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去除T细胞的自体骨髓移植疗法:免疫缺陷及晚期并发症分析

T-cell-depleted autologous bone marrow transplantation therapy: analysis of immune deficiency and late complications.

作者信息

Anderson K C, Soiffer R, DeLage R, Takvorian T, Freedman A S, Rabinowe S L, Nadler L M, Dear K, Heflin L, Mauch P

机构信息

Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.

出版信息

Blood. 1990 Jul 1;76(1):235-44.

PMID:2194591
Abstract

Fourteen patients with T-cell-derived leukemia and lymphoma underwent high-dose chemoradiotherapy and anti-T-cell monoclonal antibody-treated autologous bone marrow transplantation (ABMT). All patients were either in sensitive relapse or had adverse prognostic features, and five patients had a history of bone marrow involvement with disease. Patients received a median of 2 (1 to 3) prior chemotherapy regimens; 10 patients received local radiotherapy. After high-dose ablative therapy, greater than 500/mm3 granulocytes and greater than 20,000 untransfused platelets/mm3 were noted at a median of 23 (13 to 48) and 26 (15 to 43) days post-ABMT, respectively. Natural killer (NK) cells, T cells (predominantly T8+), and monocytes were noted within the first 1 to 2 months post-AMBT, as seen in other series. Disease-free survival was a median of 10.1 months, 5.9 months for patients with T acute lymphoblastic leukemia or lymphoblastic lymphoma and 25.6 months for patients with T non-Hodgkin's lymphoma (NHL). Toxicities were common and severe. Thirty-six percent of patients developed bacteremias early post-BMT. Late complications included a skin rash consistent with graft versus host disease; infections with Herpes zoster, hepatitis, and Pneumocystis carinii; and the development of Epstein-Barr virus associated lymphoproliferative syndrome. Our findings suggest that patients who have undergone T-depleted ABMT have a profound immunodeficiency not reflected in the phenotypic reconstitution of the T and NK cells. Characterization of the functional deficiency may facilitate the development of methods to reduce the long-term toxicity of AMBT in these patients.

摘要

14例T细胞源性白血病和淋巴瘤患者接受了大剂量放化疗及抗T细胞单克隆抗体治疗的自体骨髓移植(ABMT)。所有患者均处于敏感复发期或具有不良预后特征,5例患者有骨髓受累病史。患者接受的化疗方案中位数为2(1至3)种;10例患者接受了局部放疗。在大剂量清髓治疗后,ABMT后中位数23(13至48)天和26(15至43)天时分别出现大于500/mm³的粒细胞和大于20,000/mm³未输注血小板。如其他系列研究所示,在ABMT后的前1至2个月内可检测到自然杀伤(NK)细胞、T细胞(主要为T8⁺)和单核细胞。无病生存期的中位数为10.1个月,T急性淋巴细胞白血病或淋巴细胞淋巴瘤患者为5.9个月,T非霍奇金淋巴瘤(NHL)患者为25.6个月。毒性反应常见且严重。36%的患者在BMT后早期发生菌血症。晚期并发症包括与移植物抗宿主病一致的皮疹;带状疱疹、肝炎和卡氏肺孢子虫感染;以及爱泼斯坦-巴尔病毒相关淋巴增殖综合征的发生。我们的研究结果表明,接受T细胞去除的ABMT的患者存在严重的免疫缺陷,这在T细胞和NK细胞的表型重建中未得到体现。对功能缺陷的特征描述可能有助于开发降低这些患者ABMT长期毒性的方法。

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