儿童造血干细胞移植后中枢神经系统并发症的临床分析

目的：探讨儿童造血干细胞移植（HSCT）后中枢神经系统（CNS）并发症的发病情况、病因、临床特点、高危因素及预后,提高 CNS 并发症的诊断和治疗水平,改善患儿的生存质量。方法回顾性分析113例行HSCT治疗的患儿发生癫痫、高血压脑病、可逆性后部白质脑病综合征和移植相关的血栓性微血管病等HSCT后CNS并发症的诱因、发病特点及预后。结果113例行HSCT治疗患儿中共7例（6.2％）发生了CNS并发症,其中1例死亡。7例患儿中,6例为HLA不全相合,1例患儿为HLA全相合。7例患儿在预处理时均应用ATG。结论 VHLA配型不全相合可能是HSCT后发生CNS并发症的高危因素。早期发现、早期诊断并积极治疗CNS 并发症,可降低其病死率及后遗症的发生,有效改善患儿的生存质量。     

Unrelated hematopoietic stem cell transplantation for Cernunnos-XLF deficiency

Abstract:  Cernunnos-XLF deficiency is a rare CI characterized by a defective DNA DSB repair mechanism. Its clinical manifestations are growth retardation, dysmorphic features, malformations, and severe B- and T-cell lymphopenia. BM failure may complicate the clinical picture. To date, there have been no described patients with CSy undergoing allogeneic HSCT. We report a case of CSy treated successfully with unrelated allogeneic HSCT after a reduced-intensity conditioning regimen. Two yr after HSCT, the patient maintains full donor engraftment, normal hematopoiesis, and progressively improving immune competence, thus suggesting that HSCT may be the treatment of choice for CSy.     

儿童造血干细胞移植患者的人巨细胞病毒感染

人类巨细胞病毒(human cytomegalovirus,HCMV)属于疱疹病毒β亚科,人感染HCMV后病毒可在体内长期甚至终身潜伏,在免疫受损或抑制时可再次激活,引起临床症状.HCMV是造血干细胞移植(hemopoietic stem celltransplantation,HSCT)患儿术后中期(2～3个月)感染最常见的病原,引起较高的发病率和死亡率,严重影响预后[1].因此,密切监测HSCT患儿的HCMV感染,及时准确的诊断和治疗对于HSCT至关重要.本文应用实时荧光定量PCR方法检测血清中HCMV-DNA,对HSCT患儿的HCMV感染进行了监测.     

Hematopoietic stem cell transplantation for severe combined immunodeficiency

Severe combined immunodeficiency (SCID) is a heterogeneous group of congenital diseases characterized by their presentation with life threatening infections in the first months of life. The clinical presentation and the therapeutic outcome is influenced by multiple factors: the genetic defect, infectious complications, the presence of maternal T cells the development of Omenn syndrome, as well as non-immunological signs and symptoms of the disease. Hematopoietic stem cell transplantation (HSCT) to date is the only established curative option and allows long-term cure of the disease. Therapeutic objectives of HSCT in SCID clearly differ from those in malignant or hematological disease. Disease specific aspects and their influence on the therapeutic strategy in SCID will be discussed in this review.     

亲缘单倍型造血干细胞移植治疗儿童急性白血病疗效分析

目的评价单倍型造血干细胞移植(haplo-HSCT)治疗儿童急性白血病(AL)的疗效。方法收集自2006年1月-2011年12月在我院移植病房进行的亲缘haplo-HSCT治疗儿童AL共23例,总结临床特征,观察haplo-HSCT后植入情况、无病及总体生存率、白血病复发及相关并发症,分析影响生存率的因素。结果 23例AL患儿中,男16例,女7例,中位年龄8.0(4.0～13.5)岁。供者中父亲8例,母亲9例,兄弟姐妹6例,HLA配型3/6相合11例,4/6相合8例,5/6相合3例,6/6相合1例(来自患儿母亲)。回输CD34+细胞平均数10.59(2.90～39.44)×106/kg,回输MNC平均数16.58(6.06～27.49)×108/kg。所有患儿均获得完全植入。急性移植物抗宿主病(GVHD)Ⅰ°～Ⅱ°20例,占87%;Ⅲ°～Ⅳ°3例,占13%;慢性GVHD发生率59%(13/23)。中位随访时间896(62-2443)d。死亡病例中5例为白血病复发,6例死于移植相关并发症,12例无病存活。5年总生存率52.2%。复发率21.7%。仅复发为影响生存率的因素,与白血病类型、病人性别、年龄、移植前状态,预处理方案、aGVHD之间差异均无显著性。结论 haplo-HSCT治疗儿童AL总生存率可达到50%以上,复发率相对较低,GVHD以轻度为主,重度GVHD可控制理想。多因素分析影响生存率的主要原因为原发病复发,但是GVHD仍是可能影响因素,由于病例数较少,需要扩大样本量再评估。     

无关供体造血干细胞移植治疗46例儿童难治性白血病疗效分析

目的 评估无关供体造血干细胞移植(UDT)治疗儿童难治性白血病的疗效.方法 回顾性分析连续在我院接受UDT的46例白血病患儿的临床资料.急性淋巴细胞性白血病(ALL)患儿接受全身放疗为主的预处理、急性髓细胞性白血病(AMI)和慢性粒细胞性白血病(CML)患儿采用白消安清髓.结果 中位年龄8.0(2～17)岁,3年总存活率(OS)63.0%,23.9%患儿死于移植相关并发症,13.0%患儿死于白血病复发.移植过程中33.3%出现Ⅲ～Ⅳ度急性移植物抗宿主病(aGVHD),55.6%发生慢性移植物抗宿主病(GVHD)(13.9%为慢性广泛性GVHD).大于10岁、小于10岁患儿的OS差异有统计学意义(45.0%vs. 76.9%,P=0.015);ALL患儿3年OS明显差于CML和AML(38.4%、66.7%vs. 80.0%,P=0.034);高危白血病疗效明显差于低危患儿(45.8% vs.81.8%,P=0.012);人类白细胞抗原(HLA)高分辨6/6全相合、1/6不合较2/6位点不合患儿的OS显著增高(75.0%,75.0% vs.16.7%,P=0.007);移植中出现Ⅲ～Ⅳ度与0～Ⅱ度aGVHD患儿相比OS差异无统计学意义(66.0% vs.66.7%,P=0.494).结论 UDT治疗我国儿童难治性白血病疗效令人满意.小于10岁、HLA相合度高是UDT的有利因素,髓系、低危白血病疗效优于其他白血病.     

Rapid,low-cost MR imaging protocol to document central nervous system and sinus abnormalities prior to pediatric hematopoietic stem cell transplantation

Patients undergoing bone marrow transplant (BMT) are at risk for infectious complications, including those of the sinus. Central nervous system (CNS) abnormalities related to the chemotherapy or radiation that the patient received for the treatment of underlying malignancy or to transplant-related effects are also commonly seen. The only effective way to differentiate pre- and post-transplant causes is to have a baseline evaluation prior to the admission for transplant. The current method used to evaluate these patients is head CT. However, CT is not accurate to demonstrate CNS abnormalities and exposes the patient to radiation. MRI, despite better sensitivity for white matter abnormalities, has not been routinely used because of the higher cost and longer duration of the exam. Therefore, we designed a fast, low-cost and radiation-free MRI-based protocol to simultaneously evaluate sinus and brain abnormalities.     

Two SCID cases with Cernunnos-XLF deficiency successfully treated by hematopoietic stem cell transplantation

SCID affects T and B cell differentiation and functions, presenting with severe opportunistic infections in the early postnatal period. It is fatal unless stem cell transplantation is performed. RS SCID forms are caused by defects in the NHEJ pathway, the enzymatic process required for the repair of DNA double-strand breaks. Cernunnos-XLF defect is one of the defects in this pathway. Here, we present two patients with Cernunnos-XLF defect, both having microcephaly, prominent growth retardation, and T-B-NK+SCID, one of whom had AHA. These patients received hematopoietic stem cells from HLA identical related donor without conditioning regimen and recovered without any complication. Now, both of the patients are well and alive seven and one yr after transplantation, respectively. A remarkable observation was the severe diarrhea that occurred in both patients soon after transplantation.     

Successful HLA-identical hematopoietic stem cell transplantation in a patient with purine nucleoside phosphorylase deficiency

PNP deficiency is an autosomal recessive metabolic disorder characterized by severe combined immunodeficiency, autoimmune hemolytic anemia, and by a complex of neurologic manifestations including ataxia, developmental delay, and spasticity. PNP protein catalyzes the phosphorolysis of deoxyinosine and deoxyguanosine. It is found in most tissues of the body but is expressed at the highest levels in lymphoid tissues. This tissue distribution explains why the lymphoid system is predominantly affected in PNP deficiency. We describe a five-yr-old boy with muscular hypertonia, impaired growth, autoimmune hemolytic anemia, and neutropenia who underwent HSCT from his HLA-identical sister. One yr post-HSCT, the boy developed normal immunological functions, and his neurological status improved.     

儿童造血干细胞移植后巨细胞病毒感染的临床研究

目的了解儿童造血干细胞移植后巨细胞病毒的感染率和防治方法。方法对从2001年8月到2007年3月北京儿童医院血液病中心37例作造血干细胞移植的血液肿瘤及先天遗传性疾病患儿进行回顾性分析。结果31例可研究病例中,5例自体造血干细胞移植及5例同基因造血干细胞移植患儿无人类巨细胞病毒（HCMV）感染,21例异基因造血干细胞移植患儿,发生HCMV感染7例,感染率为33.3%,大剂量阿昔洛韦加丙种球蛋白预防及早期更昔洛韦加大剂量静脉丙种球蛋白治疗,仅1例发生巨细胞病毒相关性间质性肺炎（CMV-IP）,无1例发生巨细胞病毒感染相关死亡。结论巨细胞病毒感染是儿童造血干细胞移植术后的主要并发症,临床上进行定期监测、前瞻性预防、早期诊断和及时合理治疗,对降低移植术后巨细胞病毒感染和提高移植成功率至关重要。     

原发性免疫缺陷病造血干细胞移植患儿呼吸道合胞病毒感染特征

目的 了解原发性免疫缺陷病(PID)患儿在造血干细胞移植过程中呼吸道合胞病毒(RSV)感染临床特征和转归.方法 移植前以及移植后连续收集白2009年4月到2010年9月于重庆医科大学附属儿童医院接受造血干细胞移植的9例患儿鼻咽吸取物(NPA),采用荧光定量PCR法检测RSV,对阳性标本进行病毒分离,扩增G基因用于遗传进化分析,并收集临床资料分析其临床感染特征.结果 9例患儿中3例检出RSV,检出率为33.3%,且在3例阳性患儿NPA中多次分离出RSV,并通过G基因序列分析发现,3例患儿均感染RSV B亚型毒株,在体内持续复制数月之久.其临床表现均为肺炎,未见明显重症倾向.1例患儿抗病毒治疗,3例患儿均静脉滴注丙种球蛋白(IVIG),均好转出院.而同期于该院呼吸病房因急性下呼吸道感染(ALRTI)住院儿童RSV感染率仅为20%,且以B亚型为优势流行株,10例RSV B亚型同期呼吸科病房普通患儿临床症状与PID造血干细胞移植患儿相似.结论 PID造血干细胞移植患儿更易感染RSV,且可在体内可持续复制数月,及时诊断和治疗,随着免疫功能逐步重建,RSV感染多可恢复.

Abstract：

Objective To understand the clinical characteristics and outcome associated with respiratory syncytial virus(RSV)infection in hematopoietic stem cell transplantation(HSCT)recipients with primary immunodeficiencies(PIDs).Method Nasopharyngeal aspirate samples were collected consecutively before and after HSCT from 9 recipients from Apr. 2009 to Sep.2010 and analyzed for the presence of RSV using real-time polymerase chain reaction assay.To further verify the presence of the virus, positive samples for PCR were isolated for RSV.RSV G gene was amplified,sequenced and used for phylogentic analysis. Result The presence of RSV was detected in 3 out of 9 children. The viral replication in all the patients was prolonged for months. All the 3 patients with RSV infection were treated with intravenous immune globulin (IVIG) and one was treated with antiviral medication. All patients survived and achieved successful immune reconstitution. Conclusion This study indicates that the HSCT recipients with PID are at increased risk for RSV infection. RSV can shed for months after the initial infection and the patients recover with the course of immune reconstitution.     

Allogeneic hematopoietic stem cell transplantation is associated with cure and durable remission of late‐onset primary isolated central nervous system hemophagocytic lymphohistiocytosis

Primary isolated CNS presentation of HLH is exceedingly rare and typically associated with significant morbidity and mortality. We describe an adolescent patient with late‐onset, primary isolated CNS HLH and a compound heterozygous PRF1 mutation (c50delT (p.L17 fs); c.1229G>C (p.R410P)), not previously reported with this phenotype. He was successfully treated with allogeneic HSCT following a reduced‐intensity conditioning regimen, despite a high pre‐HSCT comorbidity index. Two years after transplant, he is alive and in disease remission. While patients with systemic HLH and active CNS disease have relatively poorer outcomes, a high index of suspicion may aid with early diagnosis of primary isolated CNS HLH; prompt treatment with HSCT may be associated with improved cure and durable remission of this rare disease.     

Successful treatment of disseminated mixed invasive fungal infection after hematopoietic stem cell transplantation for severe aplastic anemia

Concomitant infections are frequent and usually the causes of death in patients with severe AA. HSCT can restore hematopoiesis in AA, but it is usually life threatening when patients simultaneously have an IFI. Mixed IFIs have been reported on rare occasions. The exact diagnosis of IFIs is difficult because of low fungus culture rate, difficultly obtaining tissue specimens in severely immunocompromised patients or those with bleeding tendencies. Otherwise, treatment with anti-fungal drugs alone for DMIFI was always lethal in previous reports. Surgical resection is crucial for invasive zygomycosis, but severe pancytopenia and bleeding tendency make therapy difficult. Herein, we report that with a combination of aggressive anti-fungal drugs, HSCT, and surgery, we successfully treated a 10-yr-old boy with severe AA and pulmonary zygomycosis before HSCT and disseminated mixed invasive zygomycosis and aspergillosis after HSCT.