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

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.

Gastrointestinal acute graft-versus-host disease (GI aGVHD) remains a major complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT), and early risk identification and intervention are essential for improving outcomes. Mucosal-associated invariant T (MAIT) cells are mucosa-enriched unconventional T cells with major histocompatibility complex class I-related protein 1 (MR1)-restricted, major histocompatibility complex (MHC)-independent recognition, suggesting a potentially reduced risk of alloreactivity. Our previous work showed that higher graft MAIT-cell levels were associated with improved post-transplant MAIT-cell reconstitution and a lower incidence of GI aGVHD. Single-cell ribonucleic acid (RNA) sequencing (sc-RNA-seq) and murine models revealed their functional heterogeneity in immune regulation, tissue repair and chemotaxis-supporting their role as both biomarkers and therapeutic targets. In this prospective study, spectral flow cytometry was used to characterize MAIT-cell phenotypes in peripheral blood stem cell grafts. higher graft MAIT-cell abundance was associated with more robust early post-transplant MAIT-cell reconstitution and a lower risk of GI aGVHD. A three-marker predictive panel based on MAIT-cell functional markers (C-C chemokine receptor type 2 [CCR2], interleukin-4 [IL-4], interleukin-17A [IL-17A]) achieved an area under the receiver operating characteristic curve (AUC) of 0.80, increasing to 0.85 after adjustment for clinical covariates. These findings identify graft-derived MAIT cells as a predictive immune-associated biomarker for GI aGVHD, enabling pre-transplant risk stratification and supporting precision prevention strategies. Trial registration: ChiCTR2500095349.

OBJECTIVES:Comparisons of safety and efficacy of Allogeneic hematopoietic stem cell transplantation (allo-HSCT) following complete remission (CR) achieved by Chimeric antigen receptor T (CAR-T) cell therapy versus chemotherapy for B-cell acute lymphoblastic leukemia (B-ALL) have not been fully discussed. METHODS:We performed a comparison of transplant outcomes in 443 consecutive B-ALL patients who received allo-HSCT after achieving CR with CAR-T therapy (n = 50) or with chemotherapy (n = 393). The median follow-up time was 30 months (range: 1-62 months). RESULTS:The CAR-T group had a lower incidence of chronic graft-versus-host disease (30.9% vs. 44.0%, p = 0.020). We also found that the incidence of veno-occlusive disease was higher in the CAR-T group compared to the chemotherapy group (4% vs. 0.5%; p = 0.003). The study revealed that both the CAR-T and chemotherapy groups exhibited comparable overall survival (90.9% vs. 94.6%, p = 0.158) and relapse incidences (9.1% vs. 8.4%, p = 0.513). However, incidences of non-relapse mortality after transplantation were higher in the CAR-T group (10.9% vs. 4.3%, p = 0.016), and leukemia-free survival was lower in the CAR-T group compared to the chemotherapy group (80.0% vs. 86.8%, p = 0.040). CONCLUSIONS:Our data indicate that, in B-ALL patients, most treatment-related complications and survival were comparable between CAR T-cell therapy and chemotherapy followed by allo-HSCT.

KMT2A partial tandem duplication (KMT2A-PTD) is a recurrent genetic alteration in acute myeloid leukemia (AML), but its role as a measurable residual disease (MRD) marker before allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We retrospectively analyzed 180 KMT2A-PTD AML patients undergoing allo-HSCT at Peking University People's Hospital between 2015 and 2025. Pre-transplant KMT2A-PTD MRD was quantified by real-time quantitative PCR, with positivity defined as ≥1500 copies/10⁵ ABL1. Among 158 patients transplanted in complete remission (CR), 144 had pre-transplant MRD assessment, and 34 (24%) were MRDpositive. Compared with MRD-negative patients, MRD-positive patients had significantly inferior 3- year overall survival (OS, 49% vs. 80%; p.

ObjectiveCytomegalovirus (CMV) infection can cause severe morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Letermovir is recommended as CMV prophylaxis for allo-HSCT recipients. This study aimed to further confirm the efficacy of letermovir prophylaxis in different subgroups based on a large cohort of acute leukemia patients following allo-HSCT.Methods1331 acute leukemia patients who underwent allo-HSCT (including 978 and 353 patients with and without letermovir prophylaxis, respectively) were enrolled. The occurrence of clinically significant CMV infection (cs-CMVi), CMV disease, and refractory CMV infection were evaluated. Propensity score matching (PSM) was applied to balance baseline characteristics between patients with and without letermovir.ResultsIn patients receiving letermovir, the 100-day cumulative incidence of cs-CMVi after allo-HSCT was 7.1% (95% CI, 5.5−8.7%), and this rate was greater in children; however, no variables increased the risk of cs-CMVi at 100 days according to multivariate analysis. The cumulative incidence rates of cs-CMVi and CMV disease between 100 and 200 days after allo-HSCT for patients receiving letermovir prophylaxis were 12.5% (95% CI, 10.3−14.7%) and 1.6% (95% CI, 0.8−2.4%), respectively. For the subgroup of patients who did not experience a CMV infection within the first 100 days, these rates were 11.7% (95% CI, 9.5−13.9%) and 1.4% (95% CI, 0.6−2.2%), respectively. Donor-/recipient+ CMV serostatus (44.2%, HR, 5.00; P<0.001) independently increased the risk of cs-CMVi, and age > 60 years (5.0%, HR, 4.01; P = 0.030) increased the risk of CMV disease between 100 and 200 days after allo-HSCT. After PSM adjustment, letermovir prophylaxis was associated with a lower incidence of cs-CMV infection (grade II–IV: 1.9% vs. 10.7%, P = 0.024; grade III–IV: 0% vs. 27.3%, P<0.001) in patients with acute graft-versus-host disease (GVHD). The incidence of cs-CMVi was 18.4% (95% CI, 7.4−29.4%) among chronic GVHD patients receiving letermovir prophylaxis. The incidence of cs-CMVi between 100 and 200 days after allo-HSCT was comparable between patients with prolonged letermovir prophylaxis and those without letermovir prophylaxis.ConclusionWe confirmed the efficacy of letermovir prophylaxis in different subgroups, but the subgroup who would benefit most from prolonged prophylaxis should be further clarified in the future.

Limited data are available on bronchiolitis obliterans syndrome (BOS) in children undergoing haploidentical hematopoietic cell transplantation (haplo-HCT). To describe the clinical characteristics, treatment response, and factors influencing first-line treatment response in BOS patients undergoing haplo-HCT using a granulocyte colony-stimulating factor/antithymocyte globulin-based protocol. We conducted a single-center retrospective study including 60 pediatric patients with BOS at Peking University People's Hospital between January 2016 and December 2022. BOS was diagnosed at a median of 12.85 (interquartile range: 10.52 to 16.82) mo after haplo-HCT, and patients were followed for a median of 28.4 (95% confidence interval [CI]: 22.9 to 37.8) mo from BOS diagnosis. Among the 52 evaluable patients with long-term follow-up, the overall response rate (ORR) for first-line treatment was 33%. For 15 evaluable patients receiving second-line treatment, the ORR was 13%, resulting in a total ORR of 46% across first-line and second-line therapy. Three significant independent predictors of first-line treatment response were identified: NIH lung score 3 at baseline (odds ratio [OR], 0.112; 95% CI, 0.014 to 0.866; P = .036), disease status of greater than or equal to second complete remission at haplo-HCT (OR, 0.034; 95% CI, 0.002 to 0.488; P = .013), and a duration of ≥12.85 mo from haplo-HCT to BOS diagnosis (OR, 9.890; 95% CI, 1.725 to 56.692; P = .010). Pulmonary function trajectories showed that patients with baseline NIH lung scores of 2 or 3 experienced a more pronounced decline in percent of predicted FEV1 after BOS diagnosis compared to those with a score of 1. These findings highlight the importance of early diagnosis of BOS and initiating treatment for patients with early stages of the disease.

BACKGROUND:Thrombotic microangiopathy (TMA) is a common and potentially fatal complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thrombotic thrombocytopenic purpura (TTP), a distinct form of TMA caused by severe deficiency of plasma ADAMTS-13 activity, has been reported to be rare in the posttransplant population. OBJECTIVES:To investigate the clinical features and outcomes of TTP after allo-HSCT. METHODS:This retrospective cohort study used a nested case‒control approach. For each patient with TTP, 3 patients with high-risk transplant-associated TMA (TA-TMA) were matched as controls according to the time of transplantation. RESULTS:A total of 26 patients with TTP were identified and included in the cohort. Compared with patients with high-risk TA-TMA, patients with TTP had greater proportions of central nervous system (50.0% vs 19.2%, P = .002) and gastrointestinal tract involvement (65.4% vs 32.1%, P = .003), with central nervous system dysfunction occurring later (8.0 days vs -1.0 days since the diagnosis of TTP, P = .008). Patients with TTP had a significantly lower overall survival rate than those with high-risk TA-TMA (26.9% vs 48.7%, log-rank P = .026). Age >40 years at the time of TTP diagnosis was identified as an independent predictor of 60-day overall survival. CONCLUSION:TTP occurring in the setting of HSCT is rare but can be differentiated from TA-TMA and is associated with a worse prognosis.

Introduction: Delayed platelet (PLT) recovery is a common complication following haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Improved platelet recovery may reduce the need for transfusions and improve transplant outcomes. Thrombopoietin receptor agonists (TPO-RAs) have been used in various types of thrombocytopenic disorders, including prolonged thrombocytopenia after allo-HSCT. Our previous retrospective study revealed the safety and efficacy of avatrombopag, a TPO-RA, in the treatment of primary delayed platelet engraftment and secondary failure of platelet engraftment after haplo-HSCT. However, prospective evidence is limited. In this study, we performed a randomized, double-blind, multicenter, placebo-controlled trial to investigate the safety and efficacy of avatrombopag in enhancing platelet recovery after haplo-HSCT. This study is registered at ClinicalTrials.gov as NCT06202625. Methods: This prospective multicenter trial were performed in 10 centers in China and included patients 18–65 years old who underwent haplo-HSCT. Patients were excluded if they had active infection; liver or kidney injury (ALT or AST>3 ULN, or total Bil>2 ULN, or Ccr<50 mL/min); a history of arteriovenous thrombosis or cardiovascular disease; a history of drug use to promote platelet production two weeks before enrollment, including but not limited to TPO-RAs; or secondary or multiple HSCTs. Patients known to be allergic to avatrombopag and any of its excipients were also excluded. The enrolled patients received avatrombopag 20 mg/day or placebo on a 1:1 randomization schedule starting on Day 7. The primary objective was to assess the proportion of participants who achieved a PLT count of ≥50×10⁹/L and remained independent of PLT transfusion for ≥7 consecutive days by Day 60. Key secondary endpoints included: the proportions of participants with a PLT count of ≥50×10⁹/L and ≥20×10⁹/L on Day 30; and the proportion of participants with a PLT count of ≥100×10⁹/L on Day 60 who remained free from PLT transfusion for ≥7 consecutive days. Avatrombopag 20 mg/d or placebo was taken orally from +D7 after haplo-HSCT until reaching the adjustment indication or to Day 60 after haplo-HSCT. Results: From March 1st, 2024, to July 21st, 2025, 100 patients (50 in the avatrombopag group and 50 in the control group) were included. The median time to platelet recovery (>20×109/L) was 13 days for patients treated with avatrombopag and 14 days for controls (P= 0.087). Compared with patients in the control group, significantly more patients in the avatrombopag group achieved a PLT level ≥50×109/L without the need for PLT transfusion for ≥7 consecutive days by Day 30 (78.0% vs. 56.0%, P=0.019). On Day 60, 74.0% of patients in the avatrombopag group had a platelet count of ≥50×10⁹/L and did not require platelet transfusion for 7 or more consecutive days, whereas 60.0% of patients in the control group did (P=0.164). The proportion of participants whose PLT level ≥20×109/L or ≥100×109/L on Day 60, PLT≥50×109/L or PLT≥100×10^9/L on Day 90 after haplo-HSCT independent of PLT transfusion for ≥7 consecutive days were comparable between the avatrombopag group and the control group . No patients in either group experienced grade ≥3 adverse events. The number of platelet transfusions received, overall survival, progression-free survival, GVHD rate, relapse rate, and nonrelapse mortality were similar between the two groups. Conclusion: Overall, this represents the first randomized, double-blind, multicenter, placebo-controlled trial to confirm that avatrompag is effective and safe in improving platelet recovery after haplo-HSCT.

Graft-versus-host disease (GVHD) remains an important cause of morbidity and mortality after allo-HSCT. Upadacitinib is a selective JAK1 inhibitor. This study investigated the clinical outcomes of upadacitinib in patients with steroid refractory (SR) chronic graft-versus-host disease (cGVHD). Thirty-two patients with steroid refractory cGVHD (SR-cGVHD) who received upadacitinib treatment were enrolled from three hospitals in China. The overall response rates (ORRs) at 24 weeks and at any time were 81.3% (complete response [CR] rate: 21.9%; partial response [PR] rate: 59.4%) and 84.4% (CR rate: 21.9%; PR rate: 62.5%) respectively. In particular, the cutaneous-specific ORRs at week 24 and at any time were 84.4% (CR rate: 40.6%, PR rate: 43.8%) and 87.6% (CR rate: 43.8%; PR rate: 43.8%) respectively. The rates of infection and haematological toxicity were 18.75% and 6.25%, and two patients (6.25%) experienced grade III adverse events after upadacitinib treatment. One patient died from relapse, and no patient died from non-relapse mortality. The 1-year probabilities of overall survival, failure-free survival and disease-free survival after upadacitinib were 96.6%, 64.9% and 83.1% respectively. In summary, upadacitinib may be an effective and safe treatment for SR-cGVHD.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). With mortality rates up to 90% without timely treatment, effective management remains a challenge. Complement dysregulation plays a central role in TA-TMA pathogenesis. We reported two TA-TMA cases successfully treated with iptacopan, a factor B inhibitor targeting the alternative pathway. A 40-year-old male with early T-cell precursor acute lymphoblastic leukemia developed early-onset TA-TMA post-HSCT, and a 41-year-old female with acute myeloid leukemia arising from previous myelodysplastic syndrome developed delayed-onset TA-TMA after allo-HSCT. Iptacopan administration led to significant clinical and biochemical recovery in both two patients. These two cases highlight iptacopan's potential as an effective therapy for TA-TMA.

Introduction Transplant-associated thrombotic microangiopathy (TA-TMA) represents a critical complication in hematopoietic stem cell transplantation (HSCT) with substantial morbidity and mortality risks. Current diagnostic and prognostic approaches rely predominantly on individual laboratory parameters and clinical criteria and lack comprehensive predictive models that integrate multiple inflammatory and hemolytic biomarkers. The heterogeneous clinical presentation, variable treatment responses, and complex pathophysiology of TA-TMA necessitate more sophisticated AI-driven risk stratification approaches. We investigated whether an unsupervised machine learning model, by incorporating pre- and early post-transplant inflammatory and endothelial injury signatures, could stratify patients into distinct subgroups to predict clinical outcomes, particularly mortality, more accurately than conventional methods. Methods This nationwide, multicenter, retrospective cohort study enrolled adult patients who underwent allogeneic HSCT and were subsequently diagnosed with TA-TMA across multiple transplant centers from January 2015 to December 2023. Patient data were retrospectively reviewed and classified according to the 2023 international harmonized diagnostic criteria. The primary cohort comprised 847 patients from our center, with external validation performed in 238 patients from independent centers. We developed STRATOS (STRAtification Tool for TA-TMA OutcomeS), an unsupervised quantitative model integrating eight laboratory biomarkers capturing hemolysis, thrombosis, and complement activation: soluble C5b-9 (sC5b-9), schistocyte ratio, LDH, platelet count, hemoglobin, serum creatinine, haptoglobin, and total bilirubin. The model utilized t-distributed stochastic neighbor embedding (t-SNE) for dimensionality reduction and K-means clustering for patient stratification. The primary endpoint for prognostic evaluation was 1-year non-relapse mortality (NRM). Results Among the 847 patients in the primary cohort (median age, 45 years; 58% male), the median onset of TA-TMA was day +57 post-transplantation. Baseline characteristics at diagnosis revealed a median platelet count of 28×10⁹/L, LDH level of 445 U/L, and schistocyte percentage of 2.1%. t-SNE dimensionality reduction and K-means clustering identified three distinct phenotypic clusters with significantly different mortality risks. Cluster 1 (Severe Endothelial Injury, n=189), characterized by extremely high sC5b-9 levels, marked elevation in LDH, and severe thrombocytopenia, represented the highest-risk patients with the poorest prognosis. Cluster 0 (Hemolytic-Dominant, n=312), defined by pronounced hemolytic markers but moderate complement activation, represented the intermediate-risk group. Cluster 2 (Compensated, n=346), exhibiting relatively preserved hemoglobin and only mild-to-moderate abnormalities in biomarkers, had the best prognosis. In the validation cohort, the risk stratification derived from STRATOS demonstrated excellent performance, achieving an area under the curve (AUC) of 0.87 for predicting 1-year NRM. This significantly outperformed assessment based on individual markers (LDH alone: AUC, 0.64; platelet count: AUC, 0.59; p<0.001). Feature importance analysis revealed that sC5b-9 was the most discriminative biomarker for separating the clusters (variability contribution: 0.91), followed by the schistocyte ratio (0.83) and LDH level (0.70). Conclusions This nationwide, multicenter study establishes and validates the first AI-driven biomarker signature for prognostic risk stratification in patients with established TA-TMA. Compared with conventional approaches, STRATOS provides superior prognostic accuracy for mortality by identifying three distinct phenotypic clusters with disparate outcomes. Future prospective validation studies are warranted to establish guidelines for the real-time clinical integration of this stratification tool.

Patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) are typically placed in a laminar air flow room until hematopoietic reconstitution occurs. In this study, we compared the differences in clinical outcomes between patients receiving allo-HSCT in a conventional laminar flow room ( n = 200) and those receiving allo-HSCT in a plasma sterilizer environment ( n = 201). The overall infection rates (20.4% vs 25.5%, P = 0.224) and the sites of infection (sepsis, perianal infection, and catheter-related infection) were comparable between the two groups. Additionally, the engraftment times were comparable between the two groups in terms of time to allo-HSCT, leukocyte engraftment time, and platelet engraftment time. The 100-day posttransplantation clinical outcomes were also comparable between the two groups in terms of the probability of overall survival (98.5% vs 99.5%, P = 0.316), leukemia-free survival (96.5% vs 96.5%, P = 0.991), the cumulative incidence of relapse (2.0% vs 3.0%, P = 0.523), non-relapse mortality (1.5% vs 0.5%, P = 0.316) and acute graft-versus-host disease (23.4% vs 22.0%, P = 0.723). Thus, our results demonstrated that receiving allo-HSCT via a plasma sterilizer did not increase the risk of pre-engraftment infection, and the clinical outcomes of these patients were comparable to those of patients in a conventional laminar flow room.

Experience using olverembatinib as maintenance therapy in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) after allogeneic hematopoietic cell transplantation (allo-HCT) is limited. We retrospectively collected data from 26 patients with Ph+ ALL who received only olverembatinib as maintenance therapy after allo-HCT. Olverembatinib was administered as prophylaxis in 18 patients (69.2

Donor lymphocyte infusion (DLI) represents a standard approach for relapse prevention following allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study compared outcomes between prophylactic DLI (Pro-DLI)-administered early post-transplant (median 51 days) to patients in remission without active graft-versus-host disease (GVHD)-and preemptive DLI (Pre-DLI)-triggered by measurable residual disease (MRD) positivity (>0.1% blasts)-in acute leukemia patients. The analysis included 64 patients receiving Pro-DLI and 84 patients managed with Pre-DLI. Notably, the Pro-DLI cohort demonstrated higher 2-year leukemia-free survival (LFS: 56.3% versus 40.5%, P = .045) and markedly reduced 2-year cumulative incidence of relapse (CIR: 23.4% versus 48.8%, P < .001) compared to the Pre-DLI cohort. While Pro-DLI was associated with a higher incidence of chronic GVHD (64.1% versus 40.5%, P < .001), rates of acute GVHD, non-relapse mortality (NRM), and overall survival (OS) did not differ significantly between groups. These findings indicate that early prophylactic DLI significantly improves relapse prevention and long-term leukemia-free survival in refractory/relapsed AML patients post-allo-HSCT, compared to MRD-triggered preemptive DLI.

BACKGROUND:This study examined the impact of measurable residual disease (MRD) dynamics in adults with lysine methyltransferase 2a rearrangement (KMT2Ar) in acute myeloid leukemia (AML) during the peritransplant period (before and early after allogeneic hematopoietic stem cell transplantation [HSCT]). METHODS:This study involved 144 adult patients with AML with KMT2Ar who underwent HSCT between 2015 and 2024. Patients were enrolled if they survived without relapse for at least 3 months post-HSCT. MRD was measured via real-time quantitative polymerase chain reaction. RESULTS:The cohort was categorized into four groups on the basis of MRD status before and after HSCT, respectively: MRD negative/MRD negative (n = 81), MRD negative/MRD positive (n = 2), MRD positive/MRD negative (n = 43), and MRD positive/MRD positive (n = 18). Significant differences were found in 3-year overall survival (OS), leukemia-free survival (LFS), and cumulative incidence of relapse (CIR) (all p < .001), with the MRD-negative/MRD-negative group having the best outcomes (88% OS, 85% LFS, and 10% CIR), whereas the MRD-negative/MRD-positive group (0% OS, 0% LFS, and 100% CIR) and MRD-positive/MRD-positive group (29% OS, 31% LFS, and 69% CIR) had the worst outcomes. The MRD-positive/MRD-negative group had an intermediate prognosis (63% OS, 58% LFS, and 32% CIR). Peri-HSCT MRD dynamics served as an independent factor, which distinguished patient groups with differential risk probabilities of mortality and relapse. C-statistic values were greater when peri-HSCT MRD dynamic testing was used than when isolated pre- or post-HSCT MRD was used to predict CIR (0.68 vs. 0.58 vs. 0.56), LFS (0.74 vs. 0.69 vs. 0.64), and OS (0.73 vs. 0.68 vs. 0.66). CONCLUSIONS:Compared with single-time point MRD assessments, peritransplant MRD dynamics confer superior prognostic accuracy.

Gastrointestinal acute graft-versus-host disease (GI aGVHD) remains one of the major clinical challenges following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early identification and intervention are critical to improving patient outcomes. Mucosal-associated invariant T (MAIT) cells are unconventional, mucosa-enriched T cells whose MR1-restricted, MHC-independent recognition may reduce GVHD risk. Our previous work showed that higher levels of donor-derived MAIT cells in grafts were associated with better immune reconstitution and a lower incidence of GI aGVHD. Single-cell RNA sequencing and murine transplant models revealed their functional heterogeneity in immune regulation, tissue repair, and chemotaxis—supporting their role as both biomarkers and therapeutic targets. In this prospective study, we used spectral flow cytometry to analyze MAIT cell phenotypes in peripheral blood stem cell grafts. Early MAIT cell reconstitution post-transplant strongly correlated with graft abundance, and lower MAIT cell levels were associated with increased GI aGVHD risk. Based on MAIT cell functional markers, we developed a three-marker predictive panel (CCR2, IL-4, IL-17A) that achieved an AUC of 0.80, increasing to 0.85 after adjusting for clinical covariates. This MAIT cell–based risk score enables pre-transplant risk stratification and early warning of GI aGVHD, offering strong clinical and translational value. Trial registration: ChiCTR2500095349.

Granulocyte colony-stimulating factor (G-CSF) enhances acute graft-versus-host disease (aGVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (allo-HSCT) by inducing T-cell tolerance and altering graft cell composition. Previous studies have shown that the number of mucosa-associated invariant T (MAIT) cells in G-CSF-induced graft was associated with a low incidence of gut aGVHD. However, the effect of G-CSF mobilization on MAIT cell and its role in MAIT-mediated protection against gut GVHD remain unclear. Here, using single-cell RNA sequencing, we found that the interaction of G-CSF with its receptor CSF3R enhances immunosuppression and tissue repair functions of MAIT cells, contributing to the anti-gut aGVHD effect. The chemokine receptor CXCR6 was identified as potentially crucial for recruiting these functional MAIT cells to gut tissues. Furthermore, we simulated the dynamic distribution of MAIT cells from donor G-CSF-mobilized peripheral blood stem cells (G-PBSC) grafts in recipient mouse, and further confirmed that the circulating MAIT cells migrated into gut tissue in a CXCR6-CXCL16-dependent manner. To further validate these findings, we developed a flow cytometry panel that effectively predicts the gut aGVHD occurrence following allo-HSCT by analyzing the frequency and functional markers of MAIT cells in G-PBSC. The predictive model shifts aGVHD prediction and intervention to the pre-transplant stage and offers a new strategy for the prevention and management of gut aGVHD in clinical practice.

BACKGROUND:Cytokine release syndrome (CRS) after graft infusion under anti-thymocyte globulin (ATG)-based haploidentical (haplo)-hematopoietic stem cell transplantation is unclear. OBJECTIVE:The purpose of this study was to explore the clinical implications of CRS after graft infusion under ATG-based haplo-SCT. STUDY DESIGN:We retrospectively analyzed the data of 259 patients who underwent haplo-SCT, graded CRS, and evaluated transplant outcomes. RESULTS:CRS occurred in 103/259 (39.8%) of the recipients. Severe CRS (Grades 3-5) was not observed. Fever was the most common manifestation (89.3%), and all cases occurred only after peripheral blood stem cell (PBSC) infusion. According to the multivariable analysis, being older than 55 years (OR 2.486 (1.124-5.496), p = 0.024), having higher CRP levels during conditioning (OR 3.011 (95% CI, 1.766-5.134), p < 0.001), and receiving PBSC as the sole stem cell source (OR 2.478 (95% CI, 1.077-5.700), p = 0.033) could predict the development of CRS, whereas an HCT-CI score ≥ 2 was an independent risk factor for Grade 2 CRS (OR 4.259 (95% CI, 1.515-11.969, p = 0.006)). The 3-year OS was not significantly different between the two groups, with 79% (95% CI, 61-97) for Grade 2 CRS and 85% (95% CI, 80-90) for Grade 0-1 CRS (p = 0.288). The GRFS rates in the two groups were 69% (95% CI, 49-90) and 67% (95% CI, 60-74), respectively (p = 0.644). CONCLUSION:Our results suggest that CRS is common in patients receiving ATG-based haplo-SCT and does not affect survival.