多发性骨髓瘤影像学研究进展

多发性骨髓瘤（MM）是以骨髓中单克隆浆细胞恶性增殖为特征的血液系统肿瘤,常引起骨髓浸润和骨质破坏。X线平片是常用的影像学检查方法,可用于MM的Durie-Salmon分期及危险分层。目前CT、MRI、PET/CT和PET/MRI等先进的影像学技术已广泛应用于MM的诊断和治疗中,为准确分期、预后评估和疗效监测提供重要影像学依据。本研究对MM的影像学研究进展进行综述。     

Sodium measurements in multiple myeloma: two techniques compared

Sodium was determined by flame photometry and by direct potentiometry in 56 serum or plasma samples from 24 patients with multiple myeloma or macroglobulinemia. We observed differences between the two techniques as large as 17 mmol/L (12%). The flame-photometric values decreased relative to the direct-potentiometric values as protein increased or water content decreased. Moreover, the two sodium measurements could not be interconverted simply on the basis of correcting for protein or water content. There was significantly lower residual variance (p less than 0.005) when the direct-potentiometric sodium values were compared with the osmolality (corrected for the influence of glucose and urea nitrogen) than when the flame-photometric values for sodium were so compared. We conclude that direct potentiometric measurements of sodium in patients with multiple myeloma gives clinically relevant results but flame photometry does not. Clearly, the method by which sodium is measured in patients with multiple myeloma must be considered if results are to be interpreted correctly.     

3种实验技术在多发性骨髓瘤检测中的应用

目的评估形态学、免疫组化和流式细胞检测技术在多发性骨髓瘤(MM)检测中的应用价值。方法收集新乡医学院第一附属医院2013年9月至2014年5月MM患者30例,采用免疫组化和流式细胞术分析骨髓瘤细胞免疫表型,探讨其表达率与骨髓瘤细胞形态特征及相关检测指标的关系。3种检测方法组间差异采用配对样本t检验,率的比较用χ2检验。结果形态学检测瘤细胞比例在6.00%~95.00%,免疫组化检测瘤细胞比例在9.00%~88.00%,流式细胞检测瘤细胞比例在4.07%~87.42%。形态学与免疫组化、形态学与流式细胞之间差异有统计学意义(P0.05),免疫组化与流式细胞之间差异无统计学意义(P0.05)。结论流式细胞术、免疫组化与形态学3种技术相结合,更有助于MM的诊断及预后判断。     

Phagocytic myeloma cells in asymptomatic multiple myeloma

A newly observed case of asymptomatic multiple myeloma in which phagocytic myeloma cells were observed is described. Bone marrow aspirates contained 16% myeloma cells, 2% of which engulfed red blood cells, lymphocytes, and platelets. The possibility is discussed that phagocytizing ability may be one of the markers for malignant plasma cells. Nothing is so far known of the phagocytosis by plasma cells in benign monoclonal gammopathy which is strictly defined.     

多发性骨髓瘤与新生血管形成

尽管大剂量化疗和和造血干细胞移植提高了多发性骨髓瘤(MM)的完全缓解率,但其复发率高,是一种不可治愈的疾病。目前,研究新生血管形成尤其是血管内皮生长因子(VEGF)已经成为生物医学的焦点,由此产生的单克隆抗VEGF抗体bevazicumab等各类靶向药物,显示出显著的临床前和临床的抗肿瘤活性。已知浆细胞的累积可以诱导骨髓层面的基础血管形成,支持肿瘤细胞的生长,加速疾病的进展。这里,我们讨论肿瘤血管生成的机制,并总结现有的和潜在的抗MM血管生成剂,以寻求MM新的治疗方案。     

Velcade in multiple myeloma

AIM: To study efficacy of velcade therapy in patients with progressive or refractory multiple myeloma (MM). MATERIAL AND METHODS: From April 2005 to November 2006 velcade was used in therapy of 18 patients (11 females and 7 males) with progressive or refractory to prior standard therapy MM course. The patients' age median was 55 years (36 to 76 years). Velcade was injected intravenously on the course days 1, 4, 8 and 11 with interval 10 days between the courses. A total of 77 courses were made (median 4.5). RESULTS: Overall efficacy was assessed according to EBMT criteria in 16 (68%) patients. Partial remission (PR) was achieved in 9 patients, complete remission (CR)--in 1, minimal response (MR)--in 1 patient. Five patients failed the treatment. In 5 of 11 patients with confirmed efficacy of velcade the drug was used in induction of remission before high-dose chemotherapy (HDC) and autotransplantation of hemopoietic stem cells (HSC), in 3--as monotherapy, in 1--in combination with high-dose dexamethasone, in--with high dose dexamethasone and doxorubicin. Four patients achieved PR, one--MR. HSC were obtained before velcade therapy in one patient, in 4--after its conduction. After HDC there were one CR and 4 PR. Recovery of hemopoiesis after HDC took the same time as after standard induction therapy. In 6 of 11 patients HDC was not performed. Velcade therapy is continued in 2 patients, in 1 case with CR the treatment was stopped. In 3 cases PR for 2 to 6 months was followed by the disease progression. CONCLUSION: Velcade as a new effective antitumor drug can be used for treatment of progressive and refractory forms of MM.     

Anemia in multiple myeloma

Anemia is a common complication in patients with multiple myeloma (MM) and occurs in more than two thirds of all patients. The most frequent underlying pathophysiological mechanism is anemia of chronic disease (ACD), relative erythropoietin (EPO) deficiency (due partly to renal impairment) and myelosuppressive effects of chemotherapy, but many other factors may account for or contribute to anemia in myeloma. In patients who achieve complete remission after chemotherapy, anemia usually normalizes. Nonresponders and relapsing myeloma patients often continue to suffer from anemia. Treatment options for anemic myeloma patients include red blood cell (RBC) transfusions and recombinant human erythropoietin (rHuEPO). Red blood cell transfusions convey an immediate effect and rapidly increase the patient's hemoglobin level. Unfortunately, effects of RBC transfusions are only transient and can be associated with several risks, including infections and mild to even life-threatening immunologic reactions. rHuEPO is biologically equivalent to the human endogenous hormone EPO, and its application leads to an increase of hemoglobin levels over an extended time without the risks of blood transfusions. Several studies reported a significant improvement of erythropoiesis, reduction in transfusion need, and improved quality of life by using rHuEPO as long-term treatment of myeloma-associated anemia. Recently, an international expert panel recommended the use of rHuEPO for anemic myeloma patients where other possible causes of anemia have been eliminated.     

Carfilzomib in multiple myeloma

Introduction: Advances in drug therapy for multiple myeloma (MM) during the previous decade have improved survival outcomes; however, the disease remains incurable as patients eventually relapse or become refractory to all available therapies. Therefore, there is a clear need for more effective and well-tolerated treatments.

Areas covered: We review preclinical and clinical data regarding the use of carfilzomib, a proteasome inhibitor that is structurally and mechanistically distinct from bortezomib, for the treatment of MM patients. Carfilzomib pharmacokinetics, pharmacodynamics, efficacy, safety and tolerability are summarized, based on Phase I/II trial data.

Expert opinion: Carfilzomib represents a significant advance in the management of relapsed and/or refractory MM patients, including those intolerant or resistant to bortezomib. High response rates have been demonstrated with carfilzomib as a single agent or in combination with alkylating agents, immunomodulators and corticosteroids, even among patients who have failed multiple prior therapies. Carfilzomib also has significant potential in the frontline setting, with encouraging response and survival rates observed for combination regimens. Further evaluation of carfilzomib-containing regimens is ongoing in Phase III trials and investigator-sponsored studies, which include combinations with novel investigational agents. These findings will shape the future role of carfilzomib for MM patients across multiple settings.     

Nonsecretory multiple myeloma

Nonsecretory multiple myeloma (NSMM) is a rare variant of the classic form of multiple myeloma (MM) and accounts for 1% to 5% of all cases of MM. The clinical presentation and radiographic findings of NSMM and MM are the same. The diagnosis of MM requires the detection of a monoclonal gammopathy in the serum or urine. In NSMM, however, no such gammopathy can be demonstrated, making the diagnosis more difficult. We describe a 43-year-old African American woman who initially had back pain and pathologic vertebral compression fractures that were thought to be due to osteoporosis. Five months later, hypercalcemia developed and NSMM was diagnosed. No monoclonal gammopathy was found in the serum or urine, but skeletal survey showed diffuse osteolytic lesions, and bone marrow biopsy revealed marked plasmacytosis. The immunohistochemical techniques and chromosomal analysis methods that are currently available are discussed.     

Bone lesion in multiple myeloma

Bone destruction is a hallmark of multiple myeloma(MM). Almost all MM patients develop osteolytic bone lesions that can cause pathologic fractures and severe bone pain. Osteolytic lesions result from increased bone resorption due to osteoclast stimulation and decreased bone formation due to osteoblast inhibition. Plain radiography, CT, and MRI are established imaging techniques in MM. FDG-PET imaging is promising newer scanning technique under current evaluation. The aggressive features of MM bone lesions have significantly contributed to poor prognosis. Therefore, a systemic approach to analgesia, which includes radiotherapy and orthopedic intervention, must be applied as a part of the comprehensive care plan of MM patient. Bisphosphonates have been shown to reduce vertebral fractures and bone pain.