Quinones R R, Gutierrez R H, Dinndorf P A, Gress R E, Ney A B, Taylor B, Karandish S, Carter C S, Luban N L, Reaman G H
Department of Hematology/Oncology, Children's National Medical Center, Washington, DC 20010.
Blood. 1993 Jul 1;82(1):307-17.
We report the development of a double-cycle elutriation (DCE) technique separating 3 or greater logs of T cells from a stem-cell-enriched marrow fraction and the results of phase I T-cell depletion studies with HLA-disparate related bone marrow transplantation (BMT) donors in two patient groups. In group 1, 10 patients with refractory hematopoietic malignancies received combination chemotherapy, total body irradiation (TBI), and immunosuppression (pre- and post-BMT), and hematopoietic rescue with a marrow transplant, depleted of T cells by elutriation. Potentially to promote engraftment and a graft-versus-leukemia (GVL) effect, 0.5 to 0.75 x 10(5) T cells/kg were added back. All 10 patients engrafted. Five patients developed acute graft-versus-host disease (GVHD; four grade II, one grade III) and two subsequently developed chronic GVHD. Two patients have relapsed (median follow-up, 206 days; range, 46 to 1,035). Four patients died of BMT-related complications (three of infection, one of veno-occlusive disease [VOD]). Four patient are disease-free survivors (median follow-up, 960 days; range, 670 to 1,035). Group 2 included five infants, four with congenital lymphohematopoietic deficiencies and one with refractory acute lymphocytic leukemia (ALL). In these infants, busulfan and increased cyclophosphamide were substituted for TBI. Only the ALL patient received added T cells. Three patients engrafted: one has stable mixed chimerism, one relapsed with ALL, and one rejected the marrow. One patient had primary autologous recovery, while another failed to engraft. None developed GVHD. We conclude that, in this setting of HLA-disparate BMT with post-BMT antithymocyte globulin (ATG) and corticosteroids, DCE significantly depletes T cells from the marrow and that a defined number of T cells can be added without the occurrence of severe GVHD.
我们报告了一种双循环淘洗（DCE）技术的进展，该技术可从富含干细胞的骨髓组分中分离出3个或更多对数的T细胞，并报告了在两个患者组中对HLA不相合的相关骨髓移植（BMT）供体进行I期T细胞清除研究的结果。在第1组中，10例难治性血液系统恶性肿瘤患者接受了联合化疗、全身照射（TBI）和免疫抑制（BMT前后），并通过淘洗清除T细胞后进行骨髓移植造血挽救。为了潜在地促进植入和移植物抗白血病（GVL）效应，回输了0.5至0.75×10⁵个T细胞/kg。所有10例患者均实现植入。5例患者发生了急性移植物抗宿主病（GVHD；4例为II级，1例为III级），2例随后发生了慢性GVHD。2例患者复发（中位随访时间为206天；范围为46至1035天）。4例患者死于与BMT相关的并发症（3例死于感染，1例死于静脉闭塞性疾病[VOD]）。4例患者为无病生存者（中位随访时间为960天；范围为670至1035天）。第2组包括5名婴儿，4名患有先天性淋巴造血缺陷，1名患有难治性急性淋巴细胞白血病（ALL）。在这些婴儿中，用白消安和增加剂量的环磷酰胺替代了TBI。只有ALL患者接受了额外的T细胞。3例患者实现植入：1例具有稳定的混合嵌合体，1例ALL复发，1例排斥骨髓。1例患者出现原发性自体恢复，而另1例未能植入。无人发生GVHD。我们得出结论，在这种采用BMT后抗胸腺细胞球蛋白（ATG）和皮质类固醇的HLA不相合BMT情况下，DCE可显著清除骨髓中的T细胞，并且添加一定数量的T细胞不会发生严重GVHD。
