亲缘单倍体造血干细胞移植治疗22例儿童高危血液肿瘤的安全性及疗效分析

目的评估亲缘单倍体造血干细胞移植在儿童高危血液肿瘤治疗中的安全性及疗效。方法回顾性分析22例14岁及以下的高危恶性血液病患儿在接受亲缘单倍体造血干细胞移植后的并发症及疗效。结果全部患儿移植后造血干细胞植入成功。I～Ⅱ度急性移植物抗宿主病（GVHD）发生率为64％（14／22）,Ⅲ-Ⅳ度为14％（3／22）;慢性广泛型GVHD发生率为23％（5／22）;6例无GVHD发生。至随访期末,移植早期（〈100d）相关死亡率为O,总生存率为86％（19／22）,多因素分析提示移植后原发病的复发为影响总生存率的高危因素（P〈0．05）,移植后未出现复发或者复发倾向、出现复发或者复发倾向的两组患儿总生存率分别为94％和60％（P=0．017）。结论亲缘单倍体因造血干细胞移植在高危儿童血液肿瘤的治疗中是安全有效的,亲缘单倍体供者为合适的供者选择。     

幼年型粒单核细胞白血病单倍体相合造血干细胞移植1例

目的探讨单倍体相合造血干细胞移植治疗幼年型粒单核细胞白血病(JMML)的可行性。方法 1岁6个月JMML患儿,行单倍体相合造血干细胞移植。采用Bu/Cy+Flu+ALG方案预处理及CSA+MMF+MTX方案预防移植物抗宿主病(GVHD)。结果于移植+10 d粒系植入成功(1.2×109/L),移植+14 d血小板植入成功(260×109/L),造血初步恢复。移植+21 d查植入证据为100%嵌合。患儿移植后反复出现Ⅰ～Ⅱ度GVHD(皮肤型),给予免疫抑制剂治疗后好转。至今已生存14个月,未见复发。结论单倍体相合造血干细胞移植可能是治愈JMML的可行方法。     

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。     

单倍体造血干细胞移植治疗儿童重型β-地中海贫血

目的：目前仅有30％左右的重型β-地中海贫血患者能找到HLA全相合的同胞供者,使造血干细胞移植治疗该病受到限制。该研究通过探讨单倍体造血干细胞移植治疗儿童重型β-地中海贫血的疗效,希望能够拓展供者源。方法：采用单倍体脐血或骨髓对10例重型β-地中海贫血患儿进行11例次移植。使用以羟基脲、氟达拉滨、白消安、环磷酰胺、抗胸腺细胞球蛋白为基础的预处理方案。结果：6例患者获长期稳定植入并脱离红细胞输注;2例短暂植入后排斥,其中1例恢复地中海贫血状态,另1例在移植早期死亡;1例行2次移植均未植入并出现移植后再障;1例未植入,出现再障,1年后恢复地中海贫血状态。8例植入者均发生急性移植物抗宿主病,仅1例发展为皮肤局限性慢性移植物抗宿主病。随访57.1（2.5～85.1）月,总体生存率90%,无病生存率为60%。结论：单倍体造血干细胞移植治疗儿童重型β-地中海贫血能长期重建造血,在无HLA相合同胞供体时,可以作为造血干细胞移植治疗的一种选择。［中国当代儿科杂志,2009,11（7）：546-548］     

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。     

后置环磷酰胺预防儿童患者造血干细胞移植后GVHD的研究进展

正1前言近年来由于造血干细胞移植技术的进步,单倍体相合的造血干细胞移植成为常规的移植手段。虽然以钙调磷酸酶抑制剂(calcineurin inhibitors, CNIs)、甲氨蝶呤、霉芬酸酯(mycophenolate mofetil,MMF)组成的GVHD防治方案作为一线方案,显著减少了全相合造血干细胞移植后GVHD的发生频率,但在单倍体移植的应用结果并不理想,移植排斥和GVHD使得早期单倍体造血干细胞移植失败率高~([1])。     

脐血移植治疗37例儿童恶性血液病的临床研究-单中心经验

目的 探讨脐血造血干细胞移植（UCBT）治疗儿童恶性血液病的疗效。方法 回顾性分析接受UCBT 的37 例恶性血液病患儿的临床资料，包括急性淋巴细胞性白血病14 例，急性髓细胞性白血病9 例，幼年粒单细胞白血病5 例，慢性粒细胞白血病和骨髓增生异常综合征各3 例，急性混合型白血病2 例，淋巴肉瘤性白血病1 例。其中34 例非血缘相关，3 例血缘相关。HLA 配型6/6 相合5 例，5/6 相合12 例，4/6 相合11 例，3/6 相合9 例。移植中位年龄5.7 岁，中位体重20 kg。结果 中性粒细胞和血小板植入中位天数分别是12 d 和25 d，植入率分别为95% 和78%。中性粒细胞植入率与CD34+ 细胞数呈正相关（P=0.011）。血小板植入率与CD34+ 细胞数和有核细胞数均有关（分别P=0.001、0.014）。急性移植物抗宿主病（GVHD）的发生率为49%，慢性GVHD 为11%。随访中位时间54 个月，5 年移植相关病死率、总生存率和无病生存率分别为27%、57%和41%。结论 脐血移植是快速获得的造血干细胞来源之一，为恶性疾病患儿争取了治疗时间。     

造血干细胞移植治疗儿童白血病进展

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。     

HLA不全相合同胞脐血移植治疗儿童白血病一例

ＨＬＡ不全相合同胞脐血移植治疗儿童白血病一例朱为国钱新华程少杰邢献志刘纯霞官贵先黄志光脐血造血干细胞丰富，再生增殖能力强，是一种良好的造血干细胞来源。１９８９年世界首例脐血移植（ＣＢＴ）成功以来，儿童ＣＢＴ被认为是比骨髓移植更优越的治疗方法。国内目前...     

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。     

Persistent Multiyear Control of Relapsed T‐Cell Acute Lymphoblastic Leukemia With Successive Donor Lymphocyte Infusions: A Case Report

There are few therapeutic options for patients with T‐cell acute lymphoblastic leukemia (T‐ALL) who have recurrent disease after initial matched sibling hematopoietic stem cell transplantation. While a second hematopoietic stem cell transplant (HSCT) from a haploidentical donor offers the conceptual possibility of greater graft versus leukemia effect, there is minimal literature to describe the efficacy of this approach in recurrent pediatric T‐ALL. We present the case of a now 9‐year‐old female in whom second haploidentical HSCT, followed by successive donor lymphocyte infusions in response to minimal residual disease reemergence, has led to 3+ years of ongoing disease control without graft versus host disease and excellent quality of life.     

CD25抗体预防移植物抗宿主病在儿童白血病半匹配骨髓移植中的应用

目的　探讨CD2 5抗体用于预防儿童白血病半匹配未去除T细胞骨髓移植重度移植物抗宿主病 (GVHD)的疗效。方法　 10例儿童白血病患者接受人类白细胞抗原 (HLA) 2～ 3个位点不合半匹配骨髓移植 ,移植方法除了供者用粒细胞集落刺激因子 (G CSF)及受者应用环孢素A(CSA)、氨甲蝶呤 (MTX)、抗胸腺细胞球蛋白 (ATG ,FreseniusHemocare ,Germany)和霉酚酸酯 (MMF)预防GVHD的综合措施外 ,加用抗CD2 5单克隆抗体 (舒莱 ,novartispharmaswitzerland)预防GVHD ,剂量各为 2 0mg ,在移植前 2h和移植后第 4天应用 ,观察移植后的疗效 ,移植结果与前期未用CD2 5抗体移植组作回顾性比较。结果　 10例移植后均获造血重建 ,粒细胞 >0 5× 10 9/L的中位天数是 19d ,血小板大于 2 0× 10 9/L的中位天数是 2 2d ,骨髓植活直接证据检测证实为完全供者造血。无一例发生急性Ⅱ～Ⅳ度GVHD ,未用CD2 5抗体对照组 8例中发生急性Ⅱ～Ⅳ度GVHD有 4例 ,差异有显著性(P =0 0 14 7)。可评价慢性GVHD的 8例均发生慢性GVHD ,为局限性慢性GVHD。中位随访 12个月 (范围 9～ 2 4个月 ) ,2例为移植相关死亡 ,1例移植后 14个月因复发死亡 ,实际无病生存率是70 %。结论　儿童半匹配未去除T细胞骨髓移植中应用舒莱 ,明显降低急性重症GVHD发生 ,临床     

Haploidentical stem cell transplantation as a salvage therapy for cord blood engraftment failure in a patient with Fanconi anemia

A 7‐year‐old male with Fanconi Anemia who developed primary graft failure following one antigen‐mismatched unrelated cord blood transplantation and a nonradiation‐based conditioning, underwent a second hematopoietic stem cell transplantation (HSCT) from his 2‐loci mismatched haploidentical father, using a nonradiation‐based regimen, 79 days after the first HSCT. A sustained hematological engraftment was achieved at 9 days post‐second HSCT. At 15 months post‐second HSCT; the patient demonstrated normal blood counts, sustained donor chimerism, and no evidence of GVHD. Haploidentical HSCTs as primary or secondary sources of stem cells, with appropriate T‐cell depletion, may be a readily available option in the absence of HLA‐matched related or unrelated donors. Pediatr Blood Cancer. 2010;55:580–582. © 2010 Wiley‐Liss, Inc.     

单倍体造血干细胞移植治疗儿童重型再生障碍性贫血的研究进展

对于缺乏人类白细胞抗原（human leukocyte antigen,HLA）全相合同胞供者并且对免疫抑制疗法反应不佳的重型再生障碍性贫血患儿来说,单倍体造血干细胞移植是一种推荐的替代治疗方法。但由于HLA不全相合,患儿体内可能存在供者HLA特异性抗体,导致移植物功能不良发生率较高。与HLA全相合移植相比,其预处理方案的选择也仍需探讨。该文对单倍体造血干细胞移植中供者HLA特异性抗体的检测和处理、预处理方案的选择、移植物功能不良的机制及处理进行综述。 引用格式:     

HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION IN CHILD HEMATOLOGIC MALIGNANCIES WITH G-CSF-MOBILIZED MARROW GRAFTS WITHOUT T-CELL DEPLETION: A Single-Center Report of 45 Cases

In this report, the authors describe a protocol for haploidentical bone marrow transplantation in children who received G-CSF-mobilized bone marrow grafts without T-cell depletion from HLA-mismatched parents. Forty-two of 45 patients achieved complete donor hematopoietic engraftment; the medium time for neutrophil and platelet recovery was 17 and 19 days, respectively. Three died of early transplantation-associated complications; other causes of death included relapse (11 cases), fungal pneumonia (5), and acute graft-versus-host disease (2). The total disease-free survival rate longer than 2 years was 53.3%. These data suggest that haploidentical hematopoietic transplantation is an alterative strategy for children who lack immediate access to HLA-matched sources.     

Bearbeitung und Transplantation hämatopoetischer Stammzellen

Background

New graft manipulation procedures make it possible to obtain highly purified hematopoietic stem cells from healthy donors.

Patients and Methods

A total of 116 children with leukemias, lymphomas, and nonmalignant diseases received purified (97%) peripheral stem cells from matched unrelated donors or mismatched related (haploidentical) donors.

Results

Acute and chronic GVHD were vastly minimized and a high overall rate of engraftment was achieved. Event-free survival at 5 years was 46% after haploidentical transplantation for children with ALL in remission who otherwise lacked a matched donor. Moreover, excellent results were observed in patients with nonmalignant diseases.

Conclusions

Graft manipulation results in well-characterized transplants with minimal risk of GVHD and makes a donor available for each patient by recruiting the parents. Thus, alternative donors should be strongly considered in all patients who need a stem cell transplantation but lack an identical donor.     

Long-time survival after unrelated bone marrow transplantation in children and adolescents and targeted therapy with CD25 blockade to prevent GVHD

To evaluate longtime survival after matched unrelated donor (MUD) transplantation a group of patients (n = 10) with intensified GVHD prophylaxis were compared to patients receiving matched sibling (MSD) transplantation (n = 10); all transplantations were done between 1989 and 1995 in the same institution. A murine monoclonal antibody against CD25 was assessed in addition to standard GVHD prophylaxis for reducing GVHD in children with advanced leukemia after MUD BMT (group I). We compared the incidence of GVHD, relapse and survival under prophylaxis with either anti-CD25 (group I, n = 10) or MSD BMT without anti-CD25 (group II, n = 10) with respect to known risk factors of transplant related morbidity, mortality and outcome. 3/10 leukemia patients in both groups were in CR3 or in relapse at time of transplant. Whereas incidence of acute GVHD grade III and IV was significantly higher in group I compared to group II (0.4 vs. 0.0), no differences in engraftment, or chronic GVHD were seen between both groups. In addition, overall (0.5 vs. 0.6) and leukemia free survival (0.5 vs. 0.6) was not different after 8 respectively 10 years from transplant. Murine anti-CD25 therapy may have contributed to matching outcome of MUD vs. MSD marrow transplants in children with advanced leukemia. In conclusion, the use of anti-CD25 in modulation of CD25+ regulatory and effector T cells in allo- and leukemia recognition merrits further exploration of its potential to improve both tolerance and leukemia control. Since the outcome of children with leukemia that received intensified GVHD prophylaxis in MUD BMT was similar to children with MSD transplants, MUD BMT has to be considered as an equivalent therapeutic option for patients, who have no HLA-identical sibling donor.