异基因造血干细胞移植与异基因骨髓移植的比较

目的探讨异基因外周血造血干细胞移植的功效及并发症。方法自1991年2月-2000年2月,所有接受同胞或近亲异基因移植的患儿,分为外周血造血干细胞移植（PBSCT)和骨髓移植（BMT）两组,纳入观察并进行比较。结果25例PBSCT与64例BMT的平均年龄无明显差异,PBSCT组的供者为一个位点不合的同胞或父母,占44%（11/25）,较BMT组［只占9.4%（6/64）］为多（P<0.01）。PBSCT组的植入有核细胞数较BMT组高（11.7108/KG\7.05108/KG,P<0.01）,而粒细胞植入速度亦较快（16.3D、19.4D,P=0.03）,但血小板植入速度差异无显著性（均为3D）。度或以上的急性移植物抗宿主病（GVHD）差异无显著性（32%、29.7%,P=0.83）。PBSCT组的慢性GVHD较BMT组为高（32.8%和9.6%）,但如只限于人类白细胞抗原（HLA）全相合同胞移植,PBSCT组并未 出现慢性GVHD。随访显示,两组的二年无病生存率差异无显著性（55%、73%,P=0.33）。白血病复发为其主要的死亡原因。结论PBSCT的白细胞植入较快,且未增加急性或慢性GVHD,而无病生存率与BMT相近,HLA相合同胞可考虑作PBSCT移植。     

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。     

异基因造血干细胞移植治疗IV期儿童神经母细胞瘤

目的：儿童IV期神经母细胞瘤生存期短,且目前尚无有效治疗措施。 该文通过异基因造血干细胞移植治疗IV期儿童神经母细胞瘤来评价其安全性及疗效。方法：对1例7岁IV期神经母细胞瘤患儿进行异基因造血干细胞移植治疗,供者为患儿母亲,HLA配型半相合,采用氟达拉滨,马法兰为预处理方案,G-CSF动员的外周血和骨髓联合移植。结果植入成功,移植后＋10 d中性粒细胞>0.5×109/L,＋11 d血小板>20×109/L。移植后+8 d出现II度肠道急性移植物抗宿主反应,治疗后缓解。随访210 d健康生存。结论： 对IV期儿童神经母细胞瘤患者,以父母为供体的半相合移植是一种可选择的、安全的、有效的挽救性治疗措施之一。     

异基因造血干细胞移植治疗儿童再生障碍性贫血临床分析

目的探讨异基因造血干细胞移植在儿童再生障碍性贫血治疗中的作用。方法10例再障患儿中,5例行HLA相合同胞供者异基因外周造血干细胞移植,3例行无关供者异基因外周造血干细胞移植,1例行无关供者骨髓移植,1例行脐血移植。结果1例接受脐血移植者未植活,其余9例均植入。中位植入时间14d（8～24d）,中性粒细胞〉0.5×10^9/L中位时间12d（8～19d）,血小板〉20×10^9/L中位时间17d（9～40d）。2例发生排斥,1例接受了第二次移植,1例移植后3个月血象开始自行恢复。结论如有HLA相合的同胞供者,异基因造血干细胞移植可作为儿童再障的一线治疗;临床重症感染无法控制的患儿,并非移植绝对反指征,相反可通过移植后的造血重建控制感染。     

异基因造血干细胞移植治疗Ⅳ期儿童神经母细胞瘤

目的儿童Ⅳ期神经母细胞瘤生存期短,且目前尚无有效治疗措施。该文通过异基因造血干细胞移植治疗Ⅳ期儿童神经母细胞瘤来评价其安全性及疗效。方法对1例7岁Ⅳ期神经母细胞瘤患儿进行异基因造血干细胞移植治疗,供者为患儿母亲,HLA配型半相合,采用氟达拉滨,马法兰为预处理方案,G-CSF动员的外周血和骨髓联合移植。结果植入成功,移植后+10 d中性粒细胞>0.5×109/L,+11 d血小板>20×109/L。移植后+8 d出现Ⅱ度肠道急性移植物抗宿主反应,治疗后缓解。随访210 d健康生存。结论对IV期儿童神经母细胞瘤患者,以父母为供体的半相合移植是一种可选择的、安全的、有效的挽救性治疗措施之一。     

造血干细胞移植治疗DOCK8基因突变致高IgE综合征2例病例报告

目的：评估异基因造血干细胞移植治疗DOCK8基因突变所致的高IgE综合征（HIES）患儿的治疗效果。方法：回顾性收集2例接受异基因造血干细胞移植治疗DOCK8基因突变所致的HIES患儿的临床特征、实验室检查、治疗和效果。结果：2例HIES患儿,例1男,移植时年龄7岁;例2女,移植时年龄9岁。例1采用同胞全相合外周血干细胞移植,例2采用非亲缘全相合脐血干细胞移植。均采用白消安联合氟达拉滨为基础的减低强度预处理方案,顺利植入并获得造血重建。中性粒细胞植入时间例1为移植后12 d,例2为移植后24 d;血小板植入时间例1为移植后13 d,例2为移植后35 d。移植后14 d嵌合检测提示为完全供者细胞嵌合。2例患儿移植期间肺部感染均有加重,经对症治疗好转。例1接受同胞供者移植,发生皮肤Ⅰ度急性移植物抗宿主反应,甲泼尼龙治疗后缓解。无其他移植相关并发症发生。2例移植后嗜酸性粒细胞及血清IgE水平均较移植前显著下降,例1和例2分别随访至移植后18和23个月,均无病生存。结论：DOCK8基因突变所致的HIES患儿可通过异基因造血干细胞移植治愈,宜采用减低强度预处理方案,同胞相合供者是最佳供者选择,非亲缘脐血干细胞移植也能取得良好疗效。     

造血干细胞移植治疗湿疹血小板减少伴免疫缺陷综合征的临床研究——单中心11年回顾性分析

目的探讨异基因造血干细胞移植(allo-HSCT)治疗湿疹血小板减少伴免疫缺陷综合征(WAS)的疗效、早期并发症、预后影响因素及脐血作为WAS移植供体选择的可行性。方法对上海儿童医学中心2006年11月-2018年9月接受allo-HSCT的29例确诊WAS患儿的临床资料进行回顾性分析。结果 29例WAS患儿接受allo-HSCT治疗,其中13例接受脐血(UCB)移植,16例接受外周血干细胞(PBSC)移植,其中同胞全相合供体(MSD)移植2例,全相合无关供体(MUD)移植8例,不全相合无关供体(MMUD)4例,亲缘不全相合供体(MMSD)移植2例。经环磷酰胺+白消安+抗人胸腺球蛋白清髓性预处理后,所有患儿均获得完全植入。总体2年无病生存率为93%(27/29)。UCB和PBSC移植中性粒细胞和血小板植入中位时间分别为12d vs.11d(P=0.215)和47d vs.26d(P=0.133)。69%患者发生aGVHD,均为2～3度皮肤GVHD,UCB移植患者与PBSC移植患者相比aGVHD发生程度及持续时间无差异(P值分别为0.445和0.345)。不全相合较全相合供体移植aGVHD持续时间更长(P=0.001),但两者间aGVHD发生程度及频率差异无显著性(P=0.875)。导管相关血行感染主要发生于围移植期,发生率26.1%。结论 allo-HSCT治疗WAS总体预后好,脐血是WAS患儿合适的造血干细胞来源。     

造血干细胞移植治疗Wiskott-Aldrich综合征一例报告及文献复习

目的 Wiskott-Aldrich综合征(WAS)是一种原发性免疫缺陷性疾病,严重病例预后不良.采用人类白细胞抗原(HLA)全相合的同胞骨髓移植成功治疗1例,特此总结并进行文献复习.方法 采用流式细胞仪检测WAS蛋白(WASP)表达和基因分析确诊WAS.患儿姐姐为人类白细胞抗原全相合骨髓供者,所采集骨髓单个核细胞数为4.38×108/kg,CD34+细胞3.78×106/kg患儿体重.采用白消安/环磷酰胺全清髓的预处理方案,环孢菌素单用预防移植物抗宿主病.移植后检测WASP表达和短串联重复序列(STR)作为植入证据.结果 患儿诊断:WAS,WASP(-IVS9+2T>C,WASP阴性).白消安/环磷酰胺预处理后骨髓回输;移植13 d中性粒细胞(ANC)绝对值0.8×109/L,移植15 d起血小板>50×109/L,1个月后正常.移植50 d起患儿WASP表达阳性,STR显示为供者DNA完全嵌合;随访至移植后510 d,患儿健康,WASP稳定表达.结论 结合病例和文献复习,人类白细胞抗原相合同胞骨髓移植治疗典型WAS近期预后较好.     

非血缘造血干细胞移植——儿童重型再生障碍性贫血的一线治疗选择?

造血干细胞移植是治疗儿童重型再生障碍性贫血(SAA)的重要措施,HLA相合的同胞供体(MSD)移植是公认的儿童SAA一线治疗方法。随着移植技术的快速发展,非血缘相关供体(MUD)移植疗效有了大幅度提高,许多中心达到了与MSD一样的治疗效果,因此HLA高分辨相合MUD有望成为儿童SAA的首选治疗。     

儿童造血干细胞移植86例临床分析

目的 分析造血干细胞移植术(HSCT)治疗儿童血液肿瘤性疾病的临床疗效。方法 回顾性分析2016年3月至2020年4月在徐州医科大学附属医院儿科行HSCT 86例患儿的临床资料。结果 86例HSCT患儿,男50例、女36例,中位年龄11(9～14)岁。急性淋巴细胞白血病(ALL)27例,急性髓系白血病(AML)28例,再生障碍性贫血(AA)16例,淋巴瘤5例,慢性粒细胞白血病(CML)4例,骨髓增生异常综合征(MDS)3例,神经母细胞瘤(NB)、系统新硬化症(SSc)及肾上腺脑白质营养不良(ALD)各1例。自体移植7例、脐血移植4例、异基因造血干细胞移植(allo-HSCT)75例。86例患儿中位随访时间29.5(17.6～44.0)月。植入成功84例,自体移植和allo-HSCT各失败1例;复发14例,自体移植复发4例,allo-HSCT复发10例;Ⅲ/Ⅳ移植物抗宿主病(GVHD)6例,均为allo-HSCT;死亡20例,其中自体移植4例,allo-HSCT 16例。Fisher精确检验结果显示自体移植、脐血移植、同胞全相合、半相合4组间发生Ⅰ/Ⅱ级aGVHD差异有统计学意义(P&l...     

儿童异基因造血干细胞移植后淋巴细胞增殖性疾病的临床研究

目的探讨儿童异基因造血干细胞移植（allo-HSCT）后淋巴细胞增殖性疾病（PTLD）的诊治及预后。方法回顾性分析4例allo-HSCT后EBV相关性PTLD（EBV．PTLD）患儿的临床资料。其中,急性淋巴细胞白血病（高危）（ALL—HR）2例,重型再生障碍性贫血（SAA）2例。异基因外周血造血干细胞移植（allo-PBSCT）3例,异基因脐血造血干细胞移植（allo-UCBSCT）1例。结果4例患儿分别于allo．HSCT后第53、101、22、42d发生PTLD。临床表现为发热、鼻塞、扁桃体肿大、淋巴结肿大和肝脾肿大,移植前均EBNA-1-IgG（＋）、VCA．IgG（＋）;移植后EBV．DNA1．69×10^4～8．62×10^8 copies／mL。经淋巴结病理活检确诊为EBV-PTLD,其中1例为T细胞来源,3例为B细胞来源。例1予减停免疫抑制剂、使用利妥昔单抗、联合COP方案化疗及供者淋巴细胞输注（DU）治疗,PTLD反复且发生严重皮肤GVHD、肺部感染,移植后第193d死亡。余3例予减停免疫抑制剂及利妥昔单抗治疗,临床表现消失且EBV．DNA转阴,分别随访17、12、7个月均无病存活。结论动态监测EBV—DNA对PTLD早期发现具有重要意义。减停免疫抑制剂联合利妥昔单抗治疗EBV-PTLD疗效明显。化疗可导致严重感染,DLI治疗存在严重GVHD危险,不宜作为一线治疗。     

Somnolence syndrome in a child following 1200-cGy total body irradiation in an unrelated bone marrow transplantation

Neurological complications may occur following intensive chemotherapy and hematopoietic cell transplantation. Postirradiation somnolence syndrome has been observed in children with acute lymphoblastic leukemia who received central nervous system preventive therapy with 1800-2400 cGy cranial irradiation. The authors report a 16-year-old boy with chronic myelogenous leukemia in chronic phase, who developed symptoms compatible with thes omnolence syndrome (SS) 6 weeks following HLA-matched unrelated bone marrow transplantation (BMT). The preparative regimen consisted of 1200 cGy total body irradiation (TBI), cytosine arabinoside and cyclophosphamide. The patient developed lethargy and low-grade fever, with intermittent rhythmical delta activity in electroencephalograph. Here covered spontaneously without specific therapy 3 weeks after developing symptoms. This is the first report describing that as low as 1200 cGy TBI can induce SS in a child. After allogeneic BMT, some patients develop neurological symptoms. The authors suggest that somnolence syndrome should be included in differential diagnosis in these patients.     

SOMNOLENCE SYNDROME IN A CHILD FOLLOWING 1200-cGy TOTAL BODY IRRADIATION IN AN UNRELATED BONE MARROW TRANSPLANTATION

Neurological complications may occur following intensive chemotherapy and hematopoietic cell transplantation. Postirradiation somnolence syndrome has been observed in children with acute lymphoblastic leukemia who received central nervous system preventive therapy with 1800-2400 cGy cranial irradiation. The authors report a 16-year-old boy with chronic myelogenous leukemia in chronic phase, who developed symptoms compatible with thes omnolence syndrome (SS) 6 weeks following HLA-matched unrelated bone marrow transplantation (BMT). The preparative regimen consisted of 1200 cGy total body irradiation (TBI), cytosine arabinoside and cyclophosphamide. The patient developed lethargy and low-grade fever, with intermittent rhythmical delta activity in electroencephalograph. Here covered spontaneously without specific therapy 3 weeks after developing symptoms. This is the first report describing that as low as 1200 cGy TBI can induce SS in a child. After allogeneic BMT, some patients develop neurological symptoms. The authors suggest that somnolence syndrome should be included in differential diagnosis in these patients.     

Efficacy and Safety of Human Umbilical Cord Derived Mesenchymal Stem Cell Therapy in Children with Severe Aplastic Anemia Following Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Case Series of 37 Patients

The treatment of pediatric severe aplastic anemia (SAA) with allogeneic hematopoietic stem cell transplantation (allo-HSCT), presents major challenges including the risks of graft failure, septic complications, and graft-versus-host disease (GVHD). Additive infusions of human umbilical cord derived mesenchymal stem cell (hUC-MSC) may be administered to improve patient survival. We retrospectively examined 37 pediatric patients with SAA who received allo-HSCT and subsequent infusions of hUC-MSC suspension at a dose of 1.0 × 10⁶ /kg. The times and doses of hUC-MSC infusions were increased in patients with severe GVHD. All patients received hUC-MSC infusions. The median time to post-transplantation neutrophil count of greater than 0.5 × 10⁹ /L was 14 days (range, 11–20 days) and time to post-transplantation platelet count of greater than 20 × 10⁹ /L was 19 days (14–29 days). The overall frequency of acute GVHD (aGVHD) was 45.9% (17/37). These aGVHD episodes occurred at a median time of post-transplantation 47 days (15–83 days). The frequency of chronic GVHD (cGVHD) was 18.9% (7/37); cGVHD developed from aGVHD in 10.8% (4/37) of patients. The GVHD-associated mortality rate was 18.9% (7/37) and aGVHD-specific mortality rate was 8.1% (3/37). The median overall survival time was 35 months (9—67 months) and the three-year overall survival rate was 74.2% (28/37). Seven patients died of GVHD, one patient died of a severe invasive fungal infection, and one patient died of renal failure. In conclusion, post-transplantation hUC-MSC infusions seemed to be safely infused in children with SAA who have previously received allo-HSCT.     

儿童再生障碍性贫血的规范诊治现状及研究进展

再生障碍性贫血(再障)是儿童期严重的血液病之一,诊断和治疗较为困难,尤其是重型再障预后较差.我国属于再障高发地区,必须引起足够的重视.目前已经明确,T淋巴细胞"免疫介导"是再障的主要发病机制,由于T淋巴细胞功能异常,而导致骨髓造血干细胞受到抑制.成功的异基因造血干细胞移植虽能根治再障,但受到供体来源困难、医疗费用昂贵、治疗难度大和医疗风险高等限制,国内难以广泛开展.近年来,根据再障免疫介导致病机制所开展的免疫抑制治疗已经获得较为满意的疗效,是无合适供体进行造血干细胞移植的重型和难治型再障的最佳替代疗法.文章对有关再障发病机制的研究进展、诊断与分型标准、鉴别诊断要点、治疗原则与治疗方法以及疗效评价标准等进行简要介绍.     

异基因造血干细胞移植治疗粘多糖病I型1例报告

目的：粘多糖病I型是一种进行性多器官受累的遗传代谢性疾病,Hurler综合征是粘多糖病I型的最严重类型,常导致进行性的中枢神经系统受损和早期死亡。该研究进行了异基因造血干细胞移植治疗该病的初步尝试,探讨异基因干细胞移植治疗粘多糖病的疗效。方法：1例男性粘多糖病I型Hurler综合征患者,2岁1个月,供者为其胞姐,HLA配型一个HLA-B位点不合。预处理方案为减低预处理剂量的BuCy方案马利兰(BU)每日3.7mg/kg,-9~-6d;环磷酰胺(Cy)每日42.8mg/kg,-5~-2d;抗胸腺细胞球蛋白每日3.5mg/kg,-7,-5,-3,-1d。输入重组人粒细胞集落刺激因子动员的供者CD34+细胞(12.8×106/kg),以环孢素A、骁悉、赛呢哌、抗胸腺细胞球蛋白和氨甲喋呤预防移植物抗宿主病(GVHD)。结果：移植后14d,短串联重复序列结合聚合酶链反应(STR-PCR)检测显示为完全供者型嵌合,中性粒细胞和血小板植活时间分别为+11d和+19d。仅出现肝、胃肠Ⅰ级预处理相关毒性,无严重预处理相关并发症。未发生急、慢性移植物抗宿主病和移植物衰竭,移植后临床症状明显改善,认知能力持续增加。结论：异基因造血干细胞移植治疗粘多糖病I型疗效肯定,减低剂量的预处理方案有利于降低预处理相关毒性;移植前后加强免疫抑制治疗,适当增加供者造血干细胞输注数量,有利于促进植入,减少移植物衰竭以及GVHD的发生。     

Intensive conditioning regimen for bone marrow transplantation in children with high-risk haematological malignancies

Between September 1987 and May 1991, 21 children aged 10 months to 15 years (median 9 years) underwent bone marrow transplantation (BMT) for advanced haematological malignancies using a conditioning regimen consisting of total body irradiation (TBI), etoposide 1.8 g/m² by continuous infusion, and cyclophosphamide 2 g/m² on 3 consecutive days. The patients included 14 with acute lymphoblastic leukaemia (ALL), 1 with chronic myeloid leukaemia (CML), 1 with juvenile CML, 4 with non-Hodgkin's lymphoma and 1 with acute nonlymphocytic leukaemia. Eleven had an allogeneic BMT from an HLA-matched sibling, and 1 from an unrelated donor. Nine patients received 4-hydroperoxycyclophosphamide purged autologous marrow. Median time to myeloid engraftment (ANC > 500/μl) was 19 days in allogeneic BMT patients and 28 days in autologous BMT patients (P < .01). Mucositis was the major regimen-related toxicity (RRT). GI toxicity in the form of diarrhoea affected ten patients and five had veno-occlusive disease of the liver. Two patients had mild bladder toxicity and one died of renal toxicity. There was no CNS or cardiac toxicity. There was no significant difference in the incidence of toxicity according to the type of BMT (autologous or allogeneic), total dose, or sequence of TBI. With a median follow-up of 44 months, ten patients are alive (6/12 allogeneic BMT patients and 4/9 autologous BMT patients). Of the 11 deaths, four were related to toxicity (2 aspergillus, 1 haemorrhage following liver biopsy, and 1 from haemolytic-uraemic syndrome), and 4/12 allogeneic and 4/9 autologous BMT patients died from relapsed disease. This conditioning regimen is well tolerated in children, demonstrating mild and reversible RRT. © 1994 Wiley-Liss, Inc.