Kröger Nicolaus, Einsele Hermann, Wolff Daniel, Casper Jochen, Freund Mathias, Derigs Günter, Wandt Hannes, Schäfer-Eckart K, Wittkowsky Georg, Schmitz Norbert, Krüger William, Zabelina Tatjana, Renges Helmut, Ayuk Francis, Krüll Andreas, Zander Axel
Bone Marrow Transplantation, University Hospital Hamburg-Eppendorf, Germany.
Bone Marrow Transplant. 2003 Jun;31(11):973-9. doi: 10.1038/sj.bmt.1704049.
We investigated toxicity and efficacy of in vivo T-cell depletion with anti-thymocyte globulin (ATG) as part of an intensified myeloablative conditioning regimen followed by allogeneic stem cell transplantation in patients with advanced multiple myeloma. The conditioning regimen consisted of modified total body irradiation, busulfan and cyclophosphamide (n=15) or in the case of prior dose-limiting radiotherapy of busulfan and cyclophosphamide (n=3). The median age was 44 years (range, 29-53) and the median time from diagnosis to transplant was 12 months (range, 6-144). Grade II-IV acute graft-versus-host disease (GvHD) occurred in six patients (35%). Severe grade III/IV GvHD developed in one patient (6%). Three patients died of therapy-related causes (17%). A complete remission (CR) with negative immunofixation after allogeneic transplantation was seen in eight of the evaluable patients (53%). After a median follow-up of 41 months (range, 8-84), the estimated overall survival at 6 years for all patients is 77% (CI 95%: 58-96%). The estimated progression-free survival at 6 years for all patients is 31% (CI 95%: 2-59%) and 46% (CI 95%: 9-83%) for patients with CR. In vivo T-cell depletion with ATG resulted in a low rate of severe GvHD with low treatment-related mortality, and a substantial number of long-term survivors.
我们研究了抗胸腺细胞球蛋白(ATG)体内清除T细胞的毒性和疗效,这是强化清髓预处理方案的一部分,随后对晚期多发性骨髓瘤患者进行异基因干细胞移植。预处理方案包括改良全身照射、白消安和环磷酰胺(n = 15),或在先前对白消安和环磷酰胺进行剂量限制性放疗的情况下(n = 3)。中位年龄为44岁(范围29 - 53岁),从诊断到移植的中位时间为12个月(范围6 - 144个月)。6例患者(35%)发生了II - IV级急性移植物抗宿主病(GvHD)。1例患者(6%)发生了严重的III/IV级GvHD。3例患者死于治疗相关原因(17%)。在可评估的患者中,8例(53%)在异基因移植后免疫固定阴性的情况下实现了完全缓解(CR)。中位随访41个月(范围8 - 84个月)后,所有患者6年的估计总生存率为77%(95%CI:58 - 96%)。所有患者6年的估计无进展生存率为31%(95%CI:2 - 59%),CR患者为46%(95%CI:9 - 83%)。ATG体内清除T细胞导致严重GvHD发生率低,治疗相关死亡率低,并有大量长期存活者。