A Comparison of the Conditioning Regimens BEAM and FEAM for Autologous Hematopoietic Stem Cell Transplantation in Lymphoma: An Observational Study on 1038 Patients From Fondazione Italiana Linfomi

BEAM (carmustine [bis-chloroethylnitrosourea (BCNU)]-etoposide-cytarabine-melphalan) chemotherapy is the standard conditioning regimen for autologous stem cell transplantation (ASCT) in lymphomas. Owing to BCNU shortages, many centers switched to fotemustine-substituted BEAM (FEAM), lacking proof of equivalence. We conducted a retrospective cohort study in 18 Italian centers to compare the safety and efficacy of BEAM and FEAM regimens for ASCT in lymphomas performed from 2008 to 2015. We enrolled 1038 patients (BEAM =?607, FEAM =?431), of which 27% had Hodgkin lymphoma (HL), 14% indolent non-Hodgkin lymphoma (NHL), and 59% aggressive NHL. Baseline characteristics including age, sex, stage, B-symptoms, extranodal involvement, previous treatments, response before ASCT, and overall conditioning intensity were well balanced between BEAM and FEAM; notable exceptions were median ASCT year (BEAM?=?2011 versus FEAM?=?2013, P?<?.001), Sorror score ≥3 (BEAM?=?15% versus FEAM?=?10%, P?=?.017), and radiotherapy use (BEAM?=?18% versus FEAM?=?10%, P?<?.001). FEAM conditioning resulted in higher rates of gastrointestinal and infectious toxicities, including severe oral mucositis grade ≥3 (BEAM?=?31% versus FEAM?=?44%, P?<?.001), and sepsis from Gram-negative bacteria (mean isolates/patient: BEAM?=?.1 versus FEAM?=?.19, P?<?.001). Response status at day 100 post-ASCT (overall response: BEAM?=?91% versus FEAM?=?88%, P?=?.42), 2-year overall survival (83.9%; 95% confidence interval [CI], 81.5% to 86.1%) and progression-free survival (70.3%; 95% CI, 67.4% to 73.1%) were not different in the two groups. Mortality from infection was higher in the FEAM group (subhazard ratio, 1.99; 95% CI, 1.02 to 3.88; P?=?.04). BEAM and FEAM do not appear different in terms of survival and disease control. However, due to concerns of higher toxicity, fotemustine substitution in BEAM does not seem justified, if not for easier supply.     

Total costs and clinical outcome of hematopoietic stem cell transplantation in adults with leukemia: comparison between reduced‐intensity and myeloablative conditioning

The total cost of hematopoietic stem cell transplantation (HSCT) as well as the financial impact of HSCT on the house holds of patients have been elusive. Between 2005 and 2012, we analyzed 191 HSCT in adult patients with leukemia with reduced‐intensity conditioning (RIC) regimen (n = 79) and with myeloablative conditioning (MAC) regimen (n = 112). The direct medical costs were calculated from healthcare claims obtained from the Seoul National University Hospital, and the direct non‐medical and the indirect costs were calculated from national statistics. The mean direct medical cost was $55 039, direct non‐medical cost was $6394, and indirect cost was $7503 from transplantation to one yr after transplantation in the RIC group and $72 916, $6993, and $9057 in the MAC group, respectively, based on the exchange rate of Korean won 1060 = US$1. The total costs for one yr were $68 938 and $88 967, constituting for 273% and 357% of the per capita income, respectively. The total costs, direct medical costs, and indirect costs showed statistically significant differences (p = 0.006, p = 0.007, and p = 0.017). No significant differences were found for leukemia‐free survival and overall survival. RIC‐HSCT provides lower costs within the first year of transplantation with comparable long‐term clinical outcomes.     

Expression and clinical implications of leucine-rich repeat containing 15 (LRRC15) in osteosarcoma

Leucine-rich repeat containing 15 (LRRC15) is a member of the leucine-rich repeat superfamily that is overexpressed in various cancers and associated with higher tumor grade and aggression. Despite its known tumorigenicity, its roles within osteosarcoma are unknown, prompting us to evaluate its expression and clinical significance within this rare yet aggressive cancer. Western blots showed differential expression of LRRC15 in the osteosarcoma cell lines MNNG/HOS, KHOS, 143B, MG63, Saos-2, and U2OS. We additionally validated this positive expression, as well as sublocalization to the cell membrane, with immunofluorescence. A tissue microarray constructed from 69 osteosarcoma patient tissues was immunohistochemically stained for LRRC15 expression, stratified, and used for clinicopathological analysis. Publicly available databases on LRRC15 expression, including RNA sequencing data from the Therapeutically Applicable Research to Generate Effective Treatments on Osteosarcoma (TARGET-OS) and the Gene Expression database of Normal and Tumor tissues 2 (GENT2) were also analyzed. We found 63 of the 69 (91.3%) patient tissues exhibited some degree of LRRC15 immunostaining, including no staining (6 of 69, 8.7%), 1+ staining (12 of 69, 17.4%), 2+ staining (25 of 69, 36.2%), and 3+ staining (26 of 69, 37.7%). The patients with osteosarcomas having elevated LRRC15 expression demonstrated comparatively increased metastasis, chemoresistance, and shorter 5-year survival rates. Our analysis of the TARGET-OS and GENT2 databases also showed increased LRRC15 gene expression in osteosarcoma. Taken together, our study supports LRRC15 as a prognostic biomarker and emerging therapeutic target in osteosarcoma.     

胰腺癌新辅助化疗的应用现状及进展

目的总结近年来胰腺癌新辅助化疗的治疗现状及进展,以期提高对胰腺癌新辅助化疗的认识,并指导临床工作。方法通过阅读并复习国内外有关胰腺癌新辅助化疗方面的文献并进行综述。结果新辅助化疗可缩小肿瘤病灶、提高R0切除率、降低术后并发症发生率且改善患者的预后,但目前尚缺乏高质量的循证医学证据。目前国际上并无统一的胰腺癌新辅助化疗方案,FOLFIRINOX、吉西他滨+白蛋白结合型紫杉醇和吉西他滨+替吉奥3种方案较为常见。同时,新辅助化疗存在化疗方案无统一标准、疗效评估手段不足等问题。结论尽管胰腺癌的新辅助化疗尚存在一些核心问题亟待解决,但其显示出的疗效正逐渐被临床工作者所认可并广泛应用,这有利于改善胰腺癌患者的预后。     

Adverse Effects of Busulfan Plus Cyclophosphamide versus Busulfan Plus Fludarabine as Conditioning Regimens for Allogeneic Bone Marrow Transplantation

Background: The side effects of conditioning regimens on the success rate of allogeneic transplantation around the world have been challenging. In this study, we aimed to investigate the side effect of Bu/Cy and Bu/Flu regimens on our patients who underwent allogeneic bone marrow transplantation. Methods: We analyzed 180 patients receiving bone marrow transplantation in Taleghani Hospital, in Tehran, Iran between April 2016 and December 2019. Patients in group A received a combination of intravenous busulfan 0.8 mg/kg QID over two hours for 4 consecutive days (12.8 mg/kg in total)(Savani et al., 2006) and cyclophosphamide 60 mg/kg per day for two consecutive days. Patients in group B received busulfan the same as the first group in combination with fludarabine equal to 40 mg/m² per day. Patients were followed up at regular intervals up to two years after transplantation. Result: Various items were evaluated for patients, including cardiopulmonary function, psychological disorders, GVHD, and endocrine disorders such as hypothyroidism, fertility, or gonad dysfunction.  Primary hypothyroidism developed in 13.3% and 11.1% of the Bu/Cy and Bu/Flu groups, respectively (p=0.230). None of the patients in either group experienced infertility or gonad dysfunction. In group A versus group B, pulmonary diseases were detected in  4.4% versus 6.6% of BMT recipients, respectively (p = 0.223). In both groups, mitral and tricuspid regurgitation were observed in patients (8.9% vs. 11.1%; p = 0.189). Incidence of Psychological disorders was no significant difference between the two groups. 32.2% of group A versus 34.45%  of group B had skin and liver GVHD, respectively (p = 0.235). Conclusion: The therapeutic-related adverse effects of the two conditioning regimens in patients who underwent allogeneic bone marrow transplant were almost similar. To improve quality of life and overall survival among BMT patients, careful evaluation of treatment-related complications should be part of the regular follow-up of them.     

An Analysis of the Nursing Diagnosis Ineffective Management of Therapeutic Regimen Compared to Noncompliance and Orem's Self-Care Deficit Theory of Nursing

The authors compare the nursing diagnosis ineffective management of therapeutic regimen with that of noncompliance and with Orem's concept of self-care deficit. The article describes how the diagnosis of ineffective management of therapeutic regimen is more comprehensive than noncompliance. A question of patient autonomy is raised considering how the patient manages his or her therapeutic regimen. The major conclusion is that the nursing diagnosis of ineffective management of therapeutic regimen is based on continuous interaction between patient and nurse. The authors recommend that noncompliance be eliminated as a nursing diagnosis.     

内镜下植入化疗缓释粒子联合DC-CIK免疫细胞输注法治疗梗阻性食管癌

目的探讨经胃镜植入化疗粒子行肿瘤局部化疗联合树突状细胞-多因子诱导的杀伤细胞(DC-CIK)免疫细胞输注法对隆起型食管癌患者的临床疗效。方法选取2013年10月-2015年4月间于该院证实为隆起型食管癌的患者共200例按随机数字法分为化疗粒子植入联合DC-CIK免疫细胞输注法组100例(联合组)及单独化疗粒子植入组100例(对照组)。联合组患者给予两种方法联合治疗,对照组患者只给予内镜下化疗粒子植入法。1~2疗程后对两组患者的症状改善情况、内镜下肿瘤缩小程度以及1年生存率数据进行提取统计。两组基础临床资料差异无显著性(P0.05),具有可比性。结果联合组症状改善患者(94%)高于对照组(80%),两组数据经χ2检验差异有显著性(χ2=11.493,P=0.003);联合治疗组中有58例达到完全缓解,而对照组仅有37例,两组数据经χ2检验差异有显著性(χ2=8.842,P=0.000);联合组的1年生存率(71%)高于对照组(57%),差异有显著性(χ2=4.253,P=0.039)。结论经胃镜植入化疗粒子行肿瘤局部化疗和DC-CIK免疫细胞输注法治疗隆起型食管癌的效果优于单用植入化疗粒子法,具有简便、副作用小且易于操作等特点。     

潜在可切除胃癌新辅助化疗的临床疗效观察

目的探讨潜在可切除胃癌新辅助化疗的临床疗效。方法收集本科收治的进展期及局部晚期潜在可切除胃癌患者31例，予以改良DCF方案（mDCF）化疗2～4个周期，观察其临床疗效及不良反应。结果全组获CR1例，PR15例，SD10例，PD5例，临床有效率为51．61％，疾病控制率为83．86％。手术切除率为64．52％（20／31），其中R0切除率为45．16％（14／31），R1切除率为12．90％（4／31），R2切除率为6．45％（2／31）。姑息性手术7例（22．58％）。2例术后出现并发症，并发症发生率为10％（2／20）。主要不良反应为骨髓抑制、恶心呕吐及轻度肝功能损害，经对症处理后均可缓解及恢复。结论改良DCF方案应用于潜在可切除胃癌的新辅助化疗的临床疗效较好，该疗法可使肿瘤降期，增加手术切除的机会，化疗相关不良反应可耐受，安全性较高。     

The heat shock response: Role in radiation biology and cancer therapy

Since prehistoric times, elevated temperatures have been used to treat cancer in a variety of forms. In modern times (the last 40 years) efforts have concentrated on combining heat with other anti-tumour modalities, principally ionizing radiation and some chemotherapeutic drugs. Despite the emphasis on combined therapy, rodent data relating to heat sensitivity and thermal tolerance development assumed principal importance. These considerations suggested treating at 43°C as a target temperature and fractionation schemes emphasizing thermal tolerance avoidance. Concomitantly crucial data on heat-induced tumour reoxygenation and its temperature dependence were largely ignored. In reality these were unrealistic and undesirable goals. The preponderance of evidence now suggests that lower temperatures (40–42°C) administered more frequently, optimally immediately before and during each administration of ionizing radiation, are likely to yield optimal results. Factoring in trimodality therapy and other combinations of chemotherapeutic drugs will require some modifications of such fractionation schemes.     

Dendritic cells: therapy and imaging

Background: Dendritic cells (DCs) play a major role in cell-mediated immunotherapy. In this approach, DCs are isolated from cancer patients and pulsed with exogenous and specific tumor antigens in vitro, and the antigen-loaded DCs are then transferred to the hosts to enhance the immune response against tumor targets. Clinical observations and animal studies have shown that tumors can elicit immune responses caused by tumor infiltration of T-lymphocytes. Several pilot clinical trials have been recently conducted using this strategy for treating several types of cancers. Objective: To optimize DC-based therapy with emerging molecular imaging techniques. Methods: A review of the most current literature on DCs and imaging work. Results/conclusion: The translational application of DC-based therapy can be supported greatly through molecular imaging. New discoveries on DC migration and behavior in vivo will lead to new advances in the treatment of a broad range of cancers.