Early detection of the cardiotoxicity induced by chemotherapy drug through two-dimensional speckle tracking echocardiography combined with high-sensitive cardiac troponin T

正Objective To investigate the clinical value of twodimensional speckle tracking echocardiography(2DSTE)combined with high-sensitive cardiac troponin T(hs-cTnT)in early detection of the cardiotoxicity induced by chemotherapy drug.Methods Seventy-five non-Hodgkin's lymphoma patients who received the     

Role of mtDNA lesions in anthracycline cardiotoxicity

Doxorubicin (adriamycin) is an effective drug in the treatment of many malignancies. Its prolonged use is, however, limited by an irreversible, dose-dependent and progressive cardiomyopathy, which may become evident even years after completion of therapy. Data from rats and humans show that oxidative phosphorylation is impaired rapidly after acute doxorubicin-exposure. Such respiratory chain dysfunction is known to enhance the production of reactive oxygen species and may lead to quantitative and qualitative injury of mitochondrial DNA (mtDNA) and its encoded respiratory chain subunits. MtDNA depletion, mtDNA mutations and respiratory defects then accumulate with time also in the absence of continued anthracycline exposure. Chronic cardiotoxicity then manifests, when the bioenergetic capacity of the organelles is severely impaired. The mitochondrial damage in late-onset doxorubicin cardiomyopathy is heart specific and not found in skeletal muscle. DOXO-EMCH, a 6-maleimidocaproyl hydrazone derivative of doxorubicin has evolved from the search for less cardiotoxic anthracyclines. At equieffective antitumor doses, DOXO-EMCH has a substantially lower heart toxicity than free doxorubicin.     

左心室心肌做功在乳腺癌患者蒽环类化疗药物心脏毒性评价中的应用价值

目的 探讨二维斑点追踪成像(2D-STI)技术新参数左心室心肌做功在乳腺癌患者蒽环类药物化疗后心脏毒性评价中的应用价值.方法 选取2018年12月至2019年9月在苏北人民医院首次接受化疗的40例患者为化疗组,另选取正常健康者20例作为对照组.应用2D-STI技术测量左心室整体长轴应变(GLS)及整体心肌做功参数,比较...     

Prolonged viremia in dengue virus infection in hematopoietic stem cell transplant recipients and patients with hematological malignancies

Fever, skin rash, headache, and thrombocytopenia are considered hallmarks of dengue infection. However, these symptoms are frequently observed in infectious and non‐infectious complications of hematopoietic stem cell transplant recipients and oncohematological patients. Thus, laboratory confirmation of dengue is relevant for prompt intervention and proper management of dengue in endemic and non‐endemic regions. Because no prospective study of dengue has been conducted in these populations, the actual morbidity and mortality of dengue is unknown. In the present series, we describe five cases of dengue in patients living in endemic areas, emphasizing the prolonged course of the disease and the occurrence of prolonged viremia.     

自噬在蒽环类药物引起的心脏毒性中的作用的研究进展

在临床中,化疗相关的心脏毒性越来越受到关注,这常常阻碍癌症的最佳治疗.蒽环类药物(AC)是最常用的抗癌药物,它对血液系统恶性肿瘤非常有效.现代成像技术虽可识别出有AC引起的心脏毒性(AIC)风险的患者,但在治疗上效果欠佳,部分原因是AIC的分子机制仍不完全清楚.虽然AIC最初被归因于细胞氧化应激所触发,但抗氧化剂不能预...     

Repetitive dobutamine stress echocardiography for the prediction of anthracycline cardiotoxicity.

AIMS: To evaluate whether repetitive assessment of systolic and diastolic cardiac function by dobutamine stress echocardiography (DSE) can predict anthracycline cardiotoxicity. METHODS AND RESULTS: Thirty-one patients (age, 57+/-13 years, 22 male) were studied before chemotherapy, with follow-ups during, at the end, and 6 months after chemotherapy. Left ventricular (LV) function was assessed by two-dimensional (2D) echocardiographic wall motion score index (WMSI) and by Doppler echocardiography of mitral valve inflow at rest and during DSE. Radionuclide ventriculography was used as an independent reference for ejection fraction (EF). A reduction of EF >/=5% occurred in 17 patients (group A) at the last follow-up. Patients without decreased EF comprised group B. Early/late diastolic velocity of mitral inflow (E/A ratio) at rest was lower in group A (0.91+/-0.2 vs 1.28+/-0.3, P<0.001), and it was an independent predictor of cardiotoxicity (adjusted for baseline patient characteristics and parameters of systolic and diastolic function). At follow-up, WMSI at rest paralleled radionuclide EF. Contractile reserve at low-dose DSE was preserved in group A. CONCLUSIONS: WMSI measured by 2D echocardiography parallels radionuclide EF at follow-up. Assessment of contractile reserve has no incremental value for the early detection of cardiotoxicity. A baseline abnormal E/A ratio is an independent predictor of anthracycline cardiotoxicity.     

Lethal infections in patients with hematological malignancies

Abstract: The hospital files of 410 patients with hematological malignancy treated at our clinic between 1977 and 1990 were reviewed to determine the importance of infections as a cause of death. The total number of infections was 203 (49.5%). A microbiologically documented infection was detected in 27.3%, a clinically documented infection in 9.5% and a possible infection in 12.7% of the patients. Gram-positive bacteria were responsible for 25.9%, gram-negative bacteria for 31.3%, anaerobic baeteria for 2.7%, viruses for 4.5% and fungi for 25.9% of the microbiologically documented infections. Of 29 systemic fungal infections only 2 were diagnosed before the patients died. The remaining diagnoses rested on autopsy findings. Empiric antifungal therapy was introduced in 1983; still, 74.2% of systemic fungal infections in 1977–1990 were detected after 1982. Patients with a verified infection had statistically significantly higher CRP concentrations than patients who died of other causes (152 mg/l vs. 117.5 mg/l, p = 0.018). We conclude that infection is a significant cause of death in patients with these diseases. The number of systemic fungal infections is increasing, despite the widespread use of antifungal medication and thus better diagnostic methods and more effective treatment are needed. –     

Copper levels in patients with hematological malignancies

BackgroundCopper levels are elevated in cancer patients compared to normal subjects. However, few studies have investigated the relationship between copper and hematological malignancies.Methods84 patients with hematological diseases were studied, along with 50 healthy individuals. Copper was measured by flame atomic absorption spectrometry. The patients were classified to 2 homogeneous groups, acute and chronic hematological neoplasms, respectively. For the patients with acute hematological malignancies, relapse and remission were investigated in relation to serum copper levels. For chronic hematological neoplasms, serum copper was connected either with stable or progressive disease. Zeta-chain-associated protein kinase 70 (ZAP70) and CD38 expression, along with the unmutated VH immunoglobulin genes (IgVH) status were also determined for the 22 chronic lymphocytic leukemia (CLL) patients.Results54 patients with relapse or progressive disease had elevated copper levels (mean value 1.8 mg/l), whereas 30 patients either in remission or in stable disease had normal copper levels (mean value 1.01 mg/l) (normal range 0.8–1.3 mg/l).ConclusionHence, our study indicates that serum elevated copper levels are associated with hematological malignancies either in relapse or in disease progression, whereas normal copper levels are linked with hematological neoplasms in remission or in stable disease. Furthermore, we report for the first time an association between high serum copper levels and several adverse prognostic markers in CLL, such as increased expression of ZAP70 and CD38, along with elevated percentage of unmutated IgVH.     

An introduction to the metabolic determinants of anthracycline cardiotoxicity

Antitumor therapy with doxorubicin and other anthracyclines is limited by the possible development of cardiomyopathy upon chronic administration. Several lines of evidence suggest that a close link exists between cardiotoxicity and the amount of anthracycline that accumulates in the heart and then undergoes one- or two- electron reduction to toxic metabolites or by-products. Alternative metabolic pathways lead to an oxidative degradation of anthracyclines, possibly counteracting anthracycline accumulation and reductive bioactivation; unfortunately, however, the actual role of anthracycline oxidation is only partially characterized. Here, we briefly review the biochemical foundations of reductive versus oxidative anthracycline metabolism. We show that multiple links exist between one pathway of toxic biactivation and another, limiting the search and clinical development of “better anthracyclines” that retain antitumor activity but induce less cardiotoxicity than the available analogues.     

Bridging the gap in hematological malignancies

After the success of the BTG Series in Singapore in 2010 and 2011, meeting organizers held the 3rd International Hematologic Malignancies Conference in Hong Kong. Held on 23-25 February, the BTG meeting provided an opportunity to further scientific discourse in the Asia-Pacific region. Featuring the world-renowned medical faculty and an abundance of discussion forums, the conference provided attendees the opportunity to interact with field leaders and exposed them to the latest research. The BTG conferences focus on hematologic malignancies, especially leukemia, lymphoma and myeloma. The BTG series provides an exceptional platform for the exchange of ideas for the Asia-Pacific hematology oncology healthcare community. It offers many novel opportunities for practicing physicians as well as fellows in training to meet with the world thought leaders. The annual conference brings together key opinion leaders from the Asia-Pacific region, the USA and Europe. The underlying motto is to bring the continents together and generate a global community in the quest against cancer. BTG recognizes the contributions of the Asia-Pacific physicians who are among the world leaders and gives the younger generation opportunities to present their work in a world arena.     

Treatment of hematological malignancies with monoclonal antibodies

The success of rituximab, the first monoclonal antibody ever licensed for the treatment of a human malignancy, has not only increased survival and cure rates in many non-Hodgkin lymphomas of the B-cell type, but has prompted an explosion in the development of novel antibodies and biologically active substances with specific cellular targets ("targeted therapy") both in the field of hematological malignancies and solid tumors. The chimeric anti-CD20 monoclonal antibody rituximab is the first drug that was shown to increase overall survival in follicular lymphomas and to cut lymphoma-associated deaths in patients with CD20+ aggressive lymphomas into half. In this review the current role of monoclonal antibodies in the treatment of different hematological neoplasms will be discussed and perspectives for their future use in leukemia and lymphomas will be shown.     

Evaluation of a polymorphism in MYBPC3 in patients with anthracycline induced cardiotoxicity

Cardiotoxicity is the most serious side effect of anthracyclines (doxorubicin, daunorubicin or epirubicin). The incidence of anthracycline induced late cardiac toxicity (AIC) that is overt clinically is 3–5% in the Indian population. Polymorphism in intron 32 (deletion of 25 bp) of MYBPC3 has been shown to be present exclusively in Asians and more so in South India (3–8%). The frequency of the polymorphism is significantly higher (13%) in patients with cardiomyopathy in India. Fifteen patients were identified to have cardiac dysfunction following treatment for malignant lymphoma with doxorubicin containing regimens. Peripheral blood DNA from control, amplified by polymerase chain reaction yielded a 467 bp fragment while in the presence of the 25 bp deletion only a 442 bp fragment was detected. To confirm the presence or absence of the polymorphism, amplified DNA was restricted using Bgl1 in all samples. Bgl1 restricted amplified DNA only if the 25 bp deletion was absent. A 467 base pair band was observed in all the 15 samples, which suggested the absence of polymorphism in MYBPC3. In a sample of DNA from a patient with a deletion in exon 33 (confirmed by sequencing) a 442 bp fragment was detected. Amplified DNA from this patient was not restricted with Bgl1. Wild type MYBPC3 when amplified gave a distinct restriction banding pattern consisting of two bands of 401 bp and 66 bp. Amplified DNA from all peripheral blood samples restricted with Bgl1 suggesting the absence of the polymorphism. In this preliminary report, MYBPC3 does not seem to play a role in anthracycline induced cardiotoxicity.     

Rasburicase for the treatment of tumor lysis in hematological malignancies

Tumor lysis syndrome (TLS) is a common oncologic emergency in patients with hematological malignancies sensitive to cytotoxic treatment that present a high proliferative rate. High proliferative cancer rate, high sensitivity of cytotoxic treatment and renal failure represent risk factors for development of TLS. TLS is also responsible for several electrolytic alterations, such as hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. There are different established therapeutic options for the treatment of TLS such as hydration, allopurinol and rasburicase. Rasburicase reduces uric acid levels within 4 h, both in pediatric and adult patients, catalyzing the oxidation of uric acid into allantoin, rapidly excreted by the kidneys. Rasburicase is well tolerated and was approved in the EU and in the USA for the management of acute hyperuricemia.     

Dendritic cell-based immunotherapy for the treatment of hematological malignancies

Dendritic cells (DCs) are professional antigen-presenting cells and are frequently used in current immunotherapy protocols. The administration of DCs loaded with tumor-associated proteins or peptides results in the induction of immune responses against different types of malignant cells. Methods for large-scale generation of DCs in a sufficient quality and quantity have permitted their use in clinical experiments. DC-based vaccines have already shown promise in follicular non-Hodgkin's lymphoma, and to some extent, in other hematological malignancies. Several strategies have been developed to boost their potency as a new and relatively non-toxic treatment modality. Our review focuses on clinical trials using DCs in the treatment of hematologic malignancies and on recent studies of the immunophenotype, development, and maturation of DCs may have an important impact on designing DC-based antitumor vaccines.