Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Transplant Cell Ther. 2021 Sep;27(9):769.e1-769.e8. doi: 10.1016/j.jtct.2021.05.026. Epub 2021 Jun 6.
Our group published a double phase III trial showing that patients infused with an autograft absolute lymphocyte count (A-ALC) ≥0.5 × 10 cells/kg experienced superior survival post-autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). Based on the results from our phase III study, as well as published retrospective studies, on April 1, 2017, our Bone Marrow Transplant Program changed our standard practice to collect an A-ALC ≥0.5 × 10 cells/kg in addition to stem cells for lymphoma patients undergoing APBHSCT. The primary objective of the present study was to continue to assess the prognostic ability of A-ALC by evaluating overall survival (OS) and progression-free survival (PFS) of diffuse large B cell lymphoma (DLBCL) patients who underwent APBHSCT after April 1, 2017, compared with matched control groups at a 1:1:1 ratio with DLBCL patients infused with an A-ALC <0.5 × 10 cells/kg and A-ALC ≥0.5 × 10 cells/kg before April 1, 2017. Using the GREEDY algorithm, 85 DLBCL patients (cases) infused with an A-ALC ≥0.5 × 10 cells/kg after April 1, 2017, were matched at a 1:1:1 ratio with control groups of DLBCL patients who underwent transplantation before April 1, 2017: patients infused with an A-ALC <0.5 × 10 cells/kg (control 1) and patients infused with an A-ALC ≥0.5 × 10 cells/kg (control 2) before April 1, 2017. Groups were matched in terms of sex, age, stage, lactate dehydrogenase (LDH) level, performance status, extranodal disease, International Prognostic Index (IPI), and disease status before APBHSCT (complete or partial response). Survival follow-up was truncated at 3 years from the date of transplantation. Cases, control 1, and control 2 were balanced as to age (P = .8), sex (P = .9), LDH (P = .6), performance status (P = .5), extranodal disease (P = .2), IPI (P = .6), and disease status before APBHSCT (P = .2). Cases and control 2 showed superior OS and PFS compared with control 1. Multivariate analysis including all patients continued to show A-ALC ≥0.5 × 10 cells/kg as an independent predictor for OS (hazard ratio [HR], 0.382; 95% confidence interval [CI], 0.241 to 0.605; P < .0001) and PFS (HR, 0.437; 95% CI, 0.279 to 0.629; P < .0001). Our matched case-control study supports the results of previously published retrospective studies and our phase III study showing that the infusion of A-ALC is a prognostic factor for survival in DLBCL patients undergoing APBHSCT. Our findings support the practice of collecting not only enough stem cells for hematologic engraftment, but also enough immune effector cells (ie, A-ALC) to improve clinical outcomes in DLBCL patients post-APBHSCT.
我们的团队发表了一项双 III 期临床试验结果,表明输注绝对淋巴细胞计数(A-ALC)≥0.5×10 个细胞/kg 的患者在自体外周血造血干细胞移植(APBHSCT)后具有更好的生存。基于我们的 III 期研究结果以及已发表的回顾性研究,我们的骨髓移植项目于 2017 年 4 月 1 日改变了标准做法,除了收集干细胞外,还收集淋巴瘤患者的 A-ALC≥0.5×10 个细胞/kg,用于接受 APBHSCT 的患者。本研究的主要目的是通过评估 2017 年 4 月 1 日后接受 APBHSCT 的弥漫性大 B 细胞淋巴瘤(DLBCL)患者的总生存(OS)和无进展生存(PFS),继续评估 A-ALC 的预后能力,与 1:1:1 比例的接受 A-ALC<0.5×10 个细胞/kg 和 A-ALC≥0.5×10 个细胞/kg 输注的 DLBCL 患者进行匹配,2017 年 4 月 1 日之前接受 APBHSCT 的患者。使用 GREEDY 算法,85 例 2017 年 4 月 1 日以后接受 A-ALC≥0.5×10 个细胞/kg 输注的 DLBCL 患者与对照组 1:1:1 比例的接受 APBHSCT 患者相匹配,2017 年 4 月 1 日之前接受 APBHSCT 的患者:A-ALC<0.5×10 个细胞/kg 输注的患者(对照组 1)和 A-ALC≥0.5×10 个细胞/kg 输注的患者(对照组 2)。组间在性别、年龄、分期、乳酸脱氢酶(LDH)水平、体能状态、结外疾病、国际预后指数(IPI)和 APBHSCT 前疾病状态方面相匹配(完全或部分缓解)。生存随访截止于移植后 3 年。病例、对照组 1 和对照组 2 在年龄(P=0.8)、性别(P=0.9)、LDH(P=0.6)、体能状态(P=0.5)、结外疾病(P=0.2)、IPI(P=0.6)和 APBHSCT 前疾病状态(P=0.2)方面平衡。病例和对照组 2 与对照组 1 相比,OS 和 PFS 均有优势。包括所有患者的多变量分析继续显示 A-ALC≥0.5×10 个细胞/kg 是 OS 的独立预测因子(危险比[HR],0.382;95%置信区间[CI],0.241 至 0.605;P<0.0001)和 PFS(HR,0.437;95%CI,0.279 至 0.629;P<0.0001)。我们的匹配病例对照研究支持之前发表的回顾性研究和我们的 III 期研究结果,表明输注 A-ALC 是 DLBCL 患者接受 APBHSCT 后生存的预后因素。我们的研究结果支持收集不仅足够的造血干细胞进行血液植入,而且还收集足够的免疫效应细胞(即 A-ALC),以改善 DLBCL 患者 APBHSCT 后的临床结果。