To investigate the clinical characteristics, risk factors, and impacts of chronic graft-versus-host disease (cGvHD) on survival outcomes in patients with severe aplastic anemia (SAA) following haploidentical hematopoietic stem cell transplantation (haplo-HSCT), a cohort of 530 patients was analyzed. The findings revealed that 156 patients developed cGvHD, with a 5-year cumulative incidence of 29.6% (72.4% mild, 17.9% moderate, 9.6% severe). Multivariate analysis identified patient age ≥18 years (hazard ratio [HR] = 1.38, P = 0.044) and a history of grade II-IV acute GvHD (HR = 1.69, P = 0.002) as independent risk factors for cGvHD development. For severe cGvHD, risk factors included previous antithymocyte globulin treatment (HR = 2.99, P = 0.035) and a history of grade III-IV acute GvHD (HR = 4.37, P = 0.010). No significant difference in OS was observed between cGvHD and non-cGvHD groups, but the 5-year OS rate was significantly lower in patients with moderate to severe cGvHD compared to those without the condition (84.3% vs. 95.1%, P = 0.006). Among patients with cGvHD, patients with severe cGvHD had significantly lower 5-year OS (80.0%) than those with mild (97.3%) or moderate (96.4%) cGvHD (P = 0.007). These findings contribute to understanding cGvHD in SAA patients after haplo-HSCT, aiding in personalized management to improve outcomes.

Haploidentical haematopoietic stem cell transplantation (haplo-HSCT) provides curative potential for older patients with haematological malignancies. Since multiple haploidentical donors may be available for a given patient, identifying factors that influence transplant outcomes, particularly donor-related characteristics, is critical. This study aimed to identify donor factors that are associated with transplant outcomes, particularly focusing on the impact of donor age on overall survival (OS), disease-free survival (DFS), and transplant-related mortality (TRM) in patients aged ≥55 yr undergoing haplo-HSCT. This retrospective study included 460 patients aged ≥55 yr with acute leukaemia or myelodysplastic syndromes who underwent haplo-HSCT. Multivariate analysis was used to assess the association between donor factors and transplant outcomes, with subgroup comparisons for younger (<33 yr) versus older (≥33 yr) donors. Multivariate analysis showed that increasing donor age was significantly associated with inferior OS (HR 1.22, 95% CI: 1.10 to 1.36; P < .001), poorer DFS (HR 1.20, 95% CI: 1.09 to 1.32; P < .001), and higher TRM (HR 1.20, 95% CI: 1.07 to 1.34; P = .001). Compared with donors aged ≥33 yr, younger donors (<33 yr) were associated with better OS (80.8% versus 67.6%, P = .002), improved DFS (73.8% versus 62.6%, P = .002), and lower TRM (16.6% versus 24.2%, P = .03). This study indicated that donor age significantly influences the outcomes of haplo-HSCT in patients ≥55 yr. Younger donors, particularly those aged <33 yr, were associated with better OS and DFS and lower TRM, suggesting that younger donors may be preferred for older patients undergoing haplo-HSCT.

Post-transplant relapse remains a major clinical challenge in Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph + ALL). Real-time quantitative PCR (RQ-PCR) for BCR::ABL1 is the current standard for measurable residual disease (MRD) monitoring, whereas digital PCR (dPCR) offers substantially higher analytical sensitivity. Whether this increased sensitivity translates into additional prognostic value after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. In this prospective study (NCT06211166), 270 patients with Ph + ALL were longitudinally monitored after allo-HSCT. MRD was assessed in parallel using dPCR, RQ-PCR, and MFC. Based on the first post-transplant MRD detection pattern, patients were categorized into four groups: double-negative (n = 80), dPCR–single-positive (n = 158), RQ-PCR–single-positive (n = 3), and double-positive (n = 29). The dPCR–single-positive pattern was the most prevalent MRD status, accounting for 58.5

Poor hematopoietic reconstitution (PHR), a serious complication after chemotherapy or radiotherapy in patients with hematological or solid malignancies, which lacks effective treatment options because its underlying pathogenesis remains unclear. Bone marrow macrophages (BM MΦs) are multifunctional, plastic cells essential in hematopoiesis though our previous study demonstrated distinct hematopoietic regulatory role between M1 and M2 subtypes. However, the specific phenotype of M2-MΦ and pathways involved in hematopoietic support remain unclear. Here, we identified a novel population of BM-MΦs, SELENOP+ MΦs, that exhibit an M2-biased phenotype with hematopoietic stem cell (HSC)-supporting ability. These cells were markedly impaired in patients with poor graft function (PGF) after allogeneic HSC transplantation, potentially because of defective autocrine GAS6-AXL (ligand-receptor) signaling. Both in vitro and BM MΦ-specific AXL knockdown mouse models confirmed that reduced AXL activity contributed to MΦ dysfunction and the downstream reduction in IGF1 secretion. Notably, treatment with GAS6 partially restored the HSC-supporting ability of impaired BM MΦ from PGF patients in vitro. Overall, our study identified an HSC-supportive SELENOP+ MΦ subset regulated by GAS6-AXL signaling, offering novel therapeutic insights for impaired hematopoiesis.

Objective: To evaluate the efficacy and prognostic factors of haploidentical haematopoietic stem cell transplantation (haplo-HSCT) for paroxysmal nocturnal haemoglobinuria (PNH). Methods: We retrospectively analyzed 36 PNH patients (2 classic PNH, 34 AA-PNH syndrome) undergoing haplo-HSCT (G-CSF/ATG-based protocol) from June 2013 to December 2024, with BU/CY/ATG (n = 28) or BU/CYlow/FLU/ATG (n = 8) conditioning and uniform GVHD prophylaxis. Results: The overall myeloid engraftment rate was 100

Human herpesvirus 7 (HHV-7) encephalitis commonly occurs in immunocompromised individuals and has a poor prognosis. We here reported 3 cases of HHV-7 encephalitis following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with typical neurological symptoms, including altered consciousness and epileptic seizures, and conducted a systematic review of the literature to identify clinical characteristics and management strategies in these patients. Cerebrospinal fluid next-generation sequencing (NGS) was the key evidence that led to their diagnosis. Foscarnet and cidofovir appeared effective, particularly with at least four weeks of treatment. All three patients showed at least partial improvement in neurological symptoms. Furthermore, a systematic search was conducted in PubMed, Google Scholar, and Web of Science to identify related cases. Clinical presentation, diagnostic findings, treatment strategies, and outcomes were analyzed. A total of 10 publications were included, together with our 3 cases, comprising 7 cases of HSCT recipients for detailed analysis. Our study suggested that early recognition and prompt antiviral therapy are critical for improving prognosis. Further exploration is needed regarding risk factors and treatment strategies.

Steroid-refractory (SR) gastrointestinal (GI) acute graft-versus-host disease (aGVHD) is the major cause of early mortality after allogeneic hematopoietic stem cell transplantation. Vedolizumab could be used as the second- or third-line treatment of GI-aGVHD. Our real-world, retrospective multicenter study, in which 100 SR-GI-aGVHD patients who received vedolizumab were enrolled, confirmed its effectiveness. Note that 411 SR-GI-aGVHD patients who received the best available treatments (BATs) during the same period were enrolled as controls. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were conducted as sensitivity analyses. The overall response rates (ORRs) for SR-GI-aGVHD on day 28 and at any time point were 68.0% and 81.0%, respectively, and the 2-year probabilities of overall survival and nonrelapse mortality were 58.3% and 31.9%, respectively, after vedolizumab treatment. Multivariate analysis revealed that initiating vedolizumab treatment within 7 days after SR-aGVHD onset could help improve the ORR. In the sensitivity analysis, compared with the BATs, vedolizumab improved the ORR and complete response rate, particularly in the stage 3-4 SR-GI-aGVHD subgroup, and it reduced the infection rate after IPTW and PSM adjustment. These findings confirmed the efficacy of vedolizumab in a real-world setting, which can help to control SR-GI-aGVHD more effectively and safely.

The Endothelial Activation and Stress Index (EASIX) is a prognostic score including creatinine, lactate dehydrogenase, and thrombocytes. Its prognostic value in the context of haploidentical SCT (haplo-HSCT) remains to be fully elucidated. To explore the significance of pre-transplant EASIX for clinical outcome, we conducted a retrospective study in 434 consecutive patients who received haplo-HSCT with ATG/G-CSF-based protocol for the treatment of hematologic malignancies In multivariate analysis, the EASIX score was independently associated with graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS, (HR = 1.2, P < 0.001)). The cutoff value of EASIX for GRFS was 1.6, with 3-year GRFS being 63% and 72% in the high- and low-risk groups, respectively ( P < 0.001). The cumulative incidences of grade III-IV aGVHD were 24% and 12% ( P = 0.004), and the 3-year cumulative incidences of moderate to severe cGVHD were 40% and 20% in the high- and low-risk groups, respectively ( P < 0.001). In the MDS subgroup, an optimal cutoff of 0.7 was established, and EASIX remained significantly associated with the GRFS (HR = 5.4, P = 0.02). Pre-transplant EASIX serves as an independent predictor for GRFS as an easily accessible tool.

Background We aim to investigate whether the myelodysplastic syndrome stem cell (MDS-SC)-based assay could be used to predict relapse and survival after treatment in patients with MDS with excess blasts (MDS-EB). Methods A total of 143 cases receiving allografting were prospectively enrolled. A single-cell proteogenomic technique was used to evaluate the characteristics of CD34 + MDS subsets. These cells were detected using multiparameter flow cytometry (MFC) at diagnosis and post-treatment. Results The MDS-SCs could be detected based on CD34 + CD38 − cocktail + immunophenotype by MFC, which exhibit greater stemness and quiescence than CD34 + CD38 − CD33 + MDS cells, CD34 + CD38 − CD45RA + MDS cells, and CD34 + CD38 − CD123 + MDS cells. A high-level of CD34 + CD38 − cocktail + MDS-SCs (≥ 0.1064%) before allograft independently predicted 3-year cumulative incidence of relapse (CIR, P < 0.001). No association of MDS cells evaluated by the traditional MFC method before transplantation with relapse was observed. Patients with positive CD34 + CD38 − cocktail + MDS-SCs (≥ 0.0081%) after allografting experienced a higher 3-year CIR (40.4% vs. 6.5%, P < 0.001) and lower disease-free survival (DFS, 57.4% vs . 85.1%, P < 0.001) than those with negative CD34 + CD38 − cocktail + MDS-SCs (< 0.0081%). Multivariate analysis revealed that positive CD34 + CD38 cocktail + MDS-SCs after transplantation independently predicted the CIR ( P < 0.001) and DFS ( P < 0.001). Patients with traditional MFC MRD positivity after allografting also had a higher CIR (60.0% vs. 12.8%, P < 0.001) and lower DFS (40.0% vs. 80.2%, P < 0.001) than those with negative results. Compared with the traditional MFC method, the MDS-SC-based assay has higher sensitivity and C-index for disease burden determination and MRD detection. Conclusions Our data suggest the superiority of the MDS-SC-based assay over the traditional MFC method for outcome prediction in MDS-EB patients.

Graft-versus-host disease (GVHD) is a common and potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The impact of GVHD on the long-term survival of critically ill patients after allo-HSCT for hematological malignancies is underestimated. In this study, we aimed to elucidate the impact of concurrent GVHD on the long-term survival of critically ill patients after transplantation for hematological malignancies. Between January 2010 and June 2025, all critically ill patients after transplantation for hematological malignancies were retrospectively identified and included in this cohort. A total of 726 critically ill patients were finally analyzed. In total, 198 (27.3%) patients with concurrent GVHD and 528 (72.7%) patients without concurrent GVHD were included in the cohort. The 12-month overall survival rate of the cohort was 27.7%, which was significantly lower in patients with concurrent GVHD than in those without concurrent GVHD (16.2% versus 32.8%, log rank P < .001). Multivariate analyses revealed that concurrent GVHD (P = .002, hazard ratio [HR] 1.342, 95% confidence interval [CI] 1.117 to 1.613), relapse of hematological malignancies (P = .015, HR 1.510, 95% CI 1.083 to 2.105), sinusoidal obstruction syndrome (P = .048, HR 1.632, 95% CI 1.004 to 2.651), and ≥2 organ failures in the intensive care unit (P < .001, HR 1.864, 95% CI 1.559 to 2.228) were independent risk factors for overall survival. In conclusion, for critically ill patients who underwent allo-HSCT for hematologic malignancies, concurrent GVHD significantly reduced long-term survival.

The wider application of posttransplant cyclophosphamide (PTCY) and granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG)-based protocols has revolutionized haploidentical hematopoietic stem cell transplantation (haplo-HSCT) by decreasing graft-versus-host disease and facilitating engraftment. In this study, we compared the clinical outcomes and the immune reconstitution of propensity score-matched (1:1:1) patients receiving PTCY (n = 45), ATG (n = 45), or PTCY plus ATG (n = 45). Patients in the ATG group had significantly higher overall survival (OS) (p = 0.029) and leukemia-free survival (LFS) (p = 0.034). CD3+ (p < 0.01) and CD8+ T-cell counts (p = 0.02) were greater at 3 months after transplantation in the ATG group. After adjustment for relevant covariables, Cox models revealed a significant association between CD8+ T-cell reconstitution and OS in all patients (p = 0.008); CD8+ T-cell recovery and LFS showed a similar trend (p = 0.034). Sensitivity analysis revealed stable results. Restricted cubic spline curve analysis to visualize the relationship between immune reconstitution and outcomes revealed that the CD8+ T-cell count at 3 months post-HSCT strongly correlated with survival prognosis. These findings demonstrate that conditioning regimens profoundly impact immune reconstitution, which may contribute to differences in survival prognosis. Moreover, increasing the probability of CD8+ T-cell reconstitution after HSCT may become an important strategy for improving outcomes.

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) is the predominant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with gastrointestinal involvement (SR-GI-aGVHD) remaining a key obstacle. We conducted a multicenter, single-arm, pivotal trial to assess the efficacy and safety of hUC-MSC PLEB001, a human umbilical cord-derived mesenchymal stromal cells (MSCs) product, plus anti-CD25 monoclonal antibody as second-line therapy for SR-GI-aGVHD. Eligible patients with grade II or higher SR-GI-aGVHD received hUC-MSC PLEB001 with protocol-defined anti-CD25 monoclonal antibody therapy. hUC-MSC PLEB001 was infused at a dose of 106 cell/kg twice weekly for 4 consecutive weeks, starting at day 1, and efficacy was assessed on day 28. Patients achieving complete response (CR), progressive disease (PD) or no response (NR) concluded treatment; those with partial response (PR) continued the same regimen for additional 4 weeks. The primary endpoint of the study is the overall response rate (ORR) at day 28. Fifty-four patients (median age 43, range 14–68) were enrolled. The number of Grade II–IV SR-aGVHD patients was 21, 16, 17, respectively. Thirty-seven patients were GI-involved only, 15 patients were GI and skin involved, and 2 patients were GI and liver involved. The ORR at day 28 was 63.0

Graft-versus-host disease (GVHD) are still key obstacles of haploidentical transplantation. Interleukin-2 (IL-2) could promote natural killer (NK) cells and T-regulatory cells (Tregs) cells expansion in vitro and in vivo. We explored whether low-dose IL-2 administration at an early stage could promote NK cells and Tregs reconstitution and reduce GVHD after haplo-HSCT. This cohort trial included 10 recipients of accepting IL-2 treatment and case-pairing 30 recipients without IL-2 treatment post haplo-HSCT. In contrast to the control group, the 5-year incidence of chronic GVHD (cGVHD) was lower (p = 0.018), and GVHD progression-free survival (GPFS) was better (p = 0.025) in the IL-2 group. Blood NK-cells, Treg cells, conventional T cells (Tcon) cells, and the expression of CD62L+ on Tregs and Tcon cells reconstitution were increased post-IL-2 treatment. NKG2A expression on NK cells increased significantly post-IL-2 treatment. Meanwhile, IL-2 administration shortly increased the plasma levels of IFN-Ƴ, TNF-a, IL-10, and IL-2 in subjects post haplo-HSCT. Relative to the control group, low-dose IL-2 increased NK cell counts and the expression of CD122, DNAM-1, and NKG2D on NK cells post transplantation. Administration of low-dose IL-2 after haplo-HSCT correlated with reduced cGVHD, which should be explored further with randomized trial.

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic infection that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The risk factors and prognostic factors for PJP under current transplantation and monitoring practices are not well understood. In this retrospective cohort study, we aimed to characterize the clinical features, identify risk factors for its occurrence, and determine prognostic factors of PJP for survival. Between 2012 and 2022, 8596 patients underwent allo-HSCT at the Peking University Institute of Hematology. From this cohort, 88 patients with PJP were retrospectively identified, and after 16 patients were excluded because of incomplete data or loss to follow-up, 72 patients were included in the final analysis. We also conducted a nested case-control study to identify risk factors associated with PJP onset. For every patient diagnosed with PJP, three control subjects were randomly chosen and matched by transplant date within 90 d and follow-up duration within 180 d. Finally, 72 PJP patients and 216 controls without PJP were analyzed. In this study, the prevalence of PJP post allo-HSCT was 1.0% (88/8596). Patients who developed PJP had significantly lower 5-yr overall survival (OS) (58.7% versus 84.3%; P < .001) and 5-yr disease-free survival (57.3% versus 82.0%; P < .001) and higher 5-yr nonrelapse mortality (33.0% versus 8.5%; P < .001) than the controls did. The median time from transplantation to PJP diagnosis was 10 mo, with 29.2% of cases occurring more than 1 yr post-HSCT. Multivariate analysis revealed that an age greater than 45 yr at transplantation, peak corticosteroid dose, and lower CD4+ T cell count were independent risk factors for developing PJP. Among patients with PJP, the presence of chronic graft-versus-host disease, coexisting EBV infection, anemia (hemoglobin <100 g/L), and respiratory failure were independent predictors of poor OS. Our findings revealed that patients with PJP had a poor prognosis. These results suggest that the standard duration of prophylaxis may be insufficient for many patients, underscoring the need for individualized, risk-adapted strategies. Early identification of high-risk patients could guide prolonged prophylaxis and improve outcomes.

Febrile neutropenia develops in approximately three-quarters of recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Among them, carbapenem-resistant Enterobacterales (CRE) associated mortality reaches up to 70%. Thus, rapid identification of CRE-high-risk patients and prompt empiric CRE coverage are critical. Two allo-HSCT recipients whose febrile neutropenia persisted on empiric carbapenem were promptly escalated to imipenem/cilastatin/relebactam, alone or combined with aztreonam and tigecycline-before culture confirmation. Defervescence occurred within 24-48 h, inflammatory markers declined progressively, and clinical infection control was achieved. Successful neutrophil and platelet engraftment followed. Immediate empiric imipenem/cilastatin/relebactam for CRE-high-risk allo-HSCT recipients with febrile neutropenia rapidly controlled infections and permitted successful hematopoietic recovery. Prospective studies are warranted.

Core binding factor acute myeloid leukemia (CBF-AML) is defined by t(8;21) or inv. (16), which give rise to the RUNX1::RUNX1T1 and CBFβ::MYH11 fusion genes, respectively. CBF-AML is a favorable-risk AML subtype, yet differences in mutation profiles, measurable residual disease (MRD) response, and relapse risk may warrant tailored treatment approaches. We reviewed adult AML patients treated at five transplant centers across China and identified 825 de novo CBF-AML cases, of which 779 met our eligibility criteria: 536 harbored the RUNX1::RUNX1T1 fusion and 243 the CBFβ::MYH11 fusion. The 3-year overall survival (OS) was 80.6% for RUNX1::RUNX1T1 and 90.2% for CBFβ::MYH11 cases (p = 0.011). Among patients with RUNX1::RUNX1T1, those achieving MRD negativity after two consolidation cycles (PC2) had significantly better OS than nonresponders (86.3% vs. 76.5%, p = 0.008); no difference was observed for CBFβ::MYH11 patients. For RUNX1::RUNX1T1 nonresponders, allogeneic hematopoietic cell transplantation (allo-HCT) in first complete remission (CR1) reduced relapse (CR1-HCT vs. non-CR1-HCT, 8.3% vs. 18.9%; p = 0.024) and improved OS (CR1-HCT vs. non-CR1-HCT vs. chemotherapy, 85.8% vs. 71.4% vs. 64.9%; p < 0.001). In CBFβ::MYH11 patients, deferring allo-HCT until second complete remission (CR2) was associated with comparable outcomes. In RUNX1::RUNX1T1 patients, older age, elevated initial white blood cell count, lower hemoglobin, lower initial fusion transcript load, and the presence of FLT3-ITD or KIT D816/D822 mutations were associated with an increased likelihood of PC2 nonresponse. Based on these variables, we developed a weighted scoring system with good discrimination to identify RUNX1::RUNX1T1 patients at high risk of PC2 nonresponse.