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供体淋巴细胞输注治疗复发的慢性粒细胞白血病:初始细胞剂量对预后的影响

Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose.

作者信息

Guglielmi Cesare, Arcese William, Dazzi Francesco, Brand Ronald, Bunjes Donald, Verdonck Leo F, Schattenberg Anton, Kolb Hans-Jochem, Ljungman Per, Devergie Agnes, Bacigalupo Andrea, Gomez Marta, Michallet Mauricette, Elmaagacli Ahmet, Gratwohl Alois, Apperley Jane, Niederwieser Dietger

机构信息

Università La Sapienza, Dipartimento di Biotecnologie Cellulari ed Ematologia, Unità TMO Allogenico Giuseppe Papa, Rome, Italy.

出版信息

Blood. 2002 Jul 15;100(2):397-405. doi: 10.1182/blood.v100.2.397.

DOI:10.1182/blood.v100.2.397
PMID:12091328
Abstract

Donor lymphocyte infusion (DLI) can produce durable remissions in patients with chronic myelogenous leukemia (CML) who have a relapse after an allogeneic stem cell transplantation. However, the best modality to administer DLI is still unclear. The effect of the initial cell dose (ICD; ie, mononuclear cells x 10(8)/kg received in the first instance) on outcome was retrospectively analyzed in 298 of 344 patients treated with DLI at 51 centers. Patients were classified into 3 groups according to the ICD: 98 in group A (<or= 0.20), 107 in group B (0.21-2.0), and 93 in group C (> 2.0). Additional infusions were given to 62%, 20%, and 5% of patients in groups A, B, and C, respectively. A lower ICD was associated with less graft-versus-host disease (GVHD; A, 26%; B, 53%; C, 62%; P <.001), less myelosuppression (A, 10%; B, 23%; C, 24%; P =.01), and similar response rate (A, 78%; B, 73%; C, 70%; P =.48). Nonadjusted estimates of 3-year survival, failure-free survival, and DLI-related mortality were 84%, 66%, and 5% respectively, in group A; 63%, 57%, and 20% in group B; and 58%, 45%, and 22% in group C. Outcome analysis was adjusted for patient age, donor type, sex of donor, sex mismatch, disease phase at transplantation, T-cell depletion, interval from transplantation to DLI, GVHD prior to relapse, relapse type, and date of DLI. After adjustment, lower ICD was associated with less GVHD, less myelosuppression, same response rate, better survival, better failure-free survival, and less DLI-related mortality. Our results suggest that the first DLI dose should not exceed 0.2 x 10(8) mononuclear cells/kg.

摘要

供体淋巴细胞输注(DLI)可使慢性粒细胞白血病(CML)患者在异基因干细胞移植后复发时获得持久缓解。然而,DLI的最佳给药方式仍不明确。对51个中心接受DLI治疗的344例患者中的298例进行回顾性分析,以研究初始细胞剂量(ICD;即首次接受的单核细胞×10⁸/kg)对治疗结果的影响。根据ICD将患者分为3组:A组98例(≤0.20),B组107例(0.21 - 2.0),C组93例(>2.0)。A、B、C组分别有62%、20%和5%的患者接受了额外输注。较低的ICD与较少的移植物抗宿主病(GVHD;A组26%,B组53%,C组62%;P<0.001)、较少的骨髓抑制(A组10%,B组23%,C组24%;P = 0.01)以及相似的缓解率(A组78%,B组73%,C组70%;P = 0.48)相关。A组、B组和C组未调整的3年生存率、无失败生存率和DLI相关死亡率估计分别为84%、66%和5%;63%、57%和20%;以及58%、45%和22%。对患者年龄、供体类型、供体性别、性别不匹配、移植时疾病分期、T细胞去除、从移植到DLI的间隔时间、复发前的GVHD、复发类型和DLI日期进行了结果分析调整。调整后,较低的ICD与较少的GVHD、较少的骨髓抑制、相同的缓解率、更好的生存率、更好的无失败生存率以及较少的DLI相关死亡率相关。我们的结果表明,首次DLI剂量不应超过0.2×10⁸单核细胞/kg。

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