Fred Hutchinson Cancer Research Center, Seattle, Washington.
BMT & Cellular Therapy Program, Medical College of Wisconsin, Milwaukee, Wisconsin.
Transplant Cell Ther. 2021 Jun;27(6):483.e1-483.e6. doi: 10.1016/j.jtct.2021.02.031. Epub 2021 Feb 26.
Several prospective randomized trials comparing conditioning intensity before allogeneic hematopoietic cell transplantation (HCT) have been performed, with conflicting results. Although reduced-intensity conditioning (RIC) leads to lower treatment-related mortality (TRM), this is offset by higher rates of relapse. Long-term follow-up of randomized comparative trials are limited. Here we present long-term follow-up of a randomized comparison of myeloablative conditioning (MAC) compared with RIC before HCT for acute myelogenous leukemia (AML) or myelodysplasia (MDS). Long-term comparative analyses of overall survival, relapse, and relapse-free survival were performed. Patients age 18 to 65 years with <5% marrow myeloblasts were randomized to receive MAC (n = 135) or RIC (n = 137), followed by HCT from an HLA-matched donor. The primary endpoint of the trial was an 18-month pointwise comparison of overall survival. The analyses were performed using a proportional hazards model. The median follow-up of the entire cohort was 51 months. At 4 years, the transplant-related mortality (TRM) was 25.1% for MAC, compared with 9.9% for RIC (P < .001). Patients who received RIC had a significantly higher risk of relapse compared to those who received MAC (hazard ratio [HR], 4.06; 95% CI, 2.59 to 6.35; P < 0.001). Among the patients who relapsed after HCT, postrelapse survival was similar at 3 years (24% for MAC and 26% for RIC). Overall survival was superior for patients who received MAC compared to those who received RIC (HR, 1.54; 95% CI, 1.07 to 2.2; P = .03). Our data show that patients who received MAC were at higher risk of late TRM compared with those who received RIC; however, because of the exceedingly high rates of relapse in the RIC arm, overall survival remained significantly better for patients who received MAC. Among patients with MDS or AML eligible for either MAC or RIC regimens, long-term follow up demonstrates a survival advantage for patients who received MAC.
几项比较异基因造血细胞移植（HCT）前预处理强度的前瞻性随机试验已经进行，结果存在矛盾。虽然减强度预处理（RIC）导致治疗相关死亡率（TRM）降低，但这被复发率升高所抵消。随机对照试验的长期随访有限。在这里，我们报告了一项比较异基因造血细胞移植（HCT）前清髓性预处理（MAC）与 RIC 治疗急性髓细胞白血病（AML）或骨髓增生异常综合征（MDS）的随机比较的长期随访结果。对总生存、复发和无复发生存进行了长期比较分析。年龄在 18 至 65 岁之间、骨髓中原始细胞<5%的患者被随机分为接受 MAC（n=135）或 RIC（n=137）治疗，然后接受 HLA 匹配供者的 HCT。该试验的主要终点是 18 个月时的总生存点比较。分析采用比例风险模型进行。整个队列的中位随访时间为 51 个月。4 年时，MAC 的移植相关死亡率（TRM）为 25.1%，而 RIC 为 9.9%（P<.001）。与接受 MAC 的患者相比，接受 RIC 的患者复发风险显著增加（风险比[HR]，4.06；95%CI，2.59 至 6.35；P<.001）。在 HCT 后复发的患者中，3 年时的无复发生存率相似（MAC 为 24%，RIC 为 26%）。与接受 RIC 的患者相比，接受 MAC 的患者总生存更好（HR，1.54；95%CI，1.07 至 2.2；P=0.03）。我们的数据表明，与接受 RIC 的患者相比，接受 MAC 的患者发生晚期 TRM 的风险更高；然而，由于 RIC 组的复发率极高，接受 MAC 的患者的总生存仍然显著更好。在有资格接受 MAC 或 RIC 方案的 MDS 或 AML 患者中，长期随访显示接受 MAC 的患者具有生存优势。
