Acute myeloid leukemia (AML) harboring KMT2A rearrangement (KMT2Ar) was generally associated with poor prognosis. We enrolled 490 patients with KMT2Ar from the East China Leukemia Alliance between March 2013 and August 2025. KMT2A::MLLT3 was the most frequent KMT2Ar (31.6%), followed by KMT2A::MLLT4 (25.1%), KMT2A::ELL (20%), and KMT2A::MLLT10 (12.7%). KMT2A::MLLT4 showed an inferior prognosis. The most co-occurring gene mutations were KRAS (20.1%), NRAS (19.0%), TET2 (10.2%), WT1 (8.6%), and PTPN11 (7.4%). Trisomy 8 was more common in patients < 60 years, while FLT3-ITD was only detected in patients < 60 years. With a median follow-up time of 42.6 months, the median overall survival (OS) of all patients was 30.9 months, and the 3-year OS rate was 49.9%. Patients treated with venetoclax plus intensive chemotherapy (Ven+IC) showed the best composite complete remission (CRc) rate and OS compared to intensive chemotherapy, venetoclax plus reduced-intensive chemotherapy, and reduced-intensive chemotherapy (CRc rate: 89.5% vs. 62.4% vs. 57.3% vs. 61.4%; median OS: not reached vs. 39.9 months vs. 34.8 months vs. 12.7 months). Multivariate analysis identified multiparameter flow cytometry minimal residual disease negativity post-induction therapy, allogeneic hematopoietic stem cell transplantation, and Ven+IC as independent favorable prognostic factors for event-free survival (EFS), and KMT2A::MLLT4 fusion, EVI1 overexpression were independent unfavorable prognostic factors for EFS. In summary, our study showed characteristics and prognostic implications in newly diagnosed KMT2Ar AML in China.

Worldwide, the diagnosis and treatment of immune thrombocytopenia (ITP) and Henoch-Schönlein purpura (HSP) remain a major and ongoing challenge in hematology. Emerging clinical evidences suggest serum mineral elements are associated with ITP or HSP, but the causal relationship between them is still unclear. Conducting a two-sample, bidirectional Mendelian randomization (MR) study to evaluate the causal association between serum mineral elements including zinc, copper, magnesium, iron and calcium with ITP and HSP. In this two-sample, bidirectional MR study, summary statistics data of genome-wide association studies (GWAS) on exposures including zinc, copper, iron, magnesium and calcium were extracted from the MRC-Integrative Epidemiology Unit (MRC-IEU). The GWAS data on study outcomes, including ITP and HSP, were obtained from the FinnGen consortium. MR-Egger intercept and MR-PRESSO global test were utilized to assess the heterogeneity and horizontal pleiotropic of instrumental variables (IVs) between the exposures and outcomes, respectively. Inverse variance weighted (IVW) test was used as the primary analysis method to evaluate the causal between serum mineral elements with the risk of ITP and HSP, and weighted-median, weighted model, MR steiger, MR-PRESSO and radial MR were used as auxiliary analysis methods, moreover, the odds ratio (OR) and 95

Background： Acute myeloid leukemia (AML) is a group of aggressive, heterogeneous, malignant diseases and is the most common type of acute leukemia in adults. The European LeukemiaNet (ELN) genetic risk stratification, which is widely used in clinical practice, categorizes patients with AML into three groups based on fusion genes, genetic mutations, and cytogenetic abnormalities, while excluding other characteristics, such as age at onset, sensitivity to chemotherapy, and relevant biochemical indicators. The aim of this study was to identify the factors affecting the survival of patients with AML and to develop and validate a prediction model. Study Design and Methods: Clinical data of 603 patients with newly diagnosed AML treated at The First Affiliated Hospital, Zhejiang University School of Medicine, from January 1, 2019, to April 30, 2023, were collected as a training set, and included 158 patients from East China Leukemia Alliance (ECLA) as a validation set.Treatment strategies were based on factors such as ELN risk stratification, mutations, age, performance status, and comorbidity. OS was defined as the time from AML diagnosis to death or the last follow-up. Results: The median follow-up durations for the training and validation sets were 24.8 (95%CI 23.1–26.5) and 50.9 (95%CI 37.1–64.8) months, respectively. The 1-, 2-, and 3-year OS rates in the training and validation sets were 79.9%, 61.9%, and 51.9%, 89.1%, 74.2%, and 60.0%, respectively.In the training set,survival-related variables including age at onset, lactate dehydrogenase (LDH) level at initial diagnosis, CBFB::MYH11 gene fusion, KMT2A rearrangement, TP53 mutation (variant allele frequency [VAF] >10%), DNMT3A mutation, RUNX1 mutation, and achievement of CRc in the first course of treatment were independent predictors that were used to construct the ZJ-AML model. The prognostic model demonstrated excellent discriminative ability with the Harrell's concordance index of 0.748, 1- ,2-and 3-year area under the receiver operating characteristic curve(AUROC) of 0.802, 0.753, and 0.691,respectively. The calibration curve of the training set showed good agreement between the model prediction results and the actual observation results in terms of 1-, 2-, and 3-year survival probabilities We assigned values to the variables according to the coefficients of the variables in multivariate analysis in the training set, which were summed and served as the risk score. The risk score was calculated as: 0.033677 × age (years) + 0.000493 × LDH (U/L) + 0.553400 × RUNX1 mutation + 0.820775 × KMT2A rearrangement + 1.256855 × TP53 mutation + 0.311104 × DNMT3A mutation − 0.635064 × CBFB::MYH11 gene fusion − 0.930328 × achievement of CRc in the first course of treatment. A nomogram and an online calculator were generated. Based on the risk score, the patients in the training set were equally divided into low- (<1.169), intermediate- (1.169–1.986), and high-risk (>1.986) groups,with significantly distinct prognosis, and the model successfully identified candidates for haematopoietic stem cell transplantation.The ZJ-AML model outperformed both the ELN 2022 (C-index: 0.793[95% CI: 0.698–0.864] vs. 0.646 [95% CI: 0.542–0.738], P = 0.025) and the ELN 2024 (C-index: 0.793[95% CI: 0.698–0.864] vs. 0.614 [95% CI: 0.495–0.720], P = 0.012) classification with a higher C-index. The model was validated in the validation set,with the Harrell's concordance index of 0.685, 1- ,2-and 3-year AUROC 0.802, 0.753, and 0.691.According to the risk score-based grouping principle, in this study population, 48 patients were at low risk, 63 patients were at intermediate risk, and 47 patients were at high risk. The survival rates of the three groups were statistically significant. Analysis of subgroups stratified by induction regimen demonstrated that the ZJ-AML model showed comparable discriminative capacity to the ELN 2022 classification in the intensive chemotherapy cohort and superior prognostic performance in patients treated with B-cell lymphoma 2 (BCL-2) inhibitor-based regimens compared with the revised ELN 2024 classification. Conclusion: In conclusion, we developed the ZJ-AML model, which demonstrated excellent discrimination and calibration in both the training and validation sets. Notably, our model exhibited superior discrimination compared to the ELN 2022 and ELN 2024 classifications, particularly for patients with AML undergoing combination therapy with a targeted BCL-2 inhibitor.

Polycomb repressive complex 2 (PRC2) is a multi-subunit complex that catalyzes the tri-methylation of histone H3 at lysine 27 (H3K27me3), serving as an epigenetic marker of gene silencing. PRC2 plays a crucial role in numerous fundamental biological processes, and its dysregulation is closely linked to cancer and developmental disorders. EZH2, a key component of PRC2, is aberrantly overexpressed in various human cancers. Inhibition of EZH2 enzymatic activity has been shown to effectively reduce cancer cell proliferation and tumorigenesis. Consequently, EZH2 is widely recognized as a driver of cancer, and the development of EZH2-specific inhibitors has become an active area of research. In this study, we screened over 2000 compounds from solid libraries using a PRC2 enzymatic activity assay and identified pyrroloquinoline quinone (PQQ) as a potent inhibitor of PRC2 methyltransferase activity in vitro. We evaluated the antitumor effects of PQQ across different tumor cell lines and found that it exhibited strong anticancer activity, specifically against B-cell lymphoma cells, which demonstrate elevated EZH2 activity. We used a combination of biochemical assays, cellular assays, and molecular docking studies to thoroughly investigate the inhibitory effects of PQQ on PRC2 activity. Furthermore, PQQ is a naturally occurring compound with various biological activities, including antioxidant and neuroprotective effects, and it has been approved as a nutritional supplement and health product in the United States. This study demonstrates, for the first time, that PQQ, a dietary supplement, selectively inhibits PRC2 methyltransferase activity, therefore providing new insights for targeted anti-lymphoma therapies involving PRC2.

Acute monocytic leukaemia, a subtype of acute myeloid leukaemia (AML), is a highly aggressive malignancy characterised by a poor prognosis, primarily due to the ability of leukaemic cells to evade immune surveillance. In this study, we demonstrate that homoharringtonine (HHT), an FDA-approved therapeutic agent for chronic myeloid leukaemia (CML), inhibits this immune evasion by targeting the FTO/m6A/LILRB4 signalling pathway in monocytic AML. Utilising RNA sequencing (RNA-seq) and various functional assays, we reveal that HHT treatment significantly reduces LILRB4 expression at both the RNA and protein levels, suggesting that the effects of HHT on LILRB4 are distinct from its well-established role as a protein synthesis inhibitor. Mechanistically, HHT treatment markedly increases global levels of RNA m6A in THP-1 cells by promoting the degradation of FTO, which subsequently diminishes the expression of its downstream targets, MLL1 and LILRB4. Furthermore, in vitro and in vivo analyses employing monocytic AML cell lines, mouse-derived AML xenograft models, and patient samples collectively support the conclusion that HHT suppresses immune evasion in monocytic AML by reducing LILRB4 expression. Importantly, the downregulation of LILRB4 resulting from HHT treatment enhances the susceptibility of THP-1 cells to CD8+ T cell cytotoxicity, accompanied by increased markers of immune activation. Overall, our findings position HHT as a promising clinical agent for enhancing CD8+ T cell-based cancer immunotherapy by mitigating immune evasion in monocytic AML.

Background The prognosis of multiple myeloma (MM),has been improved by the emergence of novel agents such as immunomodulatory drugs and proteasome inhibitors, which have become the cornerstone of MM treatment. The persistent nature of MM and the relatively long survival of MM patients have raised concerns over the safety and efficacy of continuous long-term therapy. The all-oral regimen consisting of ixazomib(I), lenalidomide(R), and dexamethasone(D)(IRD) has been widely used in the treatment of myeloma, which greatly improves patient adherence and facilitates medication application; however, there is a lack of real-world clinical data as to whether IRD maintenance therapy improves patient's outcome. This study reports long-term real-world data from 59 myeloma patients who were switched to IRD maintenance therapy. Methods The median age of 59 patients with multiple myeloma was 66 years with 35 (59%)patients≥65 years. International Myeloma Working Group (IMWG) risk stratification was highrisk in 45 (76%)patients, and Intermediate risk in 14 (24%)patients. The amplification of 1q21 (1q21 amp) was found in 18 (31%) patients. Patients included in the observation group had received at least two courses of different induction therapies with treatment outcomes of stable disease(SD) or better were converted to an IRD all-oral regimen with weekly ixazomib 4mg or 3mg for 3 weeks, lenalidomide 25mg qd for 21d consecutively, and weekly dexamethasone 20mg orally for 3 weeks. The patients were evaluated for the remission rate (patients reached partial response[PR], very good partial response[VGPR], and complete response[CR]), duration of remission, and adverse events (AEs) after IRD treatment. The cutoff time was July 1, 2024. Results Fifty-nine patients were treated with the IRD regimen for a median of 25 months(12-55), with a maximum duration of 55 months. Twenty-two (37.3%) patients received oral therapy at the cutoff for follow-up. After six courses of treatment, 79.7% of patients reached (15 vs 47)VGPR, with 6 of 9 (66.7%)SD patients achieving VGPR or higher after switching to oral therapy and 15 of 24 (62.5%)PR patients achieving VGPR. Subgroup analyses showed that patients with 1q21 amp, either in the IMWG high-risk or Intermediate-risk group, could benefit from a treatment switch, with the VGPR rate increasing from 50% to 78% after switching to I-base oral regimens and increasing to 73% and 100% in high-risk and Intermediate-risk patients, respectively. In patients ≥65 years of age after switching to an oral I-base regimen, VGPR rates increased from 28.5% to 80% with a mean DOT of 8.2 months when evaluated over 6-12 courses. The ixazomib-based oral maintenance regimen was generally well-tolerated by patients. The major adverse effect of the bortezomib-based induction regimen was peripheral neuropathy (PN), which reached grade 3 or more in 7 patients. No TAEs above grade 3 occurred after switching treatments. The major adverse effect of the ixazomib-based oral maintenance regimen was diarrhea, which mostly disappeared after the intervention, with only one patient seeing a worsening of PN that led to termination of treatment. Discuss Clinical studies have shown that continuous maintenance therapy after induction therapy for MM improves treatment outcomes and prognosis, especially to patients at high cytogenetic risk. Real-world data from our center showed that maintenance therapy with IRD improved the depth of remission and reduced the risk of disease progression in high-risk patients. Although the induction therapy regimen before the study was different, 80% of the patients improved the depth of remission after long-term sustained IRD maintenance therapy, which provides an option for follow-up treatment of high-risk myeloma patients. Despite the limited cases in this study, we still noticed that the IRD regimen achieved significant therapeutic responses in elderly patients with comorbidities, regardless of age, gender, ISS stage, renal insufficiency, comorbidities status, first-line therapeutic exposures, or 1q21+status, which is similar to literature. The main adverse effect of the maintenance regimen was diarrhea. The longest maintenance treatment duration reached 55 months in this study, with no significant hematologic toxicity, PN exacerbation, or herpes zoster infection during treatment. Patient compliance and quality of life were improved.

Transfusion-dependent β-thalassemia (TDT) is one of the global public health concerns highlighted by the World Health Organization. Patients with TDT require regular blood transfusion to survive. However, the availability of blood resources is extremely limited. The purpose of this study was to investigate transfusion burden and willingness to pay (WTP) for temporary remission of anemia status among patients with TDT and to explore the associated factors. Adult patients with TDT were recruited through cluster sampling across several high-incidence provinces in China. Consenting patients completed online questionnaires on demographic information, transfusion burden and WTP with real-time WeChat communication assistance from researchers. The guiding techniques of double-bounded dichotomous choices and open-ended questions in the contingent valuation method (CVM) were used to obtain participants’ WTP for 1 unit of leukocyte-depleted red blood cells. WTP calculations were performed using maximum likelihood estimation, with further insights gained through subgroup analysis based on gender, family monthly income level and convenience of blood transfusion. The analysis included 149 TDT patients from five high-incidence provinces, with an average monthly income of 198.5. Patients received an average of 3.7 units per transfusion, 15.4 times annually, with an average WTP of70.4 per unit (95

OBJECTIVE:Ruxolitinib was recently approved to treat corticosteroid-resistant acute graft-versus-host disease (GvHD). However, it is unknown as to whether starting ruxolitinib at a lower versus higher acute GvHD grade or earlier versus later affected outcomes. This study identified the impact of starting acute GvHD grade and start time after declaring corticosteroid resistance and the effect on complete and overall response rates to ruxolitinib therapy.METHODS:Retrospective, observational multi-center study. We divided cohorts into starting ruxolitinib ≤ 7 days (N = 45) versus at > 7 days after declaring corticosteroid resistance (N = 24).RESULTS:In ≤ 7 days cohort complete response (CR) rates at day 28 were 69% (54, 81%) versus 25% (11, 47%; p = .001) in > 7 days cohort, and overall response (OR) rates were 91% (78, 96%) versus 80% (48, 92%; p = .25).CONCLUSIONS:Our data suggest that starting ruxolitinib in ≤ 7 days of declaring corticosteroid failure regardless of G vHD grade improves complete response rate but not OR rates. Starting ruxolitinib at grade I and within 7 days may get a more significant response.

This multicenter, open-label, single-arm trial (ClinicalTrials.gov, NCT05236621) was conducted to confirm the efficacy and safety of generic pomalidomide plus dexamethasone in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Total 79 eligible RRMM patients were planned to be included. Patients were treated with generic pomalidomide (4 mg daily on days 1–21, orally) and low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally; 20 mg for patients aged > 75 years) in 28-day cycles until disease progression with a maximum treatment duration of 2 years. The primary endpoint is the overall response rate (ORR) assessed by the independent review committee per the 2016 International Myeloma Working Group guidelines. A total of 85 eligible patients were included in this study from 32 centers in China, with a median age of 62.0 (range, 39–76) years, a median prior line of therapy of 4 (range, 1–16), and 41.2% patients with high-risk cytogenetics. The ORR was 38.8% (95% confidence interval (CI), 28.44–50.01). The disease control rate was 67.1% (95% CI, 56.02–76.87), meanwhile, the median progression-free survival was 5.55 months (95% CI, 3.68–7.52). Among the treatment-related adverse events (TRAEs), infective pneumonia (17.6%) was the most frequent non-hematologic adverse event, while a decrease in neutrophil count (52.9%) was the most common grade ≥ 3 TRAE. The study results indicated that the generic pomalidomide demonstrated consistent efficacy and a safety profile similar to the branded pomalidomide when combined with low-dose dexamethasone in Chinese RRMM patients. Registration number ClinicalTrials.gov NCT05236621, retrospectively registered on February 11, 2022.

Background Although the multi-drug chemotherapy regimen known as VDCLP can induce hematological remission in 70-90% of adults with acute lymphoblastic leukemia, many patients, particularly young women, remain concerned about chemotherapy-related complications such as alopecia, infection, and bleeding risk. Blinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, has notably enhanced the remission rates for relapsed and refractory adult ALL when combined with chemotherapy. Additionally, the combination of blinatumomab and TKI has demonstrated significant efficacy in treating ph+ adult ALL. However, there is currently no clinical evidence indicating whether blinatumomab, as a first-line therapy, can achieve higher remission rates and reduce toxic and side effects in newly diagnosed adult ALL patients. In this report, we present the findings from our center where we have used the blinatumomab regimen as the primary treatment for adult ALL. Method A total of 12 newly diagnosed adult ALL patients were enrolled in this study. These patients consisted of 3 males and 9 females, with ages ranging from 23 to 72 years. All patients underwent bone marrow aspiration and were diagnosed according to morphology, immunophenotyping, cytogenetics, and molecular biology（MICM）. They were categorized into 7 cases of Ph+ ALL and 5 cases of Ph- ALL(Table1). All patients received a combination regimen consisting of vincristine (1.4mg/m2 on D1 and D8), prednisone (1mg/kg orally from D1-14,decrease gradually after D15), and blinatumomab. Blinatumomab was initiated on D3 and administered in an escalating dose manner for 15-28 days (9 μg/day from D1-7, 28 μg/day from D8) . Result Seven patients completed the 15-day treatment course, and five patients completed the full 28-day treatment course. Bone marrow morphology and MRD assessments were conducted on days 15 and 28 post-treatment. On day 15, the hematological remission rate (HCR) of bone marrow reached 100% (12 out of 12 patients), while the MRD negativity rate was 16.7% (2 out of 12 patients tested). five patients completed the full 28-day treatment course, and upon re-examination on day 28, maintained a 100% HCR. Among these, the MRD negativity rate improved to 80% (4 out of 5 patients). No significant difference in HCR was observed between ph+ ALL and ph- ALL groups. Five patients underwent allogeneic stem cell transplantation, and four of these patients were thriving, while one patient died of COVID-19 infection 3 months after transplantation. Of the seven patients without a transplant, two elderly patients received non-chemotherapy maintenance treatment but unfortunately passed away due to disease recurrence within 12 months. Four patients with ph+all received alternating chemotherapy and oral TKI treatment and are currently in good health and alive. One patient with ph-all received CAR-T therapy and still alive with MRD negative. (Figure1) Discuss Our center's findings further corroborate that for adults with new diagnosis Ph+/- ALL, initial treatment involving blinatumomab combined with low-dose chemotherapy can attain a 100% HCR rate, absent of pronounced toxicity or side effects, thereby offering a viable option for patients intolerant or averse to chemotherapy. Currently, there is insufficient evidence to determine the ideal duration for blinatumomab treatment in adult ALL patients. However, for refractory and relapsed ALL cases, a continuous 28-day course of blinatumomab therapy may be required. Initial findings from our center indicate that after 15 days of VP+blinatumomab therapy, all patients achieved hematological remission. This outcome is particularly advantageous for patients in developing nations and regions. Switching to chemotherapy or oral TKI promptly after 15 days of blinatumomab treatment can considerably decrease treatment expenses and minimize complications associated with combined chemotherapy. Nevertheless, the sample size in this study is limited, necessitating further clinical evidence to validate this perspective.

Relapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo-HSCT following fludarabine(≥100 mg/m2), busulfan (≥3.2 mg/kg) and melphalan (≥100 mg/m2) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML n = 171, MDS-IB-1 or 2 n = 44, CMML n = 6) with median age of 46 were enrolled in this study. The median follow-up was 507 days for survivors. The 2-year NRM, CIR, OS and DFS were 10.6% ± 2.2%, 14.8% ± 3.3%, 79.4% ± 3.7% and 74.6% ± 3.7%, respectively. In multivariate analyses, high HCT-CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; p = 0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; p = 0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; p = 0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR = 7.92, 95%CI 1.05-60.03, p = 0.045; HR = 3.64, 95%CI 1.40-9.44, p = 0.008; respectively), while post-transplantation cyclophosphamide based graft-versus-host disease prophylaxis was associated with lower CIR (HR = 0.24 95%CI 0.11-0.54, p = 0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.

急性髓系白血病(AML)是一组高度异质性的克隆性疾病,化学药物治疗和造血干细胞移植均为治疗AML的方法.对于高危AML患者而言,异基因造血干细胞移植为治疗该疾病的有效手段,但部分AML患者造血干细胞移植后仍可能面临疾病复发的问题,大多数复发患者再行化学药物治疗、二次移植等的效果不佳,是导致患者异基因造血干细胞移植后死亡的主要原因.因此,加强对异基因造血干细胞移植后AML患者的随访,并采取一些合适的手段预防移植后复发显得尤为重要.本文就高危AML患者异基因造血干细胞移植后复发的监测、药物治疗和细胞治疗进行综述,以期为改善高危AML患者异基因造血干细胞移植预后提供参考.

Background ： The 5-year overall survival rate (OS) for children with thalassemia major who undergo allogeneic stem cell transplantation is 90% and the event-free survival (EFS) rate is 86%. Due to the limited availability of matched sibling donors, the proportion of transplantations from alternative donors is increasing, particularly from haplo-identical donors. Post-transplant infections and graft-versus-host disease (GVHD) remain the major causes of mortality, especially in those who receive transplantation from alternative donors. Post-transplant cyclophosphamide (PTCY) has shown outstanding results of GVHD prophylaxis in haploidentical matched related donors transplantation with hematological malignancies. However, there is insufficient clinical evidence for its application in pediatric patients who received transplantation from haplo-identical donors with non-malignant hematological disease. Here, we retrospectively analyzed the results of 40 cases that underwent allogeneic stem cell transplantation from haploidentical matched related donors (Haplo-RD) and unrelated donors (UD) to evaluate the safety and efficacy of the novel regimen in GVHD prophylaxis. Method A total of 40 patients with β-thalassemia major received stem cell transplantation, 10 haploid donors (Group Haplo-RD), and 30 unrelated donors (Group UD). Among Group UD, 15 donors were 1 or 2 HLA locus mismatched, remaining 15 were identically matched. The median age of the patients was 5.5 years, ranging from 2 to 12. The Conditioning regimen mainly consisted of fludarabine, busulfan, cyclophosphamide, and thiotepa. GVHD prophylaxis included ATG 1.5mg/kg×3d, cyclophosphamide (CTX) 25mg/kg×2d, cyclosporin A (CsA), and mycophenolate mofetil (MMF). We analyzed the engraftment rate, GVHD incidence, survival rate, and virus reactivation rate for each group. Results Engraftment rate was 100%, with a median time of 11 (10-15) days for neutrophil implantation and 12 (6-31) days for platelet implantation. All patients achieved complete chimerism on day 30 after transplantation. Three cases (7.5%) suffered from Ⅲ-Ⅳ aGVHD, with one being in the Group Haplo-RD group and two in the Group UD. Four cases (10.0%) of cGVHD were recorded. The overall survival (OS) rate and thalassemia-free survival rate were both 92.5%. In Group Haplo-RD, both the OS and thalassemia-free survival rates were 100%. Eight cases reported cytomegaloviremia but no one developed to CMV disease. The total activation rate for CMV was 20%. Nine cases suffered from BK virus urinary tract infection, resulting in a total activation rate of 22.5%. Detailed results are shown in Table 1 and Figure 1. Discussion Due to the high risk of GVHD and infection, stem cell transplantation from haploidentical and unrelated donors cannot be routine therapy for children with thalassemia major. Standard-dose PTCY regimen significantly increases the risk of CMV and BK infection after transplantation and is not suitable for non-malignant disease. The results have been reported that low-dose PTCY/ ATG can reduce the risk of GVHD as compared with standard-dose ATG in haploidentical donor stem cell transplantation. In our study, the novel GVHD prophylaxis regimen, semi-dose PTCY (25mg/kg×2d) combined with low-dose ATG (1.5mg/kg×3d), was used for stem cell transplantation from haploidentical and unrelated mismatched donors. The incidence of III-IV aGVHD was 7.5% and cGVHD was 10.0%, and there was no rejection of the transplant. The activation rate of CMV and BKV was significantly lower than reported in the literature, and the non-relapse mortality (NRM) after transplantation was significantly reduced. There was no statistical difference in the rate of OS, EFS, aGVHD, and cGVHD between Group Haplo-RD and Group UD. The results provide an effective approach for preventing GVHD and infectious diseases in thalassemia patients who underwent allo-HSCT with high-risk GVHD.

Abstract Purpose:: Multiple myeloma(MM) is a common malignant tumor in the blood system. Despite recent advances in its treatment, its symptomatic remission rate and survival rate are still not optimistic. In the future, it is necessary to continue to search for different treatment targets and new treatment methods in order to improve the quality of life and survival time of patients with MM. The study aims to explore the potential immune related pivotal genes and immune infiltration patterns in MM. Methods: The study included peripheral blood samples from patients with MM who our hospital from October 2020 to April 2022. Obtain a gene chip for research from a comprehensive gene expression database, perform differential expression analysis on the processed gene dataset, and then perform functional enrichment analysis, weighted gene co expression network analysis, GSEA immune infiltration analysis, and LASSO regression analysis on the obtained differential expression genes to obtain the hub genes. Finally, the hub gene TNFSF14 (LIGHT) was validated by qRT-PCR. Results: In the study, three immune-related hub genes (ADAM8, CR2, and TNFSF14) and three main types of peripheral immune cells (activated CD8 T cells, macrophages, and plasma cell like dendritic cells) were obtained, which are closely related to the pathogenesis of MM. Then, by collecting peripheral blood samples from some patients in our hospital and conducting real-time fluorescence quantitative polymerase chain reaction, it was confirmed that the hub gene TNFSF14 (LIGHT) mined in this study was highly expressed in peripheral blood samples from patients with MM, which may indicate that it plays a pathogenic role in MM. Conclusion: The study found that immune-related hub genes (ADAM8, CR2, and TNFSF14) are closely related to the pathogenesis of MM, and should be further researched.

BACKGROUND:Immunogenic cell death (ICD)is a kind of regulatory cell death, which causes a series of antigen-specific adaptive immune responses by generating and emitting some danger signals or damage-associated molecular patterns (DAMPs). At present, little is known about the prognostic value of ICD and its related processes in acute myeloid leukemia (AML). The aim of the study was to explore the relationship between ICD and tumor immune microenvironment changes in AML.RESEARCH DESIGN & METHODS:In the study, AML samples were divided into two groups by consensus clustering analysis, and then gene enrichment analysis and GSEA analysis were performed on the ICD high expression group. Furthermore, CIBERSORT was used to analyze the tumor microenvironment and immune characteristics of AML. Finally, a prognostic model related to ICD was constructed by using univariate and multivariate regression analysis.RESULTS:ICD was divided into two groups according to the level of ICD gene expression. The ICD high expression group was associated with good clinical results and high levels of immune cell infiltration.CONCLUSIONS:The study constructed and verified the prognostic characteristics of AML related to ICD, which has important value in predicting the overall survival time of AML patients.

目的 分析输血依赖型地中海贫血儿童非亲缘造血干细胞移植后BK病毒(BKV)相关出血性膀胱炎的发生率、临床特征和影响因素.方法 回顾性分析2018 年2 月至2021 年2 月厦门大学附属中山医院62 例输血依赖型地中海贫血儿童接受非亲缘造血干细胞移植后的临床资料,包括患儿年龄、人类白细胞抗原(HLA)相合程度、急性移植物抗宿主病(aGVHD)和慢性移植物抗宿主病(cGVHD)的发生以及与BKV感染的关联性.结果 14 例(22.58%,14/62)发生出血性膀胱炎,尿液中均检出BKV感染,BKV copies最高达107/ml,出血性膀胱炎与BKV感染符合率为100.00%.在预处理方案相同情况下,非亲缘全相合、移植物抗宿主病(GVHD)是发生BKV相关出血性膀胱炎的影响因素.结论 BKV感染是输血依赖型地中海贫血儿童非亲缘造血干细胞移植后发生出血性膀胱炎的主要原因,非亲缘全相合、GVHD是发生BKV相关出血性膀胱炎的影响因素.

HLA-DPB1*1352:01 differs from HLA-DPB1*02:01:02:01 by one nucleotide in exon 4.

BackgroundTo evaluate the effect of addition of ruxolitinib in Graft-versus-Host Disease (GVHD) prophylaxis on pediatric patients with beta-thalassemia major after allogeneic hematopoietic stem cell transplantation(HSCT). MethodsThis retrospective study reviewed 49 consecutive beta-thalassemia major pediatric patients who underwent HSCT from unrelated or haploidentical donors from February 2018 to October 2022. All transplantation recipients received cyclosporine A (CsA), mycophenolate mofetil (MMF), and short-term methotrexate (MTX) as GVHD prophylaxis; while 27 of them in the ruxolitinib group had added ruxolitinib oral to GVHD prophylaxis regimen at 2.5 mg twice daily once successful engraftment after January 2020. ResultsThe outcome showed that the ruxolitinib group had a lower cumulative incidence than the control group regardless of acute GVHD (22.2% vs.40.9%; p = .153) or chronic GVHD (18.5% vs.40.9%; p = .072); especially, the incidence of grade III-IV acute GVHD was reported significantly less frequently in ruxolitinib group than that of the control group (0 vs. 27.3%, p = .005). No significant difference was detected between the two groups in EBV (Epstein-Barr virus)/CMV (cytomegalovirus) reactivation and BKV (BK virus) infection (p = .703, 1.000, and .436, respectively). Twenty-six patients (96.3%) in the ruxolitinib group were alive, while two patients (9.1%) in the control group died of intestinal acute GVHD. The 2-year overall survival (OS) and thalassemia-free survival (TFS) were both 96.296% in the ruxolitinib group, while both 90.909% in the control group. ConclusionThis study reveals that ruxolitinib prophylaxis is a promising option to decrease the incidence of grade III-IV acute GVHD in pediatric patients with beta-thalassemia major.

Plain Language Summary What is the context? Relative thrombopoietin deficiency is implicated in primary immune thrombocytopenia (ITP), which is characterized by increased platelet destruction and impaired megakaryopoiesis. Patients who are innately unresponsive to or have relapsed after glucocorticoid treatment have limited treatment options. Recombinant human thrombopoietin (rhTPO) improves treatment response of primary ITP patients when added to high-dose dexamethasone. What is new? This trial sought to identify an optimal dosing regimen of rhTPO for patients who had failed or relapsed after glucocorticoid therapy. Of the 4 regimens, once daily 15000 U rhTPO for 14 injections yielded the greatest median increase in platelet count (167.5 x 10(9)/L) from baseline and attained the highest total response rate on day 14 (63.2%). 30000 U rhTPO once every other day for 7 injections was effective in rapidly increasing platelet counts in the first 7 days. All 4 regimens were safe and well-tolerated. What is the impact? The 30000 U rhTPO once every other day regimen may offer an effective and safe regimen with less frequent injections, but future trials with longer follow-up are needed. Recombinant human TPO (rhTPO) is effective for refractory/relapsed primary immune thrombocytopenia (ITP), but optimal dosing regimen remains elusive. In this multicenter, randomized, controlled trial, a total of 282 adult ITP patients (mean age 47.3 years; 82 men) with a platelet count <= 30 x 10(9)/L or >30 x 10(9)/L with active bleeding randomly received a once daily (QD) subcutaneous injection of 7500 U (n = 64) or 15000 U rhTPO for 14 injections, or 15000 U or 30000 U rhTPO once every other day (QOD) for 7 injections. The primary outcomes included change from baseline in platelet count and total response rate (TRR) on day 14. On day 14, the median increase of platelet count from baseline was the highest in the 15000-U QD group (167.5 x 10(9)/L, interquartile range [IQR] 23.0-295.0 x 10(9)/L), followed by the 30000-U QOD group (57.5 x 10(9)/L, IQR 9.0-190.0 x 10(9)/L) (ANCOVA P < .001; P = .266 with baseline count as a covariate). The TRR on day 14 was also the highest in the 15000-U QD group (63.2%), followed by the 30000-U QOD group (59.7%). The rate of grade 3 and above adverse events did not differ among the four groups. There were no new safety concerns. All 4 regimens are safe and well-tolerated. The 30000-U QOD regimen is practically indistinguishable in efficacy to the 15000-U QD regimen.

Objective:To explore the key genes related to the development, progression and prognosis of acute myeloid leukemia (AML) based on bioinformatics, and to analyze their functions.Methods:The chip expression profile GSE84881 data set of AML patients including 19 AML samples and 4 normal tissue samples was downloaded from the gene expression omnibus (GEO) database. GEO online tool GEO2R was used to screen the differentially expressed genes (DEG). The DAVID online database was used to make gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEG. The STRING online database was used to analyze the protein interaction (PPI) network of DEG, and the key genes were screened by using the Cytoscape software. The weighted gene co-expression network analysis (WGCNA) was used to build co-expressed network and obtain the central genes.LC-Bio online platform was used to construct Venn diagram and the key genes and central genes in PPI were crossed to finally obtain the true key genes. RNA-seq datasets GSE2191 and GSE90062 of human tissues were downloaded from GEO database to verify the screened key genes. Kaplan-Meier method was used to analyze the effects of key genes on the overall survival (OS) of AML based on the data of GEPIA database.Results:A total of 247 DEG were identified in GSE84881 data set, including 112 up-regulated genes and 135 down-regulated genes. According to the results of GO enrichment analysis, 247 DEG were mainly enriched in the regulation of signal transduction and cell proliferation in the biological process (BP); the cell composition (CC) revealed that these genes were mainly involved in the cytoplasm and exosomes; the molecular function (MF) analysis showed that these genes were mainly enriched in protein binding and calcium binding. Further KEGG pathway enrichment analysis showed that these 247 DEG were mainly involved in NOD-like receptor signal pathway and interleukin 17 (IL-17) signal pathway. And then the 12 key genes were obtained from PPI. WGCNA software was used to screen 13 central genes from GSE84881 dataset and finally 1 real key gene EGF was obtained after taking intersection. Kaplan-Meier method showed that OS time of AML patients in EGF high expression group was decreased than that in EGF low expression group, and the difference was statistically significant( P = 0.044). Conclusions:EGF may be an important diagnosis and treatment target of AML and may become a potential biomarker for clinical treatment and prognosis prediction of AML.