异基因造血干细胞移植后肺部移植物抗宿主病1例

异基因造血干细胞移植(allo-HSCT)是目前治疗血液系统疾病的重要手段,越来越多的患者受益于allo-HSCT。但提高allo-HSCT后的长期生存仍遭遇到严重困难,其中最重要的影响因素为移植物抗宿主病(GVHD),肺是GVHD的主要靶器官之一,肺部GVHD一旦发生,其     

脐血干细胞移植的移植物抗宿主病

脐血来源广泛，并含有丰富的造血干祖细胞，是骨髓良好的替代品，脐血移植已成为先天性造血系统发育不良，白血病等多种疾病的一种重要治疗手段，脐血移植的一个主要特点是移植物抗宿主病轻，移植物抗宿主病的核心是细胞因子风暴。细胞因子风暴的强度的强度及持续时间与宿主和供体细胞产生细胞因子的能力，以及细胞因子刺激下供体细胞分裂、增殖能力的大小有关。     

HLA半相合造血干细胞移植在儿科应用的研究进展

HLA半相合造血干细胞移植指将HLA一条单体型相合的供者造血干细胞移植给受者，其供者来源广泛，适用于无HLA完全相合供者的恶性血液病患儿或急需进行移植治疗的病人。随着预处理方案及移植物处理方法的改进，其在临床上将取得更广泛的应用。本文就半相合造血干细胞移植在儿科应用的研究进展情况作一综述。     

HLA半相合造血干细胞移植在儿科应用的研究进展

ＨＬＡ半相合造血于细胞移植指将ＨＬＡ一条单体型相合的供者造血干细胞移植给受者，其供者来源广泛，适用于无ＨＬＡ完全相合供者的恶性血液病患儿或急需进行移植治疗的病人。随着预处理方案及移植物处理方法的改进，其在临床上将取得更广泛的应用。本文就半相合造血干细胞移植在儿科应用的研究进展情况作一综述。     

脐血干细胞移植的移植物抗宿主病

脐血来源广泛，并含有丰富的造血干祖细胞，是骨髓良好的替代品。脐血移植已成为先天性造血系统发育不良、白血病等多种疾病的一种重要治疗手段。脐血移植的一个主要特点是移植物杭宿主病轻。移植物抗宿主病的核心是细胞因子风暴。细胞因子风暴的强度及持续时间与宿主和供体细胞产生细胞固子的能力，以及细胞因子刺激下供体细胞分裂、增殖能力的大小有关。     

间充质干细胞对造血干细胞移植中移植物抗宿主病的防治机制

异基因造血干细胞移植是治疗多种血液系统恶性疾病以及一些自身免疫性和遗传性疾病的有效手段,而移植物抗宿主病（graft-versus-host disease,GVHD）是异基因造血干细胞移植中最常见的并发症,由于GVHD的发生机制十分复杂,目前还没有完全可靠的治疗手段。近年来,间充质干细胞（mesenchymal st...     

儿童异基因造血干细胞移植后细胞免疫重建的临床研究

目的 探讨儿童异基因造血干细胞移植（allo-HSCT）后免疫重建的临床特性。方法 选取2019年7月至2020年10月接受allo-HSCT且临床资料完整的患儿为研究对象。动态监测患儿移植后第0、14、21、28、60及100 d外周血淋巴细胞亚群（CD3⁺ T细胞、CD4⁺ T细胞、CD8⁺ T细胞、CD16⁺ CD56⁺ NK细胞、CD19⁺ B细胞、CD4⁺ CD25⁺ Treg细胞）绝对计数;将患儿按有无急性移植物抗宿主病（aGVHD）分为non-aGVHD组和aGVHD组,比较两组间淋巴细胞亚群的差异。结果 共75例患儿接受allo-HSCT,其中移植后满100 d、临床资料完整的42例患儿纳入本研究,男20例、女22例,中位年龄5.4（2.8～9.3）岁。移植前后不同时间点之间患儿CD3⁺ T细胞、CD4⁺ T细胞、CD8⁺ T细胞、...     

儿童异基因造血干细胞移植后细胞免疫重建的临床研究

目的 探讨儿童异基因造血干细胞移植（allo-HSCT）后免疫重建的临床特性。方法 选取2019年7月至2020年10月接受allo-HSCT且临床资料完整的患儿为研究对象。动态监测患儿移植后第0、14、21、28、60及100 d外周血淋巴细胞亚群（CD3⁺ T细胞、CD4⁺ T细胞、CD8⁺ T细胞、CD16⁺ CD56⁺ NK细胞、CD19⁺ B细胞、CD4⁺ CD25⁺ Treg细胞）绝对计数;将患儿按有无急性移植物抗宿主病（aGVHD）分为non-aGVHD组和aGVHD组,比较两组间淋巴细胞亚群的差异。结果 共75例患儿接受allo-HSCT,其中移植后满100 d、临床资料完整的42例患儿纳入本研究,男20例、女22例,中位年龄5.4（2.8～9.3）岁。移植前后不同时间点之间患儿CD3⁺ T细胞、CD4⁺ T细胞、CD8⁺ T细胞、...     

儿童异基因造血干细胞移植后细胞免疫重建的临床研究

目的 探讨儿童异基因造血干细胞移植（allo-HSCT）后免疫重建的临床特性。方法 选取2019年7月至2020年10月接受allo-HSCT且临床资料完整的患儿为研究对象。动态监测患儿移植后第0、14、21、28、60及100 d外周血淋巴细胞亚群（CD3⁺ T细胞、CD4⁺ T细胞、CD8⁺ T细胞、CD16⁺ CD56⁺ NK细胞、CD19⁺ B细胞、CD4⁺ CD25⁺ Treg细胞）绝对计数;将患儿按有无急性移植物抗宿主病（aGVHD）分为non-aGVHD组和aGVHD组,比较两组间淋巴细胞亚群的差异。结果 共75例患儿接受allo-HSCT,其中移植后满100 d、临床资料完整的42例患儿纳入本研究,男20例、女22例,中位年龄5.4（2.8～9.3）岁。移植前后不同时间点之间患儿CD3⁺ T细胞、CD4⁺ T细胞、CD8⁺ T细胞、...     

外周血CD34+造血干细胞加适量T细胞输注进行HLA半相合的异体移植

对1例Ph+染色体的急淋患儿进行母子间HLA半相合的异体外周血造血干细胞移植 ,为避免由于HLA不相合所产生的由T细胞介导的严重移植物抗宿主病(GVHD) ,采用了CD34+细胞正性分离去除淋巴细胞 ;同时为避免由于T细胞过度去除而引起宿主抗移植物反应(HVG)导致植入失败 ,在移植次日又加入部分T细胞 ,使病儿接受CD34 +细胞6×106/kg 和CD3 +细胞1.05×107/kg。结果 :随访1年来 ,红系、粒系和巨核系均恢复正常 ,临床上仅出现一过性的IIOaGVHD以及轻微的局限于口唇粘膜的cGVHD。STR位点DNA检验以及染色体检查 :移植后 +180天受体已从供体型嵌合体转为完全供体型 ,病儿获得植入成功。结果表明 ,常规剂量的CD34 +细胞移植加以适量CD3 +T细胞 ,可克服HLA部分不相配的难点 ,减轻GVHD ,同时也可避免由于过度的T细胞去除而出现的HVG。     

外周血造血干细胞移植联合间充质干细胞输注治疗范可尼贫血患儿1例并文献复习

目的分析造血干细胞移植联合间充质干细胞输注对范可尼贫血(FA)患儿的治疗效果。方法通过分析1例.FA患儿外周血造血干细胞移植联合间充质干细胞输注治疗的临床资料,观察此种治疗方法对患儿的治疗效果及预后的影响。结果患儿于移植+13 d中性粒细胞植活,+15 d血小板植活,移植后供受者基因嵌合率为99.83%。移植后1.5个月血清CMV-DNA、EBV-DNA阳性,经免疫抑制剂减量及抗病毒治疗后转阴。移植后2个月出现皮肤GVHD(I度),未调整免疫抑制剂剂量,行间充质干细胞输注治疗4次后GVHD消失。移植后6个月,患儿出现血红蛋白水平下降,复查供受者基因嵌合率为57.8%,考虑出现移植物排斥,逐渐减停免疫抑制剂,供受者基因嵌合率复升至81.83%,血象恢复正常,无GVHD表现。现为移植后1.5年,患儿血象持续正常,供受者基因嵌合率维持在95%以上,FA相关基因检测持续转阴。结论造血干细胞移植是根治FA的重要治疗手段,健康供者骨髓间充质干细胞输注对于本例患儿造血干细胞植入、GVHD控制可能具有重要辅助作用。     

Non-myeloablative allogenic peripheral blood stem cell transplantation in a patient with refractory osteosarcoma

The prognosis of patients with relapsed osteosarcoma is dismal despite the use of intensive chemotherapy. We describe a patient with refractory osteosarcoma who underwent non-myeloablative peripheral blood stem cell transplantation (PBSCT) from an human leukocyte antigen (HLA)-identical sibling during a third complete remission. The patient suffered pulmonary relapse after the transplantation. Cyclosporin A withdrawal induced a graft-vs.-osteosarcoma effect and graft-vs.-host disease, but eventually the tumor progressed. Although our experience in this case suggested the presence of a graft-vs.-osteosarcoma effect during non-myeloablative allogenic PBSCT, this strategy might have limited value for refractory osteosarcoma with rapid growth kinetics.     

Prediction of engraftment after peripheral blood stem cell transplantation by CD34-positive cells in grafts

total of 91 peripheral blood stem cell collections were performed in 26 children with various malignant tumors and peripheral blood stem cell transplantations (PBSCT) were performed in 15 of the children. There was a positive correlation between logarithm of total CD34⁺ cells/kg and logarithm of colony-forming unit-granulocyte macrophage (CFU-GM)/kg (r = 0.86). The time elapsed until the white blood cells (WBC) exceeded 1000/μL was related to both CFU-GM (r = 0.67) and CD34⁺ cell count (r = 0.60). The number of days elapsed until platelet count exceeded 5 times 10⁴/μL was not related to the logarithm of CFU-GM count/10⁵ per kg transfused (r = 0.47), but was related to the logarithm of CD34⁺ cell counts/10⁶ per kg transfused (r = 0.73). The number of days elapsed until the reticulocytes exceeded 5 times 10⁴/μL was not related to the logarithm of CFU-GM count/10⁵ per kg (r = 0.52), but was related to the logarithm of CD34⁺ cell counts/10⁶ per kg transfused (r = 0.91). Although CD34⁺ cell counts correlated with the number of CFU-GM, bone marrow regeneration rates in three lineages were predicted more accurately by the number of CD34⁺ cells transfused than by the number of CFU-GM. These results suggest that measurement of the CD34⁺ cell count may be useful in predicting bone marrow regeneration rate after PBSCT.     

Disseminated toxoplasmosis resulting in graft failure in a cord blood stem cell transplant recipient

Toxoplasmosis is an infrequent infection with a high mortality rate in hematopoietic stem cell transplant recipients, and is usually caused by reactivation of prior, latent infection upon intensive immunosuppression. We report a case of fatal disseminated toxoplasmosis, diagnosed at autopsy, in a 7-year-old boy who received a cord blood graft for recurrent acute lymphoblastic leukemia. This case represents both the first reported case of toxoplasmosis in an engrafted cord blood recipient, and also of graft failure due to toxoplasmosis. Recommendations for toxoplasmosis diagnosis, treatment, and prophylaxis in stem cell transplant recipients are reviewed.     

自体外周血造血干细胞移植在小儿视网膜母细胞瘤的临床应用

目的探讨大剂量化疗并自体外周血造血干细胞移植(APBSCT)治疗小儿眼外期视网膜母细胞瘤的可行性及疗效。方法对3例视网膜母细胞瘤眼外转移患儿,在常规化疗后进行APBSCT治疗。大剂量化疗(预处理)方案采用卡铂(250 mg/m2,-7～-3 d),依托泊苷(350 mg/m2,-7～-3 d),环磷酰胺(1.6 g/m2,-6～-3 d)。从第0天开始输入自体外周血造血干细胞。结果3例患儿均获得移植成功,外周血白细胞总数>1.0×109/L的平均时间为10 d,中性粒细胞>0.5×109/L的平均时间为12 d,白细胞总数恢复正常的平均时间为15 d,血小板计数>50×109/L的平均时间为23 d;血红蛋白含量平均在移植后第15天升至100 g/L;随访时间6个月～14个月,至今3例患儿均生存。结论大剂量化疗加自体干细胞移植是治疗眼外转移的视网膜母细胞瘤的有效治疗方法。因观察例数和随访时间有限,其远期效果还有待进一步评估。     

Mycophenolate mofetil for treatment of steroid‐refractory acute graft‐versus‐host disease after pediatric hematopoietic stem cell transplantation

A standard treatment is yet to be established for steroid‐refractory acute aGVHD following HSCT. The effects of MMF have not been well studied in children with aGVHD. We evaluated the effectiveness of oral MMF in 14 children with steroid‐refractory aGVHD (grade II in one patient, grade III to IV in 13 patients). The median initial dose of MMF was 40 mg/kg/day (range, 30–74) and was increased by 1.5–2 times if manifestations of GVHD did not improve. Within four wk of treatment, seven patients (50%) achieved CR, and four (29%) had a PR. Within eight wk, 11 patients (79%) achieved CR without using additional agents. Overall, 12 patients are alive and in remission with a median follow‐up of 35 months (range, 14–86). The median maximum dose of MMF was 60 mg/kg/day (range, 34–107). No fatal toxicity was observed, including MMF‐related infections. MMF appears to be highly effective for steroid‐refractory aGVHD when used at a higher dose than has been described previously. Larger studies and pharmacokinetic analysis are required to evaluate its efficacy and toxicity and find the optimal dose of MMF in children.     

美罗培南与万古霉素联用治疗自体外周血干细胞移植患儿合并感染的疗效观察

目的评价美罗培南与万古霉素联用治疗实体瘤患儿自体外周血干细胞移植过程中合并中重度感染的临床疗效及安全性。方法剂量为美罗培南10~20 mg/(kg.次),万古霉素10~20 mg/(kg.次),均为1次/12 h静脉滴注。结果美罗培南与万古霉素联用有效率为78.4%,4例合并败血症患儿中2例有效,不良反应发生率为8.1%。结论美罗培南与万古霉素联用治疗自体外周血干细胞移植过程中合并中重度感染疗效显著,而且安全性好。     

Successful treatment of refractory Langerhans cell histiocytosis by allogeneic peripheral blood stem cell transplantation

We describe a six-yr-old boy who exhibited typical signs and symptoms of LCH with EBV-associated hemophagocytic syndrome from the age of 15 months. Multiple courses of conventional chemotherapy achieved only marginal improvement over the ensuring five yr. During this period, this boy experienced recurrent episodes of hemophagocytic syndrome associated with CMV infection. Five yr after the first diagnosis of LCH, the patient was treated with allogeneic PBSCT from his HLA-identical eight-yr-old brother. PBSCT was performed using a TBI-incorporating conditioning regimen comprising TBI, busulfan, and cyclophosphamide. Diabetes insipidus, typically a permanent consequence of LCH, was well controlled by DDAVP therapy. At the time of writing, this boy is alive and well, and had been disease-free for more than two yr after the PBSCT.