多发性硬化与多发性脑转移瘤的鉴别

 目的　探讨多发性硬化（MS）与多发性脑转移瘤的鉴别要点。方法　选择1例曾被误诊为多发性脑转移瘤且做了手术的MS病例，分析其误诊原因。结果　误诊原因为忽视了病史的重要性；对 MS早期表现缺乏认识；对MS的非脱髓鞘病变认识不足；对MS和多发性脑转移瘤在头颅MRI上的不同表现注意的不够全面；过分重视影像学检查，未将影像学的表现与临床情况结合起来分析；忽略了脑脊液常规检查项目。结论　临床遇到多发性脑转移瘤应想到与MS的鉴别。对难以鉴别的病例要深入检查,切忌贸然进行手术或放疗。     

Relapsed multiple myeloma

Opinion statement The treatment of relapsed multiple myeloma remains a challenge for clinicians. Most salvage therapies result in transient responses, with median survival from relapseranging from 6 to 18 months. No randomized trials comparing salvage therapies have been performed. In the absence of a “gold standard” salvage therapy, relapsed patients should be considered for clinical trials. In light of the recent observation that thalidomide alone brings about a 30% to 35% response rate with manageable toxicities, this is the most promising single agent available to treat relapsed disease. The maximum effective dose appears to be {dy400} mg/d; virtually all responses are evident within 2 months of starting therapy. Combination therapy of thalidomide with pulse dexamethasone or other chemotherapeutic agents has shown promise in pilot trials. Even with thalidomide-responsive disease, the response duration is brief, ranging from 3 to 6 months. Therefore, the authors recommend that patients under the age of 78 years who have acceptable physiologic organ function, chemotherapy-sensitive disease, third-party financial coverage, and adequate hematopoietic stem cells be considered for high-dose therapy with autologous hematopoietic stem cell transplant. High-dose therapy with hematopoietic stem cell transplant provides the highest response rate, response duration, and survival compared with historical controls treated with conventional therapy. Patients under the age of 70 years who have human leukocyte antigen-compatible donors should be considered for immune-based therapy using nonmyeloablative preparative regimens with allogeneic hematopoietic stem cell transplant.     

IgE multiple myeloma

IgE multiple myeloma is a rare disease characterized by a high frequency of Bence-Jones proteinuria and plasma cell leukaemia when compared to other isotypes of monoclonal proteins. Only 35 cases have been reported. We describe a 70-year-old woman with a stage III IgE kappa multiple myeloma presenting with a sacral plasmacytoma. Immunological and biochemical studies showed IgE kappa producing tumoral plasma cells. Serum total IgE was high without clinical symptoms suggesting an hyperIgE syndrome or mast cell activation. The patient underwent surgical removal of the sacral tumor and monthly melphalan-prednisone treatment together with intravenous pamidronate infusions. Magnetic Resonance Imaging (MRI) of the dorsolumbar spine revealed an epidural process leading to T6-T9 radiotherapy. Bone densitometry showed a decreased bone mineral content supporting the management of myeloma-related osteoporosis with bisphosphonate infusions. A good partial response with plateau-phase and increase of bone mineral content was achieved after 1 year of treatment and still persists after a 28 months follow-up.     

Treatment of multiple myeloma

The treatment of multiple myeloma has changed dramatically in the past decade. The increase in the number of active agents has generated numerous possible drug combinations that can be used in the first-line and relapsed settings. As a result, there is considerable confusion about the choice of regimens for initial therapy, role of transplantation in the era of new drugs, end points for therapy, and the role of maintenance therapy. A hotly debated area is whether treatment approaches should achieve cure or disease control, which impacts greatly on the treatment strategy employed. This article provides an update on the treatment of multiple myeloma, with a focus on recent advances, newly diagnosed disease, role of transplantation and maintenance therapy. A synthesized approach to the treatment of myeloma is presented, along with a discussion of key paradigms that need to be challenged.     

Daratumumab in multiple myeloma

The development of effective monoclonal antibodies for the treatment of myeloma has been a long journey of clinical and drug development. Identification of the right target antigen was a critical part of the process. CD38 as a target has been considered for some time, but clinically, daratumumab, a CD38 monoclonal antibody, was the first to be tested, and it has delivered the best clinical responses as a single agent to date. Its proven safety and efficacy in combination with other antimyeloma agents have led to several US Food and Drug Administration approvals for treating myeloma. Furthermore, the results of early trials in the induction therapy setting have demonstrated a beneficial role when it is added to the existing induction regimens. This review summarizes the importance of CD38 as a target and examines the clinical development of the CD38 monoclonal antibody daratumumab and its clinical significance in combination regimens in both patients with relapsed/refractory myeloma and patients with newly diagnosed myeloma.     

Lenalidomide in multiple myeloma

Current therapies for multiple myeloma include steroids, alkylating agents and high-dose chemotherapy with autologous stem cell transplant. These approaches are typically associated with initially good response rates, but they ultimately fail as a result of disease progression. New therapies that overcome resistance, lower toxicity and maintain remission are needed. Recent advances in the treatment of multiple myeloma include bortezomib and thalidomide. Lenalidomide (Revlimid^®) is an immunomodulatory drug that has undergone rapid clinical development in multiple myeloma and was recently approved by the US FDA for use in patients with relapsed disease. Clinical trials demonstrate that lenalidomide, particularly in combination with dexamethasone, produces durable clinical responses in patients with relapsed and refractory disease and is generally well tolerated, with manageable toxicities. This review summarizes the profile of lenalidomide and the current evidence for its efficacy in multiple myeloma.     

Complications of multiple myeloma

Multiple myeloma, also known as myeloma or plasma cell myeloma, is a progressive hematologic disease. Complications of multiple myeloma include renal insufficiency, hematologic complications (anemia, bone marrow failure, bleeding disorders), infections, bone complications (pathologic fractures, spinal cord compression, hyercalcemia), and neurologic complications (spinal cord and nerve root compression, intracranial plasmacytomas, leptomeningeal involvement, among others). This article reviews these various complications connected to multiple myeloma, examining their various causes and possible treatment.     

Thrombosis in multiple myeloma

Multiple myeloma, as with other malignancies, has been associated with the development of venous thromboembolic events. Chemotherapy or steroids in combination with antiangiogenic agents can further enhance this risk. The identification of measurable factors associated with this prothrombotic state could help in the selection of patients who need antithrombotic prophylaxis. Malignancy-associated thrombophilic state, paraprotein-specific mechanisms and treatment-induced changes can explain the high rate of thrombosis in this cancer population. While the release of inflammatory cytokines induces high levels of factor VIII, von Willebrand factor and downregulate the protein C system, elevated plasma immunoglobulin can impair fibrinolysis. Strategies of thromboprophylaxis with low molecular weight heparin, warfarin or aspirin in patients treated with thalidomide/chemotherapy or lenalidomide and dexamethasone have shown efficacy. Early data indicate that the effect of low molecular weight heparin on multiple myeloma is not confined to the anticoagulant effect but could extend to survival; a similar positive trend in overall survival has also been reported in patients treated with aspirin.     

Chemotherapy for multiple myeloma

The effects of eight different drug combinations were evaluated in 256 patients with multiple myeloma. The response rate and time to remission were superior from regimens that added both vincristine and Adriamycin (doxorubicin) to an alkylating agent-prednisone combination. There was no improvement in response rate or survival time from two alternating drug combinations evaluated in an attempt to achieve more marked tumor reductions and to delay the emergence of resistant subclones. The addition of levamisole during remission maintenance did not improve survival time. Results supported the utility of unmaintained remission follow-up in selected patients with marked reductions in myeloma cell mass.     

Lenalidomide in multiple myeloma

Current therapies for multiple myeloma include steroids, alkylating agents and high-dose chemotherapy with autologous stem cell transplant. These approaches are typically associated with initially good response rates, but they ultimately fail as a result of disease progression. New therapies that overcome resistance, lower toxicity and maintain remission are needed. Recent advances in the treatment of multiple myeloma include bortezomib and thalidomide. Lenalidomide (Revlimid) is an immunomodulatory drug that has undergone rapid clinical development in multiple myeloma and was recently approved by the US FDA for use in patients with relapsed disease. Clinical trials demonstrate that lenalidomide, particularly in combination with dexamethasone, produces durable clinical responses in patients with relapsed and refractory disease and is generally well tolerated, with manageable toxicities. This review summarizes the profile of lenalidomide and the current evidence for its efficacy in multiple myeloma.     

血管发生与多发性骨髓瘤

 多发性骨髓瘤（MM）是发生于骨髓的多灶性浆细胞肿瘤,尽管造血干细胞移植及新型靶向药物的应用延长了患者总体的生存率,但是由于内在或获得性化疗的耐药性,MM仍然是不可治愈的疾病。骨髓中MM细胞和骨髓间质细胞（SC）间的相互依存关系导致了一些具有血管生成潜能的细胞因子（VEGF、IL-6等）的过度增生,它们通过旁分泌或自分泌的途径促进MM细胞的生存和增生。有学者认为,血管发生是肿瘤生长和转移的前提,而丰富的临床前和临床资料证明了血管发生在MM中的重要性。对MM中与血管生成相关的细胞因子及具有血管生成抑制功能的新型药物进行概括,以更清楚地了解MM的发病机制和治疗靶向。     

血管发生与多发性骨髓瘤

多发性骨髓瘤(MM)是发生于骨髓的多灶性浆细胞肿瘤,尽管造血干细胞移植及新型靶向药物的应用延长了患者总体的生存率,但是由于内在或获得性化疗的耐药性,MM仍然是不可治愈的疾病.骨髓中MM细胞和骨髓间质细胞(SC)间的相互依存关系导致了一些具有血管生成潜能的细胞因子(VEGF、IL-6等)的过度增生,它们通过旁分泌或自分泌的途径促进MM细胞的生存和增生.有学者认为,血管发生是肿瘤生长和转移的前提,而丰富的临床前和临床资料证明了血管发生在MM中的重要性.对MM中与血管生成相关的细胞因子及具有血管生成抑制功能的新型药物进行概括,以更清楚地了解MM的发病机制和治疗靶向.     

Interferon and multiple myeloma

In vivo andin vitro studies are used to investigate interferon’s use treating human multiple myeloma.In vitro studies demonstrate that the production of monoclonal immunoglobulin by myeloma plasma cells is reduced by alpha interferon; furthermore, interferon alpha seems to inhibit myeloma cell lines development.In vivo studies using interferon in the treatment of multiple myeloma experimentally reproduced in mice show low percentages of mortality among mice treated with high doses of interferon as opposed to high mortality among those treated with low doses. Clinical trials to evaluate the interferon efficacy in the treatment of human multiple myeloma demonstrate that the therapy of previously untreated patients using interferon is not useful because the response rate is lower than that of chemotherapy. There is no homogeneity of results of combined chemotherapy plus interferon as induction treatment of previously untreated patients. Homogeneous results are also not obtained using interferon alone or in combination with chemotherapy as a second induction treatment of relapsed patients. However, interferon seems to be effective as maintenance therapy of a response obtained with previous chemotherapy.