Impact of platelet transfusion refractoriness in the first 30 days post-hematopoietic stem cell transplantation on outcomes of patients with myelodysplastic syndrome.

Introduction: Currently, no study has determined whether platelet transfusion refractoriness (PTR) post-hematopoietic stem cell transplantation (HSCT) before engraftment in patients with myelodysplastic syndrome (MDS) would impacts clinical outcomes. Methods: We performed a MDS-specific retrospective analysis to determine whether PTR in one-month post-HSCT in patients with MDS could influence outcomes. Results and discussion: Among the 315 patients enrolled, 110 (34.9 %) had PTR from stem cell infusion to one-month post-HSCT. Baseline characteristics of the PTR and non-PTR groups were similar. We found that patients with PTR had a slower and lower rate of platelet engraftment by day 28, as well as a slower recovery of neutrophils. The median days of neutrophil and platelet engraftment were 14 days (9-23) and 17 days (8-28) in the PTR groups versus 13 days (9-23) and 15 days (7-28) in the non-PTR group (P<0.001). By day 28, 84 of 110 patients (76.4%) with PTR achieved platelet engraftment compared with 181 of 205 patients (88.3%) without PTR achieving platelet engraftment (P=0.007). In addition, patients in the PTR group received significantly more red blood cell (median, 17 units vs. 10 units, P<0.001) and platelet transfusions (median, 13 units vs. 7 units, P<0.001). However, the overall survival was similar between the two groups. PTR in one-month post-HSCT, haploidentical donor, and ferritin level>1041ng/ml (median level) were independent adverse factors of platelet engraftment.

Monocytes as an early risk factor for acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and contributes to high morbidity and mortality. However, our current understanding of the development and progression of aGVHD after allo-HSCT remains limited. To identify the potential biomarkers for the prevention and treatment of aGVHD during the early hematopoietic reconstruction after transplantation, we meticulously performed a comparative analysis of single-cell RNA sequencing data from post-transplant patients with or without aGVHD. Prior to the onset of aGVHD, monocytes in the peripheral blood of patients with aGVHD experienced a dramatic rise and activation on day 21 post-transplantation. This phenomenon is closely aligned with clinical cohort results obtained from blood routine examinations. Furthermore, in vitro co-culture experiments showed that peripheral blood monocytes extracted from patients with aGVHD approximately 21 days post-transplantation induced a significantly higher proliferation rate of allogeneic T cells compared to those from patients without aGVHD. Our study indicates that monocytes could be a crucial early clinical risk factor for the development of aGVHD, and this insight could potentially guide the timing of monitoring efforts, recommending assessments at the pivotal juncture of approximately day 21 post-transplantation, shedding fresh light on the significance of early hematopoietic regeneration in relation to the onset of aGVHD.

Impact of bone marrow fibrosis on outcomes of allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia.

Bone marrow fibrosis (BMF) of unknown etiology was common in hematological malignancies, but its prognostic value for acute myeloid leukemia (AML) is unclear. We interrogated data from 532 newly diagnosed subjects with AML receiving allogeneic hematological stem cell transplantation to evaluate the prognostic impact of BMF on transplant outcomes. Using the European consensus on the grading of BMF at diagnosis, 255 (48%) subjects were BMF-0, 209 (39%), BMF-1 and 68 (13%), BMF-2-3. Subjects with BMF-2-3 had poor overall survival (P < 0.001), disease-free survival (P < 0.001) and a higher incidence of relapse (CIR, P < 0.001). Multi-variable analyses in subjects achieving pre-transplant complete remission showed BMF-2-3 was an independent risk factor for CIR (Hazard Ratio [HR] = 2.17, (95% CI, 1.11, 4,24); P = 0.02). Furthermore, BMF-2-3 group showed delayed neutrophil and platelet engraftment and delayed B cell recovery post-transplantation. These findings demonstrate the significance of BMF in transplant outcomes and attract more attention to AML with BMF.

Application patterns and outcomes of hematopoietic stem cell transplantation in peripheral T-cell lymphoma patients: a multicenter real-world study in China.

The optimal timing and type of hematopoietic stem cell transplantation (HSCT) for treating peripheral T-cell lymphoma (PTCL) remain controversial. This retrospective real-world study investigated the application pattern and outcomes of HSCT in China. The analysis encompassed 408 PTCL patients with a median age of 45.5 years, all of whom received initial adequate therapy at five hospitals. Among patients with nodal PTCL who responded effectively to first-line therapy (the "responders", n = 127) and subsequently underwent HSCT consolidation (n = 47, 37.0%), 93.6% received auto-HSCT, while 6.4% underwent allo-HSCT. Front-line auto-HSCT showed potential for long-term disease control in nodal PTCL responders. Among non-nodal PTCL responders (n = 80) with HSCT (n = 26, 32.5%), 46.2% underwent allo-HSCT and 53.8% received auto-HSCT. Upfront allo-HSCT provides longer progression-free survival (PFS) for non-nodal PTCL responders, with lower 3-year cumulative incidence of relapse (CIR) (16.7% vs. 56.0%) and comparable non-relapse mortality (NRM) (10.4% vs. 11.0%) compared to auto-HSCT. For patients who achieved remission with second-line salvage regimens, allo-HSCT was the primary choice (82.4%) for non-nodal PTCL, while auto-HSCT was more common (82.4%) in nodal PTCL. Nodal PTCL patients underwent auto-HSCT after ≥ 3 lines of treatment had a higher 3-year CIR (81.0%) compared to those treated in the first (26.0%) or second line (26.0%). Non-nodal PTCL patients underwent allo-HSCT after ≥ 3 lines had a higher 3-year NRM (37.5%) compared to after first (10.4%) or second line treatment (8.5%). These findings highlight distinct HSCT application patterns for PTCL in China, emphasizing the impact of early disease control and upfront consolidative HSCT.

WT1 gene mutations impact post-transplant relapse in myelodysplastic syndrome with excess blasts 2 patients.

Wilms tumor 1 (WT1) gene mutations are infrequent in myelodysplastic syndrome (MDS), but MDS with WT1 mutations (WT1mut) is considered high risk for acute myeloid leukemia (AML) transformation. The influence of WT1 mutations in patients with MDS after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear. We performed a retrospective analysis of 136 MDS with excess blasts 2 (MDS-EB2) patients with available WT1 status who underwent their first allo-HSCT between 2017 and 2022 in our center. There were 20 (20/136, 15%) cases in the WT1mut group and 116 (116/136, 85%) cases in the WT1 wild-type (WT1wt) group. WT1mut patients had a higher 2-year cumulative incidence of relapse (CIR) than WT1wt cases (26.2% vs. 9.4%, p = 0.037) after allo-HSCT. Multivariate analysis of relapse showed that WT1 mutations (HR, 6.0; p = 0.002), TP53 mutations (HR, 4.2; p = 0.021), and ≥ 5% blasts in bone marrow (BM) at transplantation (HR, 6.6; p = 0.004) were independent risk factors for relapse. Patients were stratified into three groups according to the risk factors. Two-year CIR differed significantly in high-, intermediate-, and low-risk groups (31.8%, 11.6%, and 0%, respectively). Hence, WT1 mutations may be related to post-transplant relapse in patients with MDS-EB2, which warrants further study.

Posaconazole gastro-resistant tablets for preventing invasive fungal disease after haematopoietic stem cell transplantation: a propensity-matched cohort study.

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

Prophylactic therapy using epigenetic agents for RUNX1::RUNXT1-positive high-risk AML after Allo-HSCT.

Disease recurrence is the leading cause of treatment failure in patients with RUNX1::RUNXT1-positive acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Post-transplant maintenance therapy, guided by monitoring minimal residual disease (MRD), is commonly administered; however, relapse rates remain high. This prospective study aimed to assess the effectiveness and safety of epigenetic agents as prophylactic therapy in patients with RUNX1::RUNXT1-positive AML. Thirty high-risk patients received prophylactic therapy (n = 17 and n = 13 in the chidamide and AZA groups, respectively) between January 2019 and July 2023. 34 high-risk patients who received preemptive treatment due to molecular relapse were included in the analysis. The two-year relapse-free survival (RFS) and overall survival (OS) were significantly higher in the prophylactic group compared to the preemptive group (82.82% vs. 51.38%, P = 0.014; 86.42% vs. 56.16%, P = 0.025, respectively); 2-year cumulative incidence of relapse rates were 13.8% and 36.40%, respectively (P = 0.037). In conclusion, prophylactic therapy with epigenetic agents may improve long-term prognosis and is well-tolerated in patients with RUNX1::RUNXT1-positive high-risk AML. Timely post-transplant prophylactic therapy may be more effective than preemptive therapy based on positive MRD results.

Exploring strategies to optimise outcomes in hepatitis-associated aplastic anaemia patients following haematopoietic stem cell transplantation.

This study aimed to assess haematopoietic stem cell transplantation (HSCT) safety and efficacy while exploring strategies for optimising outcomes in patients with hepatitis-associated aplastic anaemia (HAAA). We retrospectively reviewed 35 HAAA patients who underwent HSCT at a large Chinese blood disease hospital between 2008 and 2022. HAAA patients receiving HSCT typically presented with severe (28.6%) and very severe (65.7%) AA. Male patients predominated (68.6%), with a median onset age of 23 years (range, 9-44). Haploidentical donor-HSCT and matched sibling donor-HSCT were in comparable proportions. The 5-year overall survival (OS) rate was 74.0%, with cumulative incidences of grade II-IV acute and chronic graft-versus-host disease (GVHD) at 37.1% and 22.4%, respectively. A diagnosis-to-HSCT interval ≥ 75 days, acute GVHD, and post-HSCT liver events (e.g., hepatic GVHD and a three-fold increase in aminotransferase or bilirubin) significantly worsened 5-year OS. In the multivariate models, recipients with sex-matched grafts had better OS, and those with younger male donors had a lower incidence of II-IV aGVHD. Higher HLA matching degree (HLA > = 7/10) was an independent prognostic factor associated with better OS and GFFS. A diagnosis-to-HSCT interval ≥ 75 days was predictive of post-transplant liver events in HAAA patients. In conclusion, HSCT was a safe and effective treatment for HAAA. Early transplantation, careful donor selection and improving post-transplant liver events were crucial to optimise outcomes.

Ursodeoxycholic acid does not reduce SARS-CoV-2 infection in newly allogeneic hematopoietic stem cell transplantation recipients: a prospective NICHE cohort.

Introduction: Retrospective studies have suggested that Ursodeoxycholic Acid (UDCA) provide a protective effect against SARS-CoV-2 infection, particularly in patients with liver disease. However, it is uncertain whether this finding can be extended to the allogeneic hematopoietic stem cell transplantation (allo-HSCT) cohort. Therefore, we aim to examine the protective potential of UDCA against SARS-CoV-2 infection in recently received allo-HSCT patients. Methods: During the initial Omicron variant wave in China (December 2022 to February 2023), we conducted a prospective observational study involving 91 hospitalized patients who had undergone allo-HSCT within the previous 6 months as part of the National Longitudinal Cohort of Hematological Diseases (NICHE). Throughout hospitalization, we continuously monitored the status of COVID-19 using SARS-CoV-2 PCR kits or SARS-CoV-2 Antigen Rapid Tests. Results: Among these patients, 67.0% (n = 61) were confirmed to have contracted SARS-CoV-2 infection. For the 52 patients evaluated, 23.1% experienced a severe or critical clinical course. There was no difference in the infection rate or severity of COVID-19 between the UDCA group and the non-UDCA group. We found that only patients transplanted between 3 and 6 months ago demonstrated a higher risk of SARS-CoV-2 infection compared to those who received allo-HSCT within 3 months (Odds Ratio [OR]: 3.241, 95% Confidence Interval [CI]: 1.287-8.814, P = 0.016). But other clinical factors, such as administration of UDCA, showed no difference. Notably, only age ≥38 years old remained as an independent risk factor for a severe clinical course of SARS-CoV-2 infection (OR: 3.664, 95% CI: 1.129-13.007, P = 0.035). Conclusion: The effectiveness of UDCA in protecting newly allo-HSCT recipients against SARS-CoV-2 infection remains unconfirmed. Presently, the most effective strategy appears to be minimizing exposure to SARS-CoV-2. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04645199, identifier NCT04645199.

Identification of key genes of diabetic cardiomyopathy in hiPSCs-CMs based on bioinformatics analysis.

Diabetic cardiomyopathy (DbCM) is one of the most common vascular complications of diabetes, and can cause heart failure and threaten the life of patients. The pathogenesis is complex, and key genes have not fully identified. In this study, bioinformatics analysis was used to predict DbCM-related gene targets. Published datasets from the NCBI Gene Expression Omnibus with accession numbers GSE62203 and GSE197850 were selected for analysis. Differentially expressed genes (DEGs) were identified by the online tool GEO2R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID online database. Protein-protein interaction network construction and hub gene identification were performed using STRING and Cytoscape. We used 30 mM and 1 µM hydrocortisone-stimulated AC16 cells as an in vitro model of diabetic cardiomyopathy. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression levels of hub genes. A total of 73 common DEGs were identified in both datasets, including 47 upregulated and 26 downregulated genes. GO and KEGG pathway enrichment analyses revealed that the DEGs were significantly enriched in metabolism, hypoxia response, apoptosis, cell proliferation regulation, and cytoplasmic and HIF signalling pathways. The top 10 hub genes were LDHA, PGK1, SLC2A1, ENO1, PFKFB3, EGLN1, MYC, PDK1, EGLN3 and BNIP3. In our in vitro study, we found that PGK1, SLC2A1, PFKFB3, EGLN1, MYC, EGLN3 and BNIP3 were upregulated, ENO1 was downregulated, and LDHA was unchanged. Except for PGK1 and ENO1, these hub genes have been previously reported to be involved in DbCM. In summary, we identified DEGs and hub genes and first reported PGK1 and ENO1 in DbCM, which may serve as potential candidate genes for DbCM targeted therapy.

Outcomes of acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: validation, comparison and improvement of 2022 ELN genetic risk system.

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

Ceftazidime-avibactam in the treatment of bacteremia due to carbapenem-resistant gram-negative bacteria in hematological patients: Experience in a single center.

INTRODUCTION: Limited experience exists with ceftazidime-avibactam (CAZ-AVI) in treating bacteremia caused by carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA) in hematological patients. METHODS: We performed a single-center, retrospective, observational study including patients who received CAZ-AVI for bacteremia due to CRE or CRPA between 2018 and 2022. The primary outcome was 30-day survival. We conducted a multivariable analysis to identify predictors of survival. RESULTS: 56 patients were included and 57 (41 CRE and 16 CRPA) strains were isolated. 35 strains produced carbapenemase, including 25 metallo-beta-lactamase (MBL) and 10 serine-beta-lactamase. 48 patients (85.7 %) received combination therapy. All patients with MBL-CRE bacteremia (n = 24) received combination therapy with aztreonam (AZT). The susceptibility rates to CAZ-AVI were only 26.8 % (11/41) in CRE and 80.0 % (8/10) in CRPA. The 30-day survival rates were 85.0 % (34/40) in the CRE group and 81.3 % (13/16) in the CRPA group. In patients with MBL-CRE bacteremia, the 30-day survival was as high as 91.7 % (22/24) due to combination with AZT. Ceftazidime did not influence the activity of aztreonam-avibactam against MBL-CRE in-vitro. Multivariable cox analysis revealed neutropenia >14 days (P = 0.002, HR: 34.483, 95%CI: 3.846-333.333) and a higher Pitt bacteremia score (P = 0.005, HR: 2.074, 95%CI: 1.253-3.436) were risk factors for 30-day survival. CONCLUSIONS: CAZ-AVI is highly effective in treating bacteremia due to CRPA and serine-beta-lactamase CRE. The combination of avibactam with AZT is highly effective in treating bacteremia due to AZT-resistant MBL producers.

Refractory patients with favorable/intermediate-risk acute myeloid leukemia benefit from azacytidine maintenance therapy following allogeneic hematopoietic stem cell transplantation.

Recurrence following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the major cause of treatment failure in patients with myeloid malignancy. Azacytidine (AZA) maintenance is a promising therapy to prevent relapse and improve survival. We conducted a prospective, one-arm study involving 78 patients with myeloid malignancy at a high risk of recurrence who were enrolled between September 2019 and April 2022. Furthermore, 102 matched historical controls were selected using propensity score matching. With a median follow-up time of 19.6 (3.5-91.7) months, AZA maintenance therapy significantly improved relapse-free survival (RFS; log-rank test, p = 0.01). The AZA and control groups had a 1-year RFS of 87.7% (95% confidence interval [CI], 0.80-0.96) and 72.2% (95% CI, 0.64-0.82), respectively, with a hazard ratio (HR) of 0.21 (95% CI, 0.09-0. 47; p < 0.01). There were no grade 4 adverse effects or deaths related to AZA. Refractory patients with favorable/intermediate-risk acute myeloid leukemia (AML) benefited more from AZA maintenance therapy than those with adverse-risk AML according to the European Leukemia Net guidelines (RFS in favorable/intermediate-risk AML, HR = 0.29, 95% CI, 0.11-0.79; RFS in adverse-risk AML, HR = 0.57, 95% CI, 0.21-1.6; p for interaction = 0.03). Our findings suggest that AZA maintenance therapy following allo-HSCT was safe and could reduce the incidence of relapse, particularly for refractory patients with favorable/intermediate-risk AML.

Elevated plasma levels of specific antiplatelet glycoprotein autoantibodies in patients with primary Sjögren syndrome with thrombocytopenia.

INTRODUCTION: Thrombocytopenia is one of the primary Sjögren's syndrome (pSS) hematological manifestations. The objective of this study was to evaluate the possible roles of antiplatelet glycoprotein autoantibodies in the pathogenesis of thrombocytopenia in primary Sjögren's syndrome (pSS). METHODS: The level of plasma anti-glycoprotein Ib, IIIa and IIb/IIIa autoantibodies in 36 pSS patients without thrombocytopenia and 35 pSS patients with thrombocytopenia, 36 Idiopathic thrombocytopenic purpura (ITP) patients and 39 normal control were measured with enzyme-linked immunosorbent assay (ELISA). RESULTS: The level of anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies (A490) in the pSS with thrombocytopenia was significantly higher than that of pSS without thrombocytopenia (0.813 ± 0.161 vs 0.688 ± 0.133; 0.917 ± 0.094 vs 0.802 ± 0.070; 0.911 ± 0.125 vs 0.782 ± 0.109). Incidences of the anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies in the pSS with thrombocytopenia was significantly higher than that of pSS without thrombocytopenia (25.7% vs 0%; 65.7% vs 11.1%; 31.4% vs 0%). In patients with pSS, there was a lower platelet count in anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies positive patients ((25.67 ± 5.5) × 10^9/L vs (116.8 ± 84.52) × 10^9/L; 29.04 ± 11.33 × 10^9/L vs (152.0 ± 75.47) × 10^9/L; (31.55 ± 14.0) × 10^9/L vs (118.8 ± 85.24) × 10^9/L). CONCLUSION: Elevated plasma levels of anti-platelet glycoprotein autoantibodies may play a role in the pathogenesis of thrombocytopenia in pSS. Key Points • The level of anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies (A490) in the pSS with thrombocytopenia was increased. • Incidences of the anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies in the pSS with thrombocytopenia was increased. • In patients with pSS, there was a lower platelet count in anti-GPIb, GPIIIa, GPIIb/IIIa autoantibodies positive patients.

Comparison of autologous, matched sibling, and alternative donor stem cell transplant outcomes for acute myeloid leukemia patients in first remission: A propensity score matching study.

Autologous hematopoietic stem cell transplantation (auto-HSCT), matched sibling donor HSCT (MSD-HSCT), and alternative donor HSCT (AD-HSCT) are viable post-remission treatment options for acute myeloid leukemia (AML). A total of 283 de novo favorable- and intermediate-risk AML patients, based on the ELN 2022 criteria, in first complete remission were initially included for propensity score matching. Following the matching process, 126 patients were selected for further analysis, with 42 patients in each of the auto-HSCT, MSD-HSCT, and AD-HSCT groups. Among the AD-HSCT group, 38 of 42 (90.5%) patients received haploidentical HSCT. In patients with persistent undetectable measurable residual disease (uMRD) before transplant (n = 83), overall survival (OS) was similar across the groups. However, auto-HSCT showed a trend of increased disease-free survival (DFS) compared to AD-HSCT (HR 2.85, P = 0.09), resulting in a 3-year DFS and OS of 79.1% and 82.8%, respectively. In the non-persistent uMRD group (n = 38), auto-HSCT exhibited a tendency to increase the risk of relapse, particularly when compared to AD-HSCT (HR 0.24, P = 0.07), but this did not result in inferior OS. The monthly direct medical cost per patient within the first 2 years after HSCT was significantly lower in auto-HSCT compared to MSD-HSCT (P = 0.015) and AD-HSCT (P < 0.001). Our results provide evidence for the use of auto-HSCT as a viable therapeutic option for favorable- and intermediate-risk de novo AML patients in first complete remission with persistent uMRD. Additionally, our findings demonstrated a notable cost advantage associated with auto-HSCT compared to MSD-HSCT and AD-HSCT.

Hematopoietic stem cell transplantation from an infected SARS-CoV2 haploidentical donor: A case report.

Introduction: We report a case of an adult hematopoietic stem cell donor who developed active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the donation of stem cells, the final transplantation was successfully completed without SARS-CoV-2 transmission. Case report: We report on a 34-year-old female diagnosed with acute lymphoblastic leukemia who underwent hemiploid hematopoietic stem cell transplantation (HSCT). Both patient and donor received three doses of inactivated SARS-CoV-2 vaccine before transplantation. PB-HSC was collected by the donor during the process of infection with SARS-CoV-2 (mild), and the patient did not show symptoms related to SARS-CoV-2 after transplantation. Nucleic acid and antigen were negative in regular tests. Conclusion: In the context of the current Omicron epidemic and high vaccination rate in the population, it is feasible to receive PB-HSC from infected donors even for immunocompromised patients. This also provides some references for our later donor selection.

Explorations of post-gDLI low-dose cyclophosphamide for preventing severe aGVHD.

OBJECTIVE: Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a serious life-threatening complication. The granulocyte colony-stimulated factor mobilized donor lymphocyte infusions (gDLI) combined with chemotherapy is currently a commonly used treatment method. Nevertheless, gDLI may cause so severe acute graft-versus-host disease (aGVHD) as to impact prognosis. Posttransplant cyclophosphamide (PTCy) has been the backbone for GVHD prophylaxis by inducing tolerance to minor histocompatibility antigens in recipients, while the application of post-gDLI low-dose cyclophosphamide (PDCy) for GVHD prophylaxis has not yet been attempted. METHODS: To explore this possibility, a retrospective study was conducted. 20 patients relapsing after HSCT were administered 20 mg/kg/d cyclophosphamide（Cy）on day 3 (for matched related transplantation) or on days 3 and 4 (for haplo-identical or unrelated transplantation) after gDLI to prevent aGVHD (the PDCy group). Furthermore, through propensity score matching, 58 matched controls received other (for HID and URD) or no (for MSD) immunosuppressive therapy for GVHD prophylaxis (the Non-Cy group). RESULTS: With a median follow-up of 4.8 (0-37.1) months, the PDCy group had lower cumulative incidence of severe aGVHD (III-IV, 5 % vs 31 %, p = 0.02; II-IV, 25 % vs 52 %, p = 0.04), but no significant differences existed in 4-month OS (64 % vs 59 %, p = 0.51), 4-month CIR (20 % vs 47 %, p = 0.11), rates of objective response (68.8 % vs 54.5 %, p = 0.6) (hematological or extramedullary relapse), MRD complete response (25 % vs 42 % p = 1) and MRD response (25 % vs 50 %, p = 0.6) (molecular relapse) between the PDCy group and the Non-Cy group. The PDCy regimen didn't increase the incidence of adverse infection, hemorrhagic cystitis, and cardiac events. CONCLUSION: On the premise of safety, the PDCy regimen could effectively protest against severe aGVHD after gDLI while preserving therapeutic response rates. However, the research results still require verification through longer follow-up and large prospective randomized studies.

Efficacy of venetoclax combined with decitabine conditioning regimen for allogeneic hematopoietic stem cell transplantation in high-risk and elderly patients with myeloid neoplasms.

This prospective clinical investigation focused on the addition of venetoclax and decitabine to myeloablative conditioning regimens, targeting high-risk and elderly individuals undergoing allogeneic hematopoietic stem cell transplantation. In total, 19 patients were enrolled in the trial between December 2021 and February 2023, and their progress was monitored for a median follow-up period of 258 days, ranging from 35 to 544 days. In the initial regimen (n=11), venetoclax was administered at a dosage of 400 mg per day from day -14 to day -1, while in the modified regimen (n=8), it was administered from day -14 to day -5. Decitabine was orally administered at a dosage of 20mg/m2/day from day -7 to day -3. Grade 3/4 adverse events observed included hematological events, hypertension, infections, allergy, and increased amylase. In the entire cohort, the overall survival (OS) and relapse-free survival (RFS) rates at 6 months were 63% (95% CI, 45-89) and 63% (95% CI, 45-89), respectively. The non-relapse mortality (NRM) rate at 6 months was 37% (95% CI, 16-58), while the cumulative incidence of relapse (CIR) was 0. However, the incidence of grade II-IV acute graft-versus-host disease (aGVHD) and grade III-IV aGVHD within 100 days was found to be 31% (95% CI, 12-53) and 26% (95% CI, 9-47), respectively. These rates indicate a relatively high occurrence, making it less suitable to administer the regimen to elderly patients. Therefore, further high-quality studies are required to enhance the conditioning regimen specifically for high-risk and elderly patients diagnosed with myeloid neoplasms. Clinical trial registration: ChiCTR2100050272.