Hematology Section, Department of Emergency and Organ Transplantation, University of Bari, Piazza Giulio Cesare 11,Bari, Italy.
Biol Blood Marrow Transplant. 2013 Mar;19(3):495-9. doi: 10.1016/j.bbmt.2012.11.015. Epub 2012 Nov 27.
The therapeutic efficacy of allogeneic peripheral blood stem cell transplantation (PBSCT) for hematological malignancies relies largely on the graft-versus-leukemia (GVL) effects exerted by the donor CD3 cells, but there is a risk of onset of uncontrolled graft-versus-host disease (GVHD). Regulatory T cells (Tregs) (CD4+CD25(high) Foxp3+) are believed to maintain tolerance and to inhibit acute GVHD (aGVHD) after allogeneic PBSCT. Nevertheless, when looking at post-allotransplantation patient outcomes, although the impact of aGVHD on survival is amply documented, so far there is no evidence that the donor graft CD3/Tregs ratio may affect overall survival (OS), nonrelapse mortality (NRM), disease-free survival (DFS), and relapse rates. Our aim was to study the possible impact of the gCD3/Tregs ratio on survival after myeloablative allogeneic PBSCT. We analyzed 74 consecutive patients diagnosed with acute myeloid leukemia (n = 62), acute lymphoblastic leukemia (n = 10), and chronic myeloid leukemia (n = 2) who underwent transplantation with unmanipulated PBSCs from a human leukocyte antigen-identical related donor (n = 48) or a human leukocyte antigen-identical unrelated donor (n = 26). Patients were subdivided into a high gCD3/Tregs ratio (≥36) group (HR group, n = 30) and a low gCD3/Tregs ratio (<36) group (LR group, n = 44). The OS, DFS, NRM, and relapse rates at 3 years were 53%, 51%, 29%, and 34%, respectively. Comparing the LR and HR groups, a statistically significant difference was demonstrated for the 3-year OS, DFS, and NRM rates (65% vs 31%, P = .0001; 67 versus 26%, P = .0001; 5% versus 71%, P < .0001, respectively) but not for relapse (30% vs 25%, P = ns). By multivariate analysis, LR significantly predicted better OS (P = .019), DFS (P = .003), and NRM (P = .05), whereas there was no statistically significant association between LR and relapse (P = .155). Overall, our data may suggest that LR preserves GVL effects but is also protective against aGVHD in allotransplantation patients.
同种异体外周血造血干细胞移植（PBSCT）治疗血液系统恶性肿瘤的疗效在很大程度上取决于供体 CD3 细胞发挥的移植物抗白血病（GVL）效应，但存在不受控制的移植物抗宿主病（GVHD）的风险。调节性 T 细胞（Tregs）（CD4+CD25(high)Foxp3+）被认为可以维持耐受，并抑制同种异体 PBSCT 后的急性 GVHD（aGVHD）。然而，在观察移植后患者的结局时，尽管已有充分证据表明 aGVHD 对生存的影响，但迄今为止，尚无证据表明供体移植物 CD3/Tregs 比值可能影响总生存（OS）、非复发死亡率（NRM）、无病生存（DFS）和复发率。我们的目的是研究在清髓性同种异体 PBSCT 后，gCD3/Tregs 比值对生存的可能影响。我们分析了 74 例连续诊断为急性髓系白血病（n=62）、急性淋巴细胞白血病（n=10）和慢性髓系白血病（n=2）的患者，这些患者均接受了未处理的来自人白细胞抗原-同基因相关供体（n=48）或人白细胞抗原-同基因无关供体（n=26）的 PBSC 移植。患者分为高 gCD3/Tregs 比值（≥36）组（HR 组，n=30）和低 gCD3/Tregs 比值（<36）组（LR 组，n=44）。3 年时 OS、DFS、NRM 和复发率分别为 53%、51%、29%和 34%。比较 LR 和 HR 两组，3 年 OS、DFS 和 NRM 率的差异具有统计学意义（65%比 31%，P=0.0001；67%比 26%，P=0.0001；5%比 71%，P<0.0001），但复发率无统计学差异（30%比 25%，P=ns）。多因素分析显示，LR 显著预测 OS 更好（P=0.019）、DFS 更好（P=0.003）和 NRM 更低（P=0.05），而 LR 与复发之间无统计学关联（P=0.155）。总体而言，我们的数据可能表明，LR 既能保留 GVL 效应，又能在移植患者中预防 aGVHD。
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