Search

Qiaoding Dai,1 Di Zhou,2 Liping Xu,1 Xinwei Song1 1Department of Rheumatology and Immunology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang, People’s Republic of China; 2Nephrology Department, First People’s Hospital of Xiaoshan District, Hangzhou 311200, Zhejiang, People’s Republic of China Purpose: Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease characterized by aggressive and symmetric polyarthritis. Mammalian target of rapamycin (mTOR) was reported to be a new target for RA therapy and its inhibitor rapamycin can significantly reduce the invasive force of fibroblast-like synoviocytes. Here, we determined the effect of curcumin to alleviate inflammation and synovial hyperplasia for the therapy of RA.Materials and methods: Collagen-induced arthritis (CIA) was developed in Wistar rats and used as a model resembling RA in humans. Rats were treated with curcumin (200 mg/kg) and the mTOR inhibitor rapamycin (2.5 mg/kg) daily for 3 weeks. Effects of the treatment on local joint, peripheral blood, and synovial hyperplasia in the pathogenesis of CIA were analyzed.Results: Curcumin and rapamycin significantly inhibited the redness and swelling of ankles and joints in RA rats. Curcumin inhibited the CIA-induced mTOR pathway and the RA-induced infiltration of inflammatory cells into the synovium. Curcumin and rapamycin treatment inhibited the increased levels of proinflammatory cytokines including IL-1β, TNF-α, MMP-1, and MMP-3 in CIA rats.Conclusion: Our findings show that curcumin alleviates CIA-induced inflammation, synovial hyperplasia, and the other main features involved in the pathogenesis of CIA via the mTOR pathway. These results provide evidence for the anti-arthritic properties of curcumin and corroborate its potential use for the treatment of RA. Keywords: rheumatoid arthritis, curcumin, rapamycin, mammalian target of rapamycin, collagen-induced arthritis

Hai-Fei Chen,1,2 Li-Ping Xu,1 Zhi-Yong Luo,1 Zi-Qiang Yu,2 Zheng-Yang Li,1 Qing-Ya Cui,1 Long-Mei Qin,1 Yong-Ya Ren,1 Hong-Shi Shen,1 Jie-Qing Tang,1 Ling-Juan Jin,1 Jing-Jing Zhu,1 Jing Wang,1 Ke-Yuan Wang,1 Tian-Qin Wu,1 Zhao-Yue Wang21Department of Hematology, 100th Hospital of People's Liberation Army, 2Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, People's Republic of ChinaAbstract: A 41-year-old male had suffered from gradual hearing loss in his right ear for 2 years. Head computed tomography and magnetic resonance imaging scans showed a neoplasm in the cerebellopontine angle region, which was confirmed by the diagnosis of acoustic neurilemmoma by pathological findings after surgery. Following surgery, he routinely received valproic acid (VPA) to prevent seizures. However, the patient presented with hypofibrinogenemia and cerebral hemorrhage after taking VPA for 12 days. The hypofibrinogenemia recurred when VPA was re-administered. After withdrawal of VPA, his fibrinogen concentration rose to normal within several days. As far as we are aware, this is the first case of cerebral hemorrhage due to VPA to have been reported. Herein, as well as reporting on this case, a mini review of the relevant literature is also presented.Keywords: side effect, hypofibrinogenemia, cerebral hemorrhage, cerebellopontine angle, neoplasm

Skeletal editing represents an attractive strategy for adding complexity to a given molecular scaffold in chemical synthesis. Isodesmic reactions provide a complementary skeletal editing approach for the redistribution of chemical bonds in chemical synthesis. However, catalytic enantioselective isodesmic reaction is extremely scarce and enantioselective isodesmic reaction to synthesize atropisomeric compounds is unknown. Herein, we report a facile method to synthesize axially chiral aminoaryl quinoxalines through Cu(I)-catalyzed dearomatization and sequential chiral phosphoric acid (CPA) catalyzed enantioselective isodesmic C-N bond formation and cleavage from indoles and 1,2-diaminoarenes under mild reaction conditions. In this process, the five-membered ring of the indole scaffold was broken and a novel quinoxaline skeleton was constructed. This method allows the practical and atom-economical synthesis of valuable axially chiral aminoaryl quinoxalines in high yields (up to 95 %) and generally excellent enantioselectivities (up to 99 % ee). Notably, this novel type of quinoxaline atropisomers has promising applications in developing axially chiral ligand in asymmetric catalysis. This strategy represents the first example of CPA-catalyzed enantioselective isodesmic reaction to form axially chiral compounds., (© 2024 Wiley-VCH GmbH.)

To validate the ability of the haematopoietic cell transplantation comorbidity index (HCT-CI) to predict the outcomes of patients with severe aplastic anaemia (SAA) receiving haploidentical haematopoietic stem cell transplantation (haplo-HSCT), we conducted a retrospective study including 530 SAA patients. Patients were stratified based on their HCT-CI scores into three distinct risk categories: low-risk (HCT-CI scores of 0, n = 343), intermediate-risk (HCT-CI scores of 1, n = 126), and high-risk groups (HCT-CI scores ≥ 2, n = 61). The 100-day platelet engraftment rate was significantly higher in the low-risk group compared to the intermediate-risk and high-risk groups (92.1% vs. 86.5% vs. 83.6%, P = 0.014). In addition, compared with the intermediate-risk and high-risk groups, the low-risk group demonstrated superior 5-year overall survival (OS, 91.8% vs. 83.3% vs. 70.1%, P < 0.001) and graft-versus-host disease-free/graft failure-free survival (GFFS, 80.1% vs. 71.3% vs. 63.6%, P = 0.009). Multivariate analysis revealed that elevated HCT-CI scores and previous antithymocyte globulin treatment were independent risk factors for OS, whereas elevated HCT-CI scores and donor age ≥ 40 years were correlated with worse GFFS. Consequently, the HCT-CI is associated with the clinical outcomes of SAA patients following haplo-HSCT, and it is imperative to closely monitor patients with a high comorbidity burden., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Experience using olverembatinib as maintenance therapy in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) after allogeneic hematopoietic cell transplantation (allo-HCT) is limited. We retrospectively collected data from 26 patients with Ph + ALL who received only olverembatinib as maintenance therapy after allo-HCT. Olverembatinib was administered as prophylaxis in 18 patients (69.2%), and preemptively in 8 patients (30.8%). The median time of olverembatinib initiation after transplantation was 2.5 months (range, 1-7.3). The median starting dose of olverembatinib was 35 mg qod (range, 15-40). The median duration of olverembatinib treatment was 12.5 months (range, 6-23). Olverembatinib maintenance treatment was discontinued in 8 patients (8/26,30%), seven stopped the drug for a long-lasting BCR-ABL1 negativity and 1 for recurrent fever associated with the drug. BCR-ABL1 turned positive in 3 patients in 2, 3 and 6 months after discontinuation. During olverembatinib treatment, three patients developed grade ≥ 3 hematologic side effects, which resolved with dose interruption or dose reduction. The median follow-up time after allo-HCT were 17.75 months (range 7-31). The hematologic relapse rate was 7.7% (2/26), with no event in the preemptive group. The 3-year probability of overall survival and relapse free survival after allo-HCT was 91.7% and 79.1%, respectively. Only one patient in prophylaxis group died of central central nervous system (CNS) relapse. Thus, our data suggest that olverembatinib is effective and safe as maintenance treatment in patients with Ph + ALL who underwent allo-HSCT. The main adverse effect was hematologic toxicity, which was tolerated., Competing Interests: Declarations. Ethical approval: All procedures were conducted in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, revised in 2008. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: Informed consent was obtained from all individual participants included in the study. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

A novel reduced-toxicity conditioning (RTC) regimen of busulfan, fludarabine, cyclophosphamide, and antithymocyte globulin (Bu/Flu/Cy/ATG) followed by haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in older patients with hematologic malignancies has been reported and the results was encouraging. However, the safety and efficacy of this regimen was unknown in older myelodysplastic neoplasms (MDS) patients. From January 2018 to December 2021, 68 consecutive older patients (aged over 50) using the RTC regimen for T-cell replete haplo-HSCT (RTC group) at our center were eligible, 68 patients aged under 50 using modified busulfan, cyclophosphamide plus antithymocyte globulin regimen (Bu/Cy/ATG) (Bu/Cy/ATG group) were randomly selected from 223 MDS patients during the same period in a 1:1 ratio matched-pair analysis for patient sex, World Health Organization (WHO) category, international prognostic scoring system (IPSS) risk group, time from diagnosis to HSCT, chemotherapy in advanced, response after chemotherapy, donor sex, infused mononuclear cells and the CD34-positive cell count. The transplant outcomes were also compared between the RTC group and the matched sibling donor (MSD) haploidentical stem cell transplantation (HSCT) with the busulfan and cyclophosphamide (Bu/Cy) conditioning regimen. The cumulative incidences of grade II-IV acute graft versus host disease (aGVHD) in the RTC group were significantly lower than that in the Bu/Cy/ATG group. The 3-year cumulative incidences of treatment related mortality (TRM) in the two groups were 12.3% versus 14.7% (P=0.613). The cumulative incidences of relapse, disease-free survival (DFS) and overall survival (OS) were comparable between the two groups. The outcomes were better in RTC group than those patients received MSD transplant, with lower incidence of TRM, and higher OS and DFS. The advantages were still significant when comparing patients receiving children donors HSCT in RTC group with MSD transplant in survival and TRM. Children donor with the RTC regimen could be a better choice than the MSD HSCT with Bu/Cy regimen for the elderly MDS patients. The encouraging results suggest that the RTC regimen followed by haplo-HSCT is a potentially promising method for older MDS patients. The trail number of the prospective study is "NCT03412409" and the trial URL is "https://clinicaltrials.gov/study/NCT03412409?term=NCT03412409&rank=1"., Competing Interests: None., (AJCR Copyright © 2025.)

Acute myocardial infarction (AMI) accounts for a significant proportion of global fatalities, and early detection is crucial for improving patient outcomes. However, current diagnostic methods often struggle to detect AMI in its early stages. Herein, we present an electrochemical sensor utilizing a fractal gold (FracAu) electrode and hybridization chain reaction (HCR) amplification technology to detect AMI-specific microRNAs (miRNAs). When the target sequence was added, the HCR was triggered, leading to the formation of a long-nicked DNA double helix that efficiently captured a larger quantity of positively charged RuHex molecules, resulting in significant electrochemical signal amplification. More importantly, to avoid false positive signals, exonuclease I (Exo I) was introduced to selectively cleave single-stranded DNA (ssDNA) probes. These ssDNA probes, underwent random hydrolysis from hpDNA probes, could hybridize with helper DNA1 in the absence of the target, initiating the HCR process and producing a false positive signal. The inclusion of Exo I effectively avoided false positive signals and reduced background noise. Under optimized conditions, the fabricated sensor exhibited significant sensitivity and selectivity, showing a broad linear detection range from 10 pM to 10 nM and a low limit of 0.9 fM. The fabricated electrochemical sensor also successfully detected AMI-specific miRNA in real serum samples, underscoring its diagnostic promise. By providing a reliable tool for early detection, the innovative sensor holds significant potential in combating global cardiovascular disease-related mortality rates.

Objective: This study aimed to investigate the clinical characteristics of oral mucositis (OM) in patients with hematological diseases who received secondary allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: This study retrospectively analyzed data on 58 patients with hematological diseases who underwent secondary allo-HSCT at the Peking University People's Hospital from January 2018 to December 2023. The control group included 116 randomized patients after primary allo-HSCT during this period (1:2 ratio) with matched gender, age, and diagnosis. The incidence of OM and overall survival (OS) were compared between the two groups. Results: The secondary allo-HSCT and control groups reported 17 (29.31%) and 16 (13.79%) cases that developed OM ( P =0.014), whereas 10 (17.24%) and 7 (6.03%) developed grade ≥3 OM ( P =0.019). The median time for OM to occur was 4 days (1-9 days) and 5 days (1-10 days) posttransplantation in the secondary allo-HSCT and control groups, respectively. The multivariate analysis revealed that the use of whole-body radiation therapy as the main pretreatment regimen was an independent risk factor for OM occurrence ( P =0.019). Among patients with OM, an age of <55 years is a risk factor for developing grade 3-4 OM ( P =0.028). All patients who underwent the secondary allo-HSCT received granulocyte implantation. The median time of granulocyte implantation in 17 patients with OM was 14 days posttransplantation, whereas the median time of granulocyte implantation in patients without OM was 12 days posttransplantation. The difference was not statistically significant ( P =0.721). The presence of OM did not affect the occurrence of acute graft-versus-host disease ( P =0.938). No statistically significant difference was observed in the 2-year OS rate between patients with and without OM during the secondary allo-HSCT (51.9% vs 50.4%, P =0.943). No statistically significant difference was observed in the 2-year OS rate between patients with OM undergoing the secondary allo-HSCT and those undergoing the primary allo-HSCT (51.9% vs 81.3%, P =0.185) . Conclusions: The proportion of patients with concurrent OM was significantly increased in the secondary allo-HSCT, and the severity was more severe. Whether or not to merge OM does not affect granulocyte implantation, acute graft-versus-host disease incidence, and 2-year OS rate.

Myeloid sarcoma (MS) is a rare hematological neoplasm with poor prognosis, posing a significant clinical challenge due to the absence of effective and standardized treatments. We conducted a retrospective analysis of 162 MS patients treated at 12 centers to compare outcomes between intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our analysis revealed that allo-HSCT demonstrated superior overall survival (OS) within the initial 36 months compared to intensive chemotherapy alone (p = 0.037). However, beyond 36 months (36-60 months), a reverse trend was observed (p = 0.056). Subgroup analysis revealed potential benefit for isolated MS patients with allo-HSCT, but not for those with leukemic MS. Additionally, in patients achieving first complete remission (CR1) after induction chemotherapy, allo-HSCT did not significantly improve 5-year OS compared with intensive chemotherapy alone (p = 0.25). Conversely, allo-HSCT significantly improved 5-year OS in non-CR1 patients (p < 0.001). Notably, HLA-matched HSCT and haploidentical HSCT showed comparable outcomes in terms of OS, disease-free survival, and cumulative incidence of relapse. In conclusion, allo-HSCT improved outcomes for MS patients within 36 months of disease onset, and haploidentical HSCT emerged as a viable treatment option for patients without matched donors., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Relapse was the major cause of treatment failure in patients with myeloid malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients who still suffer from the disease while cannot be detected by morphological analysis can be identified by the minimal residual disease (MRD) monitoring. The most used first-line regimens for MRD are immunotherapies. However, for patients who were ineligible for or failed in first-line immunotherapies, options were limited., Methods: A total of 20 patients with myeloid malignancies with recurrent MRD after allo-HSCT were included in this study. The safety and efficacy of venetoclax-based regimens were analyzed., Results: There were 13 patients (65%) treated with venetoclax combined with hypomethylating agents concomitantly and seven patients (35%) treated with venetoclax monotherapy. After venetoclax-based regimens, MRD was eliminated in 11 patients (55%) with 6 subsequently developing recurrent MRD and 5 remaining in molecular remission. MRD declined in two patients (10%), and no responses in seven patients (35%). Among the two patients with declined MRD, one patient finally eliminated MRD after two cycles of the venetoclax-based regimen, and the other patient's MRD further declined after the second regimen. The objective response rate (ORR) was 65%. The median duration of response was 103 (12-313) days. The incidences of grades 3-4 neutropenia, anemia, and thrombocytopenia independently of pretreatment status were 30%, 20% and 20%, respectively., Conclusion: Venetoclax-based regimens are efficient and safe for MRD in patients with myeloid malignancies ineligible for or failed in the first-line immunotherapies after allo-HSCT.

Over past two years, a total of 39,918 hematopoietic stem cell transplantation (HSCT) cases were reported, with 18,194 and 21,714 transplants performed in 2022 and 2023, respectively. Autologous HSCT accounted for 6562 cases (31%) in 2022, while allogeneic HSCT comprised 12,632 cases (69%). In 2023, the number of allogeneic HSCTs exceeded 15,000, maintaining a 69% share. Participation in the 2022 and 2023 surveys included 193 and 212 transplantation teams, respectively, from 27 provinces, municipalities, or autonomous regions. The leading indication of HSCT was acute leukemia, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and mixed phenotype acute leukemia, with a total of 17,421 cases. AML was the most common disease (10,339, 38%) for allogeneic HSCT, which was followed by ALL (5925 cases, 21%). Peripheral blood emerged as the primary source of stem cell grafts, utilized in 54% of matched sibling donor transplants and 77% of haploidentical donor transplants. The BuCy-based conditioning regimen was the most prevalent, used in 53% of allogeneic HSCT cases in the past two years. This survey offers a comprehensive overview of the current HSCT landscape and serves as a valuable resource for clinical practice., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with CEBPA-bZIP mutation., Methods: Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with CEBPA-bZIP mutation. The nomogram model for leukemia-free survival (LFS) rate was generated by combining genetic abnormalities and clinical data. Risk stratification was conducted based on prognostic variables and the effect of risk-adjusted consolidation therapy was investigated by Kaplan-Meier method., Results: Four variables were finally included in our nomogram model after multivariate Cox analysis, and an equation for risk score calculation was obtained, risk score=1.300 2×white blood cell (WBC) (≥18.77×10 9 /L)+1.406 5× CSF3R mutation positive+2.648 9× KMT2A mutation positive+1.012 8×DNA methylation-related genes mutation positive. According to the nomogram model, patients were further divided into low-risk group (score=0, n =46) and high-risk group (score>0, n =95). Prognostic analysis showed that the 5-year LFS rate, 5-year overall survival (OS) rate, and 5-year cumulative incidence of relapse (CIR) of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the high-risk group were 93.5%, 97.1%, and 3.5%, while those in patients who received maintenance chemotherapy were 32.9%, 70.5%, and 63.4%, respectively. The differences were statistically significant (all P < 0.05). Allo-HSCT could significantly improve the prognosis of patients in high-risk group. However, no corresponding benefit was observed in the low-risk group., Conclusion: Adult CN-AML with CEBPA-bZIP mutation has a complex co-mutation pattern. The nomogram model based on mutations of CFS3R, KMT2A and DNA methylation-related genes together with WBC count can further divide this subset of patients into a relatively low-risk group and a relatively high-risk group. For individuals in the high-risk group, allo-HSCT is proposed as post-remission therapy. The above data will benefit the prognosis estimation and treatment decision for adult CN-AML with CEBPA-bZIP mutation.

The transition metal-catalysed dicarbofunctionalisation of unactivated alkenes normally requires exogenous strong coordinated directing groups, thus reducing the overall reaction efficiency. Here, we report a ligand-enabled Ni(II)-catalysed dicarbofunctionalisation of unactivated alkenes with aryl/alkenyl boronic acids and alkyl halides as the coupling partners with a diverse range of native functional groups as the directing group. This dicarbofunctionalisation protocol provides an efficient and direct route towards vicinal 1,2-disubstituted alkanes using primary, secondary, tertiary amides, sulfonamides, as well as secondary and tertiary amines under redox-neutral conditions that are challenging to access through conventional methods. The key to the success of this reaction is the use of a bulky β-diketone ligand, which could enable the insertion of alkene to aryl-Ni(II) species, stabilize the alkyl-Ni(II) species and inhibit the homolytic alkyl-Ni(II) cleavage, supporting by both experimental and computational studies. This dicarbofunctionalisation reaction features the use of native directing group, a broad substrate scope, and excellent scalability., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Not available.

We aimed to prospectively explore the risk factors for measurable residual disease (MRD) positivity after allogeneic stem cell transplantation (allo-SCT) in AML patients (n = 478). The cumulative incidences (CIs) of post-SCT MRD positivity at 100 days, 360 days and 3 years were 4.6%, 12.1% and 18.3%, respectively. Positive pre-SCT MRD and pre-SCT active disease were risk factors for post-SCT MRD positivity at both 360 days and 3 years (P < 0.001). European LeukemiaNet (ELN) 2017 risk stratification was a risk factor for positive post-SCT MRD at 360 days (P = 0.044). A scoring system for predicting post-SCT MRD positivity at 360 days was established by using pre-SCT MRD, pre-SCT active disease and ELN 2017 risk stratification. The CI of positive post-SCT MRD at 3 years was 13.2%, 23.7%, and 43.9% for patients with scores of 0, 1, and 2, respectively (P < 0.001). Multivariate analysis demonstrated that the scoring system was associated with a higher CI of post-SCT MRD positivity, leukemia relapse and inferior survival. Our data indicate that positive pre-SCT MRD status, pre-SCT active disease, and ELN 2017 risk stratification are risk factors for positive post-SCT MRD status in AML patients., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate Research was performed in compliance with all applicable guidelines and regulations. The study was performed in accordance with Declaration of Helsinki and was approved by Institutional Review Board of Peking University (Ethics Committee of Peking University People’s Hospital), the reference number was 2017PHB033-01. Informed consent All of the patients who were included in the study provided signed informed consent., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: This study aimed to analyze the clinical manifestations of human herpesvirus 6 (HHV-6) infection within 100 days after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to investigate the association of HHV-6 viral load with clinical outcomes as well as the effect of antiviral treatment on the course of HHV-6 infection. Methods: This retrospective study included patients who tested positive for HHV-6 within 100 days after allo-HSCT at the Peking University Institute of Hematology from February 2016 to February 2023. The study analyzed the patients' baseline characteristics, including age and transplantation type, as well as their clinical manifestations. Additionally, post-transplant complications were examined. Results: This study detected that 305 patients with HHV-6 infection were positive with a median time of 20 days post-transplant. Fifteen patients were asymptomatic, whereas the remaining patients exhibited the following symptoms: fever, rash, diarrhea, hemorrhagic cystitis, delayed platelet engraftment, central nervous system symptoms, abdominal pain, pneumonia and perioral numbness. Acute graft-versus-host disease (aGVHD) was diagnosed in 189 patients, with 45 cases of HHV-6 infection occurring before the onset of aGVHD and 120 cases occurring after aGVHD developed. Quantitative HHV-6 detection was available for 45 patients, and no statistically significant differences were found in the clinical manifestations according to the viral titer. A total of 108 (35.41%) patients experienced coactivation with other viruses, including cytomegalovirus, BK virus, and Epstein-Barr virus (EBV). Notably, coinfection with EBV was determined as an independent risk factor for overall survival (OS). No statistically significant difference in the time to HHV-6 viral clearance was observed between the antiviral treatment and non-treatment groups [7 (5-10) days vs 8 (4-14) days, P =0.199]. Similarly, the 5-year OS rates between the two groups were not significantly different [ (82.7 ± 2.6) % vs (91.3 ± 3.1) %, χ (2)=3.304, P =0.069]. Discussion: The most prevalent clinical manifestations were fever, rash, and diarrhea in patients with HHV-6 infection after allo-HSCT. No significant correlation was found between the severity of the clinical symptoms and the viral titer. Additionally, no significant differences in the time to HHV-6 clearance or 5-year OS were observed between patients who received antiviral treatment and those who did not.

Objective: This study aimed to assess the infection status of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in healthy populations in China over the past decade and analyze the differences in CMV and EBV infection and related risk factors in healthy populations before and after the lifting of coronavirus disease 2019 (COVID-19) pandemic control measures. Methods: This study retrospectively analyzes the CMV and EBV infection status of 8 827 healthy donors who underwent prehematopoietic stem cell transplantation screening at Peking University People's Hospital from January 2014 to December 2023. Logistic regression analysis was conducted to determine the risk factors for CMV and EBV infection. Results: The CMV and EBV IgG positivity rates were 94.52% and 95.40% among the healthy donors, respectively, with no significant differences before and after the lifting of pandemic control measures (all P value>0.05). However, IgG antibody titers increased [CMV: (100.44±36.50) U/ml vs (109.98±36.31) U/ml, P <0.001; EBV: (281.57±226.79) U/ml vs (361.08±268.58) U/ml, P <0.001] after lifting the COVID-19 restrictions. However, the CMV IgM positivity rate remained unchanged. The EBV IgM positivity rate significantly increased after lifting measures (2.77% vs 6.29%, P <0.001), reaching 8.10% within 3 months. Further analysis of the factors affecting EBV IgM positivity revealed that gender ( OR =1.479, 95% CI 1.169-1.872, P =0.001), age[compared with the group younger than 18 years, the 18-50-year age group ( OR =0.584, 95% CI 0.421-0.820, P =0.002), the >50-year age group ( OR =0.389, 95% CI 0.248-0.610, P <0.001) ], and the lifting of COVID-19 restrictions ( OR =2.360, 95% CI 1.287-3.047, P <0.001) were independent factors influencing EBV IgM positivity in the general population. The EBV IgM positivity rate in individuals under 18 years old was not affected by gender or the lifting of COVID-19 restrictions when stratified by age group. Both genders ( OR =1.499, 95% CI 1.138 - 1.975, P =0.004) and the lifting of COVID-19 restrictions ( OR =2.608, 95% CI 1.940-3.507, P <0.001) were independent factors affecting EBV IgM positivity in the 18-50-year age group. The lifting of COVID-19 restrictions ( OR =2.222, 95% CI 1.101-4.484, P =0.026) was the sole independent factor affecting EBV IgM positivity in individuals over 50 years old. Conclusions: Previous infection rates of CMV and EBV are high in healthy populations in China, which increase with age. COVID-19 infection may increase EBV reactivation rates in healthy individuals, with a more pronounced effect on those aged >18 years.

Objective: To delineate the clinical characteristics and outcomes associated with severe cardiac toxicity during the preconditioning phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aplastic anemia (AA). Methods: This retrospective case series study included 31 patients with severe AA who underwent allo-HSCT and were diagnosed with severe cardiac toxicity at the Hematology Department of Peking University People's Hospital from August 2012 to June 2022. The clinical manifestations of severe cardiac toxicity observed during the preconditioning process were assessed. Patient survival was assessed using the Kaplan-Meier method. Results: In this cohort of 31 patients, the median follow-up period was 9 days (range: 4-365 days). Severe cardiac toxicity manifested within 6 days after the initial cyclophosphamide (Cy) administration. Twenty patients died within 30 days of initiating Cy preconditioning, of which 16 patients died due to severe cardiac toxicity within 25 days. Patients whose cardiac function improved within 30 days post-preconditioning showed a median survival duration of 222 days ( n =11). Troponin I (TNI) levels in patients who died within 30 days of initiating Cy preconditioning began increasing on day 5 post-Cy, peaking sharply by day 9 after a notable rise on day 8. B-type natriuretic peptide (BNP) levels in patients who died within 30 days of initiating Cy preconditioning started to rise from day 1, stabilized between days 2 and 5, and then doubled daily from days 6 to 8, remaining elevated thereafter. Notably, the initial increases in BNP and TNI correlated with electrocardiogram (ECG) signs of low voltage and T-wave inversion in 83.87% of cases ( n =26). Most patients ( n =28, 90.32%) were administered corticosteroid therapy. In those with restored cardiac function, the ejection fraction returned to >50% within 30 days of initiating Cy preconditioning. Conclusions: Patients with severe cardiac toxicity during the preconditioning phase of allo-HSCT typically exhibit early, sustained, and marked elevations in myocardial damage markers, including BNP and TNI, accompanied by ECG abnormalities following Cy administration, with BNP often increasing first. These indicators are associated with rapid disease progression and high mortality. Prompt initiation of treatment upon clinical diagnosis is critical for improving survival outcomes.

Patients with relapsed/refractory acute myeloid leukaemia (R/R AML), especially those who failed in novel target agents are related to dismal survival. We developed a multi-institutional, single-arm, prospective phase II trial, to investigate intensified conditioning with 'Mega-Dose' decitabine (MegaDAC) following allogeneic haematopoietic cell transplantation (allo-HCT) for R/R AML. From 2019 to 2023, 70 heavily treated R/R AML patients in active disease were consecutively enrolled. Significantly, every patient (n = 18) harbouring specific mutations exhibited no response to their best available target agents (BATs). Moreover, 74.3% of the enrolled patients did not reach remission following venetoclax-based regimens. All patients underwent intravenous decitabine (400 mg/m 2 ) along with busulfan and cyclophosphamide. Median follow-up was 26 months (8-65) after HCT. All engrafted patients achieved MRD negativity post-HCT, with a median 3.3-log reduction in recurrent genetic abnormalities. The regimen was well tolerated, without irreversible grades III-IV toxicity peri-engraftment. The estimated 2-year CIR was 29.6% (18.4%-41.7%) and the est-2-year NRM was 15.5% (7.8%-25.5%). The est-2-year LFS, OS, and GRFS were 55.0% (43.5%-69.4%), 58.6% (47.0%-73.0%), and 42.9% (31.9%-57.6%), respectively. Multivariate analysis showed that pre-HCT drug exposures had no significant impact on primary outcomes. MegaDAC is highlighted as an effective and safe option for R/R AML in the new era of targeted therapies., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Oral ulcers are a prevalent oral mucosal disorder, characterized by benignancy and self-limiting progression. However, a subset of these ulcers exhibits resistance to conventional therapeutic interventions, necessitating alternative treatment strategies. In this study, we present two cases of refractory oral ulcers that demonstrated limited responsiveness to standard treatments but achieved significant therapeutic benefits following the application of a compound Chinese herbal mouthwash. Case 1 involved a 60-year-old female patient diagnosed with Behçet's syndrome. Initial treatment with glucocorticoids and immunosuppressants yielded limited improvement in her oral ulcers; however, combination therapy involving the Chinese herbal mouthwash resulted in significant improvement and complete healing after a 2-week period. Case 2 presented a 48-year-old female patient with chronic tongue ulceration pain persisting for one year without any detectable systemic etiology. Despite receiving oral vitamin supplementation and local analgesic jelly, her symptoms remained unalleviated. A 3-week treatment regimen involving the administration of the Chinese herbal mouthwash in conjunction with thalidomide led to the complete resolution of her oral ulcers. The findings from this study suggest that the compound Chinese herbal mouthwash may serve as an adjuvant therapeutic approach for managing chronic oral ulcers that are resistant to conventional treatment., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The incidence of herpes zoster (HZ) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients is significantly higher than that of the general public. Although routine antiviral prophylaxis is recommended, late-onset HZ has been highlighted, yet limited information is known about its clinical features and predictors. Here, we conducted a retrospective nested case-control study to identify patients with late-onset HZ, defined as a diagnosis of HZ after 1 year of transplantation, among allo-HSCT recipients between 2012 and 2017 at Peking University People's Hospital. Three controls were matched for each patient. A total of 201 patients developed late-onset HZ. Age over 20 years, absence of neutrophil engraftment by 14 days, mental disorders, immunosuppressant use at 1 year, and a peripheral CD4+/CD8+ ratio ≥0.5 at 1 year were independent risk factors, among which the CD4+/CD8+ ratio demonstrated good discriminative power for predicting late-onset HZ. For patients with a CD4+/CD8+ ratio <0.5, patient age, neutrophil engraftment time, mental disorders, and immunosuppressant use were potential risk factors. A stratification algorithm was accordingly established, classifying the transplant recipients into three risk groups. Whether the algorithm could facilitate the administration of posttransplant antiviral prophylaxis merits further validation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Immunomagnetic particles are extensively used for the separation of biological molecules and particles, and have exhibited great potential in many fields including biosensors, disease diagnosis and biomedical engineering. However, most immunomagnetic particles exhibit a smooth surface, resulting in a limited separation efficiency for biological particles featuring enormous surface nanostructures, such as tumor cells. Here we report flower-like immunomagnetic particles (FIMPs) prepared by streptavidin (SA)-assisted biomineralization and one-step antibody modification, and demonstrate their superior capability for highly efficient and selective separation of circulating tumor cells (CTCs). SA can link inorganic nanosheets and magnetic nanoparticles together to obtain FIMPs with programmable hierarchical flower-like nanostructures and provide enormous binding sites for post-antibody modification. The synergetic effect of nano-sized petals and micro-sized particles in the hierarchical nanostructure enhances the interaction between the cells and the matrix, thus enabling FIMPs to separate CTCs with high selectivity and high efficiency. Our study provides a promising platform for the selective separation of trace biological molecules and particles from complex samples and shows great potential for downstream detection and diagnosis.

This study aimed to demonstrate the clinical outcomes of granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG), posttransplantation cyclophosphamide (PTCy) and PTCy combined with lowdose ATG (PTCy with ATGlow)-based haploidentical transplantation protocols in patients with haematologic malignancies. The comparisons were conducted via propensity score matching (PSM) analysis to balance the basic characteristics among different groups and were based on the transplantation data reported to the Chinese Bone Marrow Transplantation Registry Group (CBMTRG) from January 2020 to December 2022. For each patient in the PTCy or PTCy with ATGlow group, patients (at a 1:2 ratio) from the GCSF/ ATG group were selected. In total, the PTCy group (n=122) was matched with G-CSF/ATG Group 1 (n=230), and the PTCy+ATGlow group (n=123) was matched with G-CSF/ATG Group 2 (n=226). Compared with those in the PTCy group, the incidences of 28-day neutrophil engraftment (P=0.005), 100- day platelet engraftment (P=0.002), median time to neutrophil engraftment (P.

The objective of this study was to identify independent prognostic factors of viral encephalitis (VE) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) and establish a prognostic model to identify post-transplant VE patients with a greater likelihood of mortality. Among 5380 patients in our centre from 2014 to 2022, 211 patients who developed VE after allo-HSCT were reviewed in this retrospective study. Prognostic factors were selected, and a prognostic model was constructed using Cox regression analysis. The model was subsequently validated and estimated using the area under the receiver operating characteristic curve (AUC), a calibration plot and decision curve analysis (DCA). Glasgow Coma Scale score <9, lesions >3 lobes on magnetic resonance imaging and severe thrombocytopenia were identified as independent prognostic risk factors for VE patients who underwent allo-HSCT. The prognostic model GTM (GTM is an abbreviation for a model composed of three risk factors: GCS score <9, severe thrombocytopenia [platelet count <20 000 per microliter], and lesions >3 lobes on MRI) was established according to the regression coefficients. The validated internal AUC was 0.862 (95% confidence interval [CI], 0.773-0.950), and the external AUC was 0.815 (95% CI, 0.708-0.922), indicating strong discriminatory ability. Furthermore, we constructed calibration plots that demonstrated good consistency between the predicted outcomes and the observed outcomes. DCA exhibited high accuracy in this system, leading to potential benefits for patients., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Objective: To evaluate the efficacy and safety of matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of myelofibrosis (MF). Methods: In this case series, the clinical data of 18 patients with MF who received allo-HSCT in the Department of Hematology, Peking University People's Hospital from December 2008 to December 2023 were retrospectively studied. Kaplan-Meier survival analysis and competitive risk model were used to evaluate the probabilities of 3-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and transplant related mortality (TRM). The transplant related complications were also analyzed. Results: Among the 18 patients included, there were 12 males and 6 females, with a median age of 50 (range: 28-64) years. All 18 patients achieved neutrophil engraftment, and the time of neutrophil engraftment [ M ( Q 1 , Q 3 )] was 16.0 (11.8, 18.0) days. Twelve patients achieved platelet engraftment, and the platelet engraftment time was 21.0 (16.2, 43.2) days. Six patients had grade Ⅱ to Ⅳ acute graft-versus-host disease (GVHD), and six patients had chronic GVHD. The 3-year OS rate and DFS rate after transplantation were 62.2% and 52.2%, respectively. The 3-year CIR and TRM were 29.7% and 24.6%, respectively. Four patients died during follow-up, with the main cause of death being infections. Conclusion: Matched sibling allo-HSCT is a feasible option for the treatment of MF.

Cell-based microarrays are widely used in the fields of drug discovery and toxicology. Precise gradient generation and automated drug feeding are essential for high-throughput screening of live cells in tiny droplets. However, most existing technologies either require sophisticated robotic equipment or cause mechanical/physiological interference with cells. Here, a heterogeneous organohydrogel is presented for automated gradient drug feeding, while ensuring minimal interference with cells. The heterogeneous organohydrogel comprises three crucial components. The bottom surface can automatically generate gradients functioning as a gradient generator, the organohydrogel bulk allows unidirectional transport of drugs without backflow, and the top surface with hydrophilic arrays can firmly anchor the cell-based droplet array to evaluate the concentration-dependent bioeffects of drugs accurately. Such a unique structure enables universal screening of different cell types and drugs dissolved in different solvents, requiring neither additional accessories nor arduous drug functionalization. The heterogeneous organohydrogel with unprecedented automation and non-interference possesses the enormous potential to be a next-generation platform for drug screening., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

We aimed to identify dynamic changes of lysine (K)-specific methyltransferase 2A partial tandem duplications ( KMT2A -PTD) before and after haploidentical donor hematopoietic stem cell transplantation (HID HSCT) and explore the prognostic value of pre-transplantation levels of KMT2A -PTD in acute myeloid leukemia (AML) receiving HID HSCT. Consecutive 64 AML patients with KMT2A -PTD positivity at diagnosis receiving HID HSCT were included in this study. Patients with KMT2A -PTD ≥1% before HSCT had a slower decrease of KMT2A -PTD after HID HSCT. Patients with KMT2A -PTD ≥1% before HID HSCT had a higher cumulative incidence of relapse (36.4%, 95% confidence interval [CI]: 6.3%-66.5%) at 2 years after HSCT than those with KMT2A -PTD <1% (7.5%, 95% CI: 0.3%-14.7%, P = .010). In multivariable analysis, KMT2A -PTD ≥1% before HID HSCT was the only independent risk factor for relapse (hazard ratio [HR]: 4.90; 95% CI: 1.22-19.59; P = .025). Thus, pre-transplantation levels of KMT2A -PTD could predict relapse in AML patients following HID HSCT., Competing Interests: Conflict of interest: The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the Chinese Medical Association (CMA) and Institute of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College (IHCAMS).)

From January 1, 2013, to March 1, 2024, nine patients with hematological malignancies complicated by Gilbert's syndrome in Peking University People's Hospital underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). The patients comprised seven male and two female cases, with a median age of 38 (13-60) years old. Among them, three cases were acute myeloid leukemia, three cases were acute lymphocytic leukemia, two cases were myelodysplastic syndrome, and one case was chronic myelomonocytic leukemia. None of the patients had viral hepatitis. Of the nine cases, seven cases received the Bu-Cy+ATG regimen, while the other two cases received the TBI-Cy+ATG regimen (Bu, busulfan; Cy, cyclophosphamide; ATG, antithymocyte immunoglobulin; and TBI, total body irradiation). All patients achieved neutrophil engraftment, and eight received platelet engraftment. The median total bilirubin level was 45.4 (22.5-71.2) μmol/L before transplantation and 22.0 (18.0-37.2) μmol/L on -1d of preconditioning. The total bilirubin level on +20d after the transplantation of eight patients decreased compared with the baseline level before transplantation. Moreover, one patient had a transient increase in the total bilirubin level on +5d after transplantation, which was considered to be attributed to the toxicity of Bu. No patients were complicated by hepatic veno-occlusive disease. The median follow-up time was 739 (42-2 491) days. During the follow-up period, one patient died of recurrence, and the remaining eight patients had disease-free survival events.

Objective: To evaluate the safety of patients with hepatic adenoma undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: A retrospective analysis of the clinical characteristics and prognosis of eight patients with hepatic adenoma who underwent allo-HSCT in the Hematology Department of Peking University People's Hospital from January 2010 to March 2024 was conducted. Results: Of the eight patients who underwent allo-HSCT with hepatic adenoma, one patient was considered MDS-h transfusion-dependent and seven had aplastic anemia. The median age of the patients was 23 years (13-48 years). The median time from the diagnosis of AA or MDS to transplantation was 14 years (6-24 years), whereas the median time from taking androgens to diagnosing hepatic adenoma was 9 years (5-13 years). Six cases underwent haplo-HSCT, one case underwent matched unrelated donor HSCT, and one case underwent matched related donor HSCT. All patients achieved neutrophil engraftment at a median time of 11.5 days (11-20 days) and PLT engraftment within 60 days at a median of 19 days (10-37 days) after haplo-HSCT. Moreover, seven patients developed CMV anemia after transplantation, three patients had hemorrhagic cystitis, and two patients developed acute GVHD. During and after transplantation, eight patients did not show severe liver function damage or rupture of hepatic adenoma. In relation to imaging size, four patients showed varying degrees of reduction in hepatic adenoma size after transplantation, whereas four patients did not show significant changes in hepatic adenoma size after transplantation. The median follow-up time was 540.5 (30-2 989) days. Of the eight patients, six survived and two died. Furthermore, no direct correlation was observed between death and hepatic adenoma. Conclusion: Patients with hepatic adenomas undergoing allo-HSCT are not contraindications for transplantation, which will not increase transplant-related mortality.

This study included 20 patients with hematological diseases who developed Pneumocystis jirovecii pneumonia (PJP) after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) from April 2014 to October 2022 at Peking University People's Hospital. The 20 patients comprised 13 males (65.0% ) and seven females (35.0% ), with a median age of 34 (19-60) years. Eleven cases (55.0% ) of acute myeloid leukemia, four cases (20.0% ) of acute lymphocytic leukemia, two cases (10.0% ) of myelodysplastic syndrome, one case (5.0% ) of chronic myelomonocytic leukemia, one case (5.0% ) of non-Hodgkin lymphoma, and one case (5.0% ) of aplastic anemia were analyzed. Three cases (15.0% ) of HLA-identical sibling hematopoietic stem cell transplantation, three cases (15.0% ) of matched unrelated donor hematopoietic stem cell transplantation, and 14 cases (70.0% ) of haploid hematopoietic stem cell transplantation were identified. The median onset time of PJP was 353 (74-1121) days after transplantation. The clinical symptoms mainly included fever, cough, expectoration, and dyspnea. All patients presented signs of infection based on the CT scan, including bilateral diffuse ground-glass opacities, patchy shadows, and solid nodules. Nine patients (45.0% ) required respiratory support via nasal catheter oxygen inhalation, while seven patients (35.0% ) required ventilator-assisted breathing. Seven (35.0% ) severe infections and 13 (65.0% ) mild to moderate infections were recorded. Moreover, eight patients (40.0% ) were complicated with human cytomegalovirus infection, whereas two patients were complicated with EB virus infection. Furthermore, all 20 patients received treatment with compound sulfamethoxazole (standard dose, 11 cases; low dose, 9 cases). Furthermore, 19 patients survived and one patient died.

Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95 % Confidence Interval [CI], 1.34-8.5; P = 0.01) and worse survival (HR = 4.87 [1.53-15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTROPC-14005546])., Competing Interests: Declaration of competing interest RPG is a consultant to Antengene Biotech LLC; Medical Director, FFF Enterprises Inc.; A speaker for Janssen Pharma and Hengrui Pharma; Board of Directors: Russian Foundation for Cancer Research Support and Scientific Advisory Board, StemRad Ltd., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Due to regional and cultural differences, the current status of extremely preterm infants(EPIs) treatment across different areas of mainland China remains unclear. This study investigated the survival rate and incidence of major diseases among EPIs in the southwest area of Fujian province., Method: This retrospective and multicenter study collected perinatal data from EPIs with gestational ages between 22-27 + 6 w and born in the southwest area of Fujian province. The study population was divided into 6 groups based on gestational age at delivery. The primary outcome was the survival status at ordered hospital discharge or correct gestational age of 40 weeks, and the secondary outcome was the incidence of major diseases. The study analyzed the actual survival status of EPIs in the area., Result: A total of 2004 preterm infants with gestational ages of 22-27 + 6 weeks were enrolled in this study. Among them, 1535 cases (76.6%) were born in the delivery room but did not survive, 469 cases (23.4%) were transferred to the neonatal department for treatment, 101 cases (5.0%) received partial treatment, and 368 cases (18.4%) received complete treatment. The overall all-cause mortality rate was 84.4% (1691/2004). The survival rate and survival rate without major serious disease for EPIs who received complete treatment were 85.1% (313/368) and 31.5% (116/318), respectively. The survival rates for gestational ages 22-22 + 6 w, 23-23 + 6 w, 24-24 + 6 w, 25-25 + 6 w, 26-26 + 6 w, and 27-27 + 6 w were 0%, 0%, 59.1% (13/22), 83% (39/47), 88.8% (87/98), and 89.7% (174/198), respectively. The survival rates without major serious disease were 0%, 0%, 9.1% (2/22), 19.1% (9/47), 27.6% (27/98), and 40.2% (78/194), respectively., Conclusion: The all-cause mortality of EPIs in the southwest area of Fujian Province remains high, with a significant number of infants were given up after birth in the delivery room being the main influencing factor. The survival rate of EPIs who received complete treatment at 25-27 weeks in the NICU was similar to that in developed countries. However, the survival rate without major serious disease was significantly lower compared to high-income countries., (© 2024. The Author(s).)

The replacement of a CC unit with an isoelectronic BN unit in aromatic systems can give rise to molecules and materials with fascinating properties. We report here the synthesis, characterization, and reactivity of a 1,4,2,3-diazadiborole species, 2, featuring an unprecedented 6π-aromatic BN-heterocyclic moiety that is isoelectronic to cyclopentadienide (Cp - ). Bearing an unsymmetrical B=B entity, 2 exhibits reactivity toward oxidants, protic reagents, electrophiles, and unsaturated substrates. This reactivity facilitates the synthesis of a variety of novel mono- and bicyclic organoboron derivatives through mechanisms including ring retention, cleavage/recombination, annulation, and expansion. These findings reveal innovative synthetic routes to BN-embedded aromatic compounds via desymmetrization, affording unique building blocks for synthetic chemistry., (© 2024 Wiley-VCH GmbH.)

Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) are one of the most severe complications after hematopoietic stem cell transplantation (HSCT). This study includes 31 cases of aplastic anemia (AA) patients who developed PTLD after haploidentical transplantation, summarizing their clinical characteristics and categorizing them into either rituximab monotherapy group or combination therapy group based on whether their condition improved by 1 log after a single dose of rituximab. The incidence of PTLD after HSCT in children with AA was 10.16%, and the incidence of PTLD in patients with age >10 years was significantly increased ( χ (2)=11.336, P =0.010). Of the 31 patients, 27 were clinically diagnosed and 4 were pathologically confirmed. Finally, 15 patients were classified into the rituximab treatment group and 15 patients into the combination treatment groups. Finally three patients died, and the 2-year overall survival rate was (89.7±5.6) %. Standard pre-treatment protocols and EBV reactivation are risk factors affecting the prognosis of PTLD. There was no statistically significant difference in the impact of the two treatment schemes on prognosis.

Background: Philadelphia chromosome (Ph)-positive B-cell acute lymphoblastic leukemia (ALL) has a high complete remission (CR) rate, but relapse and prolonged measurable residual disease remain serious problems. We sought to describe the CR rate measurable residual disease negative rate and address the results and safety of pediatric patients who underwent after receiving chimeric antigen receptor (CAR) specific for CD19 (CAR-19) followed by hematopoietic stem cell transplantation (HSCT) for the treatment of Ph-positive ALL., Methods: A descriptive study was conducted at Peking University People's Hospital from September 2013 to January 2021. 13 patients with relapsed/refractory Ph-positive B-ALL who received CAR-T therapy followed by allo-HSCT were included. We concentrated on the overall patient survival and CR rate., Results: The median time between CAR-T therapy and allo-HSCT was 58 days. Among all the patients, the CR rate was 100%, the flow cytometry negativity rate was 84.62%, and the BCR-ABL negativity rate was 53.85% at 1 month after CAR-T infusion. All the patients achieved a major molecular response in 6 months after HSCT. After a median follow-up of 45 months, the 3-year OS rate was 66.7%, and the 3-year DFS rate was 61.5%. The 3-year OS rate of patients with BCR-ABL-positive pre-HSCT was significantly lower than that in the BCR-ABL-negative group (40.0% vs. 85.7%, P =0.042). Also, the same trend was observed for the 3-year DFS rate but did not differ significantly (40.0% vs. 75.0%, P =0.233)., Conclusions: CAR-T therapy followed by allo-HSCT can be a safe and effective treatment for Ph-positive B-ALL pediatric patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Central nervous system leukemia (CNSL) remains a serious complication in patients with acute myeloid leukemia (AML) and an ambiguous prognostic factor for those receiving allo-geneic hematopoiesis stem cell transplantation (allo-HSCT). It is unknown whether using more sensitive tools, such as multiparameter flow cytometry (MFC), to detect blasts in the cerebrospinal fluid (CSF) would have an impact on outcome., Methods: We retrospectively analyzed the clinical outcomes of 1472 AML patients with or without cytology or MFC positivity in the CSF before transplantation. Abnormal CSF (CSF+) was detected via conventional cytology and MFC in 44 patients at any time after diagnosis. A control group of 175 CSF-normal (CSF-) patients was generated via propensity score matching (PSM) analyses according to sex, age at transplant, and white blood cell count at diagnosis., Results: Compared to those in the CSF-negative group, the conventional cytology positive and MFC+ groups had comparable 8-year nonrelapse mortality (NRM) (4%, 4%, and 6%, p = 0.82), higher cumulative incidence of relapse (CIR) (14%, 31%, and 32%, p = 0.007), lower leukemia-free survival (LFS) (79%, 63%, and 64%, p = 0.024), and overall survival (OS) (83%, 63%, and 68%, p = 0.021), with no significant differences between the conventional cytology positive and MFC+ groups. Furthermore, multivariate analysis confirmed that CSF involvement was an independent factor affecting OS and LFS., Conclusion: Our results indicate that pretransplant CSF abnormalities are adverse factors independently affecting OS and LFS after allotransplantation in AML patients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Dysfunctional bone marrow (BM) endothelial progenitor cells (EPCs) with high levels of reactive oxygen species (ROS) are responsible for defective hematopoiesis in poor graft function (PGF) patients with acute leukemia or myelodysplastic neoplasms post-allotransplant. However, the underlying mechanism by which BM EPCs regulate their intracellular ROS levels and the capacity to support hematopoiesis have not been well clarified. Herein, we demonstrated decreased levels of peroxisome proliferator-activated receptor delta (PPARδ), a lipid-activated nuclear receptor, in BM EPCs of PGF patients compared with those with good graft function (GGF). In vitro assays further identified that PPARδ knockdown contributed to reduced and dysfunctional BM EPCs, characterized by the impaired ability to support hematopoiesis, which were restored by PPARδ overexpression. Moreover, GW501516, an agonist of PPARδ, repaired the damaged BM EPCs triggered by 5-fluorouracil (5FU) in vitro and in vivo. Clinically, activation of PPARδ by GW501516 benefited the damaged BM EPCs from PGF patients or acute leukemia patients in complete remission (CR) post-chemotherapy. Mechanistically, we found that increased expression of NADPH oxidases (NOXs), the main ROS-generating enzymes, may lead to elevated ROS level in BM EPCs, and insufficient PPARδ may trigger BM EPC damage via ROS/p53 pathway. Collectively, we found that defective PPARδ contributes to BM EPC dysfunction, whereas activation of PPARδ in BM EPCs improves their hematopoiesis-supporting ability after myelosuppressive therapy, which may provide a potential therapeutic target not only for patients with leukemia but also for those with other cancers., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. All co-author shave seen and approved this version of the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nickel-catalyzed transannulation reactions triggered by the extrusion of small gaseous molecules have emerged as a powerful strategy for the efficient construction of heterocyclic compounds. However, their use in asymmetric synthesis remains challenging because of the difficulty in controlling stereo- and regioselectivity. Herein, we report the first nickel-catalyzed asymmetric synthesis of N-N atropisomers by the denitrogenative transannulation of benzotriazones with alkynes. A broad range of N-N atropisomers was obtained with excellent regio- and enantioselectivity under mild conditions. Moreover, density functional theory (DFT) calculations provided insights into the nickel-catalyzed reaction mechanism and enantioselectivity control., (© 2024 Wiley-VCH GmbH.)