Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the leading cause of treatment failure in acute myeloid leukemia (AML), yet the non-coding RNA-mediated regulatory mechanisms in relapse-driving tumor clones are not fully understood. In this study, we performed transcriptomic profiling of CD34+ cells from the bone marrow of patients who had relapsed after allo-HSCT and from those in sustained remission, and observed that long non-coding RNAs (lncRNAs) exhibited the largest magnitude of differential expression relative to other RNA classes. To systematically elucidate their function, we integrated correlation analysis, neighborhood topology, and thermodynamic modeling to construct relapse-associated competing endogenous RNA (ceRNA) networks. These networks highlighted multiple lncRNA-miRNA-mRNA axes potentially promoting leukemic progression. Functional interrogation using CRISPR-based xenograft assays and a single-cell CRISPR screening platform (Perturb-seq-like strategy) revealed that relapse-associated lncRNAs regulate AML cell proliferation and survival. Among them, SNHG8 emerged as a representative regulator that promotes relapse through the SNHG8-miR-625-ZC3H13/15 signaling axis. SNHG8 knockdown markedly impaired AML cell growth and triggered apoptosis. Furthermore, treatment with hypomethylating agents (HMAs) such as azacitidine and decitabine differentially modulated lncRNA/ceRNA expression signatures, thereby linking clinical interventions to transcriptomic regulation. Together, our findings identify lncRNA-ceRNA networks in post-transplant relapse of AML and identify the SNHG8 axis as a potential therapeutic vulnerability, providing a rationale for further investigation of lncRNA-targeted strategies in this clinical setting.

Inappropriate empirical antimicrobial therapy (IEAT) significantly increases mortality in patients with resistant Gram-negative bacteremia. We developed a multitask machine learning framework to predict carbapenem resistance (CR), β-lactam/β-lactamase inhibitor combinations resistance (BL/BLI-R), and third-/fourth-generation cephalosporins resistance (3GC/4GC-R) in HM patients with monomicrobial BSIs caused specifically by Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae. Using retrospective data from 1,353 HM patients with three specific Enterobacterales BSIs (2017–2023), we trained support vector machines, eXtreme Gradient Boosting, and logistic regression models through 5-fold cross-validation with hyperparameter tuning and conducting internal validation via bootstrap. Model thresholds were optimized via Pareto front analysis to minimized IEAT and carbapenem use while maximizing sensitivity. The models achieved AUCs of 0.81 (95

Introduction Hematopoietic stem cell transplantation (HSCT) and chemotherapy are considered potentially curative options for post-remission therapy in acute myeloid leukemia (AML). However, the comparative effectiveness of these approaches in favorable- and intermediate-risk AML remains unclear and requires further investigation.Methods In this retrospective study, 111 patients diagnosed with de novo favorable- and intermediate-risk AML, categorized according to the ELN 2022 guidelines, were investigated to compare outcomes following autologous HSCT (auto-HSCT), matched sibling donor HSCT (MSD-HSCT), and chemotherapy. Through propensity score matching for disease status before HSCT, 42 cases in first complete remission were selected for each of the auto-HSCT group and the MSD-HSCT group. Additionally, 27 cases in the chemotherapy group, excluding patients with early relapse or death, were included for comparison.Results In the overall population, the 3-year overall survival (OS) rates were 85.7%, 83.1%, and 70.4% (p = 0.043), while the disease-free survival (DFS) rates were 78.6%, 83.2%, and 57.1% (p = 0.002) in the auto-HSCT, MSD-HSCT, and chemotherapy groups, respectively. Notably, both auto-HSCT and MSD-HSCT demonstrated significantly improved DFS compared to chemotherapy in patients with favorable-risk AML. Multivariate analysis further revealed that chemotherapy was significantly associated with inferior DFS compared to auto-HSCT (HR=2.82; 95% CI, 1.26-6.32, p=0.012), while DFS was similar between the MSD-HSCT and auto-HSCT groups (HR=0.80; 95% CI, 0.31-2.09, p=0.645).Discussion The findings suggested the advantages of both MSD-HSCT and auto-HSCT over chemotherapy as post-remission therapy for AML patients with favorable and intermediate risk. Further research is needed to support these conclusions.

BACKGROUND:Myeloid sarcoma (MS) is a rare extramedullary manifestation of myeloid neoplasms and usually has poorer outcomes than acute myeloid leukemia without extramedullary disease. Allogeneic hematopoietic stem cell transplantation is the most effective consolidation, but evidence on allogeneic peripheral blood stem cell transplantation (allo-PBSCT), especially from haploidentical donors, is limited. METHODS:We retrospectively reviewed 20 consecutive patients with biopsy-confirmed MS who underwent allo-PBSCT at our center (2012-2025). All grafts were peripheral blood. Donors were haploidentical in 14 patients (70.0%), matched related in 4 (20.0%), and matched unrelated in 2 (10.0%). Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan - Meier method; relapse incidence (RI), non-relapse mortality (NRM), and graft-versus-host disease (GVHD) were analyzed as competing risks. RESULTS:Twenty patients (median age, 28.5 years) were included; 45.0% had isolated extramedullary MS and 55.0% had concurrent bone marrow disease. At transplantation, 16 (80.0%) were in first complete remission, 18 (90.0%) were measurable residual disease (MRD) negative, and all had HCT-CI = 0. After a median follow-up of 38 months, 1- and 2-year OS and DFS were both 90.0%, with RI 0% and NRM 10.0%; at 3 years, OS/DFS were 81.8%, RI 8.2%, and NRM 10.0%. Haploidentical recipients (14/20) had comparable outcomes (3-year OS/DFS 92.9%, no relapse, NRM 7.1%). Acute GVHD occurred in 60.0%, but grade II - IV in only 20.0%; chronic GVHD was 30.0%, mostly mild. CONCLUSION:Allo-PBSCT can achieve durable remission in selected MS patients and is a practical option when an HLA-matched donor is unavailable.

Despite the poor prognosis for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML), an optimal treatment strategy remains undefined. Mitoxantrone (MIT) is widely used to treat R/R AML. This prospective, single-center, open-label study assessed the efficacy and toxicity of mitoxantrone hydrochloride liposome (Lipo-MIT)-containing regimen therapy, intensified by adding cytarabine (Ara-C), cyclophosphamide (CTX) or other agents. The primary endpoint was composite complete remission (CRc), including complete remission (CR), complete remission with incomplete count recovery (CRi), and morphologic leukemia-free state (MLFS). The secondary endpoints included overall response rate (ORR), event-free survival (EFS), overall survival (OS), and safety. We enrolled 20 patients (median, 38.50 years; range, 20.00–53.00 years) and treated them with a Lipo-MIT-containing regimen from April 29, 2022, to July 11, 2023. Twelve patients (60.00

Despite allo-HSCT being the primary curative treatment for high-risk AML, relapse-free survival (RFS) remains suboptimal due to high relapse incidence. Our research focuses on optimizing the conditioning regimen by incorporating Mitoxantrone Hydrochloride Liposome (Lipo-MIT), a novel nano-formulation with enhanced pharmacokinetic properties and demonstrated anti-leukemic efficacy. Preclinical studies have shown that Lipo-MIT significantly improves survival outcomes compared to conventional mitoxantrone, and our study aims to translate these findings into clinical practice. In this study, we present the results of a Lipo-MIT as part of the conditioning regimen for high-risk AML patients undergoing allo-HSCT. Our findings highlight the potential of Lipo-MIT to improve RFS, while also providing insights into patient selection and the refinement of Lipo-MIT-based conditioning strategies. We believe this work contributes valuable knowledge to the field and has the potential to impact clinical practice.

To address the overuse of antibiotics, this study examined the clinical characteristics and outcomes associated with antibiotic duration and carbapenem-sparing regimens in hematological patients with Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) bloodstream infections (BSI). We conducted a retrospective analysis of hematological patients with E. coli or K. pneumoniae BSI from 2017 to 2023. Propensity score matching (PSM) controlled for confounding variables, and data were analyzed using multivariate regression models. A total of 1,862 patients were included (E. coli: n = 932; K. pneumoniae: n = 930). Among 1,105 patients in the antibiotic duration cohort, 48.96

Chronic disseminated candidiasis (CDC) is an invasive fungal infection typically affecting patients with hematological diseases and severe neutropenia, associated with increased mortality. However, there is a global shortage of clinical evidence on CDC. We retrospectively analyzed clinical data from 49 CDC patients over the past decade. Clinical characteristics of primary hematological diseases, CDC diagnosis, treatment and response evaluations were included. Clinical factors associated with CDC remission and patients' survival were analyzed. The majority of patients had hematological malignancies (n = 43, 87.8%), and 27 patients (55.1%) had persistent severe neutropenia for more than 10 days prior to CDC. CT scans revealed liver lesions in 44 patients, spleen lesions in 34 patients, and kidney lesions in 9 patients. Proven, probable and possible CDC was diagnosed in 5 (10.2%), 3 (6.1%) and 41 patients (83.7%), respectively, and treatment outcomes at 3 months included 5 complete response (CR, 10.2%), 34 partial response (PR, 69.4%) and 10 treatment failure (20.4%). Caspofungin treatment showed a trend towards improving CR/PR rate, while severe neutropenia > 20 days and proven diagnosis were significantly associated with 3-month treatment failure. Kaplan-Meier curve showed achieving CR/PR within 3 months did not significantly prolong OS compared to treatment failure patients (1197.6 days vs. 564.8 days, P = 0.074). Additionally, no patient deaths were directly attributed to CDC infection. Age > 45 years old and malignancy non-remission were prognostic factors of overall survival (OS). Furthermore, a prediction model identified severe neutropenia > 20 days, proven/probable diagnosis and concomitant bacteremia as risk factors to effectively predict treatment failure. Also, patients with a risk score < 0.203 in the model exhibited more rapid treatment response. After CDC symptoms onset, lymphocyte levels remained consistently higher in treatment failure patients, while the neutrophil-to-lymphocyte ratio was persistently higher in CR/PR patients. Our findings recommend CT scans for diagnosis and caspofungin as first-line therapy while continuing scheduled chemotherapy or bone marrow transplantation. Notably, risk factors identified by the prediction model could be used to predict treatment response.

Letermovir (LTV) effectively prevents cytomegalovirus (CMV) reactivation in CMV-seropositive patients. To evaluate the impact of LTV in matched sibling haematopoietic stem cell transplantation (HSCT) recipients, we retrospectively compared 72 matched sibling transplantation recipients receiving LTV with 134 controls. LTV significantly reduced 200-day CMV viraemia incidence (5.6% vs. 33.3%, p < 0.001). Multivariable analysis identified anti-thymocyte globulin (ATG) use (p = 0.005) and grade III-IV acute graft-versus-host disease (aGVHD; p < 0.001) as independent risk factors for CMV viraemia, while CMV serostatus did not significantly affect CMV viraemia (p = 0.448). Stratification based on risk factors (ATG, grade III-IV aGVHD) showed that LTV had a more significant effect on high-risk patients compared to low-risk patients. Also, LTV prophylaxis was associated with increased Epstein-Barr virus (EBV) viraemia (13.9% vs. 1.4%, p = 0.025) and higher CD20 monoclonal antibody utilization (11.1% vs. 1.4%, p = 0.046). Long-term survival remained similar between both groups. Results were validated in a second cohort from our centre. In conclusion, LTV prophylaxis significantly reduced CMV viraemia, especially in high-risk patients (ATG/grade III-IV aGVHD). However, the LTV group showed an elevated risk of EBV-related complications. Risk stratification-rather than CMV serostatus alone-should guide CMV prevention strategies in matched sibling HSCT. Larger clinical studies are needed for validation.

OBJECTIVES:To evaluate posaconazole (POS) gastro-resistant tablets for preventing invasive fungal disease (IFD) in haematopoietic stem cell transplantation (HSCT) patients and analyse POS plasma concentrations. METHODS:A single-arm trial was designed with a historical cohort as a control. Patients aged 13 years and older undergoing HSCT at the HSCT Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences between December 2020 and May 2022 were enrolled, prospectively taking POS gastro-resistant tablets orally from day 1 to day 90 post-transplant and monitoring plasma concentrations. We also identified a retrospective cohort treated with alternative antifungal prophylaxis between January 2018 and December 2020, matched using propensity score methods. The primary outcome was the cumulative incidence of IFD at day 90 post-transplant. RESULTS:The prospective study involved 144 patients receiving POS gastro-resistant tablets for IFD prevention, contrasting with 287 patients receiving non-POS tablets. By day 90 post-transplant, the POS tablet group exhibited a significantly lower cumulative incidence of IFD (2.81%; 95% CI, 0.09-5.50% vs. 7.69%; 95% CI, 4.60-10.78%; p 0.044). Adverse events were comparable between the groups with liver changes in 33/144 (22.92%) vs. 84/287 (29.27%) (p 0.162), and renal injuries in 15/144 (10.41%) vs. 37/287 (12.89%) (p 0.457). Mean POS plasma concentrations on days 4, 8, 15, and 22 post-administration were 930.97 ng/mL, 1143.97 ng/mL, 1569.8 ng/mL, and 1652.57 ng/mL, respectively. DISCUSSION:Patients administered POS gastro-resistant tablets for antifungal prophylaxis experienced a lower cumulative incidence of IFD. POS plasma concentrations in HSCT patients stabilized by day 15 of medication.

Background Patients with refractory and relapsed acute myeloid leukemia (AML) face a poor prognosis, with a lack of effective treatment options available. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is usually recommended for patients with an appropriate donor, but survival remains dismal. Therefore, safer and more effective conditioning regimens are urgently needed to further reduce disease recurrence and improve the clinical outcomes. In our preliminary work, Mitoxantrone hydrochloride liposome (Lipo-MIT)-based combined chemotherapy demonstrated a high remission rate in refractory and relapsed AML, even for patients relapsed after allo-HSCT. The liposomal formulation improved the safety profiles of Mitoxantrone and enhanced the anti-tumor effects via permeability and retention effect. In this study, we focused on the addition of Lipo-MIT to myeloablative conditioning regimens. Aims To evaluate the efficacy and safety of a modified conditioning regimen containing Lipo-MIT/Cladribine/Cytarabin/Busulfan and Cyclophosphamide in the treatment of refractory and relapsed AML patients underwent allo-HSCT. Methods Adult patients with refractory and relapsed AML underwent first allo-HSCT were enrolled in this study. Bone marrow aspirates were obtained, cytogenetic and molecular characteristics were collected at the time of diagnosis and disease relapse. HLA-haploidentical donor transplants were performed if no HLA matched sibling or unrelated donor was available. This modified myeloablative conditioning utilized Mitoxantrone hydrochloride liposome (Lipo-MIT, dose levels ranged from 24mg/m2 to 36 mg/m2 for 1 day), Cladribine (5mg/m2 for 3 days), Cytarabin (dose levels ranged from 1g/m2 to 2g/m2 for 3 days), Busulfan (Bu, 3.2 mg/kg for 3 days) and Cyclophosphamide (Cy, 40mg/kg for 2 days). Patients aged over 55 years received lower dose of Lipo-MIT (24mg/m2 for 1 day) and Cytarabin (1g/m2 for 3 days). The therapeutic process and clinical outcomes were retrospectively analyzed. Results Between October 2023 and March 2024, 28 patients allografted in our clinical center were enrolled. Median age was 44 (18.0-64.0) years. Out of these patients, 11 (39.3%) had primary refractory disease and 17 (60.7%) had recurrent AML (10 patients relapsed within 12 months and 2 had relapsed ≥2 times). At the time of transplantation, 15 patients (53.6%) were found to be MRD-positive and 7 (25.0%) were transplanted with active disease. All patients engrafted successfully. The median time to neutrophil and platelet engraftment were 16 days (range 11-23) and 23 days (range 11-52), respectively. Platelet engraftment was delayed when compared with the historical controls. At the time of this analysis, 27 patients were alive, and one patient died of secondary poor graft function and septic shock, at 4 months post-transplantation. Three patients (10.7%) experienced disease recurrence and received salvage chemotherapy and donor lymphocyte infusion (DLI). OS and RFS were 95.2% (95% CI 86.2-100%) and 83.9% (95% CI 69.2-98.6%), respectively. Three patients developed cardiac insufficiency and one developed atrial fibrillation during conditioning therapy. All patients recovered after symptomatic treatments. No severe cardiotoxicity (Grade III-IV) or transplant-related mortality occurred within 100 days, which was comparable with the historical controls. Conclusions In conclusion, Lipo-MIT-based combined conditioning regimen is potentially effective with acceptable tolerability in patients with refractory and relapsed AML. Further well-designed studies are required to validate the efficacy and the optimal dosage of this conditioning regimen.

Background Failure of systemic corticosteroid therapy is quite common in patients with newly diagnosed acute graft-versus-host disease (aGVHD) above grade II. Mesenchymal stem cells (MSCs) have been used as a tolerable and potential effective second-line therapy for steroid-refractory aGVHD (SR-aGVHD) for decades, however, well-designed perspective, controlled studies are lacking.Methods This multicenter, randomized, double-blind, placebo-controlled phase 2 study enrolled patients with SR-aGVHD above grade II from 7 centers. Patients were randomized 1:1 to receive MSCs or placebo added to one center’s choice of second-line agents except for ruxolitinib. Study agents were infused twice weekly. Patients who were CR (complete response), NR (no response), and PD (progression of disease) at d28 received 8 infusions and those who were PR (partial response) at d28 received the above infusions for another 4 weeks. The per-protocol population consisted of patients who received ≥ 8 study agent infusions. The primary endpoint was overall response rate (ORR, CR + PR) at d28, and was analyzed in the per-protocol and intention-to-treat populations.Results Seventy-eight patients with a median age of 38 (range, 13–62) years were enrolled, 40 in the MSC group and 38 in the control. Patients in MSC group received a median of 8 doses with a median response time of 14 days. In per-protocol analysis (n = 62), ORR at d28 was significantly higher in the MSC group than in the control (71.9% vs. 46.7%, p = 0.043). Among patients with gut involvement, ORR at d28 was significantly higher in the MSC group than in the control (66.7% vs. 33.3%, p = 0.031). The 2-year cumulative incidence of moderate or severe cGVHD was marginally lower in the MSC group compared to the control (16.5% vs. 46.7%, p = 0.056). In intention-to-treat analysis, the main endpoint was not met (p = 0.375). The incidences of adverse events were comparable between the two groups.Conclusions Adding MSCs to one conventional second-line agent for SR-aGVHD had a gradual treatment effect at a median of 2 weeks in adult patients who completed 8 infusions and with gut involvement. The toxicities were comparable between two groups.Trial registration chictr.org.cn ChiCTR2000035740

The 2022 European LeukemiaNet (ELN) updated the previous risk classification published in 2017 but the prognostic significance for allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We enrolled 600 acute myeloid leukemia (AML) patients who underwent allo-HSCT to validate ELN-2022 genetic risk system and compared it with ELN-2017. There were 214 (35.67%), 162 (27.0%), and 224 (37.33%) patients in ELN-2022 favorable-, intermediate-, and adverse-risk group respectively and 86 patients (14.33%) experienced a shift in risk stratification compared to ELN-2017. Median and maximum follow-up time were 2.89 (95% CI 2.67 to 3.03) years and 8.78 years. The median overall survival (OS) was 73.8% (95% CI 67.5% to 80.3%), 63.9% (95% CI 56.7% to 72.0%) and 57.6% (95% CI 50.4% to 65.9%) in ELN-2022 favorable-, intermediate-, and adverse-risk group (P < 0.001). OS shortened significantly as the ELN-2022 risk stratification increased but didn’t significantly in ELN-2017 intermediate-risk compared to favorable-risk. Both ELN-2022 and ELN-2017 adverse-risk were associated with increased cumulative incidence of relapse (CIR). Time-dependent receiver operating characteristic (ROC) analysis showed that both ELN-2017 and ELN-2022 risk systems had limited prognostic ability for OS. We modified ELN-2022 risk system with pre-transplant minimal residual disease (MRD) and the modified risk system performed a significantly superior efficacy to ELN-2022 system.

Patients with hematological diseases are at high risk for Stenotrophomonas maltophilia (SM) bacteremia. This study retrospectively analyzed the clinical characteristics and risk factors for 28-day mortality among 140 adult hematological patients diagnosed with SM bacteremia from January 2012 to July 2023. he overall 28-day mortality was 31.43% (44/140), with a median age of 44 years. The median hospital stay before SM bacteremia onset was 25 days, and 69.29% of patients had unresolved neutropenia. All patients had received broad-spectrum antibiotics in the past month, and 69.29% developed breakthrough bacteremia during carbapenem therapy. Independent risk factors for mortality included a Sequential Organ Failure Assessment (SOFA) score ≥5, tigecycline exposure, age ≥60, and pulmonary infection. Patients with ≥2 risk factors were stratified into the high-risk group, with a significantly higher 28-day mortality compared with the low-risk group (56.52% vs 7.04%, P < 0.001). Treatment with trimethoprim-sulfamethoxazole (TMP/SMX) (P = 0.008) or TMP/SMX combined with cefoperazone/sulbactam (CSL) (P = 0.005) was associated with survival benefits among high-risk patients. Overall, SM bacteremia usually occurs in hematological patients with prolonged hospitalization, unresolved neutropenia, and extensive use of broad-spectrum antibiotics, especially carbapenems. Patients with high SOFA scores, advanced age, pulmonary infection, or recent tigecycline exposure are at higher risk of mortality. The preferred treatment is TMP/SMX rather than fluoroquinolones, with combination therapy of TMP/SMX and CSL considered a feasible treatment option.IMPORTANCEThis study, representing the largest cohort of adult hematological patients with SM bacteremia to date, strengthens the validity of existing findings and provides new insights into its clinical management. We identify risk factors for 28-day mortality, revealing that patients with two or more risk factors experience particularly high mortality rates. This highlights the importance of early identification and targeted management of high-risk individuals. Our findings also demonstrate that TMP/SMX is superior to fluoroquinolones and suggest that combining TMP/SMX with CSL may offer additional survival benefits.