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.

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.

OBJECTIVE:To investigate the expression and clinical significance of serum protein ROCK2 in patients with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).METHODS:The patients were divided into cGVHD group and control group (without cGVHD). The expression levels of serum protein ROCK2 were detected by ELISA in patients with or without cGVHD after allo-HSCT.RESULTS:The expression level of ROCK2 in serum of cGVHD patients was significantly higher than those in control group, moreover, the expression level of ROCK2 in severe cGVHD group was significant higher than that in moderate and mild cGVHD group (P<0.001). The expression level of ROCK2 was significantly decreased in the serum of cGVHD patients after treatment（P＜0.01）; the expression level of ROCK2 was significantly higher in the serum of cGVHD patients with lung as the target organ（P＜0.01）. The median survival time of patients with severe cGVHD were significantly shorter than that of patients with mild and moderate cGVHD（P＜0.05）.CONCLUSION:ROCK2 shows certain reference value in the evaluation of severity and prognosis of cGVHD, and may be a new target for the treatment of cGVHD.

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.

To investigate the U2AF1 gene mutation site, mutation load and co-mutations genes in patients with myelodysplastic syndrome (MDS) and their effects on prognosis. Gene mutation detection by next-generation sequence and related clinical data of 234 MDS patients were retrospectively collected and analyzed for the relationship between the clinical characteristics, treatment efficacy and prognosis of U2AF1 gene mutation. Among the 234 MDS patients, the U2AF1 gene mutation rate was 21.7% (51 cases), and the median variant allele frequency was 39.5%. Compared with the wild type, the U2AF1 mutant had a higher incidence of chromosome 8 aberration, and was positively correlated with the occurrence of ASXL1 , RUNX1 , SETBP1 gene mutation, negatively correlated with SF3B1, NPM1 genes mutation ( p < 0.05). The most common mutation site of U2AF1 was S34F (32 cases), while U2AF1 Q157P site mutations had a higher incidence of chromosome 7 abnormalities ( p = 0.003). The U2AF1 gene mutation more frequently coincided with signal pathway related gene mutations ( p = 0.043) with a trend of shortened overall survival. Among patients with U2AF1 gene mutations, those with ASXL1 mutations were prone to develop into acute myeloid leukemia, those with RUNX1 mutations had an increased risk of relapse, and those with TET2 mutations had higher 1-year survival rate. Compared with the patient group of lower mutation load (VAF ≤ 40%), the group with higher mutation load of U2AF1 (VAF > 40%) had a significantly lower 1-year survival rate (46.1% and 80.5%, p = 0.027). The criteria of U2AF1 VAF > 40% is an independent indicator for poor prognosis of MDS patients. VAF > 40% of U2AF1 is an independent factor of short OS in MDS patients. MDS patients with a mutation in the Q157P site of U2AF1 and a higher U2AF1 mutation load suggests poor prognosis, and co-mutated genes in U2AF1 can affect disease progression and prognosis.

Objective:To investigate the effect of decitabine maintenance treatment after transplantation of myelodysplastic syndrome(MDS).Methods:Seven patients with MDS after allogeneic hematopoietic stem cell transplantation in the First Affiliated Hospital of Zhengzhou University from April 2016 to October 2019 and received low-dose decitabine maintenance transplantation were included, 5 males and 2 females, aged 15 to 43 years. Seven patients were treated with decitabine or a combination of low-dose cytarabine, aclamycin, and granulocyte colony-stimulating factor regimens before transplantation, and they all achieved complete remission before transplantation, and decicabine was maintained for 56 (31~78) days after tranplantation. The treatment results were analyzed retrospectively.Results:None of the patients recurred after transplantation, 1 case died of acute intestinal graft-versus-host disease, six cases were followed-up to date, and 2 case of chronic mild liver graft-versus-host disease, with a median follow-up of 12 months (3~30 months) after transplantation.Conclusions:Low dose of decitabine could improve post-transplant survival in high-risk MDS patients, but further research is needed to confirm.

Objective To investigate the efficacy and safety of maintenance treatment with low-dose decitabine after allogeneic stem cell transplantation (allo-HSCT) for high-risk acute lymphoblastic leukemia (ALL). Methods The data of 10 patients with high-risk ALL who received maintenance therapy with low-dose decitabine after allo-HSCT in the First Affiliated Hospital of Zhengzhou University from July 2016 to March 2018 was collected. The incidence of post-transplant relapse and graft-versus-host disease (GVHD) and the safety of the treatment protocol were analyzed. The cumulative incidence of relapse (CIR) rate, disease-free survival (DFS) rate and overall survival (OS) rate were estimated by Kaplan-Meier method. Results Two patients relapsed and the median relapse time of these 10 patients was 575 days after transplantation. The 1-year CIR, OS and DSF rates were 16.7%, 100.0% and 83.3%, respectively. At the end of follow-up, the DFS time after transplantation of 2 patients with p53 mutation were 23 months and 11 months, respectively. There was no induction or alleviation of GVHD caused by decitabine treatment. Nine patients developed grade Ⅰ-Ⅱmyelosuppression. Three patients had unexplained thrombocytopenia after transplantation and their platelet counts recovered after decitabine treatment. Conclusion Maintenance therapy with low-dose decitabine has low hematologic toxicity without increasing GVHD, which could be a maintenance treatment option to prevent relapse after transplantation for patients with high-risk ALL.

Objective To observe the efficacy of maintenance treatment with decitabine and dasatinib after allogenic hematopoietic stem cell transplantation for myeloid sarcoma.Methods A 29-year-old male patient was diagnosed with abdominal myeloid sarcoma and acute myeloid leukemia with c-kit mutation and t(8;21).Allogeneic hematopoietic stem cell transplantation was performed after inducted remission.The conditioning regimen was decitabine + FLAG + modified Bu/Cy.Prophylaxis of GVHD was performed with cyclosporine mycophenolate mofetil and short-term methotrexate.The patient received 11.73 × 108 mononucleated cells/kg and 17.59 × 106CD34+ cells/kg from donor.At Day 13 post-transplantation,neutrophils reached 0.5 × 109/L and platelet count was 20 × 109/L.Decitabine was prescribed since Day 50 post-transplantation monthly for 5 courses.And dasatinib was offered orally since Day 100 for 4 months.Results It was followed up to 16 months post-transplantation.There were no obvious abnormalities of bone marrow cytology,AML/ETO fusion gene quantification,cerebrospinal fluid or abdominal enhanced computed tomography (CT).Conclusions Hematopoietic stem cell transplantation is an effective treatment for myeloid sarcoma.Decitabine has some efficacy for myeloid sarcoma and it may be used for maintenance treatment after transplantation.Tyrosine kinase inhibitors reduce recurrence in myeloid sarcoma with c-kit mutation.The treatment of decitabine and dasatinib after allogeneic hematopoietic stem cell transplantation yield excellent outcomes.This is the first report in domestic and foreign literatures.