Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by hyperinflammation. Primary HLH (primary HLH), resulting from genetic mutations, is a subtype of HLH. The mutation spectrum of primary HLH-associated genes has not been well determined in China. This study aimed to explore the mutation spectrum of 12 primary HLH-associated genes in a multicenter database. Medical records and gene sequencing data of 1224 HLH patients were retrieved from January 2014 to September 2024, and gene mutations were analyzed. Genetic variants were observed in 350 (28.59%) patients. Among them, 108 patients had a definitive genetic diagnosis, 227 patients carried single heterozygous variants, and 15 patients carried digenic/polygenic heterozygous variants. A total of 275 different variants were identified, and missense variants were most common. Variants in UNC13D were most common, followed by LYST and PRF1, while variants in MAGT1, ITK, and CD27 were rare. For UNC13D, LYST, and PRF1, variants c.2588G>A (p.Gly863Asp), c.368A>G (p.His123Arg), and c.1349C>T (p.Thr450Met) were most common, respectively. We described the mutation spectrum of primary HLH-associated genes in a largest Chinese cohort and found some mutation specificity for Chinese HLH patients. Our data might help design sequencing panels, interpret sequencing results, and understand genetic background of Chinese HLH patients.

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.

BackgroundSubstance use, including tobacco, high alcohol use, and drug use, has negative consequences on the health, economy, productivity, and social aspects of communities. Understanding trends in the burden by age, over time, and location and sex is important for policymaking. This study aims to provide a comprehensive estimation of the global burden attributable to substance use.MethodsUsing data from the Global Burden of Disease study (GBD) 2021, we estimated the burden attributable to substance use in terms of the number and age-standardized rates (ASRs) of deaths and disability-adjusted life years (DALYs) from 1990 to 2021. Using histogram plots, world maps, and Pearson’s correlation analysis, we conducted a stratified analysis of substance use by sex, age, geographic location, sociodemographic index (SDI) level, and disease. Additionally, the Bayesian model for age-period-cohort was introduced to forecast the burden.ResultsIn 2021, substance use was responsible for a substantial burden globally. From 1990 to 2021, the number of deaths and DALYs increased for nearly all substance use subtypes, while the age-standardized death rate (ASDR) and age-standardized DALY rate (ASDALYR) decreased. Furthermore, trends varied significantly by age, sex, geographic region, and SDI. The ASRs for all substance use subtypes were higher in male individuals than in female individuals, with the exception of secondhand smoke. Colder regions were associated with a higher burden attributable to high alcohol use, whereas the burden attributable to drug use increased with higher SDI levels. The burden attributable to chewing tobacco was notably more pronounced in South Asia than in other regions. Drug use disproportionately affected the 20–45 years age group. Projections indicate that the burden attributable to drug use and chewing tobacco will increase consistently from 2022 to 2040.ConclusionSubstance use is an important contributor to the global disease burden. Population-specific interventions, including raising taxes, increasing price, formulating laws and regulations, and raising public awareness on the risks of substance use, should be implemented to prevent and reduce the substance use burden.

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.

BackgroundAnemia remains a significant global health challenge, disproportionately affecting women of reproductive age (WRA, 15 to 49 years) due to physiological and socioeconomic factors. However, there is a lack of high-quality data on anemia burden and causes analysis in this population. The aim of this study is to provide a comprehensive global assessment of anemia burden and its underlying causes among WRA.MethodsUsing data from the Global Burden of Disease Study (GBD) 2021, we evaluated the prevalence, years lived with disability (YLDs), and underlying causes of anemia among WRA at global, regional, and national levels. We also evaluated the association between anemia burden and the socio-demographic index (SDI), quantified temporal trends of anemia burden from 1990 to 2021, and projected future burden to 2030.ResultsGlobally in 2021, there were 657.09 million (95% uncertainty interval [UI]: 643.59 to 671.22) anemia cases and 18.07 million (95% UI: 12.00 to 26.17) YLDs among WRA. The global age-standardized prevalence rates (ASPR) and YLDs rates per 100,000 were 33,716.77 (95% UI: 33,023.84 to 34,441.71) and 927.03 (95% UI: 615.40 to 1,342.99) in 2021, and they decreased by 0.181% and 0.539% annually from 1990 to 2021, respectively. However, the decline in ASPR stagnated after 2009, with a slight increase observed through 2021, primarily driven by rising mild anemia. An inverse relationship existed between SDI and anemia burden across regions and nations. The most common causes of anemia were dietary iron deficiency, hemoglobinopathies and hemolytic anemias, and other neglected tropical diseases, with HIV/AIDS and malaria being most prominent in specific regions. Projections indicate anemia cases and YLD counts will rise consistently from 2022 to 2030, while ASPR and age-standardized YLD rates will decline.ConclusionAnemia among WRA is a major public health burden worldwide with persistent regional and socioeconomic disparities. Mitigating this burden requires continued efforts addressing underlying causes, reducing socioeconomic inequities, and improving access to healthcare and nutritional interventions.

BACKGROUND:Patients with hematologic malignancies are at high risk of dying from infectious diseases. However, little attention has been paid to infectious diseases mortality (IDM) in these patients. The aim of our study is to determine the incidence and trends of IDM in patients with hematologic malignancies, identify risk factors associated with IDM, and compare the risk of IDM in patients with the general United States population. METHODS:The data of patients with hematologic malignancies between 2000 and 2020 was retrieved from the Surveillance, Epidemiology, and End Results program. Standardized mortality ratios (SMRs) and IDM rates were calculated. A competing risk model was performed to identify potential risk factors of IDM. RESULTS:Among 700,678 patients, 15,028 IDM were identified with an IDM rate of 401.31/100,000 person-years. Compared with the general population, the SMR of IDM was 3.34, and the elevated risk of IDM ran through the follow-up period. For all cancer subtypes, the IDM rates were highest in the first 2 months after diagnosis and gradually declined thereafter. For all patients, the early period of diagnosis, older age, male, non-Hispanic black, single or divorced/separated/widowed status, no chemotherapy, and no radiation were risk factors for IDM. For patients with Hodgkin lymphoma or non-Hodgkin lymphoma, advanced stage was also a risk factor for IDM. CONCLUSION:Given the high risk of IDM in patients with hematologic malignancies, it is extremely important to identify patients at high risk of IDM and provide timely intervention to prevent early death from infections and improve prognosis.

Background:Hemophagocytic lymphohistiocytosis can be classified as primary HLH (pHLH) and secondary HLH. The early identify of pHLH can facilitate successful treatment. The rapid screening test greatly facilitated the diagnostic process of pHLH. However, there are rare studies to explore the ability of sCD25 and cytotoxic T lymphocytes (CTLs) degranulation test to rapidly screen pHLH. Methods:We validated the accuracies of sCD25 and CTLs degranulation test in screening pHLH in 1224 clinically confirmed or suspected HLH patients through calculating area under the curve (AUC) and diagnostic parameters at optimal threshold. Results:The sensitivities of sCD25 to identify pHLH with defects in cytotoxic pathway genes was 75.9%, with specificities of 57.3% and AUC of 0.640. The sensitivities of CTLs degranulation test to identify pHLH with defects in degranulation pathway genes was 87.0%, with specificities of 69.0% and AUC of 0.794. The sensitivities of combination of sCD25 and CTLs degranulation test to identify pHLH with defects in cytotoxic pathway genes was 90.0%, with specificities of 69.8% and AUC of 0.833. Conclusion:For identifying pHLH, CTLs degranulation test is more sensitive and no less specific than sCD25 and the combination of sCD25 and CTLs degranulation test can improve the accuracy further.

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.

Despite radiotherapy (RT) is recognized as preferred initial therapy for early-stage low-grade follicular lymphoma (FL) by many international practice guidelines, the medical oncologist has improperly underutilized RT, and diverse management strategies, including systemic therapy (ST), combined modality (CM) and watch and wait (WW), are still used. Except survival outcomes, previous studies concerned little about the treatment-related toxicity, which is also important factor in choosing initial management strategy, especially second primary malignancies (SPMs). The aim of this study was to compare the overall survival (OS) and the SPMs risk between different management strategies, which can provide guidance for the choice of optimal initial management strategy. Data was acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Finally, A total 10,900 patients were identified, in which 930 cases developed SPMs. The use of radiotherapy (RT) has remained consistently low, with a utilization rate of around 20%, while most patients have received watchful waiting (WW) and systemic therapy (ST). In the rituximab era, multivariate analysis indicated that RT exhibited significantly superior OS and did not increase SPMs risk in comparison with ST and WW. At the same time, although there were no significant differences in OS between CM and RT, RT had significantly lower SPMs risk in comparison with CM. The use of RT improved the OS and did not increase the SPMs risk in comparison with other management strategies. Considering the low application rate of RT, oncologists should emphasize and increase the use of RT as an initial management strategy in patients with early-stage low-grade FL.

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.

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.

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.

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.

OBJECTIVE To investigate the incidence, clinical features of U2AF1 gene mutation in patients with acute myeloid leukemia(AML) and its effect of prognosis. METHODS A total of 161 patients with AML were enrolled. The second-generation sequencing method was used to detect U2AF1 gene mutation, and the relationship between U2AF1 mutation and clinical features, prognosis was analyzed. RESULTS The mutation rate of U2AF1 gene in 161 AML patients was 3.73%. The counts of peripheral blood leukocytes and platelets in the U2AF1 gene mutation group were lower than those in the wild type group. The complete response rate of U2AF1 gene mutation group was 66.67%, while that in wild type group was 55.48%, which shows no significant difference between the two groups (P=0.70). The median EFS of wild type group and the mutant group was not reached and reached to 133 days, respectively (P=0.03), while the medium OS in two groups was not reached and reached to 210 days (P=0.01). CONCLUSION The AML patients with U2AF1 mutation positive have a poor prognosis as compared with the wild type group, which may be a poor prognostic factor for acute myeloid leukemia.

OBJECTIVE:To analyze the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of acute leukemia in the tropical area.METHODS:Twelve acute leukemia patients who were underwent allo-HSCT from April 2013 to November 2018 in Hainan Hospital of Chinese PLA General Hospital were selected, including 5 cases of acute lymphoblastic leukemia (ALL) and 7 case of acute myeloid leukemia (AML). Three cases received HLA matched sibling hematopoietic stem cell transplantation, 8 cases received haploidentical hematopoietic stem cell transplantation, 1 cases received partially mismatched unrelated hematopoietic stem cell transplantation. Pretreatment regimen: 9 cases received modified BU/CY+ATG pretreatment regimen, 3 cases received BU/CY pretreatment regimen. Graft-versus-host disease (GVHD) prevention regimen: all patients received cyclosporine A, mycophenolate mofetil combined with short-term methotrexate regimen. The clinical efficacy of allo-HSCT in treatment of acute leukemia in the tropical area was analyzed by detecting hematopoietic reconstitution, GVHD, infection, relapse and survival after transplantation.RESULTS:All the 12 patients achieved granulocyte reconstruction and megakaryocyte reconstruction. The median time of granulocyte reconstruction was 11.5 (6-14) days, and the median time of megakaryocytic reconstruction was 12.5 (10-22) days. Within 100 days after transplantation, the acute GVHD occurved in 8 cases, including 6 cases of Ⅱ-Ⅳ degree acute GVHD and 2 cases of Ⅲ-Ⅳ degree acute GVHD, 11 cases survived more than 100 days after transplantation, and the chronic GVHD occurred in 1 case, which was mildly limited. Pulmonary infection occurred in 7 cases, cytomegaloviremia occurred in 6 cases, EB viremia occurred in 6 cases, and hemorrhagic cystitis occurred in 5 cases. 2 cases relapsed and eventually died, and the remaining 10 patients survived without disease until the date of follow-up. The median follow-up time was 4 (1-68) months, 83.3% (10/12) survived without disease, and 16.7% (2/12) relapsed.CONCLUSION:Allo-HSCT is an effective method for the treatment of acute leukemia in adults. Leukemia patients should be transplanted as soon as possible after remission. The incidence of pulmonary fungal infection in transplanted patients in tropics is high, therefore the prevention and treatment of fungal infection should be strengthened.