Pulmonary infection with Penicillium citrinum in a patient with multiple myeloma

A 60-year-old male patient undergoing chemotherapy for multiple myeloma Stage II presented to our hospital with complaints of cough, haemoptysis, fever and loose stools. Sputum sample was sent for fungal culture. Fungal culture on Sabouraud dextrose agar yielded bluish-green velvety growth with orange-to-red diffusible pigment on the reverse. The isolate was identified as Penicillium species, probably Penicillium citrinum or Penicillium pinophilus. As the isolate did not exhibit thermal dimorphism, the possibility of the fungal isolate being Penicillium marneffei was ruled out. The isolate was sent for molecular identification and confirmation, which was identified as P. citrinum. His HIV status was negative. In this case, his immunocompromised state due to multiple myeloma and chemotherapy could have predisposed him to this fungal infection, which is an emerging infection and a rare manifestation seen in high-risk patients receiving targeted therapies.     

血浆置换－血液净化治疗多发性骨髓瘤并发肾衰竭患者的诊疗分析

目的观察血浆置换－血液净化治疗多发性骨髓瘤（MM）并发肾衰竭患者的疗效。方法MM并发急性肾衰竭患者34例,其中男性19例,女性15例;年龄42～75岁,平均年龄54岁。采用HA130灌流器（珠海丽珠医用公司）,对其进行血浆置换－血液净化治疗。每3天行1次血浆置换－血液净化治疗,3次为1疗程。统计分析治疗前后的尿素氮、血肌酐（SCr）、每日尿量。结果共进行96次血浆置换－血液净化。治疗有效者22例,其中包括肾功能逆转17例,5例发展为慢性尿毒症,无效者12例（其中死亡患者2例,主动出院者3例）。尿素氮、SCr治疗后均显著下降;治疗前后比较,差异有显著统计学意义（P〈0．001）。每日尿量从（924．32±543．26）mL下降到（331．24±321．01）mL;治疗前后比较,差异有显著统计学意义（P〈0．001）。中重度贫血29例中缓解24例（82．8％）;差异有显著统计学意义（P〈0．001）。免疫球蛋白IgG型患者治疗后17例有效。结论血浆置换－血液净化治疗MM并发肾衰竭可以延长患者生存时间,促进急性肾衰竭完全康复,提高患者生活质量。     

Fine-needle aspiration biopsy of multiple myeloma in a patient with renal-cell carcinoma: A case report

A case of multiple myeloma diagnosed by fine-needle aspiration (FNA) biopsy and confirmed by laboratory studies in a patient with a history of renal-cell carcinoma is presented. The patient was diagnosed with renal-cell carcinoma of the right kidney and a radical nephrectomy was performed. Eighteen months after this diagnosis was made, the patient developed chest wall pain and was found to have osteolytic bone lesions of the ribs and vertebral bodies. FNA of an osteolytic rib lesion disclosed multiple myeloma. Additional laboratory studies confirmed the diagnosis of multiple myeloma. This case report demonstrates the value of FNA as a diagnostic tool for the follow-up of cancer patients, the subsequent discrimination between metatastic lesions and a second primary malignancy, and the cytology of multiple myeloma.     

Dural plasmacytoma mimicking meningioma in a young patient with multiple myeloma

Intracranial involvement in multiple myeloma (MM) is rarely found, especially with dural involvement. There are only a few cases found concerning MM with intracranial involvement. MM usually involves an older group of patients. Cases involving young patients are very rare. The differential diagnosis of a dural plasmacytoma includes meningioma, metastasis, lymphoma and sarcoma of the dura mater. We present a young patient, 33 years old, with MM presenting an intracerebral mass mimicking meningioma on MRI. MM was diagnosed the previous year. The patient presented with headache, balance disturbance and back pain. MRI revealed an occipital extra-axial mass with a dural tail. Histopathological examination after excision showed MM. Published literatures on intracranial involvement of MM are also discussed. Plasmacytoma should be considered in the differential diagnosis of a solitary dural mass, particularly in a patient with MM.     

一例伴有低亚二倍体异常的多发性骨髓瘤的临床和实验研究

目的 报告1例伴有低亚二倍体复杂异常的多发性骨髓瘤病例并探讨其临床和实验室特点.方法 采用骨髓细胞短期培养法制备染色体,用R显带技术进行核型分析.用13q14、p53、Rbl、lq21一系列单色探针和IgH/CCND1双色双融合探针对其进行荧光原位杂交检测.用流式细胞仪检测DNA含量.结果 R显带核型分析提示该患者5个细胞为包含35条染色体的低亚二倍体核型,3个细胞为低亚二倍体克隆的复制,另外4个细胞为正常核型.间期荧光原位杂交证实核型中存在1号、13号、14号、17号染色体单体,且显示marl来源于11号染色体并造成CCND1基因的扩增.流式细胞仪检测DNA含量显示其有低亚二倍体克隆峰,DNA指数为0.8426.结论 低亚二倍体核型在多发性骨髓瘤中发生率极低,荧光原位杂交技术是检测多发性骨髓瘤分子异常的可靠手段.     

Extravasation and homing mechanisms in multiple myeloma

Multiple myeloma (MM) is a malignant B-cell disorder characterized by a monoclonal expansion of plasma cells (PC) in the bone marrow (BM). During the main course of disease evolution, MM cells depend on the BM microenvironment for their growth and survival. Reciprocal interactions between MM cells and the BM mediate not only MM cell growth, but also protect them against apoptosis and cause bone disease and angiogenesis. A striking feature of MM represents the predominant localization and retention of MM cells in the BM. Although BM PC indeed represent the main neoplastic cell type, small numbers of MM cells can also be detected in the peripheral blood circulation. It can be assumed that these circulating cells represent the tumour-spreading component of the disease. This implicates that MM cells have the capacity to (re)circulate, to extravasate and to migrate to the BM (homing). In analogy to the migration and homing of normal leucocytes, the BM homing of MM cells is mediated by a multistep process of extravasation with adhesion to the endothelium, invasion of the subendothelial basement membrane, followed by further migration within the stroma, mediated by chemotactic factors. At the end stage of disease, MM cells are thought to develop autocrine growth supporting loops that enable them to survive and proliferate in the absence of the BM microenvironment and to become stroma-independent. In this stage, the number of circulating cells increases and growth at extramedullary sites can occur, associated with alteration in adhesion molecule and chemokine receptor expression. This review summarizes the recent progress in the study of the extravasation and homing mechanisms of MM cells.     

New therapies in multiple myeloma

The melphalan-prednisone regimen has been considered as standard therapy for patients with multiple myeloma (MM) for many years. Recently, high-dose chemotherapy with stem-cell support has extended progression-free survival and increased overall survival, and it is now considered conventional therapy in younger patients. However, most patients relapse and the salvage treatment is not very effective. New active drugs, including immunomodulatory agents, thalidomide (Thal) and lenalidomide, and the proteasome inhibitor bortezomib, have shown promising anti-myeloma activity. These novel treatments are aimed at overcoming resistance of tumour cells to conventional chemotherapy, acting both directly on myeloma cells and indirectly by blocking the interactions of myeloma cells with their local microenvironment and suppressing growth and survival signals induced by autocrine and paracrine loops in the bone marrow. Thal has been widely studied, mostly in combination regimens in patients with relapsed MM and, more recently, in front-line therapy, showing efficacy in terms of response rate and event-free survival. Bortezomib has been found to possess remarkable activity, especially in combination with other chemotherapeutic agents, in relapsed/refractory and newly diagnosed MM, as well as in patients presenting adverse prognostic factors. Lenalidomide, in combination with dexamethasone, is showing high overall response rates in relapsed and refractory MM and promising results also in first-line therapy. In this paper, the results of the most significant trials with Thal, bortezomib and lenalidomide are reported. Several ongoing clinical studies will hopefully allow the identification of the most active combinations capable of improving survival in patients with MM.     

Case report: amyloid tumors in a case of non-secretory multiple myeloma

Multiple myeloma (MM) is a neoplastic disorder characterized by proliferation of a single clone of plasma cells derived from B cells, which proliferates in the bone marrow and frequently invades the adjacent bone, producing skeletal destruction that results in bone pain and fractures. Patients with MM can furthermore present with anemia, hypercalcemia and renal failure. Non-secretory multiple myeloma (NSMM) is characterized by the absence of a monoclonal (M) protein in both the serum and urine. The reported incidence is 1-5% of all multiple myeloma cases. Development of amyloid tumors in NSMM has been described in the literature only occasionally. The clinical features of a 49-year-old female patient with NSMM and amyloid tumors in the breast, lung and rib are presented in this report. Conventional histology, Congo red staining with and without potassium permanganate pretreatment, aldehyde bisulfite-toluidine blue (ABT) reaction, sialic acid specific topo-optical reaction, toluidine blue topo-optical reaction as well as immunohistochemistry were performed. An attempt is made to explain the lack of monoclonal immunoglobulins in the serum and urine, although extensive organ amyloidosis of AL type (kappa-light chains) has been found. It is assumed that the plasmocytic plasma cells possess an excretory mechanism, which allows the pathologic immunoglobulins to be secreted either as amyloid proteins polymerizing into amyloid fibrils, or as immunoglobulin fragments that are subject to degradation as soon as they are excreted out of the tumor cell. In this paper, we review the occurrence of amyloid tumors in non-secretory multiple myeloma and, in a single case report, we confirm the existence of carbohydrate residues, including sialic acids and sulfated GAGs, in amyloid deposits.     

Characteristics and outcomes of patients with multiple myeloma at the Uganda Cancer Institute

PurposeData on multiple myeloma (MM) in sub-Sahara Africa is scarce. In Uganda, there is a progressively increasing incidence of MM over the years.MethodsWe performed a retrospective study on 217 patients with MM at the UCI using purposive sampling method. The objectives of the study were to determine the clinical characteristics, treatment outcomes, 5 year overall survival and predictors of survival of patients with MM at the UCI from 01 January 2008 to 31 December 2012.ResultsThere were 119 (54.8%) males; the mean(SD) age of the study population at presentation was 59(12.8) years; 183(84.3%) patients presented with bone pain, and 135 (61.9%) had skeletal pathology; 186(85.3%) were HIV negative, and 152(70%) had Durie-Salmon stage III. The median overall survival was 2.5 years, (95% CI, 0.393–0.595); factors significantly associated with worse survival were Durie-Salmon stage III disease, HR=5.9, 95% CI (1.61 – 21.74; P=0.007) and LDH >225 U/L HR=3.3, 95% CI (0.57 – 5.92; P=0.029).ConclusionMost patients with multiple myeloma at the UCI were diagnosed at a relatively young age, presented with late stage disease and bone pain, and had a shorter survival time. Factors associated with worse survival were Durie-Salmon stage III and LDH >225 U/L.     

Extragenitourinary malakoplakia in a patient with myeloma clinically mimicking extramedullary myelomatous disease

Malakoplakia is a rare granulomatous disorder of unknown etiology and usually affects patients with underlying immunosuppression. This disorder usually involves the genitourinary tract but has been reported in a wide array of anatomical sites. We present a case of extragenitourinary malakoplakia, developing in a patient with a history of plasma cell myeloma, which clinically mimicked recurrent extramedullary myelomatous involvement. Radiologically, this lesion was a 10-cm soft-tissue mass located in the left flank and iliacus muscle. Excisional biopsy revealed a histiocytic infiltrate with histologic features diagnostic of malakoplakia. This case demonstrates the clinical and pathologic diagnostic challenges of malakoplakia arising outside the genitourinary tract. Given that it can closely mimic malignancy in such settings, malakoplakia should be considered in the differential diagnosis of soft-tissue masses developing in patients with hematologic malignancy and iatrogenic immunosuppression. This case highlights the importance for awareness on the part of clinicians, radiologists, and pathologists that malakoplakia can present as a soft-tissue mass.     

Digoxin-quinidine interaction in patients with renal failure

Summary Investigations were performed in order to study whether or not quinidine would exert similar effects on the serum digoxin concentration in patients with renal failure as in normal subjects. Fourteen out of fifteen patients showed a significant increase of the serum digoxin level after four days of quindine application. This indicates, that the quinidine effect is not solely caused by a decrease of the renal digoxin clearance, although nine patients, not being hemodialysed, revealed a correlation between their creatinine clearance and the rise of the serum digoxin concentration after quinidine. As however, the patients on hemodialysis did not show higher digoxin levels than those treated conservatively, it is suggested that the degree of the uremic intoxication might be responsible for the observed correlation.     

阿霉素诱导下多发性骨髓瘤细胞中自噬和氧化应激的相互作用

 目的: 探讨阿霉素(doxorubicin,DOX)诱导对多发性骨髓瘤细胞系RPMI-8226细胞内自噬和活性氧簇(reactive oxidative species,ROS)生成的影响及其相互作用关系。方法: 不同浓度阿霉素诱导RPMI-8226细胞24 h,采用Western blot技术检测细胞内beclin 1、LC3等自噬相关蛋白的表达水平。采用DCFH-DA荧光染色法检测RPMI-8226细胞内ROS的水平,荧光显微镜采集图像。采用氧自由基清除剂N-乙酰半胱氨酸(N-acetyl-L-cysteine,NAC)及tempol处理RPMI-8226细胞后,通过Western blot技术检测阿霉素诱导下细胞内beclin 1、LC3等蛋白的表达水平。采用自噬抑制剂3-甲基腺嘌呤(3-methyladenine,3-MA)处理PRMI-8226细胞后,检测阿霉素诱导下细胞内ROS和凋亡的表达水平。结果: RPMI-8226细胞内beclin 1和LC3Ⅱ/LC3Ⅰ表达水平呈阿霉素剂量依赖性增加,当阿霉素诱导浓度达2 mg/L时,与对照组比较显著增加(P<0.05)。采用2 mg/L阿霉素处理RPMI-8226细胞,通过荧光显微镜观察,ROS水平较对照组明显增加。氧自由基清除剂NAC和tempol处理RPMI-8226细胞后,beclin 1和LC3Ⅱ/Ⅰ的表达水平较阿霉素处理组下降。采用自噬抑制剂3-MA处理细胞后,RPMI-8226细胞内ROS和凋亡的水平较阿霉素处理组及对照组增加。结论: 阿霉素能增加RPMI-8226细胞内自噬和ROS的生成,抑制自噬能增加阿霉素诱导下ROS和凋亡的水平,抑制ROS后能减少阿霉素诱导下多发性骨髓瘤细胞中的自噬。     

Improved survival in multiple myeloma with renal failure

Forty-four myeloma patients with large tumour cell mass and impairment of renal function (S-creatinine greater than 2 mg/dl, stage III B) were studied. Seven patients, who received no active treatment, neither cytostatics nor plasmapheresis, survived for less than 1 month (median). Twenty-one patients who were treated with chemotherapy combination (M-2 protocol: melphalan, vincristine, BCNU, cyclophosphamide, prednisone) plus plasma exchanges for three days at the start of each 5-week cycle survived longer (median 17 months, p less than 0.01) than 16 patients who were treated with melphalan-prednisolone alone (median 2 months). However, better supportive care, dialysis, and improved antibiotic treatment may also have contributed to the improved results. It is concluded that intensive chemotherapy in full dosage, plasmapheresis, and active uremia treatment including dialysis should be considered in patients with advanced myeloma and renal failure.     

miRNA-181a对多发性骨髓瘤细胞增殖和迁移的作用

目的:通过沉默人多发性骨髓瘤细胞株RPM18226中miRNA-181a的表达,观察RPM18226细胞的增殖、迁移和细胞周期的变化,并探讨其可能的作用机制。方法:实时荧光定量PCR检测多发性骨髓瘤患者和健康者血清标本中miRNA-181a的表达水平;转染miRNA-181a inhibitor后,CCK-8法与集落形成实验检测细胞的增殖能力,划痕实验检测细胞的迁移能力,流式细胞术检测细胞的周期变化,Western blot法检测cyclin D1、p-PI3K和pAkt蛋白水平的变化。结果:多发性骨髓瘤患者血清中miRNA-181a呈高表达,显著高于正常人;转染miRNA-181a inhibitor后,RPM18226细胞的存活率和集落形成能力下降,迁移能力降低,G_0/G_1期细胞比例明显减少,S期细胞比例增多,cyclin D1蛋白表达显著低于正常对照组,PI3K和Akt的磷酸化水平明显低于正常对照组。结论:沉默miRNA-181a的表达能够抑制RPM18226细胞的增殖,并降低细胞的迁移能力,可能与细胞周期及PI3K/Akt信号通路有关。     

Prolonged reversible acute renal failure in focal glomerulonephritis with severe nephrotic syndrome in an elderly patient

Summary A clinical report of a 67-year-old woman who developed reversible acute renal failure due to focal glomerulonephritis with severe nephrotic syndrome is presented. The patient required four weeks' dialysis treatment but recovered completely. The role of temporary dialysis and diuretics on the clinical course and the reversibility of the process in old age is discussed.Abbreviations ARF Acute Renal Failure - Ccr Creatinine clearance - FGN Focal Glomerulonephritis - G.N. Glomerulonephritis - MCD Minimal change disease - N.S. Nephrotic syndrome     

Peroxidase-positive Auer bodies in plasma cells in multiple myeloma: a case report

Reports of clinical cases with Auer bodies in the plasma cells in multiple myeloma (MM) are rare; however, most of those reported contain peroxidase (POX)-negative Auer bodies rather than the POX-positive Auer bodies observed in myeloid progenitors, indicating differences in their chemical properties. Furthermore, the cases with POX-positive Auer bodies similar to those observed in myeloid cells are extremely rare in non-myeloid cells. Here, we report the clinical features, laboratory investigations, diagnosis and treatment of a case of MM with POX-positive Auer bodies in plasma cells and review related the literature to advance the prognostic evaluation, diagnosis and treatment of similar cases.     

含硼替佐米方案对多发性骨髓瘤患者出凝血功能及循环中微颗粒水平的影响*

 目的：研究采用含硼替佐米方案（PAD）诱导治疗的多发性骨髓瘤（MM）患者出凝血功能及循环中总微颗粒（TMPs）水平的变化特点。方法：使用流式细胞术检测38例新诊断MM患者和30例健康志愿者TMPs水平,观察MM患者PAD治疗前后血小板、凝血、抗凝、纤溶功能和TMPs的改变。结果：治疗前MM患者FVIII:C和vWF:Rco升高［(152.89±31.14)%和(165.69±38.43)%］;血小板聚集功能下降［(63.76±21.36)%］;PAI升高［3.98(1.63)U/mL］;TMPs较健康对照组升高［（640.65±214.22）μL vs （134.29±63.09)μL,P<0.01］,并与β2-MG正相关（r=0.672,P<0.01）。PAD治疗后,血小板聚集功能恢复［(77.83±15.62)%,P=0.01］;PAI异常得到纠正［0.88(1.38)U/mL,P<0.01］;TMPs也进行性下降,3疗程PAD后降至（184.25±93.35）/μL（P<0.01）。结论：MM患者本身具有血小板、凝血、纤溶异常和TMPs水平升高;PAD方案使疾病缓解同时恢复患者血小板功能,纠正纤溶异常,并降低TMPs水平,以上改变可能是采用含硼替佐米方案治疗的MM患者血栓发生率低的部分原因。     

Long-term survival in multiple myeloma: a single-center experience

In patients with multiple myeloma the median overall survival is now approaching 5 years, following the introduction of autologous stem cell transplantation and targeted therapies. However, patients receiving conventional chemotherapy who have survived 10 years or longer have been repeatedly reported in the literature. From 723 patients with multiple myeloma seen in our department from January 1981 to June 2007, we selected 21 long-term (>/=10 years) survivors (2.9%) who had been treated with conventional chemotherapy. Potentially favourable prognostic factors, common to most patients, were: age 相似文献