Solomon S R, Nakamura R, Read E J, Leitman S F, Carter C, Childs R, Dunbar C E, Young N S, Barrett A J
Stem Cell Allotransplantation Section, Hematology Branch, NHLBI, National Institutes of Health, Bathesda, MD 20892, USA.
Bone Marrow Transplant. 2003 May;31(9):783-8. doi: 10.1038/sj.bmt.1703928.
Reduced immunosuppression may improve immune recovery and increase the graft-versus-leukemia effect after allogeneic stem cell transplantation. Furthermore, the requirement for post-transplant immunosuppression following extensive T-cell depletion remains unclear. We therefore evaluated the role of cyclosporine (CSA) in recipients of HLA-identical T-cell-depleted peripheral blood stem cell transplants (PBSCT), followed by donor lymphocyte infusions (DLIs) scheduled on days +45 and +100. Before day+45, successive cohorts of patients received decreasing amounts of CSA: standard-dose (SD) CSA, low-dose (LD) CSA, or no CSA until day+45. LD CSA was as effective as SD CSA in preventing acute graft-versus-host disease (GVHD). However, moderate-to-severe acute GVHD was significantly more frequent before the day +45 DLI in patients receiving no CSA (33.3 vs 12.7%, P=0.036, including the only four grade III-IV cases). As a result of higher rates of early acute GVHD, more patients in the 'no CSA' group failed to receive any DLI (30.7 vs 7.1%, P=0.01). Overall, there was no difference in the incidence of acute GVHD, as patients receiving CSA developed more GVHD after DLI. Similarly, no significant differences were found in chronic GVHD, transplant-related mortality, or survival. These results define a role for CSA in preventing GVHD at low T-cell doses following PBSCT.
降低免疫抑制可能会改善免疫恢复,并增强异基因干细胞移植后的移植物抗白血病效应。此外,在进行广泛的T细胞清除后,移植后免疫抑制的需求仍不明确。因此,我们评估了环孢素(CSA)在接受HLA匹配的T细胞清除外周血干细胞移植(PBSCT)患者中的作用,随后在第45天和第100天安排供体淋巴细胞输注(DLI)。在第45天之前,连续几组患者接受逐渐减少剂量的CSA:标准剂量(SD)CSA、低剂量(LD)CSA,或在第45天之前不使用CSA。LD CSA在预防急性移植物抗宿主病(GVHD)方面与SD CSA同样有效。然而,在第45天DLI之前,未接受CSA的患者中,中度至重度急性GVHD的发生率显著更高(33.3%对12.7%,P = 0.036,包括仅有的4例III-IV级病例)。由于早期急性GVHD发生率较高,“无CSA”组中更多患者未能接受任何DLI(30.7%对7.1%,P = 0.01)。总体而言,急性GVHD的发生率没有差异,因为接受CSA的患者在DLI后发生更多GVHD。同样,在慢性GVHD、移植相关死亡率或生存率方面未发现显著差异。这些结果确定了CSA在PBSCT后低T细胞剂量下预防GVHD中的作用。