Transplantation of umbilical cord blood after myeloablative therapy: analysis of engraftment.
Transplantation of umbilical cord blood after myeloablative therapy: analysis of engraftment.
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DOI：
10.1182/blood.v79.7.1874.1874
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发表时间：
1992-04
期刊：
影响因子：
20.3
通讯作者：
J. Wagner;H. Broxmeyer;RL Byrd;B. Zehnbauer;B. Schmeckpeper;N. Shah;C. Griffin;P. Emanuel;K. Zuckerman;S. Cooper
中科院分区：
文献类型：
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作者：
J. Wagner;H. Broxmeyer;RL Byrd;B. Zehnbauer;B. Schmeckpeper;N. Shah;C. Griffin;P. Emanuel;K. Zuckerman;S. Cooper
在一名青少年慢性髓细胞性白血病（JCML）患者中检测了来自HLA相同同胞的脐带血和胎盘血可能产生稳定的供者来源的淋巴造血移植的可能性。用高剂量白消安和环磷酰胺预处理后，输注冷冻保存的脐带血，其中含有0.5 x 10（8）个有核细胞/kg和2.7 x 10（4）个集落形成单位-粒细胞、巨噬细胞（CFU-GM）/kg。在移植后第39、39和47天分别观察到白细胞计数大于1，000/μ L，中性粒细胞绝对计数（ANC）大于500/μ L，血小板计数大于20，000/μ L（未输血）。早在第21天，通过细胞遗传学分析、限制性片段长度多态性（RFLP）和聚合酶链反应（PCR）在外周血和骨髓中记录供体细胞植入。此外，证实了每种淋巴造血谱系（即，CD 5 + T细胞、CD 19/20+ B细胞、CFU-GM和爆发形成单位-红细胞[BFU-E]）的供体来源。在第200天，外周血和骨髓的测定显示在不存在外源性生长因子的情况下在低接种密度下CFU-GM的异常增殖，以及对粒细胞-巨噬细胞集落刺激因子（GM-CSF）的超敏反应，这两种均为JCML的病理生理特征。在第225天组织学证实疾病复发。总之，这些结果表明，脐带血中含有足够数量的造血干细胞，这些造血干细胞对于接受清髓性治疗的白血病患者的移植是必需的，并且在治疗后检测到“自发”CFU-GM和对GM-CSF的超敏反应是JCML患者中残留或复发疾病的标志物。
The possibility that umbilical cord and placental blood from an HLA-identical sibling might produce stable donor-derived lymphohematopoietic engraftment was tested in a patient with juvenile chronic myelogenous leukemia (JCML). After conditioning with high-dose busulfan and cyclophosphamide, cryopreserved umbilical cord blood, containing 0.5 x 10(8) nucleated cells/kg and 2.7 x 10(4) colony forming units-granulocyte, macrophage (CFU-GM)/kg, was infused. A leukocyte count greater than 1,000/microL, absolute neutrophil count (ANC) greater than 500/microL, and platelet count greater than 20,000/microL (untransfused) were observed on days 39, 39, and 47 after transplantation, respectively. Donor cell engraftment was documented in the peripheral blood and bone marrow by cytogenetic analysis, restriction fragment length polymorphism (RFLP), and polymerase chain reaction (PCR) as early as day 21. Furthermore, the donor origin of each lymphohematopoietic lineage (ie, CD5+ T cells, CD19/20+ B cells, CFU-GM, and burst-forming unit-erythrocyte [BFU-E]) was confirmed. On day 200, assays of the peripheral blood and bone marrow showed an abnormal proliferation of CFU-GM at low seeding densities in the absence of exogenous growth factors, as well as a hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), both pathophysiologic characteristics of JCML. Recurrent disease was confirmed histologically on day 225. Together, these results demonstrate that umbilical cord blood contains sufficient numbers of hematopoietic stem cells necessary for the engraftment of leukemia patients treated with myeloablative therapy and that the detection of "spontaneous" CFU-GM and hypersensitivity to GM-CSF after treatment is a marker of residual or recurrent disease in patients with JCML.