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T细胞去除的外周血干细胞同种异体移植联合T细胞回输治疗血液系统恶性肿瘤患者:慢性移植物抗宿主病对预后的影响

T-cell depleted peripheral blood stem cell allotransplantation with T-cell add-back for patients with hematological malignancies: effect of chronic GVHD on outcome.

作者信息

Montero Aldemar, Savani Bipin N, Shenoy Aarthi, Read Elizabeth J, Carter Charles S, Leitman Susan F, Mielke Stephan, Rezvani Katayoun, Childs Richard, Barrett A John

机构信息

Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892-1202, USA.

出版信息

Biol Blood Marrow Transplant. 2006 Dec;12(12):1318-25. doi: 10.1016/j.bbmt.2006.08.034.

Abstract

One hundred thirty-eight patients with hematologic malignancies received myeloablative T cell-depleted peripheral blood stem cell transplant (PBSCT) from an HLA-identical sibling donor. The T cell dose was adjusted to 0.2-1 x 10(5) CD3(+) cells/kg. The CD34 dose was 2.7-16 x 10(6)/kg. Patients with acute graft-versus-host disease (GVHD) grade <2 received 1 or 2 donor lymphocyte infusions of 10(7) CD3(+) cells/kg between days 45 and 100. Patients were designated according to relapse probability as standard or high relapse risk (77 and 61, respectively). Overall survival (OS), relapse-free survival, relapse, and transplant-related mortality (TRM) were 58%, 46%, 40%, and 20%, respectively, after a median follow-up of 4 years. Fifty-three (39%) and 21 (15%) patients developed grade 2-4 and 3-4 acute GVHD. Forty-two (36%) had limited and 29 (25%) had extensive chronic GVHD. In multivariate analysis, disease risk was an independent factor for OS and relapse, day-30 lymphocyte count for OS and TRM, and chronic GVHD for OS and relapse. PBSCT with early T cell add back leads to comparable rates of chronic GVHD compared with T cell-replete PBSCT. However, this chronic GVHD after T cell add back is associated with less mortality and retains a protective effect in terms of relapse, at least in the standard-risk patients.

摘要

138例血液系统恶性肿瘤患者接受了来自 HLA 相同同胞供者的清髓性 T 细胞去除外周血干细胞移植(PBSCT)。T 细胞剂量调整为 0.2 - 1×10⁵ CD3⁺细胞/kg。CD34 剂量为 2.7 - 16×10⁶/kg。急性移植物抗宿主病(GVHD)分级<2 级的患者在第 45 天至 100 天之间接受 1 或 2 次 10⁷ CD3⁺细胞/kg 的供者淋巴细胞输注。根据复发概率将患者分为标准复发风险或高复发风险(分别为 77 例和 61 例)。中位随访 4 年后,总生存期(OS)、无复发生存期、复发率和移植相关死亡率(TRM)分别为 58%、46%、40%和 20%。53 例(39%)和 21 例(15%)患者发生 2 - 4 级和 3 - 4 级急性 GVHD。42 例(36%)有局限性慢性 GVHD,29 例(25%)有广泛性慢性 GVHD。多因素分析显示,疾病风险是 OS 和复发的独立因素,第 30 天淋巴细胞计数是 OS 和 TRM 的独立因素,慢性 GVHD 是 OS 和复发的独立因素。与 T 细胞充足的 PBSCT 相比,早期添加 T 细胞的 PBSCT 导致慢性 GVHD 的发生率相当。然而,添加 T 细胞后的这种慢性 GVHD 与较低的死亡率相关,并且至少在标准风险患者中在复发方面保留了保护作用。

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