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抗T淋巴细胞球蛋白联合移植后25mg/kg环磷酰胺与移植后50mg/kg环磷酰胺用于急性白血病患者的比较

Anti-T lymphocyte globulin plus posttransplant cyclophosphamide 25 mg/kg versus posttransplant cyclophosphamide 50 mg/kg in patients with acute leukemias.

作者信息

Karakus Abdullah, Toptas Tayfur, Dal Mehmet Sinan, Durdu Ali, Hatipoglu Ugur, Kayer Merve Apaydin, Hindilerden Ipek Yonal, Tiryaki Tarik Onur, Iskender Dicle, Ulu Bahar Uncu, Yigenoglu Tugce Nur, Erkurt Mehmet Ali, Ulas Turgay, Altuntas Fevzi

机构信息

Dicle University, School of Medicine, Department of Internal Medicine, Division of Hematology, Diyarbakir, Türkiye.

Marmara University, School of Medicine, Department of Internal Medicine, Division of Hematology and Stem Cell Transplant Center, Istanbul, Türkiye.

出版信息

Bone Marrow Transplant. 2025 Apr 13. doi: 10.1038/s41409-025-02564-8.

Abstract

In this study, we aimed to compare the engraftment days, graft-versus-host disease (GVHD) development, relapse and overall survival rates in patients using myeloablative/reduced intensity conditioning regimens with posttransplant cyclophosphamide (PTCy) 25 mg/kg x2 with Anti-T lymphocyte Globulin (ATLG) (n = 29) and PTCy 50 mg/kg x2 doses (n = 41) in patients with acute leukemias. Matched related, matched unrelated, 1 mismatched unrelated, and haploidentical donors were selected for the patients. Platelet (median 11 vs 17 days) and neutrophil (median 14 vs 15 days) engraftment times were shorter in ATLG+ PTCy25 treated patients (both p < 0.05); veno-occlusive disease rates, graft failure and poor graft functions were similar between the two approaches (all p > 0.05); cumulative incidences of grade II-IV aGVHD at +100 days, grade III-IV aGVHD at +100 days, and grade II-IV cGVHD at 1-year were comparable between ATLG+PTCy25 and PTCy50 groups (all p > 0.05). Cumulative incidences of relapse and non-relapse mortality at 1-year were similar in two cohorts (both p > 0.05). PTCy50 was associated with a statistically significant benefit in terms of GVHD-free/relapse-free survival (GRFS) at 1-year (p = 0.03). Median GRFS was 115 (95% CI: 42-214) days and 248 (95% CI: 151-not reached) days, respectively [HR was 0.51 (0.28-0.95), p = 0.03; GRFS at 1-year was 20.7% vs 44.3%, respectively]. However, the groups were comparable in terms of PFS and OS. Median PFS was 332 days (95% CI: 182 days-not reached) for ATLG+PTCy25 group. It was not reached (95% CI: 210 days-not reached) for the patients who received PTCy50. Median OS was not reached in either ATLG+PTCy25 (95% CI: 191 days-not reached) or PTCy50 groups (Log rank = 0.42). Our study showed that lowering PTCy dose with ATLG seems to accelerate platelet and neutrophil engraftment rates; confers similar survival and relapse rates, similar acute and chronic GVHD frequency despite increased GRFS at 1-year.

摘要

在本研究中,我们旨在比较接受清髓性/减低强度预处理方案联合25mg/kg×2剂量的移植后环磷酰胺(PTCy)及抗T淋巴细胞球蛋白(ATLG)(n = 29)与50mg/kg×2剂量PTCy(n = 41)的急性白血病患者的植入天数、移植物抗宿主病(GVHD)发生情况、复发率及总生存率。为患者选择了匹配的亲属供者、匹配的非亲属供者、1个位点不匹配的非亲属供者及单倍体相合供者。接受ATLG + PTCy25治疗的患者血小板(中位时间11天对17天)和中性粒细胞(中位时间14天对15天)植入时间较短(均p < 0.05);两种方法的静脉闭塞性疾病发生率、移植物失败及移植物功能不良情况相似(均p > 0.05);ATLG + PTCy25组与PTCy50组在+100天时II-IV级急性GVHD、+100天时III-IV级急性GVHD及1年时II-IV级慢性GVHD的累积发生率相当(均p > 0.05)。两个队列1年时的复发和非复发死亡率累积发生率相似(均p > 0.05)。PTCy50在1年无GVHD/无复发生存(GRFS)方面具有统计学显著益处(p = 0.03)。中位数GRFS分别为115(95%CI:42 - 214)天和248(95%CI:151 - 未达到)天[风险比为0.51(0.28 - 0.95),p = 0.03;1年时GRFS分别为20.7%对44.3%]。然而,两组在无进展生存期(PFS)和总生存期(OS)方面相当。ATLG + PTCy25组的中位PFS为332天(95%CI:18天 - 未达到)。接受PTCy50的患者未达到(95%CI:210天 - 未达到)。ATLG + PTCy25组和PTCy50组的中位OS均未达到(对数秩检验 = 0.42)。我们的研究表明,联合ATLG降低PTCy剂量似乎可加速血小板和中性粒细胞植入率;尽管1年时GRFS增加,但生存率和复发率相似,急慢性GVHD频率也相似。

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