Acute tumor lysis syndrome in a hemodialysis patient with diffuse large B cell lymphoma

Acute tumor lysis syndrome (TLS) is a life-threatening complication of cancer therapy requiring prompt recognition and aggressive management. It occurs particularly in patients with lymphoproliferative disease during potent myelosuppressive therapy. To our knowledge, acute TLS in end-stage renal disease (ESRD) patients with malignancy is extremely rare and has never been reported in English literature. We report the first case of acute TLS in an ESRD woman with diffuse large B cell lymphoma after chemotherapy. Aggressive treatments with daily hemodialysis and allopurinol rather than hydration benefit the patient. There is neither optimal therapy in treating ESRD patients with TLS nor adequate guidelines for how to adjust the chemotherapy drug in hemodialysis patients. This case provides our experience to clinician how to treat acute TLS in ESRD patients.     

侵袭性T细胞非霍奇金淋巴瘤的化疗

T细胞非霍奇金淋巴瘤是一组具有独特临床和病理特征的疾病,与B细胞淋巴瘤相比,侵袭性更强,化疗敏感性差。为探索有效的治疗方案,近年来,新的药物如吉西他滨、靶向药物联合化疗及高剂量化疗联合造血干细胞移植被研究用于治疗T细胞淋巴瘤,并取得了一些进展。     

A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma

Lenalidomide is an oral non-chemotherapy immunomodulator with direct and indirect effects on non-Hodgkin lymphoma (NHL) cells and with single-agent activity in relapsed/refractory aggressive and indolent B-cell NHL, including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma, and follicular lymphoma. Based on the pivotal phase II MCL-001 trial of lenalidomide in heavily pretreated patients with relapsed/refractory MCL, lenalidomide was approved by the US Food and Drug Administration for the treatment of relapsed/refractory MCL after failure of two prior therapies, one of which includes bortezomib, at a recommended starting dose of 25 mg on days 1–21 of each 28-day cycle. Lenalidomide enhanced the survival benefit in combination with rituximab in preclinical models, prompting clinical evaluation of the lenalidomide–rituximab (R2) combination. In phase II trials, lenalidomide 20 mg on days 1–21 in combination with different standard-dose rituximab schedules exhibited promising activity in both first-line and relapsed/refractory disease across multiple B-cell NHL subtypes. The feasibility of combining lenalidomide with immunochemotherapy, including R-CHOP and rituximab–bendamustine, has been demonstrated in phase I/II trials. These latter regimens are currently being evaluated in ongoing phase II and III trials. The role of lenalidomide monotherapy and R2 in maintenance therapy is also being examined. Based on available evidence, a comprehensive review of lenalidomide in all treatment phases of B-cell NHL—relapsed/refractory disease, first-line, and maintenance—is presented here.     

Diffuse large B-cell lymphoma with MYC gene rearrangements: Current perspective on treatment of diffuse large B-cell lymphoma with MYC gene rearrangements; case series and review of the literature

In the past decade, patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. Standard treatment is now changing as a result of deeper understanding of underlying biologic differences of such lymphomas. One of the most powerful predictors of an adverse outcome on R-CHOP therapy is the presence of a MYC gene rearrangement (MYC+ lymphoma). Determination of MYC gene rearrangement by FISH (fluorescent in situ hybridisation) has recently become a standard diagnostic procedure.In this paper, an overview of current literature on MYC function and MYC+ lymphoma patient outcome is presented. Furthermore, we present 26 patients from our tertiary referral centre who were diagnosed with MYC+ lymphoma between 2009 and 2014. In our patient series, we confirm the dismal prognosis of MYC+ lymphoma patients. Intensification of classical chemotherapy does not lead to better overall survival, justifying new treatment modalities. First line therapy should be more specifically targeted against MYC and the genes and proteins that are deregulated by MYC. To this end, the first clinical trial in which MYC+ patients will be offered targeted treatment has recently been launched.     

Bendamustine plus rituximab for relapsed or refractory diffuse large B cell lymphoma: a retrospective analysis

For patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) who are not eligible for intensive chemotherapy because of comorbidities, advanced age, or relapse after heavy salvage regimens, treatment options are very limited and prognosis is poor. We retrospectively analyzed 29 patients with relapsed/refractory DLBCL treated with combination bendamustine plus rituximab (BR) between July 2010 and January 2014 to evaluate overall response rate (ORR), progression-free survival (PFS), duration of response (DOR) and treatment safety. Twenty-eight patients were available for this analysis. ORR was 50% (14 patients), with 39.3% CR (11 patients), and 10.7% PR (3 patients). SD was reported in 2 patients (7.2%) and PD in 12 patients (42.8%). At the median follow up of 8 months (range 1–37.4 months), the median PFS was 8 months for all patients (95% CI 5.5–26.6). The median DOR was 24.7 months (95% CI 3.2–24.7). Grade 3/4 toxicity observed included hematologic events: lymphopenia (42.8%), neutropenia (32.1%), anemia (17.2%), and thrombocytopenia (14.2%). BR can be considered to have a role in the treatment of patients with relapsed/refractory DLBCL with limited therapeutic options, in that it can induce long-term remission in some patients with an acceptable toxicity profile.     

Chemotherapy and echocardiographic indices in patients with non-Hodgkin lymphoma: the ONCO-ECHO study

The cardiotoxicity of chemotherapy (CTx) for non-Hodgkin’s lymphomas is not well recognized. In order to facilitate individual risk counseling for patients, we analyzed the effect of CTx on echocardiographic indices in regard to clinical data in patients treated for non-Hodgkin’s lymphoma (NHL). A prospective multicenter ONCO-ECHO trial included 67 patients with NHL (45 patients with DLBCL (diffuse large B cell lymphoma) and 22 with non-DLBCL). Patients received standard CTx, primarily R-CHOP, CHOP, R-COP and COP regimens. Clinical data and echocardiographic indices were obtained at baseline, 3-, 6- and 12-month follow-up. The primary end point representing CTx cardiotoxicity was defined as a ≥ 10% decrease in the left ventricular ejection fraction (LVEF) during 12-month observation. In a 12-month follow-up five (7.5%) deaths occurred, while no clinical manifestations of heart failure were reported. There was an increase in left ventricular end-systolic diameter (p = 0.002) and E/e′ index (p = 0.036) in 12-month observation. Preexisting coronary artery disease was associated with significant decrease in the ΔLVEF (p = 0.008), increase in ΔLVEDV (p = 0.03) and ΔLVESV (p = 0.02) and increase in the Δ left atrium diameter (p = 0.02); while history of arterial hypertension was related to significant decrease in the ΔLVEF (p = 0.039), diabetes mellitus was related to significant increase in the ΔE/e′ index (p = 0.002). The primary end point was reported in ten (14.9%) patients. There were no independent risk factors for cardiotoxicity in the study population. Chemotherapy administered to NHL patients may induce dilatation and impaired LV diastolic function. Standard cardiovascular risk factors may predispose patients to negative LV remodeling.     

利妥昔单抗靶向治疗非霍奇金淋巴瘤中存在的问题

随着第一个单克隆抗体——利妥昔单抗被美国FDA批准用于治疗CD20^＋的B细胞淋巴瘤以来,分子靶向治疗已有十余年历史。与传统的放化疗相比,靶向治疗由于选择性高,不良反应较少,改善患者的预后和生存质量明显,而成为一种非常有前景的治疗方法。近十余年来,新的靶向治疗药物不断出现,治疗领域不断扩展,对靶向治疗的认识也在不断地加深。     

Breast implant-associated anaplastic large cell lymphoma: A comprehensive review

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognized non-Hodgkin lymphoma of T-cell origin. Despite the low incidence of this new disease, the increasing use of breast implants for cosmetic or post-mastectomy reconstruction purposes places BIA-ALC as an emerging and compelling medical challenge. The real BIA-ALCL pathogenesis has not been fully uncovered so far, while different putative causal factors have been proposed. Breast implants with textured surfaces seem to be associated with nearly all cases of BIA-ALCL, while the real the risk of disease development has not been well estimated so far. Late onset, persistent seroma around breast implant represents the classical clinical presentation. Most of the BIA-ALCL patients presents with localized disease, which confers an excellent prognosis. Unlike other non-Hodgkin lymphomas, surgical excision of the mass has a key role in the treatment. For patients with advanced and disseminated diseases, the treatment did not differ from other types of T-cell lymphoma. For these reasons, BIA-ALCL represents an emerging disease which requires multidisciplinary team approach to well define diagnostic workup and treatment for each patient. This review article aims to summarize available data on BIA-ALCL. First, we will outline available data on BIA-ALCL epidemiology, pathogenesis, diagnostic work-up, and treatment. Second, we will point out the potential psychological implications as well as the risk of perception distortion for women with breast implants, especially for those with previous breast cancer. Lastly, we will summarize the current national recommendations regarding textured breast implants and discuss the diagnostic-therapeutic algorithm for BIA-ALCL management.     

Reliability of serum 1,3‐beta‐d‐glucan assay in patients undergoing renal replacement therapy: a review of the literature

The serum 1,3‐beta‐d ‐glucan (BDG) test is a pan‐fungal serum marker considered to detect the majority of pathogenic fungi, including Aspergillus spp. and Candida spp. For this review we searched for publications dealing with serum BDG levels in patients undergoing renal replacement therapy (RRT). The influence of various different membrane materials used for RRTs in these publications on serum BDG has been reviewed. We found that unmodified cellulose containing membranes increased the serum BDG levels highly, whereas conflicting results have been observed for modified cellulose containing materials. Synthetic materials (e.g. polysuflone) had no influence on serum BDG levels in the majority of the reviewed publications.     

氟达拉滨联合异环磷酰胺治疗复发性惰性非霍奇金淋巴瘤临床观察

 目的 观察氟达拉滨联合异环磷酰胺治疗复发性惰性非霍奇金淋巴瘤（NHL）的临床疗效。方法 30例复发性惰性NHL患者分为两组。16例用COP方案（环磷酰胺600 mg·m-2·d-1,静脉滴注,第1、8天;长春新碱1.5 mg·m-2·d-1,静脉推注,第1、8天,泼尼松1 mg·kg-1·d-1,连续口服2周为1疗程）治疗至少3个疗程。14例用FI方案（氟达拉滨30 mg·m-2·d-1,静脉滴注,第1天至第5天;异环磷酰胺1.2 g·m-2·d-1,静脉滴注,第1天到第5天为1疗程）治疗至少3疗程。结果 16例用COP方案的患者中,CR3例,PR5例,有效率50.0 %。14例用FI方案的患者中CR6例,PR6例有效率85.7 %。两组有效率比较差异有统计学意义（P＜0.05）。两组患者治疗后的主要不良反应是骨髓抑制,FI方案发生粒细胞减少者为71.4 %,COP方案为68.7 %。结论 FI方案治疗复发惰性NHL的近期疗效较COP方案更好,患者具有较好的耐受性。     

A comprehensive review of protein kinase inhibitors for cancer therapy

Introduction: Protein kinases are involved in various cellular functions. About 2% of the human genome encodes for protein kinases. Dysregulation of protein kinases is implicated in various processes of carcinogenesis. The advent of protein kinase inhibitors in cancer therapy has led to a paradigm shift in cancer therapy. Several protein kinase inhibitors have been approved by FDA in the last few decades.

Areas covered: This article provides a review of the FDA approved protein kinase inhibitors as of December 2017 for the well-known oncogenic protein kinases. A list of FDA approved protein kinase inhibitors and their FDA approved clinical indications were cataloged. The role of the respective oncogenic protein kinases in carcinogenesis and cancer progression and the relevant landmark clinical trials of respective protein kinase inhibitors leading up to the FDA approval were PubMed searched and discussed.

Expert commentary: Further understanding of the molecular origin of various cancers would help identify new targets. Use of biomarker profiling might select the patient population that would benefit better from kinase inhibitors. Clinical trials should be designed to identify the appropriate sequence of the available kinase inhibitors. It would prove to be useful to test these drugs in the adjuvant setting.     

A microRNA signature profile in EBV+ diffuse large B-cell lymphoma of the elderly

Currently, there is no characteristic microRNA (miRNA) expression pattern in Epstein-Barr virus⁺ diffuse large B-cell lymphoma of the elderly (EBV⁺DLBCLe). This study aims to characterize a signature profile and identify miRNAs that can be used as biomarkers and alternative therapeutic targets for EBV⁺DLBCLe. Seventy-one DLBCL patients aged 50 years and older were included and four EBV⁺ and four EBV– samples were analyzed in two miRNA array platforms (pilot study). A larger multicenter cohort (29 EBV⁺DLBCLe and 65 EBV–DLBCL patients) was used to validate the results by real-time polymerase chain reaction. In the pilot study, 9% of DLBCL were EBV⁺DLBCLe by in situ hybridization. In multicenter study, EBV⁺DLBCLe group showed a predominance of non-germinal center B-cell origin. Overall survival duration of EBV⁺DLBCLe was significantly inferior to that of EBV–DLBCL patients. We found 10 deregulated miRNAs in the two groups, but only seven were statistically different. We confirmed overexpression of hsa-miR-126, hsa-miR-146a, hsa-miR-146b, hsa-miR-150, and hsa-miR-222 and underexpression of hsa-miR-151 in EBV⁺DLBCLe cases compared to EBV–DLBCL cases. Hsa-miR-146b and hsa-miR-222 showed high specificity for identifying EBV⁺DLBCLe. The present study proposed a miRNA signature for EBV⁺DLBCLe and our findings suggest that hsa-miR-146b and hsa-miR-222 could be biomarkers and therapeutic targets.     

Anemia Is a Novel Predictive Factor for the Onset of Severe Chemotherapy-Induced Peripheral Neuropathy in Lymphoma Patients Receiving Rituximab Plus Cyclophosphamide,Doxorubicin, Vincristine,and Prednisolone Therapy

Chemotherapy-induced peripheral neuropathy (CIPN) frequently occurs in lymphoma patients receiving R-CHOP, a drug combination therapy. Although severe CIPN may lead to reduction and/or discontinuation of the medication, predictive factors of CIPN have not been investigated sufficiently to date. We performed a retrospective exploratory research to determine associations between prevalence of severe CIPN and sociodemographic data, health characteristics, and medical conditions such as anemia at initial diagnosis. Forty patients (indolent lymphoma, n=9; diffuse large B-cell lymphoma; n=31) received R-CHOP therapy from September 2009 to July 2014. The median age of patients was 58 years (range=27–76 years). Statistical analyses were applied to the patients, who were divided into two groups: mild CIPN (no symptoms or grade 1 according to the CTCAE version 3.0 program) and severe CIPN patients (grade 2 or higher). Forward stepwise logistic regression analyses were performed using the following variables: sex, BMI, BSA, hyperglycemia, malnutrition, and anemia. Severe CIPN occurred in seven patients (17.5%). Gender and anemia remained following the stepwise procedure, and anemia predicted severe CIPN significantly (OR=19.45, 95% confidence interval=1.52–171.12). Our study suggests that anemia at initial diagnosis could be a predictive factor of R-CHOP-induced CIPN.     

Sorafenib联合化疗治疗进展期肾癌Ⅱ期临床研究

[目的]探讨Sorafenib联合吉西他滨、5-Fu治疗晚期肾细胞癌的疗效及安全性。[方法]入组转移性肾细胞癌患者19例，其中既往细胞因子治疗失败者15例。化疗方案采用吉西他滨1g／m^2，d1.8,5-Fu 400mg／m^2静脉推注d1，随后5-Fu 2．1g／m^2 46h化疗泵泵入，每4周为1个周期。同时Sorafenib治疗，400mg／次，口服，2次／d，持续使用至疾病进展或出现不可耐受的毒副反应。[结果]19例患者均可评价疗效。客观有效率37％（7／19），临床受益率79％（15／19）。6个月的PFS百分比为37％（7／19），并且该7例患者目前均无疾病进展。常见毒副作用为Ⅲ-Ⅳ度的骨髓抑制、Ⅱ度以上的手足综合征、Ⅱ度以上的胃肠道反应、Ⅱ度以上的皮疹、Ⅰ-Ⅱ度脱发、Ⅰ-Ⅱ度高血压。[结论]研究提示Sorafenib联合吉西他滨．5-Fu治疗晚期肾细胞癌表现出了较好的疗效和一定的安全性。     

Immune mechanisms in non-Hodgkin lymphoma: joint effects of the TNF G308A and IL10 T3575A polymorphisms with non-Hodgkin lymphoma risk factors

Two common single nucleotide polymorphisms in immunoregulatory genes (TNF G308A, rs1800629 and IL10 T3575A, rs1800890) have been recently reported as risk factors for non-Hodgkin lymphoma (NHL) in a large pooled analysis. We systematically investigated the effects of other established NHL risk factors in relation to the tumor necrosis factor (TNF) G308A or interleukin 10 (IL10) T3575A genotypes. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) from 1,172 cases and 982 population-based controls in a U.S. multicenter study. We investigated NHL overall and two common subtypes [diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma]. NHL risks were increased among those with both an autoimmune condition and the TNF G308A GA/AA (OR(NHL), 2.1; 95% CI, 1.0-4.2) or the IL10 T3575A TA/AA genotype (OR(NHL), 1.6; 95% CI, 0.9-2.6) compared with individuals without an autoimmune condition and with the common TNF G308A GG or IL10 T3575A TT genotype, respectively; results were similar for DLBCL and follicular lymphoma. We found that elevated DLBCL risk associated with last-born status was more pronounced among those with TNF G308A GA/AA (OR(DLBCL), 2.7; 95% CI, 1.1-6.4) or IL10 T3575A TA/AA (OR(DLBCL), 2.9; 95% CI, 1.6-5.2). Similarly, elevated DLBCL risk associated with obesity (body mass index, > or = 35 versus <25 kg/m(2)) was observed only among those with TNF G308A GA/AA (OR(DLBCL), 2.5; 95% CI, 1.1-5.7) or IL10 T3575A TA/AA genotypes (OR(DLBCL), 2.0; 95% CI, 1.1-3.5). These exploratory results require replication but provide evidence that autoimmune conditions, late birth order, and obesity act partly through a common inflammatory pathway, posing a greater risk to individuals with variant TNF and IL10 genotypes than those with wild-type alleles.     

盐酸吉西他滨治疗复发性或难治性非霍奇金淋巴瘤

目的：观察盐酸吉西他滨联合顺铂（DDP）、强的松（PDN）对复发性或难治性进展型非霍奇金淋巴瘤的疗效和毒副反应。方法：盐酸吉西他滨1000mg/m^2,d1,d8，静脉滴注；DDP 25mg/m^2，d1-3，静脉滴注；PDN 60mg/m^2,d1-5，口服。以3－4周为一个化疗周期。15例复发性或难治性进展型非霍奇金淋巴瘤患者，疗程不少于3个周期。结果：15例患者中，11例获得缓解，占73．3％。其中完全缓解（CR）5例，部分缓解（PR）6例。6例具有B类症状的患者中，4例症状消失，1例明显改善，1例无改善。化疗毒副作用主要为轻度的胃肠道反应，极少数患者出现严重的骨髓抑制。结论：盐酸吉西他滨联合DDP、PDN对复发性或难治性进展型非霍奇金淋巴瘤有较好的近期疗效，能明显改善患者症状，且大部分患者可以承受其毒性，是一个值得进一步验证的补救性化疗方案。     

化疗联合CIK细胞回输治疗转移性肾细胞癌Ⅱ期临床研究

[目的]探讨化疗联合CIK细胞回输治疗转移性肾癌的疗效。[方法]40例mRCC患者，采用GEM＋5-Fu化疗，化疗结束后分次回输CIK细胞，同时给予IL-2和IFN-α所有患者均接受至少2个周期治疗。[结果]40例患者中4例PR（10．0％），22例SD（55．0％），14例PD（35．0％），无进展生存时间（PFS）为87d。Ⅲ-Ⅳ度毒副反应占27．5％。[结论]化疗联合自体CIK细胞回输对mRCC患者有效，并延长PFS，是一种可接受的治疗模式。     

Use of prechemotherapy positron emission tomography-CT imaging, acquired in the treatment position, to help plan involved nodal radiotherapy for a patient with diffuse large B-cell lymphoma

Fused positron emission tomography/computed tomography (PET-CT) images are increasingly being used to assist radiation oncologists in the definition of treatment volumes for patients with metabolically active tumours. This is the first report in which baseline fluorodeoxyglucose-PET-CT images were acquired in the treatment position in a case of diffuse large B-cell lymphoma and incorporated directly into the radiotherapy treatment planning process. It highlights the potential benefits of using combined 3-D functional and structural imaging for the design of radiation target volumes in patients with aggressive lymphomas that are managed with combined chemo and radiotherapy.     

Systemic treatment of renal cell cancer: A comprehensive review

Kidney cancer represents about 5% of all new cancer diagnoses. The most common form of kidney cancer arises from renal epithelium, named renal cell carcinoma (RCC). This entity comprises different histological and molecular subtypes. Unraveling the molecular biology and cytogenetic of RCC has enabled the development of several targeted agents that have improved treatment outcomes of these patients. This article reviews all the agents currently approved for the treatment of RCC, and discuss upcoming molecules. Mechanism of action, preclinical and clinical development and ongoing trials, are presented for each agent, providing a broad vision of the current state of targeted therapy in RCC and possible future developments.