Zenz Thorsten, Ritgen Matthias, Dreger Peter, Kröber Alexander, Barth Thomas F, Schlenk Richard, Böttcher Sebastian, Hallek Michael J, Kneba Michael, Bunjes Donald, Döhner Hartmut, Stilgenbauer Stephan
Department of Internal Medicine III, University of Ulm, Robert-Koch-Strasse 8, D-89081 Ulm, Germany.
Blood. 2006 Sep 15;108(6):2127-30. doi: 10.1182/blood-2006-04-007898. Epub 2006 May 25.
A high incidence of autologous graft-versus-host-disease (auto-GVHD) was observed after an alemtuzumab-containing conditioning regimen and autologous stem cell transplantation (auto-SCT) for chronic lymphocytic leukemia (CLL). Skin rash developed in almost all surviving patients (87%). In 7 patients (58%), a diagnosis of auto-GVHD was made (compared with 0% after TBI/Cy; P = .01). All patients with auto-GVHD required immunosuppression, and 3 of 7 were hospitalized because of GVHD. The median duration of GVHD was 517 days (range, 60-867 days). Auto-GVHD was associated with an abnormally high CD4/CD8 ratio because of severe depletion of CD8(+) T cells, pointing to a potential pathomechanism. High non-relapse-related mortality led to the discontinuation of the trial. Current results do not support the use of high-dose alemtuzumab combined with total body irradiation (TBI) and autologous stem cell transplantation (auto-SCT). However, the addition of alemtuzumab led to improved disease control at the molecular level. Longer follow-up will show whether the GVHD-like syndrome may contribute to prolonged minimal residual disease (MRD) negativity.
在采用含阿仑单抗的预处理方案及自体干细胞移植(auto-SCT)治疗慢性淋巴细胞白血病(CLL)后,观察到自体移植物抗宿主病(auto-GVHD)的高发生率。几乎所有存活患者(87%)都出现了皮疹。7例患者(58%)被诊断为auto-GVHD(相比TBI/Cy方案后为0%;P = 0.01)。所有auto-GVHD患者都需要免疫抑制治疗,7例中有3例因GVHD住院。GVHD的中位持续时间为517天(范围60 - 867天)。由于CD8(+)T细胞严重耗竭,auto-GVHD与异常高的CD4/CD8比值相关,提示一种潜在的发病机制。高非复发相关死亡率导致试验终止。目前的结果不支持使用高剂量阿仑单抗联合全身照射(TBI)及自体干细胞移植(auto-SCT)。然而,添加阿仑单抗在分子水平上改善了疾病控制。更长时间的随访将显示GVHD样综合征是否可能有助于延长微小残留病(MRD)阴性持续时间。