免疫毒素去除T细胞在异基因造血干细胞移植中的应用

观察应用免疫毒素部分去除T细胞(TCD)的方法进行人类白细胞抗原／混合淋巴细胞培养(HLA/MLC)不相合异基因造血干细胞移植的临床疗效。采用蓖麻免疫毒素部分去T细胞对13例恶性血液病患者行HLA-MLC配型不相合的造血干细胞移植，其中慢性髓性白血病(CP1)6例；急性淋巴细胞白血病CR1 1例，CR2 1例，复发1例；急性髓性白血病CR1 2例，CR2 1例；骨髓增生异常综合征转化成急性髓性白血病M4型(CR1)1例。结果表明：13例患者中8例成功植入，其中2例发生Ⅱ度急性移植物抗宿主病(aGVHD)，2例发生Ⅲ-Ⅳ度aGVHD。随访8-90个月，2例发生Ⅲ-Ⅳ度aGvHD患者早期死亡，另有1例患者死于迟发感染，其余5例均无病存活至今。5例未植活的患者中4例回输同一供者外周血造血干细胞后3例未植入，1例植活，但死于移植相关合并症；1例再次行同基因造血干细胞移植成功并无病存活至今。结论：采用蓖麻免疫毒素部分去T细胞的方法行HLA/MLC配型不相合的异基因造血干细胞移植可减少重度aGVHD的发生，但移植早期排斥率(HVG)较高，临床应用效果有待进一步评估。     

ATG用于异体造血干细胞移植前预防移植物抗宿主反应

目的分析异体造血干细胞移植前加用抗T淋巴细胞球蛋白(ATG)预防移植物抗宿主反应(GVHD)的疗效。方法27例白血病患者分为两组,每组移植供体来源及病种类似,分别有同胞兄妹、无关供体和人类白细胞抗原(HLA)半相合供体。A组(n=12):采用经典的CsA MTX预防GVHD;B组(n=15):采用CsA MTX ATG预防GVHD。结果B组15例患者全部存活,除4例出现Ⅱ°急性GVHD(aGVHD)外,其余11例均在移植后30 d左右仅出现Ⅰ°GVHD,并很快控制。A组12例患者中,3例HLA半相合移植患者分别在移植后第7、9和10天即出现Ⅳ°超急性GVHD,另有1例无关供体患者出现Ⅲ°aGVHD,该4例患者由于重度GVHD继发肺部感染而死亡;其余8例同胞之间的移植分别出现Ⅱ°~Ⅲ°aGVHD。结论在异体造血干细胞移植前应用ATG可以有效预防GVHD的发生或减轻GVHD的严重度,明显减少移植相关死亡率。     

儿童异基因造血干细胞移植后急性肾损伤临床分析

目的分析儿童异基因造血干细胞移植(allo-HSCT)后急性肾损伤(AKI)的临床特征及危险因素。方法回顾性分析2016年8月至2020年3月于武汉儿童医院血液肿瘤科接受allo-HSCT患儿的临床资料,对比移植预处理开始前及移植后100天血肌酐(Cr)、肌酐清除率(Ccr),以及移植后1年的生存情况;采用logistic回归分析影响AKI发生的危险因素。结果共147例allo-HSCT患儿纳入研究,其中男85例、女62例,接受移植时中位年龄5.5岁(0.7个月～16岁)。其中101例(68.7%)患儿发生AKI,中位时间为移植后24.0(-5.0～91.0)d。二元logistic回归分析显示,移植后急性移植物抗宿主病(aGVHD)、肝窦间隙阻塞综合征(SOS)是AKI发生的独立危险因素(P<0.05)。按pRIFLE诊断标准将发生AKI的101例患儿分为风险期组54例、肾损伤期组31例以及肾衰竭期组16例。不同分期之间患儿Cr以及Ccr差异均有统计学意义(P<0.05),肾衰竭期组Cr较高,Ccr较低。allo-HSCT后随访1年,18例患儿死亡,其中AKI患儿死亡16...     

Primary vaccination in adult patients after allogeneic hematopoietic stem cell transplantation – A single center retrospective efficacy analysis

Allogeneic hematopoietic stem cell transplantation (alloHSCT) results in a loss of humoral immunity and subsequent risk for severe infections. Thus, re-vaccination is required but may fail due to incomplete immune reconstitution. We retrospectively analyzed predictors of immune response to primary vaccination applied according to the EBMT (European Blood and Marrow Transplantation Group) recommendations. Serologic response to vaccination against diphtheria (D), tetanus (T), Bordetella pertussis (aP) and Haemophilus influenzae (Hib) (administrated as combined DTaP-Hib-IPV vaccination) was studied in 84 alloHSCT patients transplanted between 2008 and 2015 (age at alloHSCT: 18.6–70.6 years). All patients with a relapse-free survival of ≥9 months, at least 3 consecutive vaccinations and absence of intravenous immunoglobulin administration within 3 months before and after vaccination met the primary inclusion criteria. Additionally, immunological response to a pneumococcal conjugate vaccine was analyzed in a subgroup of 67 patients. Patients’ characteristics at the time of first vaccination were recorded. Responses were measured as vaccine-specific antibody titers. Regarding DTaP-Hib-IPV vaccination, 89.3% (n = 75) of all patients achieved protective titers to at least 3 of the 4 vaccine components and were thus considered responders. 10.7% (n = 9) of the patients were classified as non-responders with positive immune response to less than 3 components. Highest response was observed for Hib (97.4%), tetanus (95.2%) and pneumococcal vaccination (83.6%) while only 68.3% responded to vaccination against Bordetella pertussis. Significant risk factors for failure of vaccination response included low B cell counts (p < 0.001; cut-off: 0.05 B cells/nl) and low IgG levels (p = 0.026; mean IgG of responders 816 mg/dl vs. 475 mg/dl of non-responders). Further, a trend was observed that prior cGvHD impairs vaccination response as 88.9% of the non-responders but only 54.7% of the responders had prior cGvHD (p = 0.073). The results demonstrate, that the currently proposed vaccination strategy leads to seroprotection in the majority of alloHSCT patients.     

The clinical and economic burden of cytomegalovirus management post allogeneic hematopoietic stem cell transplantation in Japan – a retrospective database study

Abstract

Introduction: Reactivation of cytomegalovirus (CMV) infection is a major threat and it causes significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). There remains, however, a paucity of evidence regarding the economic burden of current CMV management in Japan. The aim of this study is to characterize the healthcare resource utilization (HCRU) and cost incurred for CMV management post allo-HSCT, using a Japanese hospital claims database.

Methods: Patients who underwent allo-HSCT between April 2010 and March 2018 were identified and followed up for 180?days.

Results: In total, 916 patients were included for analysis and categorized into CMV (?) group and CMV (+) group based on the presence of a CMV episode within 100?days post allo-HSCT. A CMV episode was defined as evidence of receiving at least one dose of the following anti-CMV drugs, ganciclovir, foscarnet, or valganciclovir. The mean (± standard deviation [SD]) total length of stay was 93.6 (± 43.7) days in the CMV (+) group, which was significantly longer than 55.9 (±40.6) days in the CMV (?) group, and this trend was more pronounced in patients with multiple CMV episodes. The mean (±SD) total medical cost within 180?days post allo-HSCT was US$122,328 (±56,977) in the CMV (+) group, while the mean total medical cost was US$75,344 (±43,821) in the CMV (?) group. Moreover, transfusion and antimicrobial use was observed as the major medication cost component, which is suggestive of the indirect effect of CMV episodes.

Conclusion: This study demonstrated that CMV episodes post allo-HSCT were associated with increased HCRU and cost.     

The Role of Vitamin D in Hematologic Disease and Stem Cell Transplantation

Vitamin D is a steroid hormone with a broad range of biological effects ranging from the classical role as a mediator of calcium and phosphate balance to cellular differentiation and immune modulation. These effects impact normal and dysfunctional hematopoietic and immune function, which may allow an avenue for improved treatment and support of patients suffering from hematologic disorders. In this review, we will summarize the role of vitamin D in normal hematopoiesis, discuss ways in which vitamin D may improve outcomes, and discuss a potential role of vitamin D for treating hematologic disorders and modulating the immune system to improve the outcome of allogeneic stem cell transplant.     

Syngeneic B16-F1 cells are more efficient than allogeneic Cloudman cells as antigen source in DC-based vaccination in the B16-F1 murine melanoma model

A major obstacle to obtaining relevant results in cancer vaccination has been the lack of identification of immunogenic antigens. Dendritic cell (DC)-based cancer vaccines used preventively may afford protection against tumor inoculation, but the effect of antigen choice on anti-tumor protection is not clear. When using irradiated syngeneic tumor cells to load DCs, tumor self-antigens are provided, including tumor-associated antigens (TAAs) and neoantigens generated by tumor mutations. On the other hand, allogeneic tumor cells could only supply shared TAAs. To assess the advantages of each source in protective vaccination, we analyzed in C57BL/6 mice the effect of loading DCs with irradiated syngeneic B16-F1 or allogeneic Cloudman melanoma cells; both cell lines were characterized by whole exome sequencing and RNAseq. Tumor cell components from the two irradiated cell lines were efficiently internalized by DCs, and transported to MHC-class II positive tubulovesicular compartments (MIICs). DCs loaded with allogeneic irradiated Cloudman cells (DC-ApoNec_ALLO) induced a partially effective anti-melanoma protection, although Cloudman and B16-F1 cells share the expression of melanocyte differentiation antigens (MDAs), cancer-testis antigens (CTAs) and other TAAs. DCs loaded with syngeneic B16-F1 cells (DC-ApoNec_SYN) established a more potent and long-lasting protection and induced a humoral anti-B16F1 response, thus suggesting that neoepitopes are needed for inducing long-lasting protection.     

造血干细胞移植治疗白血病和淋巴瘤

目的：探讨造血干细胞移植治疗白血病和淋巴瘤的疗效、移植过程中的并发症及其预防和移植后的植活证据及微小残余病灶检测等问题。方法：２例行同胞间异基因骨髓移植（Ａｌｌｏ－ＢＭＴ）、５例行自体外周血干细胞移植（ＡＰＢＳＣＴ）。采用ＣｓＡ＋ＭＴＸ预防ＧＶＨＤ;ＰＧＥ１＋潘生丁预防ＨＶＯＤ;以ＡＰＯＢ、ＳＭ７和Ｄ１Ｓ８０三个位点多态性分析作为植活证据;以ｂｃｒ／ａｂｌ、ＡＭＬ１－ＥＴＯ融合基因或ＩｇＨ基因重排