Division of Hematology, University of Colorado Denver, Denver, Colorado.
Division of Hematology, University of Colorado Denver, Denver, Colorado.
Biol Blood Marrow Transplant. 2018 Aug;24(8):1671-1677. doi: 10.1016/j.bbmt.2018.04.019. Epub 2018 Apr 21.
The "Minnesota" reduced-intensity conditioning (RIC) cord blood transplantation (CBT) regimen (standard RIC) of fludarabine (Flu) (200 mg/m), cyclophosphamide (Cy) (50 mg/kg), and 200- or 300-cGy total body irradiation (TBI) is the most published RIC CBT regimen. Though well tolerated, high relapse rates remain a concern with this regimen. Intensification of conditioning may reduce relapse without increasing transplant-related mortality (TRM). We performed a retrospective cohort comparison of outcomes in adult patients who underwent first double-unit CBT with standard RIC as compared with the intensified regimen of Flu 150 mg/m, Cy 50 mg/kg, thiotepa 10 mg/kg, and 400-cGy TBI (intensified RIC). Of the 99 patients studied, 47 received intensified RIC. Acute myelogenous leukemia was the major indication for transplant. The median age at transplant was 67 years (range, 24 to 74 years) and 54 years (range, 25 to 67 years) in standard RIC and intensified RIC, respectively. Median hematopoietic stem cell transplantation comorbidity index was 3 (range, 0 to 5) and 1 (range, 0 to 6) in the standard RIC and intensified RIC groups, respectively. Median follow-up among survivors was 22 months (range, 3.7 to 79 months) following standard RIC and 15 months (range, 2.8 to 36 months) following intensified RIC. The cumulative incidence (CI) of relapse was significantly lower following intensified RIC compared with standard RIC (P = .0013); this finding maintained significance in multivariate analysis (P = .045). TRM was comparable between the 2 groups (P = .99). Overall survival (OS) was significantly improved following intensified RIC as compared with standard RIC (P = .03). Median OS was 17 months following standard RIC versus not reached followed intensified RIC. The CI of grade II to IV acute graft-versus-host disease (GVHD) was significantly higher in the intensified RIC cohort than the standard RIC-cohort (P = .007), while CI of grade III to IV acute GVHD, any chronic GVHD, and moderate-to-severe chronic GVHD was comparable in each cohort (P = .20, P = .21, and P = .61, respectively). This retrospective analysis shows an improvement in OS and decreased relapse without increase in TRM in patients receiving intensified RIC as compared with standard RIC. Our data suggest that consideration of thiotepa-based intensified RIC may improve outcomes in fit, older patients undergoing double-unit CBT.
“明尼苏达”低强度预处理（RIC）的脐带血移植（CBT）方案（标准 RIC）包括氟达拉滨（Flu）（200mg/m）、环磷酰胺（Cy）（50mg/kg）和 200-或 300cGy 全身照射（TBI），是发表最多的 RIC CBT 方案。尽管该方案耐受性良好，但仍存在高复发率的问题。强化预处理可能会降低复发率而不增加移植相关死亡率（TRM）。我们对接受首次双单位 CBT 的成年患者进行了回顾性队列比较，这些患者接受了标准 RIC 与强化方案（氟达拉滨 150mg/m、环磷酰胺 50mg/kg、噻替哌 10mg/kg 和 400cGy TBI）的结果进行了比较。在 99 例研究患者中，47 例接受了强化 RIC。急性髓细胞白血病是移植的主要适应证。标准 RIC 和强化 RIC 组的中位年龄分别为 67 岁（范围 24-74 岁）和 54 岁（范围 25-67 岁）。标准 RIC 和强化 RIC 组的中位造血干细胞移植合并症指数分别为 3（范围 0-5）和 1（范围 0-6）。标准 RIC 组和强化 RIC 组的幸存者中位随访时间分别为 22 个月（范围 3.7-79 个月）和 15 个月（范围 2.8-36 个月）。与标准 RIC 相比，强化 RIC 后的复发累积发生率（CI）显著降低（P=0.0013）；在多变量分析中，这一发现仍具有统计学意义（P=0.045）。两组间 TRM 无差异（P=0.99）。与标准 RIC 相比，强化 RIC 后的总生存（OS）显著改善（P=0.03）。标准 RIC 组的中位 OS 为 17 个月，而强化 RIC 组未达到。强化 RIC 组的 II 至 IV 级急性移植物抗宿主病（GVHD）发生率明显高于标准 RIC 组（P=0.007），而 III 至 IV 级急性 GVHD、任何慢性 GVHD 和中重度慢性 GVHD 的发生率在两组间相似（P=0.20、P=0.21 和 P=0.61）。这项回顾性分析显示，与标准 RIC 相比，接受强化 RIC 的患者的 OS 改善，复发率降低，TRM 无增加。我们的数据表明，对于接受双单位 CBT 的合适、老年患者，考虑使用噻替哌为基础的强化 RIC 可能会改善结局。
