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硼替佐米、环磷酰胺和地塞米松诱导后马法兰自体移植治疗骨髓瘤患者中动员方案与免疫重建和生存的关联。

The association of mobilising regimen on immune reconstitution and survival in myeloma patients treated with bortezomib, cyclophosphamide and dexamethasone induction followed by a melphalan autograft.

机构信息

Department of Clinical Haematology, Austin Health, Melbourne, VIC, Australia.

Department of Haematology, Princess Alexandra Hospital, and School of Medicine, University of Queensland, Brisbane, QLD, Australia.

出版信息

Bone Marrow Transplant. 2021 Sep;56(9):2152-2159. doi: 10.1038/s41409-021-01300-2. Epub 2021 Apr 28.

Abstract

G-CSF only mobilisation has been shown to enhance immune reconstitution early post-transplant, but its impact on survival remains uncertain. We undertook a retrospective review of 12 transplant centres to examine overall survival (OS) and time to next treatment (TTNT) following melphalan autograft according to mobilisation method (G-CSF only vs. G-CSF and cyclophosphamide [CY]) in myeloma patients uniformly treated with bortezomib, cyclophosphamide and dexamethasone induction. Six centres had a policy to use G-CSF alone and six to use G-CSF + CY. Patients failing G-CSF only mobilisation were excluded. 601 patients were included: 328: G-CSF + CY, 273: G-CSF only. Mobilisation arms were comparable in terms of age, Revised International Staging System (R-ISS) groups and post-transplant maintenance therapy. G-CSF + CY mobilisation generated higher median CD34 + yields (8.6 vs. 5.5 × 10/kg, p < 0.001). G-CSF only mobilisation was associated with a significantly higher lymphocyte count at day 15 post-infusion (p < 0.001). G-CSF only mobilisation was associated with significantly improved OS (aHR = 0.60, 95%CI 0.39-0.92, p = 0.018) and TTNT (aHR = 0.77, 95%CI 0.60-0.97, p = 0.027), when adjusting for R-ISS, disease-response pre-transplant, age and post-transplant maintenance therapy. This survival benefit may reflect selection bias in excluding patients with unsuccessful G-CSF only mobilisation or may be due to enhanced autograft immune cell content and improved early immune reconstitution.

摘要

仅用 G-CSF 动员已被证明可在移植后早期增强免疫重建,但它对生存的影响仍不确定。我们对 12 个移植中心进行了回顾性研究,根据动员方法(仅 G-CSF 与 G-CSF 和环磷酰胺[CY]),检查在用硼替佐米、环磷酰胺和地塞米松诱导治疗的骨髓瘤患者中接受马法兰自体移植后的总生存(OS)和下一次治疗时间(TTNT)。6 个中心有使用 G-CSF 单独动员的方案,6 个中心有使用 G-CSF+CY 动员的方案。排除了 G-CSF 单独动员失败的患者。共纳入 601 例患者:328 例接受 G-CSF+CY 动员,273 例接受 G-CSF 单独动员。动员组在年龄、修订后的国际分期系统(R-ISS)分组和移植后维持治疗方面具有可比性。G-CSF+CY 动员产生的中位 CD34+细胞产量更高(8.6 vs. 5.5×10/kg,p<0.001)。G-CSF 单独动员后第 15 天的淋巴细胞计数显著升高(p<0.001)。在调整 R-ISS、移植前疾病反应、年龄和移植后维持治疗后,G-CSF 单独动员与显著改善的 OS(aHR=0.60,95%CI 0.39-0.92,p=0.018)和 TTNT(aHR=0.77,95%CI 0.60-0.97,p=0.027)相关。这种生存获益可能反映了排除 G-CSF 单独动员不成功患者的选择偏倚,也可能是由于增强了自体移植物免疫细胞含量和改善了早期免疫重建。

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