异基因造血干细胞移植治疗儿童血液病的临床研究

目的评估异基因造血干细胞移植治疗儿童血液病的疗效及合并症.方法脐血移植(UCBT)治疗9例重症β地中海贫血(β-thal)、1例慢性特发性溶血性贫血(CIHA)、3例急性髓性白血病(AML-M3b、M2a、M5)及1例急性淋巴细胞白血病(ALL)合并中枢神经系统白血病;异基因外周血干细胞移植(allo-PBSCT)治疗5例β-thal及1例慢性粒细胞性白血病慢性期(CML-CP)患儿.同胞UCBT8例中5例HLA相合(6/6),5/6为1例,3/6为2例.6例非血缘相关脐血移植(UD-UCBT)中4例为6/6,1例5/6,双份脐血混合者为5/6和6/6.allo-PBSCT中5例均为血缘相关,HLA相合同胞及1例5/6父亲供者.输入脐血(UCB)有核细胞数(NC)为7.5(3.4～19.4)×107/kg,外周血NC为9.39(2.5～14.4)×108/kg.结果血缘相关脐血移植(RD-UCBT)8例中植入6例,其中排斥1例,死于肝静脉闭塞病(HVOD)1例,恢复地中海贫血状态2例;UD-UCBT中2例β-thal及2例AML均植入,1例AML-M5复发,AML-M3b自体恢复造血并完全缓解,1例AML-M2a死于巨细胞病毒间质性肺炎,1例ALL未植入,死于败血症.急性移植物抗宿主病(aGVHD)8例(80%),III度以上2例,广泛慢性移植物抗宿主病(cGVHD2)例.β-thal总生存率为90%,无病存活率(EFS)为60%,平均生存时间为21个月(2～42个月).allo-PBSCT病例全部植入,cGVHD5例,III°以上者2例,广泛cGVHD3例,死于HVOD1例.EFS5例,中位生存时间10个月(3～26个月).结论UCBT及allo-PBSCT是治疗儿童血液病的有效方法,UD-UCBT首次成功治疗β-thal.     

异基因造血干细胞移植治疗儿童急性髓系白血病临床研究

目的评估应用异基因造血干细胞移植(allo-HSCT)治疗儿童急性髓系白血病(AML)的临床疗效及相关影响因素。方法回顾分析2002年1月至2017年11月49例确诊中、高危及复发AML行allo-HSCT患儿的临床资料,分析危险度分级、HLA分型、移植前状态、移植方式、干细胞来源及急慢性移植物抗宿主病(GVHD)等对allo-HSCT治疗效果的影响。结果 49例患儿中男35例、女14例,中位年龄9岁。三年总体存活率(OS)为(59.2±7.3)%,无白血病存活率(LFS)为(50.9±7.4)%。其中第1次缓解状态移植、非血缘移植、外周血干细胞移植、中危组移植的三年LFS分别为69.8%、69. 2%、73. 7%、65. 8%。19例死亡,分别为复发13例、严重感染5例、多器官衰竭1例。COX回归模型结果显示,急性GVHD是影响移植OS的独立危险因素(RR=3. 16,95%CI:1. 23～8. 09,P=0. 017),移植前状态为部分缓解及未缓解是影响移植LFS的独立危险因素(RR=4.76,95%CI:1.52～14.94,P=0.008;RR=5.28,95%CI:1.68～16.58,P=0.004)。结论移植前状态及急性GVHD是影响Allo-HSCT治疗儿童AML疗效的关键因素;白血病复发及感染是导致死亡的主要原因。     

脐血移植治疗难治性儿童白血病

目的：研究和ＨＬＡ不合多个脐血移植治疗难治性儿童白血病。方法：选择难治性白血病患儿，给予强烈化学治疗杀灭残存白血病细胞，再用多个脐血混合移植解救严重抑制状态的骨髓，从而缓解白血病，延长生命。结果：治疗６例，年龄２．５－１６岁，均为男性。用ＶＡＣ或ＡＶ方案化疗后，约１１天外周血颗粒细胞降至零。输注脐血后平均１３天外周血白细胞升至１．０×１０＾９／Ｌ以上。６０天内骨髓象正常，全部患者达到完成缓解。随诊     

造血干细胞移植治疗儿童白血病若干问题

该文涉及各类儿童造血干细胞移植(HSCT),如骨髓移植(BMT)、外周血造血干细胞移植(PBSCT)和脐血移植(UCBT)治疗白血病的优缺点及HSCT在儿童白血病治疗中的地位。绝大多数儿童白血病可通过正规联合化疗根治,仅少数(约20%)高危、难治及复发的白血病是异基因HSCT的适应证,无适合的同胞供体时,可选择HLA全相合非血缘相关BMT或PBSCT,UD-UCBT更适合于儿童患者。     

脐血造血干细胞移植治疗儿童血液病14例临床观察

脐血造血干细胞移植可以根治儿童白血病、再生障碍性贫血、血红蛋白病及先天性免疫缺陷等疾病。自1988年Gluckman等首先应用脐血移植（CBT）成功治疗1例儿童Fanconi贫血以来,CBT发展迅速。由于脐血来源广、采集方便、对供者无害、移植物抗宿主病（GVHD）发生率低而得到广泛应用。我们采用脐血造血干细胞移植治疗14例儿童血液病,现报告如下。     

儿童脐血造血干细胞移植现状及动向

自1988年法国人Gluckman应用脐血移植成功治疗1例Fanconi贫血患儿以来，脐血移植陆续在世界各地开展起来。如果说该技术前期发展较慢的话，进入2l世纪后脐血移植已步入加速发展期，近几年脐血移植病例占总造血干细胞移植病例的比例快速增长。受脐血干细胞数量限制，脐血移植的治疗对象主要为儿童。与欧美等发达国家相比，我国的脐血移植开展晚，发展速度电较慢，导致目前与他们存在较大差距。鉴于我们的计划生育国策，儿童多数为独生子女，同胞供者移植可能性极小；骨髓库近几年才开始建立，距临床规模应用尚有时日；我国为第一人口大国，随着经济的发展，将有大量儿童病人需要并可能进行造血干细胞移植治疗。因此，大力开展我国的脐血移植治疗已责无旁贷地落到我们儿科工作者肩上。本文介绍脐血造血干细胞移植的基础知识、儿科应用现状、存在问题及发展动向，供同道们参考。     

二次移植治疗异基因造血干细胞移植后复发儿童急性白血病的临床疗效分析

目的 探讨二次单倍体移植治疗异基因造血干细胞移植后复发的儿童急性白血病的效果。方法 回顾性分析本中心2014年3月1日—2022年5月30日儿童急性白血病异基因造血干细胞移植术后复发后接受二次单倍体异基因造血干细胞移植的7例病例资料,其中急性髓细胞白血病5例,急性淋巴细胞白血病2例,分析二次移植后总体生存率、无病生存率、移植相关死亡率。结果 7例患儿均完成造血重建,粒细胞植入中位时间11(9-17)天,血小板植入中位时间13(9-18)天,随访至2022年5月30日,1例因原发病未缓解死亡,1例于移植+86天原发病复发,且合并休克、呼吸衰竭,家属放弃治疗死亡。2例合并慢性移植物抗宿主病(cGVHD),为皮肤局限型。1年总生存率(OS)71%(5/7),1年无病生存率(DFS)43%(3/7)。结论 二次单倍体异基因造血干细胞移植治疗儿童白血病疗效较好,是异基因造血干细胞移植后复发的儿童白血病患儿的治疗方法之一。     

异基因造血干细胞移植治疗儿童重型再生障碍性贫血

目的探讨异基因造血干细胞移植(allo-HSCT)治疗儿童重型再生障碍性贫血(SAA)的疗效及并发症。方法 4例SAA患儿,均接受氟达拉滨、环磷酰胺、抗胸腺细胞球蛋白预处理;其中3例患儿行HLA全相合同胞骨髓造血干细胞移植(BMT),1例患儿行HLA全相合同胞外周血造血干细胞移植(PBSCT)。同胞供者采集重组人粒细胞集落刺激因子5μg.kg-1.d-1,动员骨髓及外周血干细胞。采用环孢素+短疗程小剂量甲氨蝶呤方案预防移植物抗宿主病,前列腺素E预防肝静脉闭塞综合征,更昔洛韦预防巨细胞病毒感染,美司那及水化碱化预防出血性膀胱炎。通过DNA短串联重复序列多态性分析检测植入情况。结果 2例BMT患儿及1例PBSCT患儿完全植入;1例BMT患儿嵌合植入。中性粒细胞>0.5×109L-1中位时间12 d(9～15 d),血小板>20×109L-1中位时间19 d(12～30 d)。结论 allo-HSCT是治疗儿童SAA的有效方法,维持造血功能以及移植后并发症的发生及防治,仍是目前重点讨论的课题。     

异基因造血干细胞移植在溶酶体贮积症治疗中的应用

溶酶体贮积症(LSD)是因溶酶体的结构或功能异常导致水解酶缺陷,引起相应底物不能降解,进而导致多器官、多系统功能异常。该疾病种类多样,临床表现复杂且缺乏特异性,总体预后较差。目前治疗可采用方法有酶替代治疗、基因治疗及异基因造血干细胞移植(allo-HSCT)等。异基因造血干细胞移植是当前治疗部分儿童LSD的有效方式,尤其是非亲缘脐血干细胞(UCBT),被认为是治疗LSD的优先移植物来源。移植时年龄越小,受益程度越大,因此强调明确诊断尽早移植,建议在明显症状出现前进行。国内大多采用清髓性预处理方案。     

造血干细胞移植治疗儿童白血病

1 造血干细胞(HSCT)治疗儿童急性淋巴细胞白血病急性淋巴细胞白血病(ALL)规范化疗后长期无病生存率高达80%,因此,对于第一次完全缓解(CR 1)的AL患儿原则上选择化疗,但以下情况需选择HSCT.     

Allogeneic hematopoietic stem cell transplantation in children with sickle cell disease

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative treatment for sickle cell disease (SCD), being successful in around 85-90% of patients. Mortality and long-term morbidity (including infertility, gonadal failure, and chronic graft-vs.-host disease) associated with conventional approaches curtail the number of patients who undergo allo-HSCT. Recently, it has been demonstrated that cord blood is as effective as and possibly safer than bone marrow in pediatric patients with SCD. Likewise, transplant strategies based on the use of reduced-intensity regimens and the induction of mixed chimerism have been explored to decrease allo-HSCT short- and long-term complications.     

造血干细胞移植在遗传代谢病治疗中的应用

随着生化检测技术的进步和引进,我国儿童遗传代谢病检出率明显提高,随之而来更大的挑战是治疗问题。迄今已发现的500余种遗传代谢病中,多数疾病缺乏有效治疗方法,只能进行对症治疗,部分疾病通过传统的饮食、药物治疗能够得到控制,少数疾病可以进行酶替代疗法,如:Fabry病、戈谢病。为解决患者的长期治疗,细胞移植和基因治疗已成为现代研究的主流方向。从理论上讲,基因治疗是遗传代谢病的根本治疗方法,但既往Gaucher病和Hunter病基因治疗研究结果显示,未能改善患儿生化与临床表现,技术方面也存在很多短期内难以突破的困难,如:基因转染率、适…     

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造血干细胞移植是目前治疗儿童白血病的重要手段之一。造血干细胞移植的适应证因白血病类型和供者种类不同而有所不同;供者以往以同胞供者为主,目前无关供者移植的生存率已接近同胞供者,半相合移植治疗白血病也越来越被临床所接受;各种细胞辅助治疗逐渐突显优势。造血干细胞移植治疗白血病进展迅速,临床应有所了解。     

同胞脐血移植治疗儿童急性白血病

脐血移植可以根治白血病、再生障碍性贫血、血红蛋白病及先天性免疫缺陷等疾病，尤其适合于儿童患者。临床资料表明同胞脐血移植的效果优于无关供者的脐血移植。对12例白血病或重症再障患儿进行了脐血HLA配型，结果配型完全相合4例，进行脐血移植3例，均成功植活，体重最大50kg。可以在胎儿出生时留取脐血配型，同时将脐血进行低温保存。提示剖宫产和自然分娩、体内采集脐血和体外采集脐血对脐血的采集体积无明显影响。单份同胞脐血可以重建几乎全部儿童患者的造血功能。对同胞脐血移植的病例，主张在分娩时留取脐血进行HLA配型，减少产前穿刺对孕妇及胎儿的损伤，同时脐血进行冷冻，若配型相合再进行脐血移植。     

异基因造血干细胞移植治疗噬血细胞综合征

噬血细胞综合征又称噬血细胞性淋巴组织细胞增生症,分为原发性和继发性两大类.对于家族性噬血细胞综合征(familial hemophagocytic lymphohistiocytosis,FHL)和难治性EB病毒相关噬血细胞综合征(EBV-HLH),异基因造血干细胞移植是目前唯一有效的治疗手段,但其鉴别诊断尤为困难,移植后多种并发症以及高病死率也受到越来越多人的关注.该文总结了近年来异基因造血干细胞移植治疗FHL和难治性EBV-HLH在诊断、预处理方案、移植后并发症、死亡原因分析及预后等方面的研究进展.     

Comparison of survival outcome between donor types or stem cell sources for childhood acute myeloid leukemia after allogenic hematopoietic stem cell transplantation: A multicenter retrospective study of Study Alliance of Yeungnam Pediatric Hematology‐oncology

We compared transplant outcomes between donor types and stem cell sources for childhood acute myeloid leukemia (AML). The medical records of children with AML in the Yeungnam region of Korea from January 2000 to June 2017 were reviewed. In all, 76 children with AML (male‐to‐female ratio = 46:30) received allogenic hematopoietic stem cell transplantation (allo‐HSCT). In total, 29 patients received HSCT from either a matched‐related donor or a mismatched‐related donor, 32 patients received an unrelated donor, and 15 patients received umbilical cord blood. In term of stem cell sources, bone marrow was used in 15 patients and peripheral blood in 46 patients. For all HSCT cases, the 5‐year overall survival (OS) was 73.1% (95% CI: 62.7‐83.5) and the 5‐year event‐free survival (EFS) was 66.1% (95% CI: 54.5‐77.7). There was no statistical difference in 5‐year OS according to the donor types or stem cell sources (P = .869 and P = .911). There was no statistical difference in 5‐year EFS between donor types or stem cell sources (P = .526 and P = .478). For all HSCT cases, the 5‐year relapse rate was 16.1% (95% CI: 7.3‐24.9) and the 5‐year non‐relapse mortality (NRM) was 13.3% (95% CI: 5.1‐21.5). There was no statistical difference in the 5‐year relapse rate according to the donor types or stem cell sources (P = .971 and P = .965). There was no statistical difference in the 5‐year NRM between donor types or stem cell sources (P = .461 and P = .470).     

Unrelated cord blood transplantation for second hemopoietic stem cell transplantation

BACKGROUND: The Kanagawa Cord Blood Bank (KCBB) reports the treatment of 12 patients who received umbilical cord blood transplantation (CBT) from unrelated donors as their second hemopoietic stem cell transplantation (HSCT). METHODS: Provided by the KCBB, between February 1997 and September 2000, 12 patients had unrelated CBT as a second HSCT. Six patients were male and six female; nine patients were in malignant, and three were in non-malignant conditions. The median age of the patients was 7.9 years (range, 2.2-28.0), and the median bodyweight was 22.5 kg (12.0-55.0). The HLA-A and -B serological and DR genotypical disparities between the patients and CBT donors were as follows: one patient was a 0-mismatch, six were 1-mismatches, and five were 2-mismatches. RESULTS: The median time between first and second HSCT was 14.0 months (1.0-47.0). The overall survival rate was 25.0%, three years after CBT (Kaplan-Meier estimate). Mortality after CBT as a second HSCT accounted for nine cases, six from infection and three from treatment-related mortality other than infection. CONCLUSION: Cord blood transplantation offers the advantage of rapid availability, absence of donor risk, and possibly less HLA restriction. In these contexts, unrelated CBT should be considered as a source of HSCT for a second transplant.     

Allogeneic hematopoietic stem cell transplantation in pediatric chronic myelogenous leukemia cases: Hacettepe experience

Recently, there are emerging reports on the beneficial effect of imatinib mesylate for pediatric CML patients; however, the general recommendation is that high-risk CML patients with a human leukocyte antigen-identical donor should be transplanted within the first 12 months after diagnosis. Herein, the data of 16 allogeneic HSCT in 14 children with CML were analyzed retrospectively. In the present study, three-yr EFS was 54.1+/-10.8% and three-yr OS was found as 80.7+/-12.5%.     

Allogeneic hematopoietic stem cell transplantation for infants with idiopathic myelofibrosis

IMF is a rare disease in children that can present during infancy and has a protracted course. The only known curative approach for this disease in adult patients is allogeneic HSCT. There are very few reports describing the long‐term outcome of young children following stem cell transplantation for IMF. We report on eight patients less than two yr of age with IMF that did not resolve with supportive care measures. All patients underwent myeloablative conditioning regimen with busulfan and cyclophosphamide ± ATG followed by HSCT from matched related (n = 6) or unrelated donor (n = 2). All patients achieved neutrophil and platelet engraftment. Four patients had grade II‐III acute GVHD, and chronic GVHD developed in five patients (three mild and two severe). At a median follow‐up of eight and a half yr (0.7–9), all patients are alive with complete resolution of their hematologic manifestations. At the last follow‐up, all patients had normal endocrine function except for one patient who developed hypothyroidism. To date, this is the largest cohort of young children with IMF treated successfully with HSCT, with the longest duration of follow‐up. In conclusion, our study showed that HSCT is a curative option for infants with IMF.