BackgroundHematologic malignancies, including leukemia, non-Hodgkin lymphoma (NHL), multiple myeloma (MM), and Hodgkin lymphoma (HL), represent some of the most prevalent cancers. This study aims to comprehensively analyze the epidemiological trends of these malignancies in China.MethodsUsing data from the Global Burden of Disease Study 2021 (GBD 2021), we conducted a detailed assessment of incidence cases, deaths, disability-adjusted life years (DALYs), and corresponding age-standardized rates (ASR) of hematologic malignancies in China. Additionally, we compared the disparity in disease burden between China and the United States (US).ResultsIn 2021, the incidence cases, deaths, and DALYs of all hematologic malignancies reached 238051.31, 117187.70, and 3894866.98, respectively, in China. From 1990 to 2021, although the age-standardized incidence rates (ASIR) of leukemia, MM, and NHL increased, the age-standardized death rates (ASDR) and age-standardized DALYs rates (ASDALYR) declined for all subtypes of hematologic malignancies, with the exception of MM. The ASIR of all subtypes of hematologic malignancies in the US was significantly higher than that in China, while the disparity of ASDALYR between the two countries was smaller. The ASRs for all subtypes of hematologic malignancies exhibited a positive correlation with age and were generally higher in males than in females. High body mass index (BMI) emerged as a significant risk factor contributing to deaths from all hematologic malignancies, and tobacco remains the leading contributor to leukemia-related deaths. Projections indicate that the burden of MM will continue to increase from 2022 to 2040.ConclusionsWhile the ASIR of hematologic malignancies has risen over recent decades, the ASDR and ASDALYR have showed a decreasing trend, reflecting China's efforts in reducing the burden of these diseases. However, the disparity in disease burden between China and the US underscores the substantial potential for improving the diagnosis, treatment, and care levels in China.
BackgroundAs a common complication of chronic kidney disease (CKD), anemia is associated with increased mortality and reduced quality of life. Despite its severe impact, there is a lack of high-quality data on the global burden of anemia attributed to CKD. This study aims to provide a comprehensive analysis of the anemia burden attributed to CKD.MethodsUsing data from the Global Burden of Disease study (GBD) 2021, we report the prevalence and years lived with disability (YLDs) of anemia attributed to CKD across different sexes, ages, and regions; assess the association between anemia burden attributed to CKD and the socio-demographic index (SDI); and quantify and predict temporal trends of anemia burden attributed to CKD.ResultsIn 2021, there were 63.75 million (95% uncertainty interval [UI]: 59.05 to 68.37) cases and 1.70 million (95% UI: 1.13 to 2.43) YLDs of anemia attributed to CKD globally. Compared with 1990, the prevalence and YLDs increased by 96.24 and 74.78%, respectively, which was largely driven by population growth and aging. The global age-standardized prevalence rate (ASPR) and YLD rate per 100,000 were 762.12 (95% UI: 707.32 to 817.37) and 20.34 (95% UI: 13.54 to 29.09) in 2021, which decreased by 9.39 and 18.93% in comparison with those in 1990. However, the decline in ASPR stagnated after 2010, with a slight increase observed between 2010 and 2015. A negative relationship between SDI and the anemia burden attributed to CKD was observed at both regional and national levels. Women had higher ASPR and age-standardized YLD rates compared to men, and the burden attributed to CKD increased with age. Predictive analysis indicated that the prevalence of cases will continue to rise, while the YLDs, ASPR, and age-standardized YLD rates are expected to decline consistently.ConclusionAnemia attributed to CKD is a major public health issue across the world, with persistent regional and socioeconomic disparities. Continued efforts, including addressing socioeconomic disparities, improving access to healthcare, and innovative treatments, are essential to reduce the anemia burden attributed to CKD.
Background:Chronic myelomonocytic leukemia (CMML) is a heterogeneous myeloid malignancy, characterized by sustained peripheral blood monocytosis and an inherent risk of secondary acute myeloid leukemia (s-AML). This study aimed to determine the incidence, risk factors, and survival of AML secondary to CMML. Methods:We conducted this retrospective analysis based on the Surveillance, Epidemiology, and End Results (SEER) database. Results:We identified 3,218 patients with primary CMML. After a median follow-up time of 23 months, 291 patients developed s-AML and most of them occurred in the first year of CMML diagnosis, with cumulative incidence of 10.8%. In competing risk analysis, risk factors for s-AML were younger age and exposure to chemotherapy at CMML diagnosis. The post-progression survival (PPS) of s-AML was dismal with a median survival of 4 months (1-, 3-, and 5-year PPS of 26.6%, 9.6%, and 7.1%, respectively), while younger age and exposure to chemotherapy at s-AML development were protective factors for PPS. Considering CMML, s-AML development, older age, and exposure to chemotherapy at CMML diagnosis were risk factors for overall survival (OS). In addition, being married, higher income, and non-Hispanic White were important protective factors for OS of CMML. Conclusions:The risk of s-AML among CMML was high and the PPS was poor. Age and exposure to chemotherapy at CMML diagnosis were associated with the high risk of s-AML and the poor survival of s-AML. In addition to clinical factors, demographic factors, including marital status, economic level, and race/ethnicity, should also be included when assessing the CMML survival.
Histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL) can occur in both Hodgkin lymphoma (HL) and indolent B-cell non-Hodgkin lymphoma (B-NHL), typically associated with poor clinical outcomes. However, following the introduction of rituximab, the prognosis of transformed DLBCL (t-DLBCL) has shown considerable variability across studies. This study aimed to evaluate the outcomes of t-DLBCL originating from HL and indolent B-NHL, and to compare survival rates between t-DLBCL and primary DLBCL (p-DLBCL). Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with primary HL or indolent B-NHL between 2000 and 2021, and those diagnosed with p-DLBCL during the same time. A total of 3,508 cases of t-DLBCL were identified. Compared to patients without HT, those with HT exhibited significantly worse survival outcomes. The post-transformation survival (PTS) rates at 5-year were 49.4%, 49.4%, 46.2%, 31.4% and 26.4% for t-DLBCL originating from HL, follicular lymphoma (FL), marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia and chronic lymphocytic leukemia/small lymphocytic lymphoma, respectively. Factors such as age at HT, sex, marital status at HT, disease stage at HT, initial therapy prior to HT, and treatment regimen at HT were significantly associated with the prognosis of t-DLBCL. Notably, the PTS of specific subgroups of t-DLBCL, including patients younger than 65 years originating from FL with radiotherapy prior to HT, and those originating from MZL with either "watch and wait" or radiotherapy prior to HT, was comparable to that of matched p-DLBCL. Given the heterogeneous prognosis observed in t-DLBCL, treatment strategies should be tailored accordingly.
AbstractBackgroundHistological transformation (HT) to diffuse large B‐cell lymphoma (DLBCL) is a common complication of follicular lymphoma (FL) and is usually associated with a dismal outcome. However, the survival rate of these patients has improved over the last 20 years with the introduction of rituximab. This study aimed to access the outcome of transformation to DLBCL (t‐DLBCL) from FL in a retrospective series that began after the widespread use of rituximab use. In addition, we also compared survival between t‐DLBCL and primary DLBCL (p‐DLBCL) in the same timeframe.MethodsWe utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with primary FL and patients with p‐DLBCL between 2000 and 2020. Patients who had a subsequent diagnosis of DLBCL at least 2 months after FL diagnosis were identified as t‐DLBCL.ResultsFinally, we identified 50,332 FL and 95,933 p‐DLBCL. With a median follow‐up of 119 months, 1631 patients developed t‐DLBCL. The median time from FL diagnosis to t‐DLBCL was approximately 4 years. The post‐transformation survival (PTS) rate at 5 years was 49.6%, with a median PTS of 56 months. Older age, advanced stage, and early transformation were associated with worse PTS. Furthermore, t‐DLBCL receiving chemotherapy or combined modality as initial therapy before HT was also associated with worse PTS, while the result was inverse when taking the impact of initial management strategy at HT into account. Taking t‐DLBCL and p‐DLBCL as a whole, comparable survival was observed between p‐DLBCL and t‐DLBCL receiving radiation or watch‐and‐wait as initial therapy prior to HT.ConclusionThe outcome of t‐DLBCL in the rituximab era was better than historical series before the rituximab era. Due to the good prognosis, we did not recommend autologous stem cell transplantation for t‐DLBCL receiving watch‐and‐wait or radiation as initial therapy before HT.
Purpose An accurate prediction of survival prognosis is beneficial to guide clinical decision-making. This prospective study aimed to develop a model to predict one-year mortality among older patients with coronary artery disease (CAD) combined with impaired glucose tolerance (IGT) or diabetes mellitus (DM) using machine learning techniques. Methods A total of 451 patients with CAD combined with IGT and DM were finally enrolled, and those patients randomly split 70:30 into training cohort (n = 308) and validation cohort (n = 143). Results The one-year mortality was 26.83%. The least absolute shrinkage and selection operator (LASSO) method and ten-fold cross-validation identified that seven characteristics were significantly associated with one-year mortality with creatine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and chronic heart failure being risk factors and hemoglobin, high density lipoprotein cholesterol, albumin, and statins being protective factors. The gradient boosting machine model outperformed other models in terms of Brier score (0.114) and area under the curve (0.836). The gradient boosting machine model also showed favorable calibration and clinical usefulness based on calibration curve and clinical decision curve. The Shapley Additive exPlanations (SHAP) found that the top three features associated with one-year mortality were NT-proBNP, albumin, and statins. The web-based application could be available at https://starxueshu-online-application1-year-mortality-main-49cye8.streamlitapp.com/ . Conclusions This study proposes an accurate model to stratify patients with a high risk of one-year mortality. The gradient boosting machine model demonstrates promising prediction performance. Some interventions to affect NT-proBNP and albumin levels, and statins, are beneficial to improve survival outcome among patients with CAD combined with IGT or DM.
BackgroundCardiac aging and ageing-related cardiovascular diseases remain increase medical and social burden. Discovering the molecular mechanisms associated with cardiac aging is expected to provide new perspectives for delaying aging and related disease treatment.MethodsThe samples in GEO database were divided into older group and younger group based on age. Age-associated differentially expressed genes (DEGs) were identified by limma package. Gene modules significantly associated with age were mined using weighted gene co-expression network analysis (WGCNA). Protein-protein interaction networks (PPI) networks were developed using genes within modules, and topological analysis on the networks was performed to identify hub genes in cardiac aging. Pearson correlation was used to analyze the association among hub genes and immune and immune-related pathways. Molecular docking of hub genes and the anti-aging drug Sirolimus was performed to explore the potential role of hub genes in treating cardiac aging.ResultsWe found a generally negative correlation between age and immunity, with a significant negative correlation between age and b_cell_receptor_signaling_pathway, fc_gamma_r_mediated_phagocytosis, chemokine signaling pathway, t-cell receptor signaling pathway, toll_like_receptor_signaling_pathway, and jak_stat_signaling_pathway, respectively. Finally, 10 cardiac aging-related hub genes including LCP2, PTPRC, RAC2, CD48, CD68, CCR2, CCL2, IL10, CCL5 and IGF1 were identified. 10-hub genes were closely associated with age and immune-related pathways. There was a strong binding interaction between Sirolimus-CCR2. CCR2 may be a key target for Sirolimus in the treatment of cardiac aging.ConclusionThe 10 hub genes may be potential therapeutic targets for cardiac aging, and our study provided new ideas for the treatment of cardiac aging.
目的 通过分析急性髓系白血病伴初治B淋巴细胞增殖性疾病的临床资料并进行文献复习,以期提高临床对该病的认识.方法 回顾性分析解放军总医院海南医院2021年2月1日收治的1例急性髓系白血病伴初治B淋巴细胞增殖性疾病患者的临床表现,形态学、免疫学、细胞遗传学和分子生物学检查结果,治疗方案,临床结局,并进行文献复习.结果 患者为63岁男性,以发热伴腹痛就诊于解放军总医院海南医院,骨髓形态学、病理学检查等均支持急性单核细胞白血病,骨髓涂片和流式细胞仪检测发现一群单克隆成熟B细胞,免疫分型为CD19+、CD20+、CD5-、CD10-,考虑急性髓系白血病合并B淋巴细胞增殖性疾病.患者经常规化疗和联合新药维奈克拉治疗后均未获缓解,化疗后发生Ⅳ度骨髓抑制、脓毒血症等.最终因疾病进展和感染死亡.结论 急性髓系白血病合并B淋巴细胞增殖性疾病少见,容易漏诊,该类患者不易缓解,同时抵抗力低,易发生感染,治疗难度高,临床预后极差.
Purpose This prospective study with 10-year follow-up aimed to analyze potential impact of body mass index (BMI) and gamma gap on heart failure and mortality rate in older patients with coronary artery disease (CAD). Methods There were 987 consecutive older patients with CAD included and divided into four groups according to BMI and gamma gap levels. Results Median age was 86 years. The highest proportion of heart failure (46.2%) and the highest mortality rate (84.4%) was observed in patients with low BMI and high gamma gap, whereas the lowest proportion of heart failure (18.9%) and the lowest mortality rate (62.9%) was observed in those with high BMI and low gamma gap. After full adjustment in multivariate Logistic regression analysis, heart failure was most common in patients with low BMI and high gamma gap compared with those with high BMI and low gamma gap (hazard ratio [HR]: 2.82, 95% confidence interval [CI]: 1.79–4.48, P < 0.05). Meanwhile, multivariate Cox regression analysis showed that mortality rate was the highest in those with low BMI and high gamma gap compared with patients with high BMI and low gamma gap (HR: 1.65, 95% CI: 1.32–2.07, P < 0.05). Conclusion The combination of low BMI and high gamma gap could further promote heart failure and increase mortality rate in older patients with CAD. Future studies should explore the underlying mechanisms linking low BMI, high gamma gap, and mortality rate, as well as the potential benefits of nutritional and immunological interventions to improve health prognosis in older patients with CAD.
Objective Febrile neutropenia (FN) is a serious complication of patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP-21. The prophylactic use of granulocyte colony–stimulating factors (G-CSFs) can significantly reduce the risk of FN. International guidelines recommend G-CSFs for patients receiving chemotherapy with FN risk of 20% or 10 to 20% with defined risk factors. However, there are few studies on the incidence and risk factors of FN in patients with DLBCL receiving R-CHOP-21, especially in patients without primary G-CSF prophylaxis. Methods We conducted a retrospective analysis for the clinical data of 103 patients with DLBCL who underwent first R-CHOP-21 without primary G-CSF prophylaxis. The objective of the assessment was the incidence and risk factors of FN after the first chemotherapy cycle. Results After the first chemotherapy cycle, the incidence of FN was 20.4%. Multivariate analysis showed that age ≥ 65 years, bone marrow involvement, albumin < 35 g/L, and average relative dose intensity ≥ 80% were independent risk factors for FN. According to risk factors, we created a risk score system. The incidence of FN in the low-, intermediate- and high-risk groups was 5.6%, 17.2%, and 61.9%, respectively. Conclusion Our data indicated that R-CHOP-21 itself is associated with a high-risk regiment for FN. We recommend that intermediate/high-risk patients should actively consider primary G-CSF prophylaxis to reduce the incidence of FN after chemotherapy.
Background Oral mucositis (OM) affects the quality of life and therapeutic outcomes of cancer patients. More effective drugs and methods for treating OM are urgently required for clinical application. Extracellular vesicles can play important roles in cutaneous wound healing. However, their role in OM remains unclear. Our aim was to investigate the function and mechanisms of topical coatings of extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUC-MSC-EVs) in OM. Methods HUC-MSC-EVs were isolated by differential ultracentrifugation. We used glacial acetic acid to induce the formation of OM in rats. HUC-MSC-EVs were covered on the OM topically once a day. Rats’ body weights were measured on alternative days. The healing degree of OM was evaluated with macroscopic observations and histological examinations. We also analyzed the mechanisms of hUC-MSC-EVs when promoting the healing of OM. The expression levels of NF-κB, IL-6, TNF-α, and IL-1β in mucosal tissue were evaluated using immunohistochemistry. Results The median healing time of OM in the blank control, rhaFGF, 0.25 µg/µL EVs, 0.75 µg/µL EVs, and 1.50 µg/µL EVs groups was 14, 11, 10, 7, and 11 days, respectively. The most significant effect of hUC-MSC-EVs in promoting healing was at the concentration of 0.75 µg/µL. The median healing scores in the 0.75 µg/µL EVs group were 4 on day 5 and 3 on day 8 (*P<0.05 vs. the blank control group). After modeling, the body weight of rats started to recover from day 8 in the blank control group and day 4 in the 0.75 µg/µL EVs group. The 0.75 µg/µL EVs group showed lower immunostaining intensity of NF-κB, IL-6, and TNF-α on day 5 and 8 (*P<0.05 vs. the blank control group). However, there was no significant difference between the blank control group and the 0.75 µg/µL EVs group in IL-1β. Conclusions Our results showed for the first time that coating hUC-MSC-EVs topically can promote healing of OM because it may inhibit the activation of the NF-κB signaling pathway.
目的 探讨侵袭性系统性肥大细胞增生症(aggressive systemic mastocytosis,ASM)的临床病理特点、诊断和鉴别诊断要点,以及治疗与预后.方法 报道1例ASM,观察其组织形态特点、免疫组化及特殊染色结果、临床病理特点及预后.结果 女性,61岁.6个月前无诱因出现腹胀、反酸、食欲减退及体重下降等症状,检查发现盆腔、腹腔及全身多发淋巴结肿大,全身骨骼骨髓腔弥漫性糖代谢异常增高及脾大,临床先后行胃肠镜活检、骨髓穿刺活检及腹腔内淋巴结穿刺活检.组织形态学表现:在十二指肠黏膜、骨髓和淋巴组织内均可见小片状、簇状形态较一致的单核样异常细胞浸润,细胞中等大小,胞质较丰富、呈细颗粒状,胞核淡染、呈卵圆形或短梭形,部分见小核仁,未见明确核分裂象,周围见较多嗜酸性粒细胞及部分中性粒细胞.免疫组化:异常细胞CD117和CD25(+);CD2、CD3、CD20、CD30、MPO和S-100等均(-);Ki-67阳性指数30%.甲苯胺蓝染色:异常细胞(+).骨髓流式细胞学检测:异常细胞CD117(+).外周血测C-KITD816V:未见突变.结论 侵袭性系统性肥大细胞增生症是系统性肥大细胞增生症的一个特殊亚型,极为罕见,常以消化道及皮肤为首发症状,易误诊.利用免疫组化和特殊染色证实.该肿瘤预后差,易反复.
目的 探讨葡萄糖酸洗必泰棉片在热带地区血液病患者经外周置入中心静脉导管(PICC)外接无针接头消毒中的应用效果.方法 纳入热带地区携带PICC的300例血液病患者,随机分为观察组和对照组,每组150例,再将各组分为5 s、10 s、15 s亚组,各亚组均50例.观察组、对照组分别采用葡萄糖酸洗必泰棉片、碘伏医用棉签消毒无针接头,各亚组按照相应的时间进行消毒.在置管后首次输液前采集无针接头处的无菌生理盐水拭子标本,采用琼脂平板培养法检测污染情况.结果 在观察组和对照组内,15 s亚组的污染率均低于5 s亚组和10 s亚组(均P<0.05),而5 s亚组与10 s亚组的污染率差异均无统计学意义(均P>0.05).观察组的5 s亚组、10 s亚组、15 s亚组的污染率分别低于对照组的5 s亚组、10 s亚组、15 s亚组(均P<0.05).结论 采用葡萄糖酸洗必泰棉片对热带地区血液病患者PICC外接无针接头进行消毒的效果优于碘伏棉签,且消毒时间为15 s时的效果更佳.
OBJECTIVE:To analyze the clinical characteristics and risk factors of invasive fungal infection (IFI) occurenced in patients with acute leukemia (AL) during treatment in tropical regions.METHODS:The clinical data of 68 AL patients admitted to the Hainan Hospital of PLA General Hospital from April 2012 to April 2019 was retrospectively analyzed. Logistic regression analysis was used to analyze the factors affecting the occurrence of IFI in AL patients.RESULTS:Among the 68 patients, 44 were acute myeloid leukemia, 24 were acute lymphoblastic leukemia, 39 were male, 29 were female and the median age was 41(13-75) years old. The 68 patients received 242 times of chemotherapy or hematopoietic stem cell transplantation(HSCT), including 73 times of initial chemotherapy or inducting chemotherapy after recurrence, 14 times of HSCT, 155 times of consolidating chemotherapy. Patients received 152 times of anti-fungal prophylaxis, including 77 times of primary anti-fungal prophylaxis and 75 times of secondary anti-fungal prophylaxis. Finally, the incidence of IFI was 31 times, including 24 times of probable diagnosis, 7 times of proven diagnosis, and the total incidence of IFI was 12.8%(31/242), the incidence of IFI in inducting chemotherapy was 24.66%(18/73), the incidence of IFI in HSCT patients was 28.57% (4/14), the incidence of IFI in consolidating chemotherapy was 5.80% (9/155). Multivariate analysis showed that inducting chemotherapy or HSCT, the time of agranulocytosis ≥7 days, risk stratification of high risk were the independent risk factors for IFI in AL patients during treatment in tropical regions.CONCLUSION:The incidence of IFI in patients with AL in the tropics regions is significantly higher than that in other regions at homeland and abroad. Anti-fungal prophylaxis should be given to the patients with AL who have the high risk factors of inducting chemotherapy or HSCT, time of agranulocytosis ≥7 days and risk stratification of high risk.
目的:探讨bcl-2抑制剂维奈克拉+FLAG+伊达比星(IDA)方案对第1次异基因造血干细胞移植(allo-HSCT)后复发的急性髓系白血病(AML)治疗效果和安全性及第1次allo-HSCT后复发患者的治疗选择。方法:回顾性分析解放军总医院海南医院2018年7月收治的1例复发难治AML患者的诊疗过程,并复习相关文献。结果:患者,女性,23岁,诊断为AML,经过诱导化疗及巩固化疗后复发,挽救化疗无效,遂在复发状态下进行第1次allo-HSCT;移植后4个月患者再次复发,在给予挽救性治疗无效的情况下给予维奈克拉+FLAG+IDA方案治疗,达完全缓解(CR),流式细胞术检测微小残留病(MRD)阴性,遂给予第2次allo-HSCT,并于+60天给予地西他滨+维奈克拉巩固治疗。随访至移植后3个月余时,患者仍为CR和MRD阴性。结论:分子靶向药物维奈克拉与FLAG+IDA方案联合对第1次allo-HSCT后复发的AML患者安全、有效,且耐受性良好。第2次allo-HSCT可以作为年轻的第1次allo-HSCT后复发AML患者的有效治疗选择。
Objective To analyze the characteristics, prognosis and risk factors of bloodstream infection in patients with hematological malignancies in the tropics, so as to provide evidence for the prevention and treatment of bloodstream infection. Methods The clinical features, blood culture results and prognosis of patients with bloodstream infection in patients with hematological malignancies admitted to Hainan Hospital of PLA General Hospital were retrospectively studied. Results The most common primary infection site of the 81 patients with hematological malignancies was lung (46.91%), followed by PICC (11.11%). The detection rate of Gram-positive bacteria and Gram-negative bacteria in the blood culture was 60.98% and 30.02%, respectively. Coagulase-negative staphylococci was the most common Gram-positive bacteria resulting in bloodstream infection in our study. Of the Gram-negatives, Klebsiella pneumoniae (34.38%) was predominant, followed by Escherichia coli (18.75%) and Pseudomonas aeruginosa (18.75%). Gram-positive bacteria was highly sensitive (100%) to vancomycin, linezolid and tigecycline. Study showed that Gram-negative bacteria had low sensitive to quinolones, in particular, the resistance rate of Escherichia coli to quinolones was as high as 83.33%. In terms of overall survival (OS), the 30-days OS of patients with Gram-negative and Gram-positive septicemia was 77.42% and 92.00%, respectively. There was no statistically significant difference between the two groups. Multivariate analysis revealed that septic shock (P=0.001, RR=269.27) was an independent risk factor for 30-day mortality, and remission status (P=0.027, RR=0.114) was an independent predictor of a favourable outcome of bloodstream infection in patients with hematological malignancies. Conclusion Gram-positive bacteria are the main pathogens causing bloodstream infections in patients with hematological malignancies in the tropics. Improving the care of PICC is an important measure to reduce the incidence of bloodstream infection in patients with hematological malignancies in the tropics. A correct treatment relieving disease and effective prevention and treatment of septic shock can reduce mortality of patients with bloodstream infection in patients with hematological malignancies in the tropics.
We report the case of a 23-year-old man with a medical history of idiopathic thrombocytopenic purpura (ITP) and newly diagnosed with the Epstein-Barr virus (EBV)-positive multiple-site extramedullary plasmacytoma (EMP), which involves the respiratory system. The patient was referred to our hospital because of progressive nasal congestion and nasal mass. Nasopharyngoscopy and bronchoscopy were performed. The biopsy pathological hematoxylin and eosin (HE) staining indicated plasma cell myeloma, and further immunohistochemistry CD99(+), CD79a(+), CD38(+), MUM-1(+), and Lambda(+) confirmed the diagnosis. The patient's bone marrow was normal, and hypercalcemia, renal insufficiency, anemia, evident bone lesions were not observed. Serum immunoglobulin quantification, serum protein electrophoresis, and blood and urine light chain quantification were all within the normal range. The serum immunofixation electrophoresis was negative, and the serum-free light chain was normal. These results could rule out multiple myeloma (MM) and prove to be EMP involving the nasal cavity, main bronchus, lung, and left hip. No desired effect was achieved after receiving PAD (bortezomib, adriamycin, and dexamethasone) and VRD (bortezomib, lenalidomide, and dexamethasone) treatments. Even if the tumor was remarkably relieved after receiving the 2-course CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen, secondary resistance to CHOP unfortunately occurred in this case. We attempted to apply epigenetic therapy in the treatment of refractory multiple EMP. Although no complete remission (CR) was achieved, the maximum standard uptake value (SUVmax) in tumor lesions was significantly lower than before, and the patient's symptoms significantly improved. The patient tolerated decitabine and chidamide. We speculated that epigenetic drugs have potential effect in the treatment of multiple-site EMP.
Objective:To explore programmed death(PD)-1 inhibitor in treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) combined central nervous system (CNS) involvement, and review relevant literature.Methods:In April 2019, two patients with R/R DLBCL combined CNS involvement after autologous stem cell transplantation (auto-HSCT) who admitted to Department of Hematology, First Medical Center of Chinese PLA General Hospital were selected as research subjects. These 2 patients were treated with a variety of regimens based on PD-1 inhibitor camrelizumab (200 mg/time, once every 2 weeks). Retrospective analysis method was conducted to collect relevant clinical data and efficacy of these patients receiving camrelizumab treatment, and reviewed relevant literature. The follow-up data of this study was as of June 30, 2019. This study was in line with World Medical Association Declaration of Helsinki revised in 2013, and informed contents were obtained from all subjects. Results:① Patient 1 was male and 50 years old. He presented with " left eye pain for 1 month" and was diagnosed as DLBCL in February 2017. Then, he experienced DLBCL relapse in CNS after first-line R-CHOP(rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy and received auto-HSCT in October 2018. Unfortunately, he experienced DLBCL relapse in CNS and systemic in March 2019. Patient 2 was female and 44 years old. She presented with " swollen tonsillar for 1 month" and was diagnosed as DLBCL in July 2016. She experienced her first relapse after first-line R-CHOP chemotherapy. She achieved a second complete remission (CR) after second-line R-DICE(rituximab, dexamethasone, ifosfamide, cisplatin and etoposide) chemotherapy. Auto-HSCT was also performed for her in May 2018. But she experienced relapse again in December 2018. ② Patient 1 received a total of 13 times camrelizumab based regimens. And a partial remission (PR) was achieved after 10 times of camrelizumab treatment. Finally, unconfirmed CR (CRu) was confirmed in patient 1 after 13 times of camrelizumab treatment. As of the end of follow-up, this patient was still in good remission. However, no improvement was shown after 5 times of camrelizumab treatment in patient 2, and she eventually died due to progression of lymphoma 12 months after the second recurrence. ③ After receiving 4 times camrelizumab treatment, camrelizumab was detected in serum and cerebrospinal fluids samples of patient 1, at concentrations of 34 968.86 and 494.57 ng/mL, respectively. The concentration of camrelizumab in serum sample of patient 2 was 26 538.14 ng/mL. But camrelizumab wasn′t detected in her cerebrospinal fluids sample. ④ According to current literature, there was no predictive biomarker for efficacy of PD-1 inhibitors for patients with R/R DLBCL. With the exception that PD-1 inhibitors showed promising results in some selected types of lymphoma, the response rate of patients with R/R DLBCL who received PD-1 inhibitor monotherapy was very low. Combination therapy incorporating a PD-1 inhibitor seemed to be a rational approach for R/R DLBCL.Conclusions:It is advisable to detect concentration in serum and cerebrospinal fluids samples from R/R DLBCL patients using PD-1 inhibitors. The presence of PD-1 inhibitor in cerebrospinal fluids may serve as a biomarker for its efficacy for R/R DLBCL patients with CNS involvement. Whether there is a direct correlation between cerebrospinal concentration in cerebrospinal fluid and curative effect needs to be further confirmed.
B-cell lymphoma (BCL)-2 is an important protein involved in cell apoptosis signal pathway. It plays an important role in inhibiting cell apoptosis in vivo and is closely related to the occurrence and development of tumors, as well as the production of drug resistance. Venetoclax, as a highly selective oral anti-apoptotic protein BCL-2 inhibitor, can produce anti-tumor effects by restarting tumor cell apoptosis. At present, some important progresses of venetoclax alone or in combination with other drugs in treatment of hematological neoplasms have been made. This article will present the new clinical research progress of venetoclax in treatment of various hematological neoplasms, such as chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), multiple myeloma (MM), and acute myeloid leukemia (AML).
Background Intermediate-risk acute myeloid leukemia (IR-AML) without FLT3-ITD, NPM1 and biallelic CEBPA mutations (here referred to as NPM1(mut-neg)CEBPA(dm-neg)FLT3-ITDneg AML) is a clinically heterogeneous disease. The optimal post-remission therapy (PRT) is unclear for patients with NPM1(mut-neg)CEBPA(dm-neg)FLT3-ITDneg AML who achieved first complete response (CR1). This study aims to explore clinical and molecular factors that can help determine the prognosis of those patients and their choice of PRT. Methods We retrospectively analyzed 28 patients with NPM1(mut-neg)CEBPA(dm-neg)FLT3-ITDneg AML who received induction chemotherapy and achieved CR1. For PRT, 17 patients received post-remission chemotherapy (PR-CT) and 11 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results For patients with NPM1(mut-neg)CEBPA(dm-neg)FLT3-ITDneg AML, multivariate analysis indicated that allo-HSCT and negative minimal residual disease (MRDneg) before PRT were favorable prognostic factors of overall survival (OS) (allo-HSCT, P = 0.002; MRDneg, P = 0.018); whereas relapse was an adverse prognostic factor of OS (P = 0.003). Log-rank analysis showed that allo-HSCT significantly improved their OS and RFS compared with PR-CT (OS, P < 0.001; RFS, P = 001). Otherwise, allo-HSCT improved the OS and RFS of patients with NPM1(mut-neg)CEBPA(dm-neg)FLT3-ITDneg AML, whether they obtained MRDpos or MRDneg before PRT (OS: MRDneg, P = 0.036; MRDpos, P = 0.012; RFS: MRDneg, P = 0.047; MRDpos, P = 0.030). Conclusion For patients with NPM1(mut-neg)CEBPA(dm-neg)FLT3-ITDneg AML, MRDneg before PRT and allo-HSCT were favorable prognostic factors of OS. Whether they obtain MRDneg or not, allo-HSCT is the preferred PRT.