Long-Term Results of Prophylactic Donor Lymphocyte Infusions for Patients with Multiple Myeloma after Allogeneic Stem Cell Transplantation

The major reason for treatment failure after allografting in multiple myeloma (MM) is relapse. Donor lymphocyte infusions (DLIs) are considered a valuable post-transplant strategy mainly for relapsed patients but using them to prevent relapse in MM has been reported rarely. In the present study, we examined the efficacy of prophylactic DLIs after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in myeloma patients with a long-term follow-up of more than 5 years. A total of 61 patients with MM who did not relapse or develop disease progression after allo-HSCT were treated with prophylactic DLI in an escalating fashion (overall 132 DLI procedures) to deepen remission status and prevent relapse. Overall response rate to DLI was 77%. Thirty-three patients (54%) upgraded their remission status, 41 patients (67%) achieved or maintained complete remission, and 26% achieved a molecular remission. Incidence of acute graft-versus-host disease (GVHD) grade II to IV was 33% and no DLI-related mortality was noted. After a median follow-up of 68.7 months from first DLI the estimated 8-year progression-free survival (PFS), and overall survival (OS) in a landmark analysis was 43% (95% confidence interval [CI], 28% to 57%) and 67% (95% CI, 53% to 82%), respectively, with best outcome for patients who acquired molecular remission (8-year PFS was 62% and 8-year OS was 83%). Prophylactic escalating DLI in a selected cohort of MM patients to prevent relapse after allograft resulted in a low incidence of severe GVHD and encouraging long-term results, especially if molecular remission is achieved.     

Current Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Acute Lymphocytic Leukemia: Success,Failure and Future Perspectives—A Single-Center Experience, 2008 to 2016

Hematopoietic stem cell transplantation (HSCT) is the only curative option for a subset of patients with high-risk or relapsed acute lymphoblastic leukemia (ALL). Given evolving practices, it is important to continually evaluate outcomes for pediatric ALL following HSCT. Outcomes after HSCT are influenced by the type of donor used as this determines the degree and method of T cell depletion used and, consequently, specific transplant-related morbidities. We retrospectively analyzed HSCT data from our center for transplants performed between January 2008 and May 2016, comparing outcomes among different donor types. One hundred and twenty-four pediatric patients underwent HSCT from a matched sibling donor (MSD; n?=?48), an unrelated matched donor (UMD; n?=?56), or a haploidentical donor (n?=?20). We observed a similar 3-year event-free survival (EFS) for MSD recipients (of .64) and for UMD recipients (.62), but a significantly lower EFS for recipients of haploidentical transplants (.35; P?=?.01). Relapse was the main cause of HSCT failure and was significantly higher in the haploidentical donor group (.47 versus .19 for MSD and .24 for UMD; P?=?.02). Treatment-related mortality was evenly distributed among the donor groups (.17, .16, and .15 for the MSD, UMD, and haploidentical groups, respectively). Rates of infection-related mortality were lower than previously reported. Relapse is the main obstacle for successful HSCT in the contemporary era, and this effect is most evident in recipients of haploidentical donor grafts. Newer methods to improve graft-versus-leukemia effect are being evaluated and will need to be incorporated into the management of high-risk patients.     

Wilms' Tumor 1 Gene Expression Using a Standardized European LeukemiaNet-Certified Assay Compared to Other Methods for Detection of Minimal Residual Disease in Myelodysplastic Syndrome and Acute Myelogenous Leukemia after Allogeneic Blood Stem Cell Transplantation

Overexpression of the Wilms' tumor 1 (WT1) gene is informative in many patients with acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS) and is measurable in peripheral blood (PB). Despite these advantages, WT1 has not broadly been established as a marker for minimal residual disease (MRD) monitoring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to limited patient numbers, differing sample sources, and nonstandardized in-house methods. To estimate the value of WT1 as an MRD marker, we serially quantified PB WT1 expression using a standardized European LeukemiaNet-certified assay in 59 patients with AML and MDS after allo-HSCT. We compared its performance with routine methods such as chimerism, XY-fluorescence in situ hybridization (FISH), disease-specific cytogenetic, and molecular analyses, which were accessible in 100%, 34%, 68%, and 37%, respectively. Twenty-four patients (41%) relapsed within a median of 126 days after allo-HSCT, and 20 of them showed at least 1 elevated WT1 value above the validated cutoff. The other 35 patients (59%) remained in complete remission, and only 1 patient had a transient increase in WT1 expression. This reflects a sensitivity of 83% and a specificity of 97% for WT1 and appears to be favorable compared with the sensitivities and specificities observed for chimerism (33% and 91%), XY-FISH (67% and 73%), cytogenetic (33% and 77%), and molecular (78% and 85%) analyses. Further supporting its predictive impact, elevated WT1 expression prompted an earlier BM biopsy and consecutively the diagnosis of relapse in 62% of patients. The results of this real-life experience imply that PB WT1 expression is measurable by a standardized assay and predicts imminent relapse after allo-HSCT with high sensitivity and specificity in most patients with AML and MDS.     

标准化剩余肝体积与肝硬度比值预测肝脏切除术后肝功能不全的临床研究

目的 探讨应用标准化剩余肝体积与肝硬度值的比值预测肝脏切除术后肝功能不全的临床价值。方法 回顾性分析我院2015年1月~2021年6月行肝脏切除术患者61例的临床资料,术前采用CT或者MR进行肝脏增强扫描,检查图像进行三维重建。按照肝脏肿瘤的位置拟行解剖性左半肝脏或者右半肝脏切除术。并按照拟定的手术方案计算出全肝体积及剩余的肝脏体积,同时对61位患者行肝脏超声影像和瞬时弹性成像检查,检测出每位患者的肝脏硬度值（KPA）,计算出标准化剩余肝体积与肝硬度值的比值（SFLV/KPA）,并观测61位患者是否出现术后肝功能不全。把引起术后肝功能不全的可能相关因素进行单因素分析,得到与术后肝功能不全相关的影响因素,再通过二元logistics回归分析分析这些因素与术后肝功能不全的相关性,探讨标准化剩余肝体积与肝硬度值的比值（SFLV/KPA）预测肝脏切除术后肝功能不全的作用。并通过受试者工作特征曲线ROC曲线确定SFLV/KPA与术后肝功能不全的关系。结果 61例患者手术全部成功,术后有7例患者出现肝功能不全,无患者出现肝功能衰竭,无患者术后死亡。研究显示术中出血量、肝门阻断时间、SFLV/KPA、手术方式均是术后肝功能不全的影响因素。结论 通过受试者工作特征曲线ROC曲线,SFLV/KPA（标准化剩余肝体积/肝脏硬度值）比值大于30.6时,患者术后一般不出现肝功能不全,手术安全性更高。     

桩核固位和髓腔固位在磨牙冠修复中的临床效果研究

目的:探讨在已行根管治疗(Root canal treatment,RCT)的缺损磨牙修复中,桩核固位和髓腔固位两种固位修复方式的效果。方法:选择2016年6月-2017年12月来笔者医院修复科因磨牙牙体缺损RCT后需行冠修复的患者30例。根据就诊先后顺序,将所有患者分为实验组及对照组,每组15例。对照组:行桩核冠修复(3M纤维桩+铸瓷冠);实验组:行髓腔固位冠修复(铸瓷材料)。采用美国公共卫生署修正标准对两种不同固位修复方式的修复体在修复后6个月、12个月进行临床修复效果综合评价。结果:实验组髓腔固位冠在随访第12个月时有1例修复体脱落,在冠边缘密合性、邻接关系、牙龈及牙周等方面尚好;对照组在随访第3个月时有1例患牙牙龈退缩,在随访第12个月时1例患牙冠邻接关系略松,2例患牙有1例牙龈探诊轻度出血,1例牙龈退缩。不良结局发生率对照组高于实验组,但对两组数据进行统计,差异不具有统计学意义(P>0.05)。结论:髓腔固位冠与桩核冠相比在适应证范围内是临床上比较可行的修复方式。     

High expression levels of centromere protein A plus upregulation of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling pathway affect chemotherapy response and prognosis in patients with breast cancer

Centromere proteins (CENPs) are involved in mitosis, and CENP gene expression levels are associated with chemotherapy responses in patients with breast cancer. The present study aimed to examine the roles and underlying mechanisms of the effects of CENP genes on chemotherapy responses and breast cancer prognosis. Using data obtained from the Gene Expression Omnibus (GEO) database, correlation and Cox multivariate regression analyses were used to determine the CENP genes associated with chemotherapy responses and survival in patients with breast cancer. Weighted gene co-expression network and correlation analyses were used to determine the gene modules co-expressed with the identified genes and the differential expression of gene modules associated with the pathological complete response (PCR) and residual disease (RD) subgroups. CENPA, CENPE, CENPF, CENPI, CENPJ and CENPN were associated with a high nuclear grade and low estrogen and progesterone receptor expression levels. In addition, CENPA, CENPB, CENPC and CENPO were independent factors affecting the distant relapse-free survival (DRFS) rates in patients with breast cancer. Patients with high expression levels of CENPA or CENPO exhibited poor prognoses, whereas those with high expression levels of CENPB or CENPC presented with favorable prognoses. For validation between databases, the Cancer Genome Atlas (TCGA) database analysis also revealed that CENPA, CENPB and CENPO exerted similar effects on overall survival. However, according to the multivariate analyses, only CENPA was an independent risk factor associated with DRFS in GEO database. In addition, in the RD subgroup, patients with higher CENPA expression levels had a worse prognosis compared with those with lower CENPA expression levels. Among patients with high expression levels of CENPA, the PI3K/Akt/mTOR pathway was more likely to be activated in the RD compared with the PCR subgroup. The same trend was observed in TCGA data. These results suggested that high CENPA expression levels plus upregulation of the PI3K/Akt/mTOR signaling pathway may affect DRFS in patients with breast cancer.     

毛细管气相色谱法测定多西他赛注射液溶剂中乙醇含量的方法学验证

目的：建立多西他赛注射液溶剂中乙醇含量的气相色谱测定方法。方法：气相色谱法：毛细管色谱柱;载气：氮气;检测器：氢火焰离子化检测器;起始温度为50℃,维持10min,再以每分钟10℃的速率升温至110℃;进样口温度：190℃;检测器温度：220℃;柱流量：3.2ml/min;进样量：1μl。结果：定量限、检测限、溶液稳定性、线性、耐用性、重复性、进样精密度经验证,结果均良好。结论：本法可用于多西他赛注射液溶剂中乙醇含量的测定。     

桃胶改良前后的溶胀性能分析

目的:阐明溶剂、盐浓度、温度及p H对桃胶改良前后溶胀性能的影响,为阐明其缓释性能提供实验依据。方法:采用称重法测定原桃胶和改良桃胶辅料溶胀前后的干重、湿重,计算平衡溶胀率。结果:在不同溶剂中,改良桃胶的平衡溶胀率普遍明显高于原桃胶;桃胶改良前后的平衡溶胀率为二甲基亚砜水无水乙醇;在不同盐浓度中,桃胶改良前后的平衡溶胀率基本相同,均不受盐浓度影响,但显著小于水;在不同温度中,温度越高,桃胶改良前后的溶胀性能均越大,且改良桃胶更优;在不同p H溶液中,原桃胶易受酸碱度影响,而改良桃胶的平衡溶胀率不受其影响,且表现出更佳的溶胀性能。结论:改良桃胶的溶胀性能显著优于原桃胶;桃胶改良前后的溶胀性能受溶剂、温度的影响显著,而对盐浓度和p H(原桃胶易受影响)则不敏感。