Acute leukemias (ALs) are a diverse group of hematological malignancies characterized by the abnormal proliferation of immature cells. Microscopic observation of cell morphology based on the French‑American‑British classification remains a fundamental diagnostic method for ALs. However, manual screening from bone marrow smear images is often inefficient, laborious and prone to subjective bias, leading to potential misdiagnosis or missed diagnosis. Artificial intelligence (AI), particularly machine learning (ML), has expanded human capabilities in analyzing complex datasets, leading to breakthroughs in multiple fields, including medical research and clinical practice. Increasingly, ML applications are being developed to diagnose hematological diseases by extracting and aggregating morphological characteristics from peripheral blood and bone marrow smears. However, applying ML methods to recognize cell morphology in hematological diseases presents unique challenges compared with other pathology subspecialties. The present review provided an overview of AI and ML applications in ALs diagnosis, focusing on cell segmentation and data mining methods from microscopy images, and highlights their advantages over manual microscopy.

Relapse is a major cause of treatment failure after allogeneic hematopoietic stem-cell transplantation(allo-HSCT) for high-risk myeloid malignancies. This single center, retrospective study enrolled patients with high-risk acute myeloid leukemia or myelodysplastic syndromes who received allo-HSCT from January 1, 2022 to December 31, 2024. Post-transplant maintenance therapy consisted of azacitidine (32 mg/m²/day, day 1-5) plus venetoclax (400 mg/day, day 1-7), starting from the 60th day posttransplant and repeated every 28 days until up to 1-year posttransplant. Outcomes were compared with a contemporaneous control group constructed via propensity score matching (azacitidine-venetoclax, n = 35; control, n = 59). After a median follow-up of 22.5 months, the 1-year disease-free survival was 88.6% (95% CI, 78.6%-99.8%), the 1-year cumulative incidence of relapse was 5.7% (95% CI, 0%-13.5%). The azacitidine-venetoclax group demonstrated significantly superior 1-year overall survival compared to control (P = 0.037). Win ratio analysis further confirmed a significant overall clinical benefit (P < 0.001). Subgroup analysis revealed a pronounced overall survival benefit for MRD-positive patients (HR, 0.288; P = 0.037). The safety profile was manageable, no significant increase in the incidences of EBV and CMV infection or graft-versus-host disease. Immune reconstitution analysis showed delayed B-cell recovery but preserved T-cell and NK-cell recovery.

BACKGROUND:Immune reconstitution is critical for outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but its prognostic role in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) remains unclear. METHODS:We retrospectively analysed 577 patients who underwent T-cell replete haplo-PBSCT between 2016 and 2024. Longitudinal reconstitution of CD4⁺, CD8⁺ T cells and their subsets, CD3⁺CD69⁺, CD3⁺HLA-DR⁺ T cells, NK cells and B cells was assessed from 1 to 12 months post-transplant. Cox regression and causal mediation analyses were performed to identify prognostic associations and mechanisms. RESULTS:Early and robust regulatory T cell (Treg) reconstitution significantly reduced transplant-related mortality (TRM) and improved overall survival. Naïve CD8⁺ T cell recovery correlated with reduced TRM and relapse. Higher late CD3⁺CD69⁺ T cells were linked to decreased relapse risk. Sustained B cell reconstitution reduced TRM and was associated with a lower incidence of moderate-to-severe chronic graft-versus-host disease. Early Treg reconstitution was associated with lower cytomegalovirus (CMV) reactivation. Mediation analysis revealed that Treg recovery reduced TRM partially through suppression of CMV reactivation (ACME = -0.22, p = 0.032). CONCLUSION:Distinct lymphocyte subset reconstitution profiles predict transplant outcomes in haplo-PBSCT. Early Treg recovery, partly by limiting CMV reactivation, may serve as a target for immune-guided intervention.

Reduced-intensity conditioning (RIC) is associated with a high relapse rate in high-risk acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT). It remains unclear whether venetoclax, an anti-leukaemic agent, can enhance RIC efficacy. A prospective, single-arm, phase 2 trial enrolled patients with high-risk AML or MDS, aged ≥55 years, who underwent allogeneic peripheral blood stem cell transplantation (allo-PBSCT). All patients received venetoclax-enhanced RIC (VEN-RIC), comprising venetoclax, busulfan, fludarabine, cytarabine and low-dose total body irradiation (TBI). Fifty patients (median age 62) were enrolled. At a median follow-up of 14.9 months, the 1-year progression-free survival (PFS) was 72.5%, while 1-year overall survival (OS) and graft-versus-host disease/relapse-free survival (GVHD/GRFS) were 73.8% and 56.9% respectively. The 1-year cumulative incidence of relapse and non-relapse mortality were 16.8% and 10.6%. The 180-day cumulative incidence of acute GVHD was 22.9%, while the 1-year cumulative incidence of chronic GVHD was 25.8%. Multivariable analysis showed TP53 mutation was the strongest predictor of worse OS, PFS and GRFS, as well as higher relapse. We conclude that VEN-RIC is feasible and associated with encouraging survival and a manageable safety profile, warranting confirmation in randomized studies.

Post-transplant relapse remains the chief therapeutic challenge in Ph-negative B cell acute lymphoblastic leukemia (Ph - B-ALL). This retrospective study evaluated whether short-course blinatumomab for measurable resident disease (MRD) eradication could improve transplant outcomes. We compared 23 patients receiving pre-transplant short-course blinatumomab (2-week) for MRD eradication with 46 chemotherapy-only controls. All achieved MRD-negative before allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Only two patients developed grade 2 cytokine release syndrome with blinatumomab. The neutrophil and platelet engraftment times were similar between the two groups. The blinatumomab cohort had a significantly lower 18-month cumulative incidence (CI) of relapse ( p = 0.05) and chronic graft-versus-host disease (GVHD) (14.8% vs. 41.8%; p = 0.05), with comparable non-relapse mortality (NRM) ( p = 0.98) and 180-day grade II-IV acute GVHD rates ( p = 0.93). Consequently, this cohort showed superior 18-month relapse-free survival (RFS) (90.9% vs. 65.2%; HR 0.30, 95% CI 0.09-1.04; p = 0.04), improved 18-month overall survival (OS) (95.7% vs. 81.9%; HR 0.20, 95% CI 0.03-1.71), and a trend toward better GVHD-free and relapse-free survival (GRFS) (74.71% vs. 63.71%; HR 0.64, 95% CI 0.23-1.78). Multivariate analysis confirmed blinatumomab as an independent favorable factor for RFS. In conclusion, short-course blinatumomab as a bridge-to-transplantation could reduce the risk of relapse and improve survival for Ph - B-ALL patients undergoing allo-PBSCT.

Abstract Background Blood testing aids pneumonia diagnosis, but its effectiveness varies. Given the invasiveness of bronchoalveolar lavage fluid (BALF) sampling versus blood testing’s simplicity, this study investigates when blood can reliably substitute for BALF in detecting microbial presence, especially for pathogens. Results Metagenomic sequencing was performed on paired BALF-blood samples from 21 post-HSCT immunocompromised (ICP) and 21 immunocompetent (ICT) patients. The ICP cohort was expanded to 62 for biomarker validation. Host responses were profiled via metatranscriptomics (30 BALF samples). Microbial alpha and beta diversity differed significantly between blood and BALF in ICP, but not ICT, patients. ICP patients’ BALF contained a greater diversity and abundance of microbes. A higher proportion of microbial DNA sequences in ICP patients’ blood was also present in their BALF, suggesting a potentially more permeable alveolar-capillary barrier. Related genes (e.g., NABA CORE MATRISOME, extracellular matrix organization, cell-cell adhesion) were downregulated. Upregulated pathways like VEGFA-VEGFR2 signaling and Rho GTPases suggested increased vascular permeability. In ICP patients, 419 microbial sequences in blood indicated their presence in the lower respiratory tract with > 70% certainty. Conclusion Host immune status significantly influences blood-BALF microbial diversity differences. Shared blood-BALF microbial DNA sequences show potential for aiding pneumonia pathogen diagnosis, offering a novel biomarker identification approach.

Full engraftment and early immune reconstitution of donor hematopoietic stem cells (HSCs) after allogeneic HSC transplantation (allo-HSCT) are crucial. However, effective and safe clinical modality remains lacking. Here, very-late antigen (VLA-4) was identified as a pivotal target for HSC engraftment, and one of its agonists was identified, which significantly promotes donor HSC engraftment and long-term hematopoietic reconstitution by enhancing its self-renewal capacity in allogeneic transplantation and serial xenotransplantation mouse models. Furthermore, the VLA-4 agonist facilitated early immune reconstitution by augmenting T-cell differentiation from HSCs, with the reconstituted immune cells exhibiting potent antiviral effects without exacerbating acute graft-versus-host disease. Mechanistically, VLA-4 A2 activated ERK1/2 phosphorylation to regulate HSC function and lymphoid progenitor differentiation, without inducing leukemogenic gene expression. These findings underscore the significant clinical translational potential of the VLA-4 agonist in promoting HSC engraftment and early cellular immune reconstitution following allo-HSCT.

Abstract The optimal graft-versus-host disease (GVHD) prophylaxis strategy in haploidentical peripheral blood stem cell transplantation remains controversial. In this open-label, phase 3 study, patients aged 14 to 70 years with acute myeloid leukemia or myelodysplastic syndromes with excess blasts Ⅰ or Ⅱ were randomized (2:1:1) to receive low-dose antithymocyte globulin (ATG; 5 mg/kg) plus posttransplant cyclophosphamide (PTCy; 50 mg/kg; referred to as ATG/PTCy), standard-dose ATG (total dose, 10 mg/kg), or a PTCy-based (total dose, 100 mg/kg) regimen for GVHD prophylaxis. The coprimary end points were the cumulative incidence (CI) of grade 2 to 4 acute GVHD (aGVHD) by day 100 and GVHD-free, relapse-free survival at 1 year after transplant. A total of 407 patients were randomized to receive an ATG/PTCy (185 patients), ATG (113 patients), or PTCy (109 patients) regimen for GVHD prophylaxis. By day +100, the CI of grade 2 to 4 aGVHD did not differ significantly among the 3 groups (P = .210). Although the overall incidence of chronic GVHD (cGVHD) was comparable across all groups (P = .110), the 2-year CI of moderate-to-severe cGVHD was numerically lower in the ATG/PTCy (17.4%) and ATG (17.3%) groups than the PTCy group (28.3%), without reaching statistical significance (P = .095). No significant differences were observed in survival outcomes among the 3 groups. Notably, the CI of neutrophil and platelet recovery was significantly higher in the ATG/PTCy group than in the other groups (P< .001). This trial suggested that the 3 GVHD prophylaxis strategies presented similar efficacy in preventing grade 2 to 4 aGVHD and yielded comparable survival. This trial was registered at www.clinicaltrials.gov as NCT03608059.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the cornerstone of curative therapy for acute myeloid leukemia (AML), yet precise molecular prognostic tools are currently insufficient. This study developed a prognostic model, AML-PRSS, integrating genomic and clinical factors from 389 adult AML patients undergoing their first allo-HSCT between 2013 and 2021. Seven genetic mutations significantly associated with leukemia-free survival (LFS) were categorized as favorable (DNMT3A, CEBPA bZIP domain, NPM1 without FLT3-ITD or with FLT3-ITD plus tyrosine kinase inhibitors), unfavorable (NRAS and GATA2), and high-risk (TP53 and U2AF1). Multivariate analysis identified molecular risk, cytogenetic risk, pre-transplant disease status, age, and hematopoietic cell transplant-comorbidity index (HCT-CI) score as independent predictors of LFS. AML-PRSS stratified patients into four risk groups with stepwise increasing hazard of LFS failure. Validation in an independent multi-center cohort of 266 patients confirmed robust predictive accuracy, highlighting AML-PRSS as an effective tool for personalized prognostication and clinical decision-making.

The optimal intensity of conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients diagnosed with myelodysplastic syndromes with excess blasts (MDS-EB) remains debated. We retrospectively analyzed the clinical outcomes of 102 MDS-EB patients who received an individualized conditioning protocol based on age and comorbidity, including busulfan, fludarabine, cytarabine, and low-dose total body irradiation (TBI). All patients achieved successful engraftment, with a median time to neutrophil and platelet engraftment of 12 and 13 days, respectively. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) at 180 days was 16.9%, while moderate-to-severe chronic GVHD at 2 years occurred in 15.0% of patients. After a median follow-up of 23 months, the 2-year relapse incidence was 11.5%. The 2-year overall survival (OS), progression-free survival (PFS), and GVHD-free/relapse-free survival (GRFS) were 81.9%, 77.3%, and 66.4%, respectively. The very high-risk subgroup of the International Prognostic Scoring System for MDS (IPSS-M) exhibited significantly higher relapse rates compared with the lower-risk groups (17.8% vs 2.4%, P = 0.03). Multivariate analysis identified IPSS-M as the only independent predictor of PFS (hazard ratio (HR) = 3.30, P = 0.04), whereas transplant conditioning intensity (TCI) showed no association with survival outcomes. These findings suggest that the age- and comorbidity-adjusted conditioning regimen achieves high engraftment rates, low relapse, and favorable survival in MDS-EB patients, with disease biology (IPSS-M) outweighing conditioning intensity in prognostic relevance.

Our study delved into the clinical outcomes of haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) for older patients, utilizing a novel low-dose antithymocyte globin (ATG)/post-cyclophosphamide (PTCy)-based regimen to prevent graft-versus-host disease (GVHD). We juxtaposed these outcomes with transplants from matched unrelated/sibling donors (MUD/MSD) for elderly patients with myeloid malignancies from 2016 to 2023. The study encompassed 127 patients, with 40 undergoing MUD/MSD-PBSCT and 87 receiving haplo-PBSCT. The incidences of grades Ⅱ-Ⅳ and Ⅲ-Ⅳ acute GVHD were similar between the two groups, the haplo-PBSCT cohort displayed a promising trend toward reduced incidence of moderate to severe chronic GVHD compared to MUD/MSD-PBSCT (8.19% vs 23.40%, P = 0.067). The 2-year disease-free survival (74.11% vs 59.67%, P = 0.231) and overall survival (76.30% vs 64.00%, P = 0.482) rates were comparable, while haplo-PBSCT exhibited higher graft-versus-host disease-free, relapse-free survival (GRFS) (68.85% vs 46.61%, P = 0.041) and lower cumulative incidences of relapse (CIR) (11.16% vs 31.98%, P = 0.010) compared to MUD/MSD-PBSCT. Our findings underscore the potential of haploidentical transplants with the low-dose ATG/PTCy-based regimen to yield improved GRFS and lower CIR for older patients with hematologic malignancies. Thus, haploidentical donors, especially when coupled with this specified GVHD prevention strategy, emerge as a viable and appealing graft source for elderly patients requiring allo-SCT.

Background:Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a common alternative for patients with hematological malignancies. Epstein-Barr virus (EBV) reactivation is a common complication post-transplantation, but its impact on immune reconstitution and survival remains unclear. Objective:To compare immune reconstitution and survival between patients with and without EBV reactivation after haplo-HSCT. Design:A retrospective study was conducted involving 322 patients aged 18-60 years, diagnosed with hematological malignancies, who underwent haplo-HSCT at our center from January 2018 to December 2021. Methods:Data analysis was performed using SPSS (version 24.0) and R4.3.0 software. Statistical methods included Chi-square tests for qualitative variables, independent t tests for continuous variables, Kaplan-Meier method for survival analysis, and logistic regression for risk factor analysis. Results:After a median of 58 days posttransplant, 176 patients (54.6%) had EBV reactivation, but only 5 patients developed posttransplant lymphoproliferative disorder. Logistics multivariate analysis showed EBV IgA-negative donor, cytomegalovirus (CMV) reactivation, and graft-versus-host disease (GVHD) prophylaxis with anti-thymocyte globulin (ATG) were independent risk factors of EBV reactivation. Then a risk factor prediction model for EBV reactivation after transplantation was established based on the multivariate regression. The analysis based on the generalized linear mixed model showed dramatic improvements in the reconstitution of CD8+CD45RO+ memory T-cells and CD16+CD56+ NK cells of the EBV-reactivated group. There was no statistical difference in overall survival (p = 0.26), relapse-free survival (p = 0.72), GVHD-relapse free survival (p = 0.44), cumulative incidence of relapse (Gray's test p = 0.72), and transplant-related mortality (Gray's test p = 0.066) between patients with and without EBV reactivation. Conclusion:Our study showed EBV IgA-negative donor, CMV reactivation, and GVHD prophylaxis with ATG were independent risk factors of EBV reactivation. Posttransplant EBV reactivation had no significant influence on the outcomes of patients, but its impact on immune reconstitution might be complicated. The predictive model based on the study could direct our attention toward patients at high risk of EBV reactivation.

Measurable residual disease (MRD) and donor chimerism (DC) monitoring are critical for early relapse prediction after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Droplet digital PCR (ddPCR), a highly sensitive quantitative technique, offers advantages in mutation detection and MRD tracking. To explore the advantages of ddPCR in predicting relapse post-transplant, ddPCR for MRD monitoring was compared with conventional methods including WT1-qPCR, multiparameter flow cytometry (MFC), short tandem repeat (STR) and XY-FISH chimerism for 196 patients with myeloid malignancies. ddPCR demonstrated superior sensitivity (81.08%) and specificity (91.19%) compared to WT1-qPCR (75.86%/78.23%) and MFC (56.76%/94.97%). Total-DC (16.13%/94.70%), T-DC (9.68%/93.94%) and XY-FISH (46.67%/79.73%) were significantly less sensitive. In all, from robust to inconclusive, the efficacy in predicting relapse (Youden index) were as follows: 0.72 for ddPCR, 0.54 for WT1-qPCR, 0.51 for MFC, 0.26 for XY-FISH, 0.11 for total-DC and 0.04 for T-DC. Notably, ddPCR provided the earliest relapse prediction, with a median lead time of 60.5 (range: 10–461) days, outperforming MFC (43 days), WT1-qPCR (55 days), STR chimerism (total-DC: 43 days; T-DC: 37 days), and XY-FISH (54 days). This study demonstrated ddPCR as the most effective and timely tool for impending relapse post-transplant in AML/MDS.

Signal transducer and activator of transcription 3 (STAT3), a crucial transcription factor, exerts a notable influence by hyperactivating or acquiring functional mutations in the occurrence and progression of cancers. Hyperactive STAT3 is also implicated in a range of hematopoietic malignancies, especially acute myeloid leukemia (AML). The function of STAT3 is associated with the phosphorylated parallel dimer structure, enabling them to stimulate the transcription of specific genes. AML is a highly heterogeneous hematological malignancy, which is challenging in terms of therapy. The current efficacy of chemotherapy and targeted therapy remains suboptimal. Targeted inhibition of STAT3 has the potential to enhance the efficacy of AML treatment, thereby possibly improving the prognosis of individuals suffering from AML. The present review summarizes the development of inhibitors against STAT3 and discusses their applicability as AML therapeutics, which could inspire new possibilities for enhancing AML treatment strategies.

Relapse remains a major challenge after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myeloid malignancies. Early detection of relapse is critical for timely intervention, and measurable residual disease (MRD) and donor chimerism (DC) monitoring are key strategies for relapse prediction. While conventional methods such as quantitative PCR for Wilms' tumor 1 mRNA levels (WT1-qPCR), multiparameter flow cytometry (MFC), short tandem repeat (STR) chimerism, and fluorescence in situ hybridization for the X and Y chromosomes (XY-FISH) are widely used, their sensitivity and specificity vary. Droplet digital PCR (ddPCR), a highly sensitive quantitative technique, offers potential advantages in mutation detection and MRD tracking, but its comparative efficacy in predicting relapse with conventional methods post-transplantation remains to be fully established. This study aimed to evaluate the performance of ddPCR in predicting relapse after allo-HSCT compared to conventional MRD and chimerism monitoring methods (WT1-qPCR, MFC, STR, and XY-FISH). The study included 196 patients with myeloid malignancies who underwent allo-HSCT. MRD and DC were monitored using ddPCR, WT1-qPCR, MFC, STR (total-DC and T-DC), and XY-FISH. The sensitivity, specificity, false-negative rate, false-positive rate, and Youden index were calculated to assess their predictive efficacy. The lead time for relapse prediction (median days before clinical relapse) was also compared across techniques. ddPCR demonstrated superior sensitivity (81.08%) and specificity (91.19%) compared with WT1-qPCR (75.86%/78.23%) and MFC (56.76%/94.97%). The sensitivities and specificities of total-DC (16.13%/94.70%), T-DC (9.68%/93.94%), and XY-FISH (46.67%/79.73%) were significantly lower. From the most robust to inconclusive, the efficacies of the techniques in predicting relapse (Youden index) were as follows: 0.72 for ddPCR, 0.54 for WT1-qPCR, 0.51 for MFC, 0.26 for XY-FISH, 0.11 for total-DC, and 0.04 for T-DC. Notably, ddPCR provided the earliest relapse prediction, with a median lead time of 60.5 (range: 10 to 461) days, outperforming MFC (43 days), WT1-qPCR (55 days), STR chimerism (total-DC: 43 days; T-DC: 37 days), and XY-FISH (54 days). This study suggests that ddPCR may be a transformative tool for MRD monitoring with the superior sensitivity and longer lead time for predicting relapse than conventional methods in acute myeloid leukemia/myelodysplastic syndrome patients after allo-HSCT. Its outstanding performance supports its integration into routine post-transplant monitoring to enable early intervention and improve outcomes.

BACKGROUND:An optimal donor is critical for patient survival undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). The impacts of different donors on outcomes under the combination regimens of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis had limited data. METHODS:Therefore, a single-center retrospective study was performed for patients undergoing haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with ATG/PTCy combination-based regimen. RESULTS:The donors were divided into young male (age <30 years, n = 74), non-parous female (age <30 years, n = 22), older male (age ≥30 years, n = 117), and parous female (age ≥30 years, n = 42) donor groups. The cumulative incidences (CIs) of acute and chronic GVHD, and survival outcomes were similar between the 4 groups (P > 0.050), while the parous female donor could significantly reduce the cumulative incidence of relapse (CIR). CONCLUSIONS:The results showed that the parous female donor could significantly reduce CIR and might improve survival under the ATG and PTCy combination-based GVHD prophylaxis regimen after haplo-PBSCT.

Allogeneic hematopoietic stem cell transplantation represents a curative modality for patients with myelodysplastic syndrome (MDS), yet relapse risk persists. The prognostic performances of the Revised International Prognostic Scoring System (IPSS-R) and the Molecular International Prognostic Scoring System (IPSS-M) for 129 MDS patients undergoing allogeneic peripheral blood stem cell transplantation (allo-PBSCT) were evaluated. Using IPSS-M, 29.5% of patients were reclassified to a higher risk and 14.0% to a lower risk compared to IPSS-R. The two-year recurrence-free survival (RFS) and overall survival (OS) post-transplant were similar across IPSS-R groups, but significantly lower in the very-high risk category with IPSS-M (P = 0.005 for RFS; P = 0.014 for OS). Multivariate analysis revealed that patient age (P = 0.009, P = 0.017), very-high risk category in IPSS-M (P = 0.003, P = 0.001), and KPS score (P = 0.034, P = 0.055) were independent factors for OS and RFS. Only very-high risk category in IPSS-M was the independent factor affecting cumulative incidence of relapse (P = 0.003). Prophylactic interventions for relapse significantly decreased the risk of relapse (P = 0.003) and increased the survival of patients in the very-high risk category (P = 0.002 for OS, P = 0.006 for RFS). The study suggested that the IPSS-M system could identify the high relapse risk patients post-transplant who may benefit from early prophylactic interventions.

Chronic graft-versus-host disease (cGVHD) is a potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation. Standard steroid first-line treatment could not satisfy therapeutic needs due to limited efficacy. As a highly selective Janus kinase (JAK) 1 inhibitor, SHR0302 exhibits a reduced inhibition effect on JAK2 and might have less effect on hematopoiesis. This phase I clinical trial investigated the tolerability and safety of SHR0302 in combination with prednisone, and its early efficacy evidence as a potential first-line treatment to moderate/severe cGVHD. The standard 3 + 3 dose escalation was implemented to find the optimal dose of SHR0302. And prednisone was concurrently administrated with a dose of 1 mg/kg/d and then gradually tapered after 2 weeks. Eighteen patients were enrolled into the study. Grade ≥ 3 treatment-related adverse events were observed in 38.9% of patients. Only one patient developed DLT (grade ≥ 3 hypercholesterolemia) in the highest dose-level group who had pre-existing hypercholesterolemia. The maximum tolerated dose was not reached. No patient discontinued treatment due to AEs. Sixteen out of 18 patients were evaluable for responses, the ORR at week 4 and week 24 were 94.4 and 87.5%, respectively. Overall, the treatment of SHR0302 combined with prednisone was safe and well-tolerated, preliminary clinical results presented a high response for previously untreated cGVHD and a significant reduction in prednisone use in this study. A phase II trial will be conducted to further investigate its therapeutic effects clinically.

The haploidentical donor is diverse and an optimal donor is critical for the survival of patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Under anti-thymocyte (ATG) or post-transplant cyclophosphamide (PTCy) alone-based graft-versus-host disease (GVHD) prophylaxis for haplo-HSCT, young male donor is always preferred due to a lower non-relapse mortality (NRM) and better survival, while mother or collateral relative donor is usually the last resort. The combination regimens of anti-thymocyte (ATG) and post-transplant cyclophosphamide (PTCy) in haplo-HSCT were more and more utilized due to their promising efficiencies for graft-versus-host disease (GVHD) prophylaxis, however, the impact of different donors on patient outcomes under the combination regimens remains to be unclear. Therefore, we performed a retrospective study for patients undergoing haplo-HSCT with a low-dose ATG plus low-dose PCTy-based regimen for GVHD prophylaxis at our center. The study enrolled 262 patients, whose donors were categorized into the young male donor group (age <30 years, n=74), non-parous female donor group (n=25), older male donor group (age ≥30 years, n=117), and parous female donor group (n=46). For the whole cohort, the cumulative incidences (CIs) of grade Ⅱ-Ⅳ acute GVHD (aGVHD) at 180 days and moderate-to-severe chronic GVHD at 2 years after transplantation were 11.45% (95% CI, 7.95%-15.65%) and 19.04% (95% CI, 14.38%-24.22%). In multivariate analysis, the parous female donor had a strong trend to increase the risk of grade Ⅱ-Ⅳ aGVHD (HR, 3.32, 95% CI, 0.99-11.10; P=0.051) and significantly decreased the risk of relapse (HR, 0.14, 95% CI, 0.03-0.63; P=0.010). In the parous female donor group, the 2-year OS, and RFS were relatively higher with both of 73.37% (95% CI, 61.49%-87.54%). The results suggested that the parous female donors could reduce the risk of relapse and might improve survival under the combination regimen for GVHD prophylaxis.