multiple myeloma undergoing autologous hematopoietic stem cell transplantation: a retrospective CIBMTR study

IntroductionImmunoglobulin D (IgD) and IgM multiple myeloma represent uncommon immunoglobulin isotypes, accounting for 2% and 0.5% of cases, respectively. Limited information is available regarding the prognosis of these isotypes, but they have been considered to have a more aggressive course than the more common immunoglobulin G (IgG) and IgA isotypes. In particular, the outcome after autologous hematopoietic stem cell transplantation (auto-HCT) has not been well defined.Patients and MethodsUsing the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 36 patients with IgD and 11 patients with IgM myeloma among 3578 myeloma patients who received intensive therapy and auto-HCT over a 10-year period.ResultsThe progression-free and overall survival probabilities at 3 years were 38% (95% CI, 21%-56%) and 69% (95% CI, 51%-84%) for IgD myeloma, and 47% (95% CI, 17%-78%) and 68% (95% CI, 36%-93%), respectively, for IgM disease. Although formal statistical analysis was limited by the small sample size, these results were comparable to those for IgG and IgA patients autografted during the same time period. Transplantation-related mortality and disease relapse/progression of myeloma were also similar for all isotypes.ConclusionThis analysis demonstrates comparable outcomes in all immunoglobulin isotypes. Therefore, auto-HCT should be offered to eligible patients with IgD and IgM myeloma.     

Meningeal relapse after double peripheral blood stem cell transplantation in IgD myeloma

A 54-year-old man diagnosed with IgD myeloma (stage IIIA) in complete remission (CR) received peripheral blood stem cell transplantation (PBSCT) twice with an interval of 4 months using high-dose melphalan 200mg/m2. However 9 months after the second PBSCT, he was readmitted because of lumbago, lower left hemiparesis, speech disturbance and left facial nerve palsy. A lumbar puncture revealed myeloma cells in the cerebrospinal fluid (CSF). The patient did not respond to any salvage chemotherapy and died of sepsis 27 months after the initial diagnosis. The findings in this patient suggest that another treatment modality including prophylactic intrathecal injection of an anti-cancer drug as well as allogeneic cell therapy is probably necessary in patients with high-risk IgD myeloma.     

Elevated level of plasma basic fibroblast growth factor in multiple myeloma correlates with increased disease activity.

Recent reports that bone marrow angiogenesis is increased in multiple myeloma prompted us to examine plasma concentrations of angiogenic growth factors and to elucidate their clinical and biological significance. In 45 cases including 36 cases of multiple myeloma and 9 cases of monoclonal gammopathies of undetermined significance (MGUS), plasma concentrations of basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF) were evaluated. FGF-2 was significantly elevated in 25 out of 45 (56%) of the patients with multiple myeloma compared with control subjects (median 9.01 pg ml vs. 1.58 pg/ml, P < 0.0001). The 25 cases were all active multiple myeloma, and none of the non-active myeloma and MGUS patients showed a high FGF-2 level. VEGF level was also elevated in 26 out of 45 patients (58%) compared with control subjects (median 42.0 pg/ml vs. 15.8 pg/ml, P < 0.0001 for VEGF). VEGF concentration was high in 20 active myelomas, but also in one non-active myeloma and five MGUS. Elevation of FGF-2 level was associated with beta2-microglobulin level, anemia and bone marrow plasma cell percentage, which represent disease activity. Interestingly, none of five Bence-Jones type myelomas, including four clinically active cases, revealed a high plasma FGF-2 level, while all of them showed a high VEGF level. In all five responders, the plasma FGF-2 levels were significantly decreased after chemotherapy. FGF-2 was immunohistochemically detected in the bone marrow myeloma cells of the patients with high plasma FGF-2 level. We conclude that plasma concentration of FGF-2 can be a useful indicator of disease activity.