To the Editor: Allogeneic hemopoietic stem cell transplantation (allo-HSCT) represents the only long-term survival treatment choice for patients with myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasm (MPN). Unfortunately, post-hemopoietic stem cell transplantation (HSCT) relapse remains a cause of treatment failure and the results of salvage treatments are poor. Developing better conditioning regimens is urgently needed. Previous studies have shown synergistic antileukemic effects between decitabine (DEC) and idarubicin (IDA).[1] In an attempt to design a conditioning strategy with very low toxicity but considerable myelosuppressive activity and potential immune-enhancing effects for patients with high-risk MDS and MDS/MPN, we combined DEC and IDA with busulfan, cyclophosphamide, and fludarabine for a modified myeloablative regimen in this prospective, multicenter cohort study (hereafter referred to as the "DEC/IDA study"). The trial was registered with http://www.chictr.org.cn/ as ChiCTR-ONC-17012640. The protocol was reviewed and approved by the Ethic Committee of Blood Diseases Hospital, Institute of Hematology, Chinese Academy of Medical Sciences (No. IHBDH-IIT2017003). This clinical trial was conducted in accordance with the Declaration of Helsinki. All patients provided their written informed consent before participating in the study. Patients aged between 15 years and 65 years, Eastern Cooperative Oncology Group performance status ≤2, with intermediate risk MDS or worse (according to the revised international scoring system for evaluating prognosis [IPSS-R]), chronic myelomonocytic leukemia (CMML), and secondary acute myeloid leukemia (sAML) after MDS or MDS/MPN from 10 medical centers in China were eligible for enrollment. With a sample size of 120 patients, the study had a power of more than 80%, using a 5% level of significance to show significance determined by a binomial distribution calculation with the expected and threshold 2-year relapse rates (RRs) of 10% and 20%, respectively. Eligible patients in the DEC/IDA study received the myeloablative conditioning regimen consisting of 20 mg·m–2·day–1 DEC (days –9 to –5), 3.2 mg·kg–1∙day–1 busulfan (Bu, days –9 to –7), 30 mg·m–2·day–1 fludarabine (Flu, days –6 to –4), 12 mg·m–2·day–1 IDA (days –6 to –4), and 40 mg·kg–1·day–1 cyclophosphamide (Cy, days –3 to –2), followed by allo-HSCT. All patients with unrelated or mismatched-related donors received antithymocyte globulin (rabbit) at 2.5 mg·kg–1·day–1 (days –4 to –1). For graft-versus-host disease (GVHD) prophylaxis, tacrolimus at 0.03 mg/kg from day –5 and methotrexate at 15 mg/m2 on day 1, 10 mg/m2 on days 3, 6, and 11 were used. The endpoints definitions and statistical analysis method were described in Supplementary File, https://links.lww.com/CM9/B938. From January 2017 to February 2021, a total of 121 patients with MDS (≥IPSS-R intermediate risk), CMML, and sAML after MDS or MDS/MPN from 10 Chinese hospitals were registered in the DEC/IDA study, of which 120 entered the study and were included in the analysis. The study flow diagram is shown in Supplementary Figure 1, https://links.lww.com/CM9/B938. The median follow-up time after HSCT was 986 days (range, 8–2026 days; interquartile range [IQR] 461–1423 days). The demoimagedata and clinical characteristics of the patients are shown in Supplementary Table 1, https://links.lww.com/CM9/B938. The median age was 44.5 years (range, 16–64 years) at the time of allo-HSCT. Overall, 100 (83.3%) patients had MDS, 7 (5.8%) patients had CMML, and 13 (10.8%) patients had sAML. Thirty-eight (31.7%) patients were diagnosed with intermediate-risk MDS and 62 (51.7%) were diagnosed with high- or very high-risk MDS according to IPSS-R. Nighty-one (75.8%) patients had active disease before HSCT, including 24 (20.0%) patients who did not respond to chemotherapy and 67 (55.8%) patients who did not receive chemotherapy. All patients in the DEC/IDA study received peripheral blood-derived donor stem cells. Successful neutrophil repopulation was achieved in 119 (99.2%) patients with a median time of 13 (range, 6–23) days. Successful platelet repopulation was achieved in 116 (96.7%) patients with a median time of 16 (range, 9–314) days and 104 of 116 (89.7%) were within 28 days. From the conditioning regimen to hematopoietic reconstitution, a median of 7 (range, 1–62) packages of platelets and 8 (range, 0–36) units of peripheral red blood cells were transfused. All 85 evaluable patients achieved full donor chimerism within a median time of 15 (range, 12–58) days post-transplant. The DEC/IDA conditioning regimen was well tolerated. The most common non-hematologic adverse event was oral mucositis and no patient experienced grade 4 oral mucositis or died before transplantation. Overall, 30.8%, 25.0%, and 21.2% of patients developed grades 1, 2, and 3 oral mucositis, respectively. Fifty-eight (48.3%) patients experienced aGVHD within 100 days after transplantation, and cGVHD occurred in 35 (29.2%) patients (including 12 cases of extensive cGVHD). The cumulative incidences of grades 1–4 and 3–4 aGVHD at 100 days were 48.3% (95% confidence interval [CI], 39.3%–57.3%) and 20.0% (95% CI, 12.8%–27.2%), respectively. The 3-year OS rate, RFS rate, relapse incidence, and NRM incidence were 70.5% (95% CI, 62.7%–79.2%), 67.5% (95% CI, 59.6%–76.4%), 10.0% (95% CI, 5.4%–16.2%), and 22.5% (95% CI, 15.5%–30.4%), respectively Supplementary Figure 2A–C, https://links.lww.com/CM9/B938. Importantly, we observed that only 13 patients relapsed within 3 years after HSCT, and the RFS rate (67.5%) was relatively higher than that reported previously, which arranges from 30% to 50%.[2–4] Thirteen patients, including two MDS with excess blasts (MDS-EB) I, eight MDS-EB II, and three sAML, experienced a relapse in a median time of 186 (range, 59–1401) days after HSCT. Ten of 13 (76.9%) patients received at least one cycle of chemotherapy followed by donor lymphocyte infusion after relapse, while 3 of 13 (23.1%) patients only received supportive care according to the willingness of the patients. Five of 13 (38.5%) patients achieved complete remission and survived at the last follow-up. Among the 35 patient deaths, 8 (22.9%) were due to relapse, and the deaths of 27 patients were due to treatment-related complications. Two patients died from persistent neutropenia and subsequent bloodstream infection early on day 8 and 20. The causes of NRM were aGVHD (n = 15, 42.9%), followed by infectious complications (n = 9, 25.7%) and cerebral hemorrhage (n = 3, 8.6%) Supplementary Figure 2D, https://links.lww.com/CM9/B938. The median time from allo‑HSCT to death was 165 days (range, 8–789). It has been reported that with an increase in the number of oncogenic mutations, patient outcomes progressively worsen.[2] In our study, the number of mutations has no effect on RFS and OS. The OS and RFS of the patients with ≥3 mutations were 70.8% and 66.6%, respectively, superior to that reported in the previous studies (approximately 40%).[2,5] These results indicated that conditioning that consisted of DEC and IDA followed by transplantation may overcome obstacles of adverse mutations in MDS. Univariate analysis for OS and RFS of the DEC/IDA study was conducted [Supplementary Table 2, https://links.lww.com/CM9/B938]. Patient age ≥50 years and TP53 mutation were the factors significantly associated with both poor OS and poor RFS. It is noteworthy that RFS was significantly higher in high/very high-risk MDS compared to intermediate-risk MDS when patient age and TP53 mutation were included as covariates in the multivariate analysis (hazard ratio [HR], 0.47; 95% CI, 0.22–1.00; P = 0.049; Supplementary Table 3, https://links.lww.com/CM9/B938). The 3-year OS was similar between patients receiving a matched sibling donor and alternative donor HSCT (74.1% [95% CI, 61.3%–89.4%] vs. 68.7% [95% CI, 59.3%–79.7%], P = 0.410). To identify patients with more favorable outcomes from the DEC/IDA study, we compared outcomes with those of a historical cohort who received myeloablative conditioning regimen without DEC or IDA between January 2013 and January 2017, including Bu/Cy/Flu/cytarabine (Ara-c), Bu/Cy/Flu and Bu/Flu/Ara-c (dosage: Bu, 3.2 mg·kg–1·day–1, days –9 to –7; Cy, 40 mg·kg–1·day–1, days –3 to –2; Flu, 30 mg·m–2·day–1, days –6 to –4; Ara-c, 2 g·m–2·day–1, –4 to –2 days). The historical control cohort satisfied the same enrollment criteria. Ninety-five patients were included as historical controls. Patient and transplantation characteristics are shown in Supplementary Table 4, https://links.lww.com/CM9/B938. The proportion of patients with MDS-EB or sAML was higher in the DEC/IDA study than in the historical controls (78.3% vs. 60.0%, P = 0.006). Patients in the historical control cohort received transplants more from matched sibling donors than in the DEC/IDA study (76.8% vs. 33.3%, P <0.001). Although there were no significant differences in OS or RFS between the DEC/IDA study and the historical control cohort, a subgroup analysis showed that patients with MDS-EB or sAML tended to benefit from DEC/IDA treatment, which was associated with a lower risk of death (HR, 0.60; 95% CI, 0.35–1.02; P = 0.057; Supplementary Figure 3, https://links.lww.com/CM9/B938). In patients with MDS-EB or sAML, the DEC/IDA study and historical control cohort achieved a 3-year OS of 70.9% (95% CI, 62.2%–80.8%) and 53.6% (95% CI, 42.0%–68.4%), respectively (P = 0.054) and a 3-year RFS of 67.0% (95% CI, 58.1%–77.2%) and 51.9% (95% CI, 40.35%–66.8%), respectively (P = 0.130) [Supplementary Figure 4, https://links.lww.com/CM9/B938]. The subgroup survival analysis in patients with MDS-EB or sAML was performed for patients in the DEC/IDA study and the historical control cohort. The results indicated that compared to the historical control, the DEC/IDA group had a lower risk of death in alternative donor transplants (HR, 0.43; 95% CI, 0.20–0.91; P = 0.028; Supplementary Figure 5, https://links.lww.com/CM9/B938). Donor type, the percentage of blasts in the bone marrow before transplant, as well as the conditioning regimen were included as covariates in the multivariate analysis. The analysis showed that DEC/IDC was a favorable factor associated with better OS, compared to the historical control cohort in patients with MDS-EB or sAML (HR, 0.51; 95% CI, 0.29–0.92; P = 0.024; Supplementary Table 5, https://links.lww.com/CM9/B938). To enhance the credibility and generalizability of the study findings, the transition from single-arm trials to randomized controlled trials is crucial, as it allows for better control over biases, leading to more robust conclusions. In conclusion, the addition of DEC and IDA to the myeloablative conditioning regimen was feasible and effective, with acceptable toxicity. This study provides an optimized strategy to improve the outcomes of patients with MDS and MDS/MPN, especially in patients with MDS-EB or sAML. Funding This work was supported by grants from the Tianjin Health Science and Technology Project (No. TJWJ2022MS001), Clinical research project of Tianjin Society of Hematology and Regenerative Medicine (No. 2022 TSHRM08004), Key Project of Tianjin Natural Science Foundation (No. 20JCZDJC00410), CAMS Innovation Fund for Medical Sciences (No. 2021-I2M-1-073), Haihe Laboratory of Cell Ecosystem Innovation Fund (No. 22HHXBSS00034), and National Natural Science Foundation of China (Nos. 82070192, 8230012348 and 82170217). Conflicts of interest None.

Objective To investigate the risk factors of positive anti-HLA antibodies in myelodysplastic syndrome (MDS) patients and gain insights into the impact of anti-HLA antibodies in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for MDS patients. The goal is to identify high-risk patients with anti-HLA antibodies and implement timely interventions, providing a basis for personalized treatment and improving prognosis. Methods A total of 94 MDS patients who received anti-HLA antibody screening and allo-HSCT at our center from December 1, 2016 to September 1, 2023 were retrospectively collected. The general clinical data was compared between 50 patients with positive anti-HLA antibodies and 44 patients without, to identify factors influencing anti-HLA antibody positivity in MDS. Furthermore, based on pre-transplant clinical characteristics of patients and post-transplant survival, as well as the occurrence of related complications, the study analyzed the impact of anti-HLA antibodies on complications such as acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD), graft failure (GF)/poor graft function (PGF), transplant-associated thrombotic microangiopathy (TA-TMA) and long-term survival in MDS patients following HSCT. Results A total of 94 patients were included in this study, comprising 57 males and 37 females. The positive rate of anti-HLA antibody in patients with pregnancy history was higher than those without pregnancy history and male patients, and the difference was statistically significant (74.1% vs. 44.8%, P=0.022). Female sex was identified as an independent risk factor for positive anti-HLA antibodies (OR=3.741, 95%CI:1.254-11.166, P=0.018). There was a significant difference in mortality between the positive and negative anti-HLA antibody groups (46.0% vs 22.7%, P=0.018). Significant differences in mortality were observed among the three groups based on anti-HLA antibody status: continuous positive, positive to negative, and continuous negative(81.8% vs. 30.0% vs. 37.5%, P=0.043). CD34+ cell count < 4.0×106/kg was an independent risk factor for GF/PGF (OR=5.682, 95%CI: 1.258-25.667, P=0.024). Haploidentical transplantation (OR=2.239, 95%CI: 1.079-4.544, P=0.030) and IPSS-R prognosis stratified very low risk/low risk (OR=6.033, 95%CI: 1.704-21.359, P=0.005) were independent risk factors for aGVHD in MDS patients. Being stratified as high-risk according to IPSS-M classification (HR=2.745, 95%CI: 1.269-5.939, P=0.010) is an independent risk factor for overall survival (OS) in MDS transplant patients. The median OS of the positive group was 380 days, while the median OS of the negative group was not reached, with a statistically significant difference (P=0.017). The 1-year, 2-year and 3-year OS rates of anti-HLA antibody positive and negative groups were 51.7% vs. 77.2%, 47.7% vs. 70.7% and 40.9% vs. 70.7%, respectively. The median disease-free survival (DFS) of the positive group was 380 days, but the median DFS of the negative group was not reached, with a statistically significant difference (P=0.017). There were also statistically significant differences in OS(P=0.041) and DFS(P=0.033) between female and male patients in the positive group. Survival analysis showed significant differences in OS (P=0.022) and DFS (P=0.025) among the continuous positive, positive to negative, and continuous negative anti-HLA antibody groups. The risk of GVHD accumulation in anti-HLA positive group was higher than that in negative group, and there was a statistically significant difference (P=0.037). Conclusion Female patients with MDS demonstrate increased susceptibility to positive anti-HLA antibodies. In MDS patients undergoing transplantation, long-term survival rates were notably lower among female patients and those with persistent positive anti-HLA antibodies post-transplantation. The cumulative incidence of GVHD (both aGVHD and cGVHD) was significantly higher in the anti-HLA antibody-positive cohort. Additionally, MDS patients undergoing haploidentical transplantation or stratified based on IPSS-R prognosis face an elevated risk of aGVHD. Key words Myelodysplastic Syndrome; Allogeneic Hematopoietic Stem Cell Transplantation; Anti-HLA antibody; Graft-versus-host disease；Transplant-associated thrombotic microangiopathy

ObjectiveTo compare the efficacy and safety of venetoclax (VEN) in combination with chemotherapy (chemo) versus chemo alone in the treatment of acute myeloid leukemia (AML).MethodTo compare the efficacy and/or safety of VEN+chemo versus chemotherapy alone for AML, PubMed, Embase, Web of Science, and the Cochrane Library were used to searching up to June 2023. Comparisons included complete remission (CR), CR with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), overall response rate (ORR), and adverse events (AEs).ResultA total of 9 articles were included, including 3124 patients. The baseline characteristics between two patient groups were similar. The combined analysis showed that compared with the group receiving chemo alone, the VEN+chemo group exhibited higher rates of CR, CRi, MLFS and ORR. Additionally, the VEN+chemo group had longer event-free survival (EFS) and overall survival (OS) durations. The incidence rates of AEs and serious AEs (SAEs) were similar between the two groups, but the early 30-day mortality rate was lower in the VEN+chemo group than in the chemo alone group.ConclusionThe VEN+chemo therapy demonstrates significant efficacy and safety profile in AML patients. However, more prospective studies are needed in the future to provide more accurate and robust evidence for treatment selection in patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023439288, identifier CRD42023439288.

In adults with acute lymphoblastic leukemia (ALL), post-transplant relapse is a major risk factor for mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our study investigated the efficacy and safety of decitabine (dec) with ALL patients post-transplantation. We performed a retrospective cohort study to assess the efficacy of decitabine (dec) with post-transplant ALL at the First Affiliated Hospital of Zhengzhou University from February 2016 to September 2021. A total of 141 consecutive ALL patients were analyzed and divided into decitabine (dec, n = 65) and control (ctrl, n = 76) groups based on whether they were treated with decitabine after allo-HSCT. The 3-year cumulative incidence of relapse (CIR) rate in the dec group was lower than that in the ctrl group (19.6% vs. 36.1%, p = 0.031), with a hazard ratio of 0.491 (95% confidence interval [CI], 0.257–0.936). Additionally, subgroup analyses revealed that the 3-year CIR rate of T-ALL and Ph-negative B-ALL patients in the dec and ctrl groups was 11.7% vs. 35.9% and 19.5% vs. 42.2% ( p = 0.035, p = 0.068) respectively. In summary, ALL patients, especially those with T-ALL and Ph-negative B-ALL, may benefit from decitabine as maintenance therapy following allo-HSCT.

Myeloid sarcoma is a rare manifestation of acute myeloid leukemia (AML) and is associated with poor overall survival (OS). The optimal treatment remains unclear. The study retrospectively evaluated 118 patients with myeloid sarcoma who were treated at the First Affiliated Hospital of Zhengzhou University from January 2010 to July 2021. All cases were diagnosed by tissue biopsy. 41 patients underwent genetic mutation analysis. The most frequent genetic mutations were KIT (16.6%), followed by TET2 (14.6%), and NRAS (14.6%). The median survival time of 118 patients was 4 months (range, 1–51 months), while the median survival time of 11 patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) was 19 months (range, 8–51 months). 4 (36.4%) of the 11 patients experienced relapse within 1 year after transplantation. 1 patient died from a severe infection. Of the 6 surviving patients, 5 patients have received maintenance treatment with decitabine after transplantation, and all remained in a state of recurrence-free survival. Patients with myeloid sarcoma have a very unfavorable outcome. Allo-HSCT is an effective treatment option. Recurrence remains the main cause of transplant failure. Maintenance treatment with decitabine after transplantation can prolong the recurrence-free survival time, although these results must be verified in a study with expanded sample size.

目的 观察达雷妥尤单抗(Dara)治疗复发/难治性急性白血病(R/R-AL)的效果.方法 回顾性分析2019年1月至2021年6月在郑州大学第一附属医院接受Dara治疗的7例R/R-AL患者的临床资料.结果 治疗前,7例患者均存在CD38表达,中位表达量为91％(50％～100％).所有患者接受Dara治疗中位次数为4(1～6)次.5例(71.4％)患者采用Dara联合化疗,1例(14.3％)采用Dara联合全反式维甲酸,1例(14.3％)采用Dara单药治疗.治疗后1例(14.3％)患者获得完全缓解(CR),3例(42.9％)患者获得部分缓解(PR),总有效率为57.2％.其中1例难治急性髓系白血病(AML)患者经2个剂量Dara联合化疗后CR,现已无病生存11个月,1例复发急性淋巴细胞白血病患者经2个剂量Dara联合化疗后骨髓微小残留病下降90.2％,2例髓外浸润患者经Dara治疗后复查CT示淋巴结及软组织肿块明显缩小,评估为PR.结论 Dara可成功诱导难治AML完全缓解并维持较长的无病生存期,同时可能对髓外病变产生抗肿瘤作用.

Patients with severe chronic graft-versus-host disease (cGVHD) always experience debilitating tissue injury and have poorer quality of life and shorter survival time. The early stage of cGVHD is characterized by inflammation, which eventually leads to extensive tissue fibrosis in various organs, such as skin and lung, eventually inducing scleroderma-like changes and bronchiolitis obliterans syndrome. Here we review the functions of serum/glucocorticoid regulated kinase 1 (SGK1), a hub molecule in multiple signal transduction pathways and cell phosphorylation cascades, which has important roles in cell proliferation and ion channel regulation, and its relevance in cGVHD. SGK1 phosphorylates the ubiquitin ligase, NEDD4, and induces Th cells to differentiate into Th17 and Th2 phenotypes, hinders Treg development, and promotes inflammatory fibrosis. Phosphorylation of NEDD4 by SGK1 also leads to up-regulation of the transcription factor SMAD2/3, thereby amplifying the fibrosis-promoting effect of TGF-β. SGK1 also up-regulates the inflammatory transcription factor, nuclear factor-κB (NF-κB), which in turn stimulates the expression of multiple inflammatory mediators, including connective tissue growth factor. Overexpression of SGK1 has been observed in various fibrotic diseases, including pulmonary fibrosis, diabetic renal fibrosis, liver cirrhosis, hypertensive cardiac fibrosis, peritoneal fibrosis, and Crohn’s disease. In addition, SGK1 inhibitors can attenuate, or even reverse, the effect of fibrosis, and may be used to treat inflammatory conditions and/or fibrotic diseases, such as cGVHD, in the future.

Abstract Purpose: Blinatumomab has promising applications in treating relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However, there are few studies on using blinatumomab for treating R/R B-ALL patients in China. Therefore, we evaluated the efficacy and safety of blinatumomab among Chinese R/R B-ALL patients. Methods: In total, 39 R/R B-ALL patients who received blinatumomab between October 2021 and August 2022 were selected as the study subjects. The primary endpoints include overall response rate (ORR) and complete minimal residual disease (MRD) response. Secondary endpoints included overall survival (OS) and adverse events (AEs). Results: The ORR and OS for 19 patients with less than 5% bone marrow (BM) blasts were 63.2% and 11 months (7.3–14.7), respectively. The median OS for the 20 patients was unavailable, and 17 (or 85%) had a full MRD response. Twenty-seven patients (69.2%) reported having at least 1 AE. Hematologic toxicity and infections were the most common AEs. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed on nine patients who had been remission-free for a long time. In the first month, one patient (11.1%) developed thrombotic microangiopathy associated with HSCT (TA-TMA) following transplantation. Conclusion: In R/R B-ALL patients, blinatumomab is an effective option in China.

目的 观察单倍体造血干细胞移植(haplo-HSCT)治疗伴阵发性睡眠性血红蛋白尿(PNH)克隆的重型再生障碍性贫血(SAA)的临床效果.方法 回顾性分析2018年2月至2020年3月于郑州大学第一附属医院接受haplo-HSCT治疗的5例伴PNH克隆的SAA患者的临床资料.预处理方案为BU+FC+ATG.采用环孢素A联合霉酚酸酯、短程甲氨蝶呤预防移植物抗宿主病(GVHD).观察5例患者的移植相关并发症、造血重建、PNH克隆演变等指标.结果 5例伴PNH克隆的SAA患者均为男性,中位年龄21岁,初诊时PNH克隆大小中位数为57.33％,诊断至移植中位时间为4个月,期间给予环孢素A、成分输血、雄激素及细胞生长因子等治疗,移植前PNH克隆大小中位数为61.34％.输注的中位单核细胞数为7.72×108kg-1,中位CD34+细胞数为6.40×106 kg-1.5例患者移植后均快速获得造血重建,中性粒细胞及血小板中位植入时间分别为14、16d.造血重建后植活细胞嵌合鉴定证实均为完全植入.PNH克隆均在移植后1个月复查时转阴,未转化为临床型PNH.中位随访时间为15个月,1例患者于移植后48 d出现继发性植入功能不良,1例发生慢性GVHD,1例出现移植后淋巴细胞增殖性疾病,对症支持治疗后均好转,无移植相关死亡.结论 haplo-HSCT对于伴PNH克隆的SAA患者可能具有较好的疗效,且PNH克隆在移植后短期内转阴,但仍需要更多的临床研究加以验证.

Objective:To explore the clinical characteristics, treatment and prognosis of myeloid sarcoma(MS).Methods:From January 2010 to May 2019, clinical data were reviewed for 89 MS cases. Age, gender, site of onset, type, comorbid diseases, lymphatic characteristics and disease remission status were analyzed. And 1-year survival rates were explored for different treatments including whether or not chemotherapy, transplantation and using hypomethylated drugs(HMAs)for maintenance after transplantation.Results:Among them, 21 cases had the data of chromosome karyotypic analysis and next generation sequencing and 8 patients underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT). The 1-year overall survival rates(OS)of primary MS, MS with intramedullary disease and MS relapse after leukemic remission were 16.0%, 37.5% and 36.9% respectively( P=0.013). The 1-year OS of local treatment(surgical resection, intrathecal injection and local radiotherapy), chemotherapy plus local treatment and chemotherapy plus allo-HSCT was 0, 28.1% and 72.9% respectively( P=0.003). After two courses of treatment, the 1-year OS of patients with complete and incomplete remissions were 34.9% and 10.0% respectively( P=0.008). Half(4/8)MS patients relapsed within 1 year after transplantation and had a short survival.Three patients received decitabine after HSCT and all of them survived for a long time. Conclusions:Chemotherapy plus HSCT is efficacious for MS. Decitabine maintenance treatment after transplantation may prolong recurrence-free survival. However, a larger sample size is required for further clinical verifications.

Background Post-transplant relapse remains a principal leading cause of failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with adult acute lymphoblastic leukemia (ALL). The aim of this study was to investigate the efficacy and safety of low-dose decitabine on the prevention of adult ALL relapse after allo-HSCT. Methods In this prospective study, we enrolled 34 patients with ALL who underwent allo-HSCT from August 2016 to April 2020 and received low-dose decitabine maintenance treatment after transplantation. The primary objectives were cumulative incidence of relapse rate (CIR), overall survival (OS), and disease-free survival (DFS). The secondary objectives were graft-versus-host disease (GVHD) and safety. Results Among the enrolled 34 patients, 6 patients relapsed and 6 patients died. The 2-year CIR, OS, and DFS were 20.2, 77.5, and 73.6%, respectively. Subgroup analysis revealed the 2-year CIR, OS, and DFS rates of 12 patients with T-ALL/lymphoblastic lymphoma (LBL) were 8.3, 90, and 81.5%, respectively. None of the seven patients with T-ALL relapsed. During maintenance treatment, only one patient (2.9%) developed grade IV acute GVHD and four (11.8%) patients had severe chronic GVHD. Thirty-two patients (94.1%) developed only grade I to II myelosuppression, and two patients (5.8%) developed grade III to IV granulocytopenia. Conclusions Maintenance treatment with low-dose decitabine after allo-HSCT may be used as a therapeutic option to reduce relapse in patients with adult ALL, especially in patients with T-ALL. Our findings require confirmation in larger-scale controlled trials. Clinical Trial Registration Chinese Clinical Trials Registry, identifier ChiCTR1800014888.

目的 探讨人类白细胞抗原(HLA)供者特异性抗体(DSA)对异基因造血干细胞移植(allo-HSCT)的影响及脱敏处理方法.方法 收集2019年1月1日-2020年6月1日于郑州大学第一附属医院行allo-HSCT的5例DSA阳性患者临床资料,于移植前采取血浆置换、静注人免疫球蛋白、利妥昔单抗/硼替佐米等脱敏措施并动态监测DSA滴度水平.分析其植入和移植物抗宿主病(GVHD)的发生并评估脱敏方案的效果.结果 例1急性髓系白血病(AML)植入失败,例4重型再生障碍性贫血(SAA)植入不良.余3例均植入成功,但均发生不同程度的GVHD.例2 AML移植后复查HLA抗体持续阳性,且同时存在急性GVHD (aGVHD)和慢性GVHD(cGVHD),经多种抗排异药物联合治疗病情仍反复,于移植后9个月发生重度cGVHD,先后经激素冲击、巴利昔单抗、伊布替尼、西罗莫司、他克莫司等治疗仍无效.例3 SAA移植后复查HLA抗体持续转阴,在移植后2个月时发生皮肤Ⅳ度aGVHD,经输注间充质干细胞、激素联合巴利昔单抗治疗好转并随访至今.例5骨髓增生异常综合征(MDS)于移植后第18天出现肠道Ⅱ度aGVHD,输注间充质干细胞、激素联合巴利昔单抗、芦可替尼治疗效果不佳.结论 DSA阳性是导致植入失败/植入不良的重要因素,移植后抗体的持续存在可能增加GVHD发生率.脱敏处理应采取从多种不同机制联合的方式进行,单一脱敏处理的作用可能是短暂且有限的.

Objectives Ras-related dexamethasone-induced 1 (RASD1) is abnormally expressed in many solid cancers. However, its potential role in adults with B-cell acute lymphoblastic leukemia (B-ALL) is unclear. Therefore, we aim to clarify the abnormal expression of the tumor-associated biomarker, RASD1, as a potential target for diagnosis and prognosis in adult Philadelphia-negative B-ALL. Methods The expression of RASD1 was detected with RT-qPCR in 92 adults with de novo Ph-negative B-ALL and 40 healthy controls. The correlation between RASD1 transcript levels and relapse was assessed. Results RASD1 transcript levels in patients with Ph-negative B-ALL (median 81.76%, range 0.22%-1824.52%) were significantly higher than those in healthy controls (7.59%, 0.46%-38.66%; P<0.0001). Patients with low RASD1 transcript levels had a lower 5-year relapse-free survival (RFS, 47.5% [32.9%, 62.1%] vs. 63.1% [49.0%, 77.2%]; P = 0.012) and a higher 5-year cumulative incidence of relapse (CIR, 52.0% [37.4%, 66.6%] vs. 36.2% [22.2%, 50.2%]; P = 0.013) especially in patients receiving chemotherapy only. Multivariate analysis showed that a low RASD1 transcript level was an independent risk factor for RFS (HR = 2.938 [1.427, 6.047], P = 0.003) and CIR (HR = 3.367 [1.668, 6.796], P = 0.001) in patients with Ph-negative B-ALL. Conclusions RASD1 transcript levels were significantly higher in patients with Ph-negative B-ALL and a low RASD1 transcript level was independently correlated with increased relapse risk.

Acute myeloid leukaemia (AML) patients with biallelic mutations of CEBPA (bi CEBPA) have a 30-50% relapse rate. This study established the value of mutations based on next-generation sequencing (NGS) and multiparameter flow cytometric measurable residual disease (MFC-MRD) detection and compared the outcomes. From 2014 to 2018, 124 newly diagnosed bi CEBPA AML patients were treated. The median age was 37·5 (16-69) years. The 3-year cumulative incidence of relapse (CIR), relapse-free survival (RFS) and overall survival (OS) were 33·0%, 64·7% and 84·3%, respectively. Patients without additional mutations and with GATA2 mutations were defined as 'NGS low risk', which was the only favourable independent factor for CIR and RFS of pretreatment parameters. Patients with sustained positive MRD after two consolidation cycles and MRD negative losses at any time were defined as 'MRD high risk', which was the only poor independent factor for CIR, RFS and OS, including pretreatment and post-treatment parameters. In CR2 and non-remission patients who underwent allo-HSCT, superior OS was achieved. We conclude that NGS low risk was a favourable factor in the analysis of pretreatment parameters. MRD risk stratification was an independent prognostic factor in pretreatment and post-treatment parameters. Relapsed patients still have a favourable outcome followed by allo-HSCT.

Posaconazole (PCZ) is effective in preventing and salvage treatment invasive fungal infections in patients with hematologic disorders. However, PCZ displays highly variable individual pharmacokinetics affecting its efficacy and safety. To investigate the correlation between PCZ concentration and efficacy and safety, the following key influencing factors were explored. A total of 285 trough plasma concentrations (Cmin) of 81 Chinese patients receiving PCZ oral suspension for prophylaxis or treatment of invasive fungal infections were collected in this study. The relationships between Cmin values and clinical response and hepatotoxicity were investigated as well as the incidence of clinical response under different Cmin values of PCZ with a logistic regression model. The concentration of PCZ showed remarkable differences among patients with haematologic disorders. PCZ Cmin values of 0.76 and 1.0 µg/mL were both associated with an over 80% probability of successful response to prophylaxis and treatment of fungal infections, respectively. No association between Cmin values and hepatotoxicity was noted (P > 0.05). Gender, albumin, and co-administration of proton pump inhibitor (PPI) were identified as independent factors influencing PCZ Cmin by multiple linear regression analysis. Furthermore, patients’ C-reactive protein (CRP), albumin, and co-administration of PPI exhibited significant effects on the therapeutic window of patients receiving PCZ for prophylaxis. The plasma concentration is closely associated with therapeutic efficacy of PCZ. It is necessary to adjust the dosing regimens based on PCZ Cmin to obtain an optimal therapeutic response.

Objectives: Acute myeloid leukemia (AML) patients with biallelic mutations of CEBPA (bi CEBPA) have a 30-50% relapse rate after standard chemotherapy. This study established the value of multiparameter flow cytometric measurable residual disease (MFC-MRD) detection, mutations based on next-generation sequencing (NGS), and compares the outcomes of risk stratification treatment in adult bi CEBPA AML patients. Methods: From March 2014 to December 2018, 124 patients with newly diagnosed acute myeloid leukemia with bi CEBPA were treated with chemotherapy. Out of these, 93 patients were analyzed further by a sensitive NGS assay for mutations in 87 candidate genes. MRD was detected in all patients by MFC after each cycle of induction and consolidation chemotherapy and every 3 months later. Results: Among these patients, 73 patients were male (58.9%), and median age was 37.5 (16-69) years. The expression of CD34, CD117, CD7, HLA-DR, CD15, CD33 and CD13 in 124 patients were 120 (96.8%), 123 (99.2%), 112 (90.3%), 107 (86.3), 93 (75.0%), 115 (92.7%) and 107 (86.3%) respectively. The most common co-occurring mutations were found in the GATA2 (n=29/93, 31%), WT1 (n=20/93, 21.7%), NRAS (n = 13/93, 14.0%), CSF3R (n = 12/93, 12.9%), and TET2 (n = 9/93, 9.6%) genes. All patients (100%) achieved complete remission (CR) including 114 patients (91.9%) who achieved it with only 1 induction course. The median follow-up was 33.5 (4-69) months. The 3-year Cumulative incidence of relapse (CIR), disease-free survival (DFS) and overall survival (OS) were 32.8%, 64.7%, and 84.3%, respectively. Univariate analysis results shown that WT1 Wild-type was favorable factor of 3-year CIR (23.3% vs. 47.0%, P=0.022) and 3-year DFS (75.5% vs 53.0%; P=0.031), GATA2 Wild-type had good trend for lower CIR and longer DFS and CSF3R Wild-type had inferior trend for higher CIR and shorter DFS. Patients with sustained positive MRD status after 2 consolidation cycles and MRD negative status loses in any time defined as "MRD high risk" had higher CIR (3-year CIR, 100% vs 25.5%; P<0.001; 81.5% vs 6.4%; P<0.001, respectively) and worse DFS and OS (3-year DFS, 0% vs 71.5%; P<0.001; 16.8% vs 90.2%; P<0.001, respectively; 3-year OS, 39.0% vs 89.8%; P<0.001; 72.2% vs 96.5%; P=0.001, respectively ) than those with persistent negative MRD status that defined as "MRD low risk" (Figure). Multivariate analysis showed that MRD low risk was the only favorable factor of CIR, DFS and OS (CIR: HR=37.3, 95%CI: 8.6-161.3, P<0.001;. DFS: HR=24.6, 95%CI: 7.2-84.0, P<0.001; HR=28.2, 95%CI: 2.1-374.1, P=0.011; respectively). Thirty-two (91.4%) MRD high risk patients (P<0.001) relapsed at a median time of 8 months (range: 3-32 months) include 21 patients of MRD negative status loses in any time and 11 patients with positive MRD status after 2 consolidation cycles. In totally 35 relapsed patients, 3 patients give up, 19 (61.3%) patients achieved CR2 after induction again. 15 CR2 and 4 non-remission patients underwent allo-HSCT achieved superior 3-year OS (83.0% vs 5.1%; p= 0.034; 75.0% vs 0%; p=0.006; respectively) than chemotherapy. To assess the role of risk stratification treatment by transplant or non-transplant, the124 patients were divided into 2 groups by the unique risk factor: MRD high risk group (n=43, 34.7%) and MRD low risk group (n=81, 65.3%). In the MRD low risk group (median follow-up: 35 months; range: 4-65 months), there was no significant difference in probabilities of 3-year OS (92.3% vs. 96.9%, P=0.428) between the transplant and non-transplant cohorts. In the MRD high risk group (median follow-up: 30 months; range: 7-69 months), 3-year OS was significantly better in the transplant cohort than in the non-transplant cohort (84.0% vs. 44.3%, p=0.007).Conclusions: MRD high risk may better predict the outcome rather than mutations based on NGS in AML with bi CEBPA, and allo-HSCT may achieve superior survival in MRD high risk patients. Key words: Acute myeloid leukemia with biallelic CEBPA mutations; next-generation sequencing; multiparameter flow cytometric measurable residual disease; allogeneic stem cell transplantation; Chemotherapy Disclosures No relevant conflicts of interest to declare.

SummaryRefinement of risk stratification in Philadelphia chromosome (Ph)‐negative B‐cell acute lymphoblastic leukaemia (ALL) might aid the identification of patients who are likely to relapse. AbnormalS100 calcium binding proteinA16 (S100A16) has been implicated in various cancers, but its function remains unclear. We foundS100A16transcript levels were higher in 130 adults with newly‐diagnosed Ph‐negative B‐cellALLcompared with 33 healthy controls. In 115 of 130 patients who achieved first complete remission, those with highS100A16transcript levels displayed a lower 3‐year cumulative incidence of relapse (CIR; 34% [21, 47%] vs. 40% [48, 72%];P = 0·012) and higher 3‐year relapse‐free survival (RFS; 65% [53, 78%] vs. 35% [23, 46%];P = 0·012), especially when receiving chemotherapy only. In multivariate analysis a lowS100A16transcript level was independently‐associated with a higherCIR(Hazard ratio [HR] = 3·74 [1·01–13·82];P = 0·048) and inferiorRFS(HR = 5·78 [1·91, 17·84];P < 0·001). Function analysis indicated that knockdown ofS100A16promoted proliferation and anti‐apoptosis and reduced chemosensitivity.S100A16over‐expression revealed an opposite trend, especially in a xeno‐transplant mouse model. Western blotting analysis showed upregulation ofPI3K/AKTandERK1/2 inS100A16‐knockdown andS100A16‐overexpression B‐cellALLcell lines respectively. Inhibition assays suggested these two signalling pathways participated in theS100A16‐mediated proliferation and survival effects in B‐cellALLcell lines.Trial Registration:Registered in the Chinese Clinical Trial Registry [ChiCTR‐OCH‐10000940];http://www.chictr.org.cn.

Background One-half of persons with acute myeloid leukaemia (AML) have normal cytogenetics at diagnosis and a good prognosis. However, some relapse. Whether the clonal trajectory in these persons is like that of persons with unfavorable cytogenetics at diagnosis who relapse is unknown.

Background: Molecular analyses of risk cohorts in adults with B-cell acute lymphoblastic leukaemia (ALL) has lagged behind progress in children with B-cell ALL. Two widely recognized prognostic variables are mutations in BCRABL1 and in IKZF1 with mutation frequencies of about 25 and 50 percent in unselected adults.