Haploidentical hematopoietic stem cell transplantation may improve long-term survival for children with high-risk T-cell acute lymphoblastic leukemia in first complete remission

Background: The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with high-risk (HR) T-cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under evaluation. Moreover, relapse is the main factor affecting survival. This study aimed to explore the effect of allo-HSCT (especially haploidentical HSCT [haplo-HSCT]) on improving survival and reducing relapse for HR childhood T-ALL in CR1 and the prognostic factors of childhood T-ALL in...     

单倍体与同胞全相合造血干细胞移植治疗高危急性淋巴细胞白血病疗效观察

目的 分析异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,AlloHSCT)治疗高危急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)的疗效,并探讨临床预后因素.方法 对我院2007年7月至2013年8月进行Allo-HSCT治疗并随访2年以上的69例ALL患者进行临床分析.按移植方式分为单倍体组(n=42)和全相合组(n=27),对各组患者的临床特征及治疗转归进行回顾性分析,应用Kaplan-Meier法进行生存分析,COX回归模型进行多因素预后分析.结果 单倍体组2年总体生存率(overall survival,OS)及2年无白血病生存率(leukemia-free survival,LFS)分别是63.4％、59.4％,而全相合组分别是53.9％、53.7％,两组间差异均无统计学意义(P＞0.05);两组间2年累积非复发死亡率(cumulative non-relapse mortality,NRM)差异也无统计学意义(P＞0.05);但2年累积复发率(cumulative relapse rate,RR)单倍体组明显高于全相合组(39.5％ vs 19.5％,P=0.014).造血重建方面,单倍体组中性粒细胞植入时间明显晚于全相合移植组(P =0.002),两组血小板植入时间无明显差异(P =0.072).单倍体组Ⅰ～Ⅱ度急性移植物抗宿主病(graft-versus-host disease,GVHD)发生率明显高于全相合组(P =0.008),两组间Ⅲ～Ⅳ度急性GVHD及慢性GVHD发生率差异无统计学意义(P＞0.05).单倍体组半年内的感染率明显高于全相合组(P=0.02).COX多因素分析显示患者移植前的疾病状态(非CR1)为异基因移植患者的危险因素(P =0.001),其危险度为7.581;而发生局限性慢性GVHD和初诊距离移植时间较短者为预后保护因素(P=0.013和P=0.012),危险度分别为0.178和0.688.结论 在高危组ALL患者的治疗中,单倍体Allo-HSCT与全相合Allo-HSCT的整体疗效相当,因此,单倍体供者可以作为合适的造血干细胞来源.     

Generation of cytotoxic T lymphocytes specific for B-cell acute lymphoblastic leukemia family-shared peptides derived from immunoglobulin heavy chain framework region

Background Immunoglobulin heavy chain variable region （IgHV） is a well-characterized tumor antigen for B-cell malignancies. It can function as a target for T cell-mediated immune response. Clinical trials of IgHV protein vaccines against lymphoma have demonstrated induction of tumor-specific cytotoxic T lymphocyte （CTL） responses. However, complementary determining regions-based individual vaccines have disadvantages for wide clinical application. Although a recent study demonstrated that immunogenic peptides are derived from framework regions （FR） shared among patients with B-cell lymphoma, how to choose the appropriate peptides for each patient is still unsolved. The aim of this study was to investigate whether immunoglobulin heavy chain FR-derived peptides shared in each IgHV family are potential CTL epitopes presented by B-cell acute lymphoblastic leukemia （B-ALL）. Such CTL epitopes might be beneficial to shifting vaccination strategies against B-ALL from individual specificity to family specificity. Methods Seven IgHV gene families were amplified respectively by PCR and sequenced directly from 71 childhood B-ALL cases. Bioinformatics was applied in analyzing characteristics of sequences available and predicting HLA-A^＊0201-restricted CTL epitopes for each IgHV family. An antigen-specific T cell expansion system was used to generate peptide-specific CTLs. The cytotoxicity of CTLs against B-ALL cells was assessed in the lactate dehydrogenase release assay. Results Complete IgHV rearrangements were identified in all of the 71 B-ALL cases. All of 40 sequences available showed ≥98% homology with the nearest germline IgHV genes, indicating IgHV genes in B-ALL of germline nature. Twelve nonapeptides of high HLA-A^＊0201-binding scores were obtained from 26 productive IgHV protein sequences. Ten （83%） of the peptides were located in FR1 and FR3 shared among the corresponding IgHV family. CTLs specific for the peptide QLVQSGAEV located in FR1 （3-11） shared among the IgHV1 family could be successfully generated from peripheral blood mononuclear cells of two HLA-A^＊0201＋ healthy donors in vitro and were capable of killing HLA-matched B-ALL cell clones belonging to the IgHV1 family. Conclusion Anti-B-ALL CTLs against immunoglobulin heavy chain FR-derived peptides have family-specific cytotoxicity.     

清髓性异基因造血干细胞移植治疗成人急性淋巴细胞白血病非血缘脐血与血缘相关移植的比较——单中心临床研究

目的 评估并比较异基因造血干细胞移植清髓方案治疗成人急性淋巴细胞白血病(ALL)的疗效及安全性.方法 异基因造血干细胞移植治疗37例成人急性淋巴细胞白血病患者:其中17例行非血缘脐血移植(UCBT)患者中位年龄25(14～37)岁、中位体质量55(31～84)kg、男性占82%,UCBT组中高危难治患者共15例(88%...     

实时荧光定量PCR法检测外周血中BCR/ABL基因表达在Ph+急性淋巴细胞白血病患者造血干细胞移植治疗中的应用

目的:采用实时荧光定量PCR(RT-qPCR)法定期检测费城染色体阳性急性淋巴细胞白血病(Ph+ALL)患者外周血中BCR/ABL融合基因表达的动态变化,为患者制订不同的治疗方案,以提高患者总生存(OS)率.方法:回顾性分析20例初治和难治复发Ph+ALL患者的临床资料,经过酪氨酸激酶抑制剂(TKI)+长春新碱+强的松...