Hematopoietic stem cell

造血干细胞
  • 文章类型: Review
    背景:在包括输血在内的情况下,CD36缺陷型个体可能通过抗原暴露于CD36而产生抗CD36抗体。因此,从CD36阳性供体到CD36阴性患者的异基因造血干细胞移植(HSCT)仍然是一个挑战。
    方法:一名64岁的急性髓系白血病患者在化疗期间难以输注血小板。检测血清中不含抗HLA抗体的抗CD36抗体,血小板和单核细胞CD36表达缺失证实I型CD36缺乏。病人完全缓解,并接受CD36阴性血小板输注维持治疗。然而,他很快就复发了,因此接受了来自CD36阳性无关供体的外周血干细胞移植(PBSCT)。抗CD36抗体滴度在移植前有所下降,PBSCT课程顺利。患者没有任何与CD36状态不匹配相关的并发症。
    结论:在CD36缺乏症患者中出现同种异体HSCT的少数报道表明,抗CD36抗体可能与几种移植后并发症有关,如血小板恢复延迟,输血难治性,与输血相关的急性肺损伤。我们目前的病例证实,从CD36阳性供体到阴性患者的干细胞移植是可行的,当它包括仔细事先评估抗CD36抗体滴度和干预以减弱它们时。
    BACKGROUND: CD36-deficient individuals may produce anti-CD36 antibodies through antigenic exposure to CD36, in situations including blood transfusions. Therefore, allogeneic hematopoietic stem cell transplantation (HSCT) from CD36-positive donors to CD36-negative patients remains a challenge.
    METHODS: A 64-year-old man with acute myeloid leukemia became refractory to platelet transfusions during chemotherapy. Anti-CD36 antibodies without anti-HLA antibodies were detected in serum, and the absence of CD36 expression on platelets and monocytes confirmed type I CD36 deficiency. The patient achieved complete remission, and received maintenance therapy with CD36-negative platelet transfusions. However, he relapsed soon afterward, and thus underwent peripheral blood stem cell transplantation (PBSCT) from a CD36-positive unrelated donor. The anti-CD36 antibody titer had decreased before the transplant, and the PBSCT-course was uneventful. The patient has been well without any complications associated with CD36 status mismatch.
    CONCLUSIONS: The few reports of allogeneic HSCT in patients with CD36 deficiency have suggested that anti-CD36 antibodies could be involved in several post-transplant complications, such as delayed platelet recovery, transfusion refractoriness, and transfusion-related acute lung injury. Our present case confirmed that stem cell transplantation from CD36-positive donors to negative patients is feasible, when it includes careful prior assessment of anti-CD36 antibody titers and interventions to attenuate them.
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  • 文章类型: Case Reports
    探讨异基因造血干细胞移植(allo-HSCT)治疗人类疱疹病毒8型(HHV8)阳性多中心Castleman病(MCD)患者的长期临床疗效。
    河南省人民医院收治一名17岁女性患者,因发热住院半个月,头痛,2010年10月5日浅表淋巴结肿大。淋巴结活检病理诊断发现HHV8阳性混合细胞Castleman病。CHOP和Hyper-CVAD-B给药后,病人还在发热,我们管理了随后的COAP,两节VAD(长春新碱,阿霉素,地塞米松),患者接受CR。CR后六个月,病人复发了,我们给予VAD和两个疗程的硼替佐米+地塞米松化疗,然后病人接受了PR.之后,患者在接受Bu/Cy+依托泊苷+Smoustin预处理后,接受了人类白细胞抗原(HLA)匹配的非亲缘供者的allo-HSCT.移植物抗宿主病(GVHD)预防,由ATG(7.5mg/kg,qd,静脉滴注)从d-5到d-2,环孢菌素(3mg/kg/d,qd,ivdrip,24小时)从第1天开始,MMF(0.5g,tid,po.)从第+1天到第+28天开始,MTX(每次15mg,ivdrip,d+1、+4、+7、+11)。患者接受3.5×106/LCD34+细胞和8.1×108/LMNC。
    粒细胞移植发生在第+12天,血小板移植发生在第+14天。骨髓活检显示三系造血在第33天恢复正常,嵌合状态:97.6%。移植成功,随访7年。
    Allo-HSCT可能治愈难治性/复发性HHV8+MCD患者。
    To investigate the long-term clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with human herpes virus 8 (HHV8)-positive multicentric Castleman\'s disease (MCD).
    A 17-year-old female patient was admitted to Henan Provincial People\'s Hospital with the complaint of febrile for half a month, headache, and enlarged superficial lymph nodes on October 5, 2010. HHV8-positive mixed cellular Castleman\'s disease was found by pathological diagnosis of lymph nodes biopsy. After the administration of CHOP and Hyper-CVAD-B, the patient was still febrile, we administrated the followed COAP, two courses of VAD(Vincristine, Adriamycin, Dexamethasone), the patient received CR. Six months after CR, the patient relapsed, we administrated VAD and two courses of bortezomide+dexamethasone chemotherapy, and then the patient received PR. After that, the patient underwent allo-HSCT from his human leukocyte antigen (HLA)-matched unrelated donor after conditioning with Bu/Cy+Etoposide+Smoustin.graft-vs-host disease (GVHD) prophylaxis, which consisted of ATG (7.5 mg/kg, qd, ivdrip) from d-5 to d-2, cyclosporine (3 mg/kg/d, qd, ivdrip, for 24 h) started from day-1, MMF(0.5 g, tid, po.) started from day+1 to +28, and MTX (15 mg per time, ivdrip, d+1,+4,+7,+11). She received 3.5×106/L CD34+cells and 8.1×108/LMNC.
    Granulocyte engraftment occurred on day+12, platelet engrafted on day+14. Bone marrow biopsy showed normalization of trilineage hematopoiesis on day+33, chimerism: 97.6%. The transplantation was successful and followed up for 7 years with CR.
    Allo-HSCT might cure patients with refractory/relapsed HHV8+ MCD.
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  • 文章类型: Case Reports
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  • 文章类型: Journal Article
    OBJECTIVE: HLA-C*07:66 is a low-incidence HLA-C allele. The aim of the study is to report the Taiwanese and mainland Chinese ethnicities of individuals with C*07:66, together with its uniqueness and polymorphism.
    METHODS: A sequence-based typing method was employed to confirm this low-incidence allele. Polymerase chain reaction was performed to amplify exons 2, 3, and 4 of the HLA-A, HLA-B, and HLA-C loci and exon 2 of the HLA-DRB1 and HLA-DQB1 loci using group-specific primer sets. The amplicons were sequenced in both directions using BigDye Terminator Cycle Sequencing Ready Reaction kit. The blood donors in this study consisted of randomized Taiwanese and mainland Chinese individuals and family members with the C*07:66 allele.
    RESULTS: The DNA sequence of C*07:66 is identical to that of C*07:02:01:01 for exons 2, 3, and 4, except for residue 688 in exon 4. This nucleotide substitution causes a single amino acid alteration to the protein sequence of C*07:02:01:01. Confirmation of the DNA and protein sequences of C*07:66 and the Taiwanese and mainland Chinese ethnicities of individuals with this allele were established in this study. One probable HLA C*07:66-associated HLA haplotype may be deduced from these individuals.
    CONCLUSIONS: The information on the ethnicity of the C*07:66 allele and the deduced probable HLA haplotype associated with the low-incidence C*07:66 allele reported in this study may aid in HLA testing laboratories for reference purposes. In addition, they can be used by stem cell transplant donor search coordinators to help create, for patients bearing this uncommon HLA allele, strategies for finding compatible donors using bone marrow donor registries comprising unrelated individuals.
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  • 文章类型: Journal Article
    目的:HLA-C*04:82是低发生率的HLA-C等位基因。这里的目的是报告台湾个体中C*04:82的种族及其相关的HLA单倍型。
    方法:使用基于序列的分型方法来确认该低发生率等位基因。进行聚合酶链反应以扩增HLA-A的外显子2和3,HLA-B,以及使用组特异性引物组的HLA-C基因座和HLA-DRB1基因座的外显子2。使用终止子循环测序就绪反应试剂盒和制造商的方案在两个方向上对扩增子进行测序。本研究中潜在的无关骨髓干细胞捐献者是参与慈济骨髓捐献者注册的台湾种族的随机个体。研究的家庭部分中的家庭成员是自愿献血者。
    结果:C*04:82的DNA序列在外显子2、3和4中与C*04:01:01相同。它不同于外显子5中的C*04:01:01:01,其中核苷酸区段(CTAGCTGTC)插入在C*04:01:01:01的残基969和970之间。这些核苷酸的插入导致C*04:01:01:01的蛋白质序列发生35个氨基酸的改变。推断了台湾个体中与C*04:82相关的三种可能的HLA单倍型。在这项研究中,确定了C*04:82的DNA和蛋白质序列及其台湾种族。
    结论:C*04:82等位基因的种族和与低发生率C*04:82等位基因相关的推测可能的HLA单倍型对于HLA检测实验室具有参考价值。此外,搜索协调员可以使用它们来帮助创建一种策略,为携带这种罕见HLA等位基因的患者寻找相容的干细胞供体.
    OBJECTIVE: HLA-C*04:82 is a low incidence HLA-C allele. The aim here is to report the ethnicity of C*04:82 and its associated HLA haplotypes among Taiwanese individuals.
    METHODS: A sequence-based typing method was used to confirm this low incidence allele. Polymerase chain reaction was performed to amplify exons 2 and 3 of the HLA-A, HLA-B, and HLA-C loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced in both directions using Terminator Cycle Sequencing Ready Reaction kits and the manufacturer\'s protocols. The potential unrelated bone marrow stem cell donors in this study were randomized individuals with Taiwanese ethnicity who participated in the Tzu Chi Bone Marrow Donor Registry. The family members in the family part of the study were volunteer blood donors.
    RESULTS: The DNA sequence of C*04:82 was identical to C*04:01:01:01 in exons 2, 3, and 4. It differed from C*04:01:01:01 in exon 5 where a segment of nucleotides (CTAGCTGTC) was inserted between residues 969 and 970 of C*04:01:01:01. The insertion of these nucleotides caused a 35 amino acid alteration to the protein sequence of C*04:01:01:01. Three probable HLA haplotypes that were associated with C*04:82 among Taiwanese individuals were deduced. Confirmation of the DNA and protein sequences of C*04:82 and its Taiwanese ethnicity were established in this study.
    CONCLUSIONS: The ethnicity of the C*04:82 allele and the deduced probable HLA haplotypes associated with the low-incidence C*04:82 allele are of value for reference purposes for HLA testing laboratories. In addition, they can be used by search coordinators to aid the creation of a strategy for finding compatible stem cell donors for patients who carry this uncommon HLA allele.
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  • 文章类型: Journal Article
    OBJECTIVE: HLA-C*07:359 is a low-incidence allele in the human leukocyte antigen (HLA)-C locus. The objective of this study is to report the ethnicity and haplotypes of HLA-C*07:359 that were found during an analysis of Taiwanese unrelated bone marrow hematopoietic stem cell donors.
    METHODS: A sequence-based typing method was employed to confirm low-incidence al-leles. Polymerase chain reaction was performed to amplify exon 2 and exon 3 of the HLA-A, HLA-B, and HLA-C loci, as well as exon 2 of the HLA-DRB1 locus, using group-specific primer sets. The amplicons were sequenced in both directions using BigDye Terminator Cycle Sequencing Ready Reaction kits, according to the manufacturer\'s protocols. The potential unrelated bone marrow stem cell donors investigated here are individuals with Taiwanese ethnicity who are participating in the Tzu Chi Bone Marrow Donor Registry.
    RESULTS: The DNA sequence of C*07:359 is identical to that of C*07:02:01:01 in exons 2, 3, and 4 except at residue 862, where the G of C*07:02:01:01 is substituted by the A of C*07:359. The nucleotide exchange leads to an amino acid replacement at codon 264, where the glutamic acid of C*07:02:01:01 is replaced by the lysine of C*07:359. We deduced a probable HLA-B and HLA-C haplotype that is associated with C*07:359 in Taiwanese, namely B*39-C*07:359.
    CONCLUSIONS: Information on the ethnicity of the C*07:359 allele and its deduced probable HLA haplotypes that are associated with the low-incidence C*07:359 allele reported here are of value to HLA testing laboratories for reference purposes. In addition, they can be used by stem cell transplantation donor search coordinators to determine a strategy for finding compatible donors using unrelated bone marrow donor registries when patients carry this uncommon HLA allele.
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  • 文章类型: Journal Article
    目的:HLA-DRB1*16:35是HLA-DRB1位点的低发生率等位基因。这项研究的目的是报告两名台湾无关骨髓造血干细胞供体中DRB1*16:35的种族及其推导的可能的HLA相关单倍型,并确定其与DRB1*16:02:01和DRB1的变异*16:01:01。
    方法:采用基于序列的分型方法确认低发生率等位基因DRB1*16:35。使用组特异性引物组进行聚合酶链反应以扩增HLA-A和HLA-B基因座的外显子2和外显子3以及HLA-DRB1基因座的外显子2。根据制造商的方案,采用BigDye终止子循环测序就绪反应试剂盒在两个方向上对扩增子进行测序。
    结果:DRB1*16:35的DNA序列与外显子2中的DRB1*16:02:01相同,除了残基364,其中DRB1*16:02:01的C被DRB1*16:35的T取代(密码子93,CGG->TGG)。核苷酸交换导致残基93处DRB1*16:02:01的蛋白质序列的氨基酸改变,其中DRB1*16:02:01的精氨酸(R)变为DRB1*16:35的色氨酸(W)。我们推断台湾与DRB1*16:35相关的可能的HLA单倍型为A*11-B*13-DRB1*16:35。
    结论:我们在此报告的与低发病率DRB1*16:35等位基因相关的推断可能HLA单倍型的信息对于HLA检测实验室具有参考价值。此外,干细胞移植供者搜索协调员可以使用该方法来确定当患者具有这种罕见的HLA等位基因时,在无关的骨髓供者登记处寻找相容供者的策略.
    OBJECTIVE: HLA-DRB1*16:35 is a low incidence allele in the HLA-DRB1 locus. The objective of this study is to report the ethnicity of DRB1*16:35 and its deduced probable HLA associated haplotype in two Taiwanese unrelated bone marrow hematopoietic stem cell donors and to determine its variation from DRB1*16:02:01 and DRB1*16:01:01.
    METHODS: A sequence-based typing method was employed to confirm the low incidence allele DRB1*16:35. Polymerase chain reaction was performed to amplify exon 2 and exon 3 of the HLA-A and HLA-B loci and exon 2 of the HLA-DRB1 locus using group-specific primer sets. The amplicons were sequenced employing BigDye Terminator Cycle Sequencing Ready Reaction kits in both directions according to the manufacturer\'s protocols.
    RESULTS: The DNA sequence of DRB1*16:35 is identical to DRB1*16:02:01 in exons 2, except for residue 364 where the C of DRB1*16:02:01 is replaced by the T of DRB1*16:35 (codon 93, CGG->TGG). The nucleotide exchange leads to an amino acid alteration to the protein sequence of DRB1*16:02:01 at residue 93 where the arginine (R) of DRB1*16:02:01 is changed to the tryptophan (W) of DRB1*16:35. We deduced the probable HLA haplotype in association with DRB1*16:35 in Taiwanese to be A*11-B*13- DRB1*16:35.
    CONCLUSIONS: Information on the deduced probable HLA haplotype in association with the low incidence DRB1*16:35 allele that we report here is of value for HLA testing laboratories for reference purposes. In addition, it can be used by stem cell transplantation donor search coordinators to determine a strategy for finding compatible donors in unrelated bone marrow donor registries when a patient has this uncommon HLA allele.
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