Background:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a potential therapeutic option for various hematological disorders. With continuous advancement in transplantation techniques and the expansion of indications, clinical issues associated with delayed erythroid hematopoietic reconstitution (DEHR) have become increasingly prominent. Methods:This retrospective study identified independent risk factors through univariate and multivariate logistic regression analyses, subsequently constructing a prediction model. Model discrimination, calibration, and clinical utility were assessed using the area under the curve (AUC), calibration curves, Hosmer-Lemeshow tests, and decision curve analysis. Overall model performance was evaluated via Nagelkerke R², with internal validation conducted using the bootstrap method. Results:Logistic multivariate analysis results showed that the ferritin level before transplantation (OR = 1.001, 95% CI 1.000-1.001), the severity of anemia before transplantation (OR = 3.740, 95% CI 1.115-12.541), and whether the ABO blood type of the donor and recipient were compatible (OR = 3.283, 95% CI 1.262-8.540) were independent risk factors (P < 0.05). And the model's AUC was 0.835 (95% CI: 0.759-0.910), with the slope of the calibration curve approaching 1, the H-L test P = 0.346, and Nagelkerke R² = 0.349. Conclusion:The nomogram constructed based on pre-transplant ferritin levels, pre-transplant anemia severity, and donor-recipient ABO blood group compatibility demonstrates high predictive value for the occurrence of DEHR after allo-HSCT. This provides a reference for the early identification of high-risk individuals.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) remains the only curative therapy for patients with high-risk myelodysplastic syndrome (MDS). However, the optimal timing and value of pretransplant cytoreduction and post-transplant maintenance remain unclear, and transplant-modifiable variables are not well defined in real-world settings. We retrospectively analysed 215 consecutive MDS patients who underwent allo-HSCT. Clinical, molecular and transplant-related factors were evaluated for their impact on relapse, relapse-free survival (RFS) and overall survival (OS). TP53 mutation, complex karyotype, and positive measurable residual disease (MRD) after cytoreductive treatment were associated with increased relapse risk. Among transplant-related variables, younger donor age (<42 years) and higher CD34+ cell dose (≥3.1 × 106/kg) significantly reduced relapse risk. Notably, pretransplant cytoreduction did not confer measurable benefit on outcomes. In contrast, post-transplant maintenance therapy significantly reduced relapse incidence and prolonged RFS. Pretransplant cytoreduction offers limited clinical value, whereas post-transplant maintenance and modifiable transplant variables (CD34+ cell dose and donor age) substantially improve outcomes after allo-HSCT for MDS. These findings highlight actionable strategies that may refine transplant decision-making and optimize outcomes in clinical practice.

Hematological malignancies are characterized by pronounced metastatic potential associated with the chemokine receptor 4/stromal cell-derived factor-1α (CXCR4/CXCL12) signaling axis, high relapse rates, and a profoundly immunosuppressive tumor microenvironment, all of which severely limit the long-term efficacy of existing therapeutic strategies. Herein, we developed a CXCR4-targeted lipid nanozyme platform (Pt-LNP@E5), in which platinum nanozyme catalytic units and E5 peptide were hierarchically integrated to synergistically achieve metastasis blockade and immune microenvironment remodeling. E5 peptide-mediated CXCR4-specific recognition enabled precise tumor cell accumulation of Pt-LNP@E5 and effectively antagonized CXCR4/CXCL12-driven metastatic signaling, thereby markedly suppressing tumor cell migration and dissemination. Meanwhile, the lipid nanocarrier significantly increased the systemic circulation half-life of the platinum nanozyme and maintained catalytic activity. Within the tumor cell microenvironment, the catalytic system selectively generated reactive oxygen species, which not only induced efficient tumor cell killing but also promoted the transition of the immune microenvironment from an immunosuppressive to an activated state, thereby enhancing antitumor immune responses. These synergistic therapeutic effects were validated in two hematological malignancy models, demonstrating significant tumor growth inhibition, metastasis blockade, and immune microenvironment remodeling. In summary, Pt-LNP@E5 represents a promising strategy for the development of novel platinum-based nanomedicines with broad therapeutic potential.

Chronic graft-versus-host disease (cGVHD) remains a major complication following allogeneic hematopoietic stem cell transplantation for long-term survival. Emerging evidence highlights Rho-associated coiled-coil kinase 2 (ROCK2) as a promising therapeutic target for cGVHD, which can modulate immune responses and profibrotic reactions. TDI01, a potent and highly selective ROCK2 inhibitor, represents a potential breakthrough in cGVHD treatment. This was the dose-finding, phase Ib portion of a multicenter, open-label phase Ib/II study (NCT06169722) designed to evaluate the safety and preliminary efficacy of TDI01 in patients with moderate-to-severe cGVHD after failure of 1 to 5 prior therapies. Sixty patients were enrolled in two once-daily dosing cohorts: 200 mg (n = 30) and 400 mg (n = 30). The primary endpoints were the 24-week best overall response rate (BORR) and safety. As of January 17, 2025, 57 patients were evaluated for efficacy. The 24-week BORRs were 67.9% (200 mg cohort) and 86.2% (400 mg cohort), with an overall BORR of 77.2%. The median times to response were 44.5 days (200 mg cohort) and 30.0 days (400 mg cohort). Neither the median duration of response nor the median failure-free survival (FFS) was achieved. The probability of FFS at 24 weeks was 83.9%. The most common adverse events ( ≥ 20% of patients) were transient bilirubin elevation (total bilirubin elevation 81.7%, unconjugated 56.7%, conjugated 45.0%) and headache (23.3%), without significant increases in liver enzymes. Thus, TDI01, particularly at the 400 mg QD dose, demonstrated promising efficacy and safety in moderate-to-severe cGVHD, which will be confirmed in a forthcoming phase III randomized controlled trial.

Introduction:This multicenter, open-label Phase Ib/II study evaluated TDI01 in patients with moderate or severe chronic graft-versus-host disease (cGVHD) after 1-5 lines prior therapies. Our previous analysis in 57 evaluable patients showed 24-week best overall response rates (BORRs) of 67.9% (200 mg), 86.2% (400 mg), and 77.2% (total) (EBMT 2025). Here, we presented the updated results with extended follow-up, focusing on response durability, long-term safety, overall survival, pharmacokinetics (PK), and exposure–response (E–R) analysis.Methods:After a safety lead-in, patients with moderate or severe cGVHD who had failed 1–5 lines prior systemic therapies were sequentially assigned to receive TDI01 200 mg once daily (QD) (n = 30) or 400 mg QD (n = 30) until experiencing GVHD progression or unacceptable toxicity (NCT06169722). Data were collected on overall response rate (ORR), duration of response (DOR), failure-free survival (FFS), overall survival (OS), PK, E–R, and long-term safety, and are reported here.Results:As of July 18, 2025, 60 patients were evaluable for safety, PK and E–R, and 57 for efficacy. Median follow-up was 48.1 (95% CI, 48.0, 48.3) weeks and 72% (41/57) of evaluable patients had been previously treated with ruxolitinib. At week 24, ORR was 50.0% in 200 mg cohort and 55.2% in 400 mg cohort. Over the entire treatment course, the overall BORR reached 75.0% in 200 mg cohort and 86.2% in 400 mg cohort. Several subgroups (e.g., severe cGVHD and heavily pretreated patients) showed similarly high best ORR (BORR), which was 80.0%, 80.6%, 86.2%, and 80.5%, respectively, in patients with severe cGVHD, with ≥4 organs involved, with ≥3 prior lines of therapy, and those with prior ruxolitinib treatment. The median DOR was not reached in either cohort, with a lower 95% CI of 23.1 months in 200 mg cohort and 31.0 months in 400 mg cohort. At 9 months, FFS rates were 53.6% and 77.7% in 200 mg and 400 mg cohorts, respectively, while OS rates at 12 months were 88.1% and 92.5%.Organ-specific analyses demonstrated BORRs of 52.6% (10/19) in liver, 50.0% (4/8) in esophagus, 50.0% (4/8) in upper gastrointestinal (GI) tract, 47.6% (10/21) in joints/fascia, 46.3% (19/41) in mouth, 38.1% (16/42) in skin, 35.6% (16/45) in eyes, 18.4% (7/38) in lungs, and 0% (0/1) in lower GI tract. On the modified Lee Symptom Scale, 29.8% (17/57) of the patients had ≥7-point improvement.All patients had ≥1 TEAE and TRAEs occurred in 96.7% of patients. Grade ≥3 TEAEs and TRAEs were reported in 51.7% and 38.3% of patients, respectively. SAEs occurred in 31.7%, including 10% that were considered drug-related. One death occurred in the 400 mg cohort was deemed unrelated to the study drug. The most commonly reported TRAEs (≥20%) were elevations of total bilirubin (81.7%), unconjugated bilirubin (60.0%) and conjugated bilirubin (48.3%), upper-respiratory infections (25.0%), headache (23.3%), diarrhea (20.0%), and cough (20.0%). Grade ≥3 hyperbilirubinaemia occurred in 16.7% of patients, but no grade ≥ 3 ALT and/or AST elevations were observed. Treatment discontinuation due to TEAEs occurred in 6.7% of patients. TDI01 was well tolerated without dose-limiting toxicities in both dosage cohorts.PK analysis in all 60 patients showed TDI01 was rapidly absorbed with median Tmax of 4.1-4.5 hours after single doses. Plasma exposure (Cmax and AUC) increased dose-proportionally. Steady-state was achieved by day 15 with moderate accumulation (RAAUC0-t: 1.6-1.9). E–R analysis demonstrated significant correlation between TDI01 exposure parameters (Cmax,ss, AUCss, Ctrough) and 24-week BORR (p < 0.05), with 400 mg approaching maximum efficacy. A positive trend between exposure and FFS was also observed. Notably, no correlation existed between TDI01 exposure and grade ≥3 bilirubin elevations.Conclusion:TDI01 demonstrated durable responses in moderate-to-severe cGVHD. The 400 mg cohort showed a higher ORR, a longer DOR, and a favorable FFS/OS than that of 200 mg cohort. Safety was manageable with primarily reversible hyperbilirubinemia. Our data supported 400 mg QD as the recommended dose of phase III randomized controlled trial which is planned.

OBJECTIVE:To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS:The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS:Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION:Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.

To address the complexity of structural design and synergistic optimization of biological effects of nanozymes in the field of oncology therapy,this study constructed a nanozymes platform(Pt@E5)with a facile and highly efficient preparation process for precision targeting of lymphoma.Pt@E5 nanozymes assemblies were directly prepared by a one-step reduction method,and the modification of E5 peptide ensured the dimensional homogeneity and stability of the platinum nanoparticles.This nano enzymatic platform combines dual enzyme activity with chemokine receptor 4(CXCR4)targeting.It can inhibit tumor metastasis by targeting CXCR4 and thus specifically blocking the CXCR4/CXCL12(stromal cell derived factor 1α)signaling pathway.In addition,it induces mitochondria mediated apoptosis and immunogenic cell death(ICD)in tumor cells by catalyzing the production of reactive oxygen species(ROS)using dual enzyme activity.In a mouse lymphoma model,the therapeutic results showed that Pt@E5 treatment effectively remodeled the tumor immunosuppressive microenvironment by promoting cytotoxic T cell infiltration(CTLs)and reducing regulatory T cell(Treg)levels.It also eliminated A20 cells from the bone marrow and peripheral blood,leading to significant tumor regression compared to the control group.In conclusion,this study offers a promising translational strategy for the multifaceted collaborative treatment of diffuse large B-cell lymphoma(DLBCL)based on a simple nanozyme-peptide assembly.

Combining different immune checkpoint inhibitors (ICIs) is a widely used strategy in cancer treatment, but their efficacy is often limited by non-specific accumulation and inherent dysimmune toxicities. To overcome these challenges, we developed a kind of dual-functional immune checkpoint nanoblockers (DICNs) using highperformance calcium carbonate nanosponges (CaNPs) as drug delivery carriers. In this study, pravastatin sodium (Pra) was employed as a biomechanical immune checkpoint blocker and encapsulated in CaNPs, which were coated with T-cell membranes. The DICNs perform three key functions: (1) the T-cell-mimicking DICNs enable targeted delivery of the nanomedicine to tumors, reducing off-target effects; (2) they competitively bind to PD-L1 on cancer cells via the T-cell membrane, thereby blocking PD-L1-mediated immune evasion; and (3) they enhance the mechanical forces exerted by T cells on tumor cells through the action of Pra, further improving T-cell-mediated cytotoxicity. Our research results demonstrated that administration of DICNs after chemotherapy significantly inhibited B16-F10 tumor growth without evident systemic toxicity. This study presents a novel therapeutic approach that rejuvenates T-cell function by simultaneously targeting biochemical and biomechanical immune checkpoints.

Few studies have performed comparative analysis of the outcome of hematopoietic stem cell transplantation from HLA‐identical sibling donors (ISD‐HSCT) in patients with or without anti‐HLA Abs. In this study we retrospectively collected data from a multicenter study to analyze the distribution and impact of the pre‐existing anti‐HLA Abs in ISD‐HSCT. Among 402 recipients, 111 were positive for anti‐HLA Abs. Gender, time from diagnosis to transplantation and distribution of primary disease might be risk factors for the occurrence of anti‐HLA Abs. We found that patients with anti‐HLA Abs had delayed neutrophil engraftment and were more vulnerable to experience Cytomegalovirus (CMV) reactivation. The presence of anti‐HLA Abs was proved to be an independent risk factor for neutrophil engraftment (HR 1.42 95% CI 1.13–1.80, p = 0.003) and CMV reactivation (HR 2.03 95% CI 1.19–3.46, p = 0.009). We found that anti‐HLA Abs have a negative impact on the prognosis in the early period after transplantation from sibling donors and anti‐HLA Abs was also an independent risk factor for the overall survival (OS) at 180 days (HR 2.32, 95% CI 1.03–5.27, p = 0.042) among female recipients. In conclusion, anti‐HLA Abs have a negative impact on the prognosis early after ISD‐HSCT.

Background: Patients diagnosed with higher-risk myelodysplastic syndrome (MDS) have poor prognosis. IMM01 is a recombinant signal regulatory protein α (SIRPα) IgG1 fusion protein that exerts anti-tumor activities via blocking “Don't eat me” signal and activating the “Eat me” signal to induce strong antibody-dependent cellular phagocytosis (ADCP). Furthermore, IMM01 activated macrophages could process and present tumor antigen to T cells and elicit long-last tumor-specific T cell immune response. Methods: This is an open-label, multi-center, phase 2 study (NCT05140811) that evaluated safety and efficacy of IMM01 in combination with AZA as the first-line treatment for patients with untreated higher-risk MDS. Enrolled patients were aged ≥18 years with intermediate to very high risk MDS (IPSS-R >3.5) who were not eligible for stem cell transplant or intensive chemotherapy. Patients with treatment-naive MDS were administered intravenous IMM01 at a dosage of 2.0mg/kg/week and subcutaneous AZA at a dosage of 75 mg/m 2 on D1-7 per 28-day cycle. Adverse events (AEs) were reported according to CTCAE v5.0. Efficacy was assessed by IWG 2006 (MDS) criteria. Results: A total of 54 patients were enrolled from June 29, 2022 to June 11, 2023. The median age was 64 (30-83) years, with 39 (72.2%) being male, and 52 (96.3%) having an ECOG of ≥1. Based on risk classification per IPSS-R, 13 patients (24.1%) were intermediate risk (IR), 25 (46.3%) high risk (HR), and 16 (29.6%) very high risk (vHR). At baseline, the median levels of blood counts were 69 (35-95)g/L for hemoglobin, 39.5 (2-409)×10 9/L for platelets and 0.8 (0.1-8.6)×10 9/L for neutrophils. By the data cut of June 11th, 2023, the median duration of follow-up was 5.6 months (95%CI:3.6-7.9). Among the 22 efficacy evaluable patients who received initial treatment of ≥4 months, overall response rate (ORR) was 81.8% (18/22), including 36.4%(8/22) complete response (CR) rate, 22.7%(5/22) marrow CR (mCR) with hematologic improvement (HI), 9.1% (2/22) HI and 13.6% (3/22) mCR alone. Among the 17 efficacy evaluable patients who received initial treatment of ≥6 months, ORR was 88.2%(15/17), including 41.2% (7/17) CR, 29.4% (5/17) mCR with HI, 5.9% (1/17) HI and 11.8% (2/17) mCR alone. The median duration of response (DoR) was not reached. Biomarker data showed mutation burdens of several markers, including TP53, DNMT3A, ASXL1, U2AF1, were dramatically reduced on study treatment. The most frequent treatment related adverse events (TRAEs) (≥20%) were leukopenia (85.2%), thrombocytopenia (72.2%), neutropenia (66.7%), lymphopenia (57.4%), anemia (44.4%), vomiting (44.4%), pyrexia (33.3%), infusion related reaction (33.3%), constipation (29.6%), nausea (25.9%), hypoalbuminemia (22.2%) and infection (20.4%). The most common ≥G3 TRAEs (≥10%) included leukopenia (81.5%), thrombocytopenia (68.5%), neutropenia (66.7%), lymphopenia (57.4%), anemia (44.4%) and infection(16.7%). These AEs were consistent with the AE profile of the AZA monotherapy in treatment-naive MDS as commonly reported in China. Without using of a low priming dose, no Grade ≥3 hemolysis occurred. The study is ongoing. Conclusions: Preliminary data from IMM01 (without low-dose priming) combined with AZA were well tolerated and showed exciting efficacy results in patients with treatment-naive higher-risk MDS.

To the Editor: Allogeneic hemopoietic stem cell transplantation (allo-HSCT) represents the only long-term survival treatment choice for patients with myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasm (MPN). Unfortunately, post-hemopoietic stem cell transplantation (HSCT) relapse remains a cause of treatment failure and the results of salvage treatments are poor. Developing better conditioning regimens is urgently needed. Previous studies have shown synergistic antileukemic effects between decitabine (DEC) and idarubicin (IDA).[1] In an attempt to design a conditioning strategy with very low toxicity but considerable myelosuppressive activity and potential immune-enhancing effects for patients with high-risk MDS and MDS/MPN, we combined DEC and IDA with busulfan, cyclophosphamide, and fludarabine for a modified myeloablative regimen in this prospective, multicenter cohort study (hereafter referred to as the "DEC/IDA study"). The trial was registered with http://www.chictr.org.cn/ as ChiCTR-ONC-17012640. The protocol was reviewed and approved by the Ethic Committee of Blood Diseases Hospital, Institute of Hematology, Chinese Academy of Medical Sciences (No. IHBDH-IIT2017003). This clinical trial was conducted in accordance with the Declaration of Helsinki. All patients provided their written informed consent before participating in the study. Patients aged between 15 years and 65 years, Eastern Cooperative Oncology Group performance status ≤2, with intermediate risk MDS or worse (according to the revised international scoring system for evaluating prognosis [IPSS-R]), chronic myelomonocytic leukemia (CMML), and secondary acute myeloid leukemia (sAML) after MDS or MDS/MPN from 10 medical centers in China were eligible for enrollment. With a sample size of 120 patients, the study had a power of more than 80%, using a 5% level of significance to show significance determined by a binomial distribution calculation with the expected and threshold 2-year relapse rates (RRs) of 10% and 20%, respectively. Eligible patients in the DEC/IDA study received the myeloablative conditioning regimen consisting of 20 mg·m–2·day–1 DEC (days –9 to –5), 3.2 mg·kg–1∙day–1 busulfan (Bu, days –9 to –7), 30 mg·m–2·day–1 fludarabine (Flu, days –6 to –4), 12 mg·m–2·day–1 IDA (days –6 to –4), and 40 mg·kg–1·day–1 cyclophosphamide (Cy, days –3 to –2), followed by allo-HSCT. All patients with unrelated or mismatched-related donors received antithymocyte globulin (rabbit) at 2.5 mg·kg–1·day–1 (days –4 to –1). For graft-versus-host disease (GVHD) prophylaxis, tacrolimus at 0.03 mg/kg from day –5 and methotrexate at 15 mg/m2 on day 1, 10 mg/m2 on days 3, 6, and 11 were used. The endpoints definitions and statistical analysis method were described in Supplementary File, https://links.lww.com/CM9/B938. From January 2017 to February 2021, a total of 121 patients with MDS (≥IPSS-R intermediate risk), CMML, and sAML after MDS or MDS/MPN from 10 Chinese hospitals were registered in the DEC/IDA study, of which 120 entered the study and were included in the analysis. The study flow diagram is shown in Supplementary Figure 1, https://links.lww.com/CM9/B938. The median follow-up time after HSCT was 986 days (range, 8–2026 days; interquartile range [IQR] 461–1423 days). The demoimagedata and clinical characteristics of the patients are shown in Supplementary Table 1, https://links.lww.com/CM9/B938. The median age was 44.5 years (range, 16–64 years) at the time of allo-HSCT. Overall, 100 (83.3%) patients had MDS, 7 (5.8%) patients had CMML, and 13 (10.8%) patients had sAML. Thirty-eight (31.7%) patients were diagnosed with intermediate-risk MDS and 62 (51.7%) were diagnosed with high- or very high-risk MDS according to IPSS-R. Nighty-one (75.8%) patients had active disease before HSCT, including 24 (20.0%) patients who did not respond to chemotherapy and 67 (55.8%) patients who did not receive chemotherapy. All patients in the DEC/IDA study received peripheral blood-derived donor stem cells. Successful neutrophil repopulation was achieved in 119 (99.2%) patients with a median time of 13 (range, 6–23) days. Successful platelet repopulation was achieved in 116 (96.7%) patients with a median time of 16 (range, 9–314) days and 104 of 116 (89.7%) were within 28 days. From the conditioning regimen to hematopoietic reconstitution, a median of 7 (range, 1–62) packages of platelets and 8 (range, 0–36) units of peripheral red blood cells were transfused. All 85 evaluable patients achieved full donor chimerism within a median time of 15 (range, 12–58) days post-transplant. The DEC/IDA conditioning regimen was well tolerated. The most common non-hematologic adverse event was oral mucositis and no patient experienced grade 4 oral mucositis or died before transplantation. Overall, 30.8%, 25.0%, and 21.2% of patients developed grades 1, 2, and 3 oral mucositis, respectively. Fifty-eight (48.3%) patients experienced aGVHD within 100 days after transplantation, and cGVHD occurred in 35 (29.2%) patients (including 12 cases of extensive cGVHD). The cumulative incidences of grades 1–4 and 3–4 aGVHD at 100 days were 48.3% (95% confidence interval [CI], 39.3%–57.3%) and 20.0% (95% CI, 12.8%–27.2%), respectively. The 3-year OS rate, RFS rate, relapse incidence, and NRM incidence were 70.5% (95% CI, 62.7%–79.2%), 67.5% (95% CI, 59.6%–76.4%), 10.0% (95% CI, 5.4%–16.2%), and 22.5% (95% CI, 15.5%–30.4%), respectively Supplementary Figure 2A–C, https://links.lww.com/CM9/B938. Importantly, we observed that only 13 patients relapsed within 3 years after HSCT, and the RFS rate (67.5%) was relatively higher than that reported previously, which arranges from 30% to 50%.[2–4] Thirteen patients, including two MDS with excess blasts (MDS-EB) I, eight MDS-EB II, and three sAML, experienced a relapse in a median time of 186 (range, 59–1401) days after HSCT. Ten of 13 (76.9%) patients received at least one cycle of chemotherapy followed by donor lymphocyte infusion after relapse, while 3 of 13 (23.1%) patients only received supportive care according to the willingness of the patients. Five of 13 (38.5%) patients achieved complete remission and survived at the last follow-up. Among the 35 patient deaths, 8 (22.9%) were due to relapse, and the deaths of 27 patients were due to treatment-related complications. Two patients died from persistent neutropenia and subsequent bloodstream infection early on day 8 and 20. The causes of NRM were aGVHD (n = 15, 42.9%), followed by infectious complications (n = 9, 25.7%) and cerebral hemorrhage (n = 3, 8.6%) Supplementary Figure 2D, https://links.lww.com/CM9/B938. The median time from allo‑HSCT to death was 165 days (range, 8–789). It has been reported that with an increase in the number of oncogenic mutations, patient outcomes progressively worsen.[2] In our study, the number of mutations has no effect on RFS and OS. The OS and RFS of the patients with ≥3 mutations were 70.8% and 66.6%, respectively, superior to that reported in the previous studies (approximately 40%).[2,5] These results indicated that conditioning that consisted of DEC and IDA followed by transplantation may overcome obstacles of adverse mutations in MDS. Univariate analysis for OS and RFS of the DEC/IDA study was conducted [Supplementary Table 2, https://links.lww.com/CM9/B938]. Patient age ≥50 years and TP53 mutation were the factors significantly associated with both poor OS and poor RFS. It is noteworthy that RFS was significantly higher in high/very high-risk MDS compared to intermediate-risk MDS when patient age and TP53 mutation were included as covariates in the multivariate analysis (hazard ratio [HR], 0.47; 95% CI, 0.22–1.00; P = 0.049; Supplementary Table 3, https://links.lww.com/CM9/B938). The 3-year OS was similar between patients receiving a matched sibling donor and alternative donor HSCT (74.1% [95% CI, 61.3%–89.4%] vs. 68.7% [95% CI, 59.3%–79.7%], P = 0.410). To identify patients with more favorable outcomes from the DEC/IDA study, we compared outcomes with those of a historical cohort who received myeloablative conditioning regimen without DEC or IDA between January 2013 and January 2017, including Bu/Cy/Flu/cytarabine (Ara-c), Bu/Cy/Flu and Bu/Flu/Ara-c (dosage: Bu, 3.2 mg·kg–1·day–1, days –9 to –7; Cy, 40 mg·kg–1·day–1, days –3 to –2; Flu, 30 mg·m–2·day–1, days –6 to –4; Ara-c, 2 g·m–2·day–1, –4 to –2 days). The historical control cohort satisfied the same enrollment criteria. Ninety-five patients were included as historical controls. Patient and transplantation characteristics are shown in Supplementary Table 4, https://links.lww.com/CM9/B938. The proportion of patients with MDS-EB or sAML was higher in the DEC/IDA study than in the historical controls (78.3% vs. 60.0%, P = 0.006). Patients in the historical control cohort received transplants more from matched sibling donors than in the DEC/IDA study (76.8% vs. 33.3%, P <0.001). Although there were no significant differences in OS or RFS between the DEC/IDA study and the historical control cohort, a subgroup analysis showed that patients with MDS-EB or sAML tended to benefit from DEC/IDA treatment, which was associated with a lower risk of death (HR, 0.60; 95% CI, 0.35–1.02; P = 0.057; Supplementary Figure 3, https://links.lww.com/CM9/B938). In patients with MDS-EB or sAML, the DEC/IDA study and historical control cohort achieved a 3-year OS of 70.9% (95% CI, 62.2%–80.8%) and 53.6% (95% CI, 42.0%–68.4%), respectively (P = 0.054) and a 3-year RFS of 67.0% (95% CI, 58.1%–77.2%) and 51.9% (95% CI, 40.35%–66.8%), respectively (P = 0.130) [Supplementary Figure 4, https://links.lww.com/CM9/B938]. The subgroup survival analysis in patients with MDS-EB or sAML was performed for patients in the DEC/IDA study and the historical control cohort. The results indicated that compared to the historical control, the DEC/IDA group had a lower risk of death in alternative donor transplants (HR, 0.43; 95% CI, 0.20–0.91; P = 0.028; Supplementary Figure 5, https://links.lww.com/CM9/B938). Donor type, the percentage of blasts in the bone marrow before transplant, as well as the conditioning regimen were included as covariates in the multivariate analysis. The analysis showed that DEC/IDC was a favorable factor associated with better OS, compared to the historical control cohort in patients with MDS-EB or sAML (HR, 0.51; 95% CI, 0.29–0.92; P = 0.024; Supplementary Table 5, https://links.lww.com/CM9/B938). To enhance the credibility and generalizability of the study findings, the transition from single-arm trials to randomized controlled trials is crucial, as it allows for better control over biases, leading to more robust conclusions. In conclusion, the addition of DEC and IDA to the myeloablative conditioning regimen was feasible and effective, with acceptable toxicity. This study provides an optimized strategy to improve the outcomes of patients with MDS and MDS/MPN, especially in patients with MDS-EB or sAML. Funding This work was supported by grants from the Tianjin Health Science and Technology Project (No. TJWJ2022MS001), Clinical research project of Tianjin Society of Hematology and Regenerative Medicine (No. 2022 TSHRM08004), Key Project of Tianjin Natural Science Foundation (No. 20JCZDJC00410), CAMS Innovation Fund for Medical Sciences (No. 2021-I2M-1-073), Haihe Laboratory of Cell Ecosystem Innovation Fund (No. 22HHXBSS00034), and National Natural Science Foundation of China (Nos. 82070192, 8230012348 and 82170217). Conflicts of interest None.

6510 Background: Patients diagnosed with higher-risk myelodysplastic syndrome (MDS) have poor prognosis. Azacitidine (Aza) has been shown to prolong survival in patients with treatment-naive, higher-risk MDS compared to a menu of standard of care options. IMM01 is a fusion protein comprising a recombinant signal regulatory protein α (SIRPα) and IgG1, exerting anti-tumor effects by inhibiting the "Don't eat me" signal and activating the "Eat me" signal, leading to robust antibody-dependent cellular phagocytosis (ADCP). Methods: This is an open-label, multi-center, phase 2 study (NCT05140811) that evaluated safety and efficacy of IMM01 in combination with AZA as the first-line treatment for patients with untreated higher-risk MDS. Enrolled patients were aged ≥18 years with intermediate to very high risk MDS, as defined by the Revised International Prognostic Scoring System (IPSS-R) score >3.5, and were not eligible for stem cell transplant or intensive chemotherapy. Patients were received intravenous IMM01 at a dosage of 2.0mg/kg/week and subcutaneous AZA at a dosage of 75 mg/m 2 on days1-7 per 28-day cycle. Results: By the cutoff-day of Dec 22, 2023, 57 patients were enrolled in the study. The median age was 64 (30-83) years, with 41 (71.9%) being male, and 55 (96.5%) having an ECOG of ≥1. Based on risk classification per IPSS-R, 43.9% were high risk (HR) and 31.6% were very high risk (vHR). At baseline, the median levels of blood counts were 69 (35-136)g/L for hemoglobin, 43 (2-409)×10 9 /L for platelets and 0.8 (0.1-8.6)×10 9 /L for neutrophils. The median duration of follow-up was 12.8 months (95%CI:9.7-15.3). Among the 51 efficacy evaluable patients, overall response rate (ORR) was 64.7%, including 29.4% complete response (CR) rate, 15.7% marrow CR (mCR) with hematologic improvement (HI), 5.9% HI and 13.7% mCR alone. The median time to response (TTR) was 1.9 months (95%CI:1.8-2.8) and the median duration of response (DoR) was not reached(NR). The median of progression-free survival (PFS) was not reached, with an estimated 12-month PFS of 54.4% (95% CI, 31.4-72.6). NGS analysis identified common mutations in DNMT3A, ASXL1, U2AF1 and RUNX1. Notably, NPM1 mutations significantly correlate with treatment response, particularly achieving CR. The most common ≥G3 treatment related adverse events (TRAEs) (≥10%) included leukopenia (78.9%), thrombocytopenia (66.7%), neutropenia (66.7%), lymphopenia (56.1%), anemia (43.9%), infection (15.8%) and pneumonia (10.5%). Without using of a low priming dose, the Grade ≥3 hemolysis was rare (only 1.8%). Conclusions: IMM01 (without low-dose priming) combined with AZA were well tolerated and showed exciting efficacy results in patients with treatment-naive higher-risk MDS. Clinical trial information: NCT05140811 .

Objective To investigate the risk factors of positive anti-HLA antibodies in myelodysplastic syndrome (MDS) patients and gain insights into the impact of anti-HLA antibodies in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for MDS patients. The goal is to identify high-risk patients with anti-HLA antibodies and implement timely interventions, providing a basis for personalized treatment and improving prognosis. Methods A total of 94 MDS patients who received anti-HLA antibody screening and allo-HSCT at our center from December 1, 2016 to September 1, 2023 were retrospectively collected. The general clinical data was compared between 50 patients with positive anti-HLA antibodies and 44 patients without, to identify factors influencing anti-HLA antibody positivity in MDS. Furthermore, based on pre-transplant clinical characteristics of patients and post-transplant survival, as well as the occurrence of related complications, the study analyzed the impact of anti-HLA antibodies on complications such as acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD), graft failure (GF)/poor graft function (PGF), transplant-associated thrombotic microangiopathy (TA-TMA) and long-term survival in MDS patients following HSCT. Results A total of 94 patients were included in this study, comprising 57 males and 37 females. The positive rate of anti-HLA antibody in patients with pregnancy history was higher than those without pregnancy history and male patients, and the difference was statistically significant (74.1% vs. 44.8%, P=0.022). Female sex was identified as an independent risk factor for positive anti-HLA antibodies (OR=3.741, 95%CI:1.254-11.166, P=0.018). There was a significant difference in mortality between the positive and negative anti-HLA antibody groups (46.0% vs 22.7%, P=0.018). Significant differences in mortality were observed among the three groups based on anti-HLA antibody status: continuous positive, positive to negative, and continuous negative(81.8% vs. 30.0% vs. 37.5%, P=0.043). CD34+ cell count < 4.0×106/kg was an independent risk factor for GF/PGF (OR=5.682, 95%CI: 1.258-25.667, P=0.024). Haploidentical transplantation (OR=2.239, 95%CI: 1.079-4.544, P=0.030) and IPSS-R prognosis stratified very low risk/low risk (OR=6.033, 95%CI: 1.704-21.359, P=0.005) were independent risk factors for aGVHD in MDS patients. Being stratified as high-risk according to IPSS-M classification (HR=2.745, 95%CI: 1.269-5.939, P=0.010) is an independent risk factor for overall survival (OS) in MDS transplant patients. The median OS of the positive group was 380 days, while the median OS of the negative group was not reached, with a statistically significant difference (P=0.017). The 1-year, 2-year and 3-year OS rates of anti-HLA antibody positive and negative groups were 51.7% vs. 77.2%, 47.7% vs. 70.7% and 40.9% vs. 70.7%, respectively. The median disease-free survival (DFS) of the positive group was 380 days, but the median DFS of the negative group was not reached, with a statistically significant difference (P=0.017). There were also statistically significant differences in OS(P=0.041) and DFS(P=0.033) between female and male patients in the positive group. Survival analysis showed significant differences in OS (P=0.022) and DFS (P=0.025) among the continuous positive, positive to negative, and continuous negative anti-HLA antibody groups. The risk of GVHD accumulation in anti-HLA positive group was higher than that in negative group, and there was a statistically significant difference (P=0.037). Conclusion Female patients with MDS demonstrate increased susceptibility to positive anti-HLA antibodies. In MDS patients undergoing transplantation, long-term survival rates were notably lower among female patients and those with persistent positive anti-HLA antibodies post-transplantation. The cumulative incidence of GVHD (both aGVHD and cGVHD) was significantly higher in the anti-HLA antibody-positive cohort. Additionally, MDS patients undergoing haploidentical transplantation or stratified based on IPSS-R prognosis face an elevated risk of aGVHD. Key words Myelodysplastic Syndrome; Allogeneic Hematopoietic Stem Cell Transplantation; Anti-HLA antibody; Graft-versus-host disease；Transplant-associated thrombotic microangiopathy

ObjectiveTo compare the efficacy and safety of venetoclax (VEN) in combination with chemotherapy (chemo) versus chemo alone in the treatment of acute myeloid leukemia (AML).MethodTo compare the efficacy and/or safety of VEN+chemo versus chemotherapy alone for AML, PubMed, Embase, Web of Science, and the Cochrane Library were used to searching up to June 2023. Comparisons included complete remission (CR), CR with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), overall response rate (ORR), and adverse events (AEs).ResultA total of 9 articles were included, including 3124 patients. The baseline characteristics between two patient groups were similar. The combined analysis showed that compared with the group receiving chemo alone, the VEN+chemo group exhibited higher rates of CR, CRi, MLFS and ORR. Additionally, the VEN+chemo group had longer event-free survival (EFS) and overall survival (OS) durations. The incidence rates of AEs and serious AEs (SAEs) were similar between the two groups, but the early 30-day mortality rate was lower in the VEN+chemo group than in the chemo alone group.ConclusionThe VEN+chemo therapy demonstrates significant efficacy and safety profile in AML patients. However, more prospective studies are needed in the future to provide more accurate and robust evidence for treatment selection in patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023439288, identifier CRD42023439288.

Background:Lung cancer remains one of the leading causes of cancer-related mortality worldwide, with a substantial proportion of patients suffering from concurrent pulmonary infections. Despite advances in treatment modalities, the early diagnosis of lung cancer complicated by pulmonary infection remains challenging, often resulting in delayed intervention and poorer prognosis. Objective:This study aimed to investigate the expression and significance of serum long non-coding RNA (lncRNA) NEAT1 and microRNA-31 in patients with advanced lung cancer complicated by pulmonary infection. Methods:A total of 48 patients diagnosed with lung cancer complicated by pulmonary infection and admitted to the hospital between January 2021 and December 2021 constituted the experimental group, while 48 healthy volunteers recruited during the same period served as the healthy control group. The expression levels of NEAT1 and microRNA-31 in plasma samples obtained from peripheral blood were measured using quantitative real-time polymerase chain reaction (qRT-PCR), and their differential expression in plasma was compared between the two groups. Results:Significantly elevated levels of serum lncRNA NEAT1 and microRNA-31 were observed in the experimental group compared to the healthy control group. Furthermore, the expression levels of NEAT1 and microRNA-31 showed correlations with patient age and tumor size. Notably, the expression of NEAT1 exhibited no significant association with smoking status, whereas microRNA-31 expression displayed a significant relationship with smoking. Conclusions:Our findings demonstrate that lncRNA NEAT1 and microRNA-31 are markedly upregulated in the plasma of patients with advanced lung cancer complicated by pulmonary infection. These molecules hold promise as potential diagnostic markers for advanced lung cancer complicated by pulmonary infection and may provide early auxiliary diagnostic value for lung cancer.

Aplastic anemia (AA) is a bone marrow (BM) failure syndrome mediated by hyperactivated T-cells with heterogeneous pathogenic factors. The onset of BM failure cannot be accurately determined in humans; therefore, exact pathogenesis remains unclear. In this study, a cellular atlas and microenvironment interactions is established using unbiased single-cell RNA-seq, along with multi-omics analyses (mass cytometry, cytokine profiling, and oxidized fatty acid metabolomics). A new KIR+ CD8+ regulatory T cells (Treg) subset is identified in patients with AA that engages in immune homeostasis. Conventional CD4+ T-cells differentiate into highly differentiated T helper cells with type 2 cytokines (IL-4, IL-6, and IL-13), GM-SCF, and IL-1β. Immunosuppressive homeostasis is impaired by enhanced apoptosis of activated Treg cells. Pathological Vδ1 cells dominated the main fraction of γδ T-cells. The B/plasma, erythroid, and myeloid lineages also exhibit substantial pathological features. Interactions between TNFSF12-TNFRSF12A, TNF-TNFRSF1A, and granzyme-gasdermin are associated with the cell death of hematopoietic stem/progenitor (HSPCs), Treg, and early erythroid cells. Ferroptosis, a major driver of HSPCs destruction, is identified in patients with AA. Furthermore, a case of twins with AA is reported to enhance the persuasiveness of the analysis. These results collectively constitute the cellular atlas and microenvironment interactions in patients with AA and provide novel insights into the development of new therapeutic opportunities.

To explore the characteristics of hemogram in patients with aplastic anemia (AA), especially mean corpuscular volume (MCV) and red cell distribution width (RDW). We examined the blood routine of 180 new-onset AA patients and used 166 patients with myelodysplastic syndrome (MDS) as controls. Among the 180 AA patients, 105 (58.3%) were diagnosed with severe AA (SAA), while 75 (41.7%) were diagnosed with non-severe AA (NSAA). Compared to MDS, patients with SAA generally had unfavorable hemogram, including significantly lower white blood cell (WBC), absolute neutrophil count (ANC), hemoglobin (Hb), platelet (PLT) and reticulocyte counts (RET). However, WBC, ANC and lymphocyte counts were higher in the NSAA group than in the MDS group; Hb and Ret were comparable between the two groups. 8.5% of SAA patients and 58.1% of NSAA patients presented with macrocytic anemia, whereas 25.7% of SAA and 64.0% of NSAA had a high RDW. In the MDS group, 54.7% of patients presented with macrocytic anemia, and 84.7% had increased RDW. WBC, ANC, PLT, and Ret in a high-RDW group (25.7% of SAA) were significantly higher than in a normal-RDW group (74.3% of SAA). Overall, most SAA patients exhibited normocytic-normochromic anemia, and their hemograms decreased more significantly; more than half of NSAA patients showed macrocytic-heterogeneous anemia, and their hemograms were similar to those of MDS. Patients with elevated RDW may have better residual bone marrow hematopoietic function than those with normal RDW but with more severe anemia.

We retrospectively analyzed the outcomes of 136 consecutive patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our center. Among them, 76 cases used hypomethylating agents (decitabine, n = 40; azacitidine, n = 36) as post-transplant maintenance therapy, whereas 60 contemporaneous patients did not adopt maintenance therapy. The 3-year incidences of relapse in two groups were 16.6% and 39.2% (p = .001). The 3-year OS and DFS in maintenance group were 84.0% and 78.6%, which were remarkably improved than in control group (60.0% and 58.0%) (p = .004, p = .011). Moreover, the 3-year relapse rates for patients receiving decitabine and azacitidine therapy were 8.5% and 25.0%, respectively (p = .019). Patients utilizing decitabine had more common possibility of grade 3-4 neutropenia than azacitidine (20.0% vs. 2.8%, p = .031). These results indicate that maintenance therapies using hypomethylating agents could reduce the risk of post-transplant recurrence, resulting into remarkable superior survival. Decitabine might lower relapse after allo-HSCT with somewhat more severe myelosuppression when being compared to azacitidine.