Körbling M, Hunstein W, Fliedner T M, Cayeux S, Dörken B, Fehrentz D, Haas R, Ho A D, Keilholz U, Knauf W
Department of Internal Medicine V, Heidelberg University, Federal Republic of Germany.
Blood. 1989 Nov 1;74(6):1898-904.
Autologous bone marrow transplantation (ABMT) makes it possible to escalate the dose of cytotoxic treatment to a lethal range. Disease-free survival (DFS) following myeloablative therapy and ABMT has been shown to be superior to conventional treatment in high risk patients with acute myelogenous leukemia (AML). It was the purpose of the present study to compare hematopoietic reconstitution, actuarial DFS, and relapse rate of patients transplanted in first complete remission (CR) of AML with those in second or subsequent CR, and to evaluate transplant related mortality. Fifty-two patients with AML, 22 in first CR (low risk) and 30 in second or subsequent CR (high risk), underwent total body irradiation (12.1 to 16.7 Gy) and cyclophosphamide (CY) treatment (200 mg/kg) followed by ABMT. The autograft was incubated with the active CY derivative Mafosfamide (ASTA Werke, Bielefeld, Federal Republic of Germany) to reduce the number of possibly contaminating clonogenic tumor cells. All patients showed three lineage engraftments with platelet recovery observed as being the slowest. The transplant related death rate was low at 5.8%. There was no significant difference in the kinetics of polymorphonuclear (PMN) cell or platelet reconstitution between the low and high risk patient subgroups. The estimated probability of DFS (relapse) after ABMT in first CR was 61% (36%) compared with 34% (65%) in second or subsequent CR, the longest follow-up being 55 months and 57 months, respectively (median follow-up 31 months and 19 months, respectively). ABMT offers a stable long-term DFS when performed in first CR with no relapses occurring in over a year after transplantation. Six later relapses, however, were seen after ABMT in second or subsequent CR, although DFS was not statistically different from that of first remission patients (P = .72).
自体骨髓移植(ABMT)使得将细胞毒性治疗剂量提升至致死范围成为可能。对于急性髓性白血病(AML)高危患者,清髓性治疗及ABMT后的无病生存期(DFS)已被证明优于传统治疗。本研究的目的是比较AML首次完全缓解(CR)期移植患者与第二次或后续CR期移植患者的造血重建、精算DFS及复发率,并评估移植相关死亡率。52例AML患者,22例处于首次CR期(低危),30例处于第二次或后续CR期(高危),接受全身照射(12.1至16.7 Gy)及环磷酰胺(CY)治疗(200 mg/kg),随后进行ABMT。将自体移植物与活性CY衍生物马磷酰胺(德国比勒费尔德市阿斯塔制药公司)一同孵育,以减少可能污染的克隆性肿瘤细胞数量。所有患者均出现三系造血重建,其中血小板恢复最慢。移植相关死亡率较低,为5.8%。低危和高危患者亚组之间在多形核(PMN)细胞或血小板重建动力学方面无显著差异。首次CR期ABMT后DFS(复发)的估计概率为61%(36%),而第二次或后续CR期为34%(65%),最长随访时间分别为55个月和57个月(中位随访时间分别为31个月和19个月)。在首次CR期进行ABMT时可提供稳定的长期DFS,移植后一年多未出现复发。然而,第二次或后续CR期ABMT后出现了6例晚期复发,尽管DFS与首次缓解患者无统计学差异(P = 0.72)。