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.

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.

OBJECTIVE: The prognostic indictors of age-related poor outcomes in patients with acute myeloid leukemia (AML) are still controversial. The aim of this work was to provide comprehensive insights into the effect of different hemocytes and to investigate the association between age and clinical features in adult patients with AML. STUDY DESIGN: A retrospective study was performed to determine the role of age in the therapeutic outcomes of AML. A total of 166 newly diagnosed adult patients' data from January 2015 to November 2019 in Zhongshan Hospital of Xiamen University were collected and analyzed. RESULTS: Older patients presented a poorer prognosis (p=0.001) with shorter overall survival, which is served as age-related outcomes. Binary logistic regression demonstrated that cytogenetic risk (OR=4.508, 95% CI 2.733-7.435), leukocyte (OR=7.410, 95% CI 1.139-5.910), and bone marrow blast cells (OR=3.261, 95% CI 1.075-5.615) were independent indictors for age-related prognosis. In addition, Kaplan-Meier curve also revealed that the above factors were associated with overall survival (all p values < 0.001). CONCLUSION: Cytogenetic risk, leukocyte, and bone marrow blast cells are dominant factors which account for the age-related poor outcomes and shorter overall survival in AML.

目的:探讨骨髓增生异常综合征（MDS）伴Sweet综合征的临床特点及治疗方案选择。方法:回顾性分析厦门大学附属中山医院2019年12月收治的1例MDS伴Sweet综合征患者的临床资料，并进行文献复习。结果:该患者实验室及病理活组织检查提示MDS伴Sweet综合征诊断明确，使用激素类药物治疗后肺部浸润病灶吸收不明显，疗效不佳。采用激素和地西他滨治疗后，皮肤损害明显改善，肺部浸润吸收明显。结论:去甲基化治疗对于MDS和Sweet综合征均具有疗效。

目的 探讨泊沙康唑预防性抗真菌治疗在重型地中海贫血儿童干细胞移植中的疗效和安全性.方法 分析2017年2月-2019年7月在厦门大学附属中山医院完成的38例重型地中海贫血患儿异基因干细胞移植的临床资料.移植过程中中性粒细胞＜0.5×109/L的第1天开始同步口服泊沙康唑每次4 mg/kg,3次/d,持续服用至中性粒细胞恢复正常,或发生侵袭性真菌病(IFD),或发生无法耐受的不良反应.记录并统计泊沙康治疗期间IFD发生率,临床不良反应发生率,测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBIL)、直接胆红素(DBIL)、肌酐,以及环孢素A的血药浓度水平.结果 38例患者中临床诊断IFD 1例,拟诊IFD 1例,真菌感染发生率为5.3％.未发生3级以上胃肠道反应(恶心、呕吐、腹泻)、皮疹、肌酐升高.3级肝功能损害事件发生率为7.9％(3/38),停药率5.3％(2/38),不同Pesaro分级之间肝功能损害事件发生率差异无统计学意义.结论 泊沙康唑预防性抗真菌治疗在该组接受造血干细胞移植的重型地中海贫血患儿中的应用有效而安全.

Objective To observe the efficacy and safety of intensive cladribine-based conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT ) in children with major thalassemia .Methods Retrospective analysis was performed for the clinical data of 12 children with major thalassemia undergoing allo-HSCT from March 2017 to July 2018 .All of them were diagnosed definitely and the median age at transplantation was 5 years (range:2-13 years ) , including HSCT from HLA-matched unrelated donor (n= 8 ) , HLA8/10-matched unrelated donor (n=1) ,HLA-matched sibing donor (n=2) and haploidentical donor (n=1) .They received a new intensive conditioning regimen of cyclophosphamide (CTX ) , cladribine , busulfan (Bu ) and antithymocytic globulin .The median doses of mononuclear cell (MNC) and CD34 positive cell were 10 .97 × 108/kg (range:5 .72-12 .49 × 108/kg) and 12 .2 × 106/kg (range:6 .7-22 × 106/kg) .Graft-versus-host disease (GVHD) was prevented by cyclosporine A (CSA) ,methotrexate (MTX) and mycophenolate mofetil (MMF) .Results Engraftment succeeded (n= 11) and failed (n= 1) .The median time of neutrophil and platelet engraftment was 11 days (range:8-17 days) and 13 days (range:8-37 days) respectively .There were grade II acute GVHD (n= 6) and grade IV intestinal acute GVHD (n=1) at 35 days post-transplantation .The latter one finally died of severe infection at 70 days post-transplantation .Two recipients of DLI developed limited chronic GVHD .Three cases ( 25％ ) developed cytomegaloviremia . None suffered from severe transplantation-related complications , such as cytomegalovirus diseases , hepatic veno-occlusive disease ( HVOD ) , hemorrhagic cystitis or septicemia ,etc .The median follow-up time was 15(8-18) months .Among 11 survivors ,ten became transfusion-independent .Conclusions Cladribine-based conditioning regimen is both safe and effective for allo-HSCT in children with major thalassemia . However , vigorous immunosuppression may increase the risks of infection and viral activation after transplantation .

This study was aimed to investigate the expression and clinical significance of forkhead box protein O3a (FoxO3a) in the patients with acute myeloid leukemia (AML). Western blot was used to detect the FoxO3a protein expression in bone marrow samples from 44 newly diagnosed AML patients and 5 healthy donors. Additionally, 14 patients' samples were reevaluated when they got complete remission (CR). The results showed that FoxO3a expression (FoxO3a/β-actin 0.43 ± 0.19) in newly diagnosed AML patients was much higher than that in healthy donors (FoxO3a/β-actin 0.19 ± 0.06) (P < 0.001). The FoxO3a level was down-regulated when CR was got and there was not significant difference between patients in CR and healthy donors (P > 0.10). The correlation analysis showed that the level of FoxO3a expression positively correlated with the white blood cell count of AML patients at the time of diagnosis. Although FoxO3a expression did not positively correlate with the CR rate, the higher FoxO3a expression in AML patients showed a shorter remission duration. It is concluded that FoxO3a may be a oncoprotein in AML, and the high FoxO3a expression is associated with poor prognosis.

1 病历简介 患者男性,33岁,因肾衰竭1年,咳嗽10 d,伴发热、气促1 d入院.发病前有疑似甲型H1N1流感(甲流)患者接触史.患者1年前诊断为恶性高血压、慢性肾衰竭(尿毒症期)、乙型肝炎(乙肝)病毒携带者,行维持性血液透析治疗.