The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

INTRODUCTION: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a curative option for relapse/refractory (R/R) lymphomas that have failed autologous transplantation or for high-risk lymphomas in the upfront setting. We conducted a retrospective analysis on consecutive lymphoma patients who underwent allo-HSCT over a 20-year period (2003- 2022) at Singapore General Hospital and National University Hospital Singapore. METHOD: A total of 121 patients were included in the study. Median age was 41 years. Diagnoses include Hodgkin lymphoma (HL, 15%), B-cell non- Hodgkin lymphoma (B-NHL, 34%), T-cell non-Hodgkin lymphoma (T-NHL, 31%) and natural killer T-cell lymphoma (NKTL, 20%). Moreover, 27% of patients had prior auto-haematopoietic stem cell transplanta-tion (auto-HSCT), and 84% received reduced intensity conditioning (RIC). Donor types were matched sibling donor (45%), matched unrelated donor (29%), haploidentical donor (19%) and cord blood (CB, 7%). RESULTS: After median follow-up of 56 months, estimated 4-year progression-free survival (PFS) and overall survival (OS) for all patients were 38% and 45%, respectively. Non-relapse mortality (NRM) was 15% at day 100 and 24% at 1 year. On univariate analysis, complete remission status at transplant and RIC confers superior OS. On multivariate analysis, HL was associated with superior OS compared to NHL, whereas matched unrelated donor transplant was associated with significantly inferior OS compared to matched sibling donor. CONCLUSION Long-term curative durability was observed with allo-HSCT for patients with relapsed/ refractory lymphomas. This real-world data serves as a valuable historical benchmark for future studies on lymphomas in Singapore and the Asia Pacific region.
Humans ; Singapore/epidemiology* ; Adult ; Male ; Retrospective Studies ; Female ; Hematopoietic Stem Cell Transplantation/methods* ; Middle Aged ; Transplantation, Homologous ; Young Adult ; Transplantation Conditioning/methods* ; Lymphoma/mortality* ; Adolescent ; Hodgkin Disease/mortality* ; Aged ; Lymphoma, B-Cell/mortality*

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
Aged ; Betacoronavirus ; Coronavirus Infections ; complications ; mortality ; Extracorporeal Membrane Oxygenation ; Humans ; Lung Transplantation ; methods ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; complications ; mortality ; Pulmonary Fibrosis ; mortality ; surgery ; Respiratory Distress Syndrome, Adult ; mortality ; surgery

Heart failure (HF) is an important cardiovascular disease because of its increasing prevalence, significant morbidity, high mortality, and rapidly expanding health care cost. The number of HF patients is increasing worldwide, and Korea is no exception. There have been marked advances in definition, diagnostic modalities, and treatment of HF over the past four decades. There is continuing effort to improve risk stratification of HF using biomarkers, imaging and genetic testing. Newly developed medications and devices for HF have been widely adopted in clinical practice. Furthermore, definitive treatment for end-stage heart failure including left ventricular assist device and heart transplantation are rapidly evolving as well. This review summarizes the current state-of-the-art management for HF and the emerging diagnostic and therapeutic modalities to improve the outcome of HF patients.
Biomarkers ; Cardiovascular Diseases ; Diagnosis ; Genetic Testing ; Health Care Costs ; Heart Failure* ; Heart Transplantation ; Heart* ; Heart-Assist Devices ; Humans ; Korea ; Mortality ; Prevalence ; Prognosis

We investigated the value of autoantibodies as biomarkers of chronic graft-versus-host disease (cGVHD) by analyzing the autoantibody profiles of 65 patients (34 cGVHD and 31 non-cGVHD) surviving longer than three months after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Autoantibodies to at least one antigen were detected in 45 patients (70.8%), with multiple autoantibodies detected in 30 patients (46.2%). Antinuclear antibodies (ANAs) were the most frequently detected autoantibodies, with a significantly higher prevalence in non-cGVHD patients and cGVHD patients than that in healthy controls (HCs). ANA-nucleolar (ANA-N) was the main immunofluorescence pattern of ANA-positivity in both the non-cGVHD and cGVHD groups. There was a higher prevalence of anti-Ro52-positivity in non-cGVHD and cGVHD patients than in HC. Liver cGVHD was significantly associated with anti-Ro52-positivity. However, cGVHD activity and severity were not associated with the presence of autoantibodies. Similarly, there were no significant differences in overall survival or relapse among the four groups of patients expressing autoantibodies. Our results suggest that autoantibodies have limited value in predicting cGVHD.
Adolescent ; Adult ; Aged ; Antibodies, Antinuclear/blood* ; Autoantibodies/blood* ; Biomarkers/blood* ; Chronic Disease ; Female ; Graft vs Host Disease/diagnosis* ; Hematopoietic Stem Cell Transplantation/mortality* ; Humans ; Male ; Middle Aged ; Recurrence ; Transplantation, Homologous ; Young Adult

OBJECTIVE: Abnormal body composition is an important modifiable risk factor in lung transplantation. Therefore, precise quantification of different body components, including muscle and fat, may play an important role in optimizing outcomes in lung transplant patients. The purpose of the study was to investigate the prognostic significance of muscle and subcutaneous fat mass measured on chest CT with regard to lung transplantation survival and other post-transplant outcomes. MATERIALS AND METHODS: The study population included 45 consecutive adult lung transplant recipients (mean age of 47.9 ± 12.1 years; 31 males and 14 females) between 2011 and 2017. Preoperative cross-sectional areas of muscle and subcutaneous fat were semi-automatically measured on axial CT images at the level of the 12th thoracic vertebra (T12). Additional normalized indexed parameters, adjusted for either height or weight, were obtained. Associations of quantitative parameters with survival and various other post-transplant outcomes were evaluated. RESULTS: Of the 45 patients included in the present study, 10 mortalities were observed during the follow-up period. Patients with relative sarcopenia (RS) classified based on height-adjusted muscle area with a cut-off value of 28.07 cm²/m² demonstrated worse postoperative survival (log-rank test, p = 0.007; hazard ratio [HR], 6.39:1) despite being adjusted for age, sex, and body mass index (HR, 8.58:1; p = 0.022). Weight-adjusted parameters of muscle area were negatively correlated with duration of ventilator support (R = −0.54, p < 0.001) and intensive care unit (ICU) stay (R = −0.33, p = 0.021). CONCLUSION: Patients with RS demonstrate worse survival after lung transplantation that those without RS. Additionally, quantitative parameters of muscles measured at the T12 level on chest CT were associated with the duration of post-lung transplant ventilator support and duration of stay in the ICU.
Adult ; Body Composition ; Body Mass Index ; Cohort Studies ; Follow-Up Studies ; Humans ; Intensive Care Units ; Lung ; Lung Transplantation ; Male ; Mortality ; Muscles ; Retrospective Studies ; Risk Factors ; Sarcopenia ; Spine ; Subcutaneous Fat ; Thorax ; Tomography, X-Ray Computed ; Transplant Recipients ; Ventilators, Mechanical

Multiple studies have shown that oral antiviral therapies reduced the incidence of hepatocellular carcinoma (HCC) and improved the survival of patients with chronic hepatitis B when compared with that of untreated patients. In particular, entecavir and tenofovir share the qualities of high efficacy in reducing the HBV DNA levels, and they have excellent tolerability and safety. These drugs modified the natural history of liver fibrosis, improve liver function, decrease the incidence of HCC, decrease the need for liver transplantation, and improve survival. Many studies have suggested that long-term antiviral therapy reduces the risk of HCC and liver cirrhosis in patients with chronic hepatitis. The mechanism of these drugs in reducing the risk of HCC is not clear. This article reviews the mechanisms of carcinogenic HBV by conducting a review of the literature on the efficacy of therapy for reducing the risk of HCC. A few recent articles have suggested that tenofovir offers advantages over entecavir in terms of HCC prevention, but these articles have the inherent limitations of observational data. No other head-to-head randomized trials exist. Further randomized studies would help provide stronger evidence of the association between the type of antiviral agent and the HCC outcomes. Only achieving complete viral eradication from the liver will truly decrease the mortality and incidence of HCC.
Antiviral Agents ; Carcinoma, Hepatocellular ; DNA ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Incidence ; Liver ; Liver Cirrhosis ; Liver Transplantation ; Mortality ; Natural History ; Tenofovir

BACKGROUND: Kidney transplant is always emergent operations and frequently need to be performed at nighttime to reduce cold ischemia time (CIT). Previous studies have revealed that fatigue and sleep deprivation can result in adverse consequences of medical procedures. This study aimed to evaluate whether nighttime operation has adverse impact on kidney transplant. METHODS: A retrospective analysis of recipients accepted kidney transplant from deceased donors in one center from 2014 to 2016 was performed. Daytime transplant was defined as operation started after 8 AM or ended before 8 PM and nighttime operation was defined as operation ended after 8 PM or started before 8 AM. The incidences of complications such as delayed graft function, acute rejection, surgical complications and nosocomial infections were compared between 2 groups. Student's t-test was used to analyze continuous variables such as serum creatinine (Scr) at 1-year of post-transplant. The Chi-square test was used to analyze categorical variables. Differences in recipients and graft survival were analyzed using Kaplan-Meier methodology and log-rank tests. RESULTS: Among the 443 recipients, 233 (52.6%) were classified into the daytime group and the others 210 (47.4%) were in the nighttime group. The 1-year survival rate of recipients was similar for the recipients in the daytime and nighttime groups (95.3% vs. 95.2%, P = 0.981). Although the 1-year graft survival rate in the nighttime group was slightly superior to that in the daytime group, the difference was not significant (92.4% vs. 88.4%, P = 0.164). Furthermore, Scr and incidence of complications were also not significantly different between the 2 groups. CONCLUSIONS Our results suggested that operation time of kidney transplant with short CIT has no significant impact on the outcome of kidney transplant. Nighttime operation of kidney transplant with short CIT could be postponed to the following day to alleviate the burden on medical staffs and avoid the potential risk.
Adult ; Cadaver ; Cold Ischemia ; Female ; Graft Survival ; Humans ; Kidney Transplantation ; adverse effects ; mortality ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Time Factors

BACKGROUND: Non-Hodgkin T/NK cell lymphoma is a rare and widely variable type of lymphoma with the most dismal prognosis. This study aimed to investigate varied impact of the clinical indicators to the overall survival (OS). METHODS: We conducted a retrospective study to identify the non-invasive clinical features of T cell lymphoma that can predict prognosis with an innovative analysis method using quantile regression. A total of 183 patients who visited a top-tier hospital in Beijing, China, were enrolled from January 2006 to December 2015. Demographic information and main clinical indicators were collected including age, erythrocyte sedimentation rate (ESR), survival status, and international prognostic index (IPI) score. RESULTS: The median age of the patients at diagnosis was 45 years. Approximately 80% of patients were at an advanced stage, and the median survival time after diagnosis was 5.1 months. Multivariable analysis of the prognostic factors for inferior OS associated with advanced clinical staging [HR=3.16, 95%CI (1.39-7.2)], lower platelet count [HR = 2.57, 95%CI (1.57-4.19), P < 0.001] and higher IPI score [HR = 1.29, 95%CI (1.01-1.66), P = 0.043]. Meanwhile, T cell lymphoblastic lymphoma [HR = 0.40, 95%CI (0.20-0.80), P = 0.010], higher white blood cell counts [HR = 0.57, 95%CI (0.34-0.96), P = 0.033], higher serum albumin level [HR = 0.6, 95%CI (0.37-0.97), P = 0.039], and higher ESR [HR = 0.53, 95%CI (0.33-0.87), P = 0.011] were protective factors for OS when stratified by hemophagocytic lymphohistiocytosis (HLH). Multivariable quantile regression between the OS rate and each predictor at quartiles 0.25, 0.5, 0.75, and 0.95 showed that the coefficients of serum β2-microglobulin level and serum ESR were statistically significant in the middle of the coefficient curve (quartile 0.25-0.75). The coefficient of IPI was negatively associated with OS. The coefficients of hematopoietic stem cell transplantation (HSCT) and no clinical symptoms were higher at the middle of the quartile level curve but were not statistically significant. CONCLUSIONS The IPI score is a comparatively robust indicator of prognosis at 3 quartiles, and serum ESR is stable at the middle 2 quartiles section when adjusted for HLH. Quantile regression can be used to observe detailed impacts of the predictors on OS.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Large B-Cell, Diffuse ; mortality ; pathology ; Lymphoma, Non-Hodgkin ; mortality ; pathology ; Lymphoma, T-Cell ; mortality ; pathology ; Male ; Middle Aged ; Prognosis ; Regression Analysis ; Retrospective Studies ; Survival Rate ; Young Adult

Adolescent ; Busulfan ; therapeutic use ; Child ; Child, Preschool ; Cyclophosphamide ; therapeutic use ; Cyclosporine ; therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Infant ; Leukemia ; drug therapy ; mortality ; therapy ; Leukemia, Myeloid, Acute ; drug therapy ; mortality ; therapy ; Male ; Mycophenolic Acid ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; mortality ; therapy ; Retrospective Studies ; Treatment Outcome