Stem cell transplantation with chemoradiotherapy myeloablation and interleukin-2.
Stem cell transplantation with chemoradiotherapy myeloablation and interleukin-2.
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干细胞移植联合放化疗、清髓术和白细胞介素-2。
DOI：
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发表时间：
1996
期刊：
影响因子：
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通讯作者：
A. Mazumder
中科院分区：
文献类型：
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作者：
K. Meehan;Udit Verma;C. Rajogopal;R. Cahill;S. Frankel;A. Mazumder
白细胞介素2（IL-2）在体外和体内均刺激T细胞的增殖。当鼠或人外周血（PB）或骨髓（BM）单核细胞与IL-2在体外孵育24小时时，产生细胞毒性T细胞。如果将这些活化的细胞输注到小鼠中，如果施用低剂量IL-2，则增强的细胞毒性继续。给予活化细胞与随后的低剂量IL-2输注的这种组合导致增强的肿瘤细胞破坏和改善的急性髓性白血病小鼠的存活率。这些实验室实验的令人鼓舞的结果促使在难治性/复发性恶性血液病患者和乳腺癌患者（II-IV期）中启动I期临床试验。这些试验的结果表明，用IL-2活化的干细胞（PB或BM）进行的干细胞移植伴或不伴IL-2的胃肠外施用导致造血重建，具有轻度至中度毒性。该方案还产生皮肤和内脏自体移植物抗宿主病（AuGVHD）。我们的大多数复发性/难治性恶性血液病或乳腺癌患者的临床和/或组织学证据的AuGVHD。正在进行进一步的研究，以确定发展AuGVHD的患者是否从可能的自体移植物抗肿瘤（GVT）效应中获得改善的无病生存期。目前的实验室评价包括阐明AuGVHD的发病机制和IL-2的清除功效的分子评价。
Interleukin 2 (IL-2) stimulates the proliferation of T-cells both in vitro and in vivo. When murine or human peripheral blood (PB) or bone marrow (BM) mononuclear cells are incubated with IL-2 in vitro for 24 hours, cytotoxic T-cells are generated. If these activated cells are infused into mice, the enhanced cytotoxicity continues if low dose IL-2 is administered. This combination of administering activated cells with the subsequent low dose IL-2 infusion results in enhanced tumor cell destruction and improved survival rates in mice with acute myeloid leukemia. The encouraging results of these laboratory experiments prompted the initiation of phase I clinical trials in patients with refractory/relapsed hematologic malignancies and patients with breast cancer (Stages II-IV). Results from these trials demonstrate that stem cell transplantation with IL-2 activated stem cells (either PB or BM) with or without parenteral administration of IL-2 results in hematopoietic reconstitution with mild-to-moderate toxicities. This regimen also generates cutaneous and visceral autologous graft versus host disease (AuGVHD). The majority of our patients with relapsed/refractory hematologic malignancies or breast cancer developed either clinical and/or histological evidence of AuGVHD. Further studies are being conducted to determine if patients who develop AuGVHD experience improved disease-free survival from a possible autologous graft versus tumor (GVT) effect. Current laboratory evaluations include the elucidation of the pathogenesis of AuGVHD and molecular evaluation of the purging efficacy of IL-2.