Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital, Cincinnati, OH.
Blood. 2016 Jan 28;127(4):503-12. doi: 10.1182/blood-2015-07-659672. Epub 2015 Dec 7.
Reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) with alemtuzumab, fludarabine, and melphalan is an effective approach for patients with nonmalignant disorders. Mixed chimerism and graft-versus-host-disease (GVHD) remain limitations on success. We hypothesized that higher levels of alemtuzumab at day 0 would result in a low risk of acute GVHD, a higher risk of mixed chimerism, and delayed early lymphocyte recovery and that alemtuzumab level thresholds for increased risks of these outcomes would be definable. We collected data from 105 patients to examine the influence of peritransplant alemtuzumab levels on acute GVHD, mixed chimerism, and lymphocyte recovery. The cumulative incidences of initial grades I-IV, II-IV, and III-IV acute GVHD in patients with alemtuzumab levels ≤0.15 vs ≥0.16 μg/mL were 68% vs 18% (P < .0001), 47% vs 13% (P = .0002), and 32% vs 8%, respectively (P = .005). The cumulative incidence of mixed chimerism in patients with an alemtuzumab level ≤0.15 μg/mL was 21%, vs 42% with levels of 0.16 to 4.35 μg/mL, and 100% with levels >4.35 μg/mL (P = .003). Patients with alemtuzumab levels ≤0.15 or 0.16 to 0.56 μg/mL had higher lymphocyte counts at day +30 and higher T-cell counts at day +100 compared with patients with levels ≥0.57 μg/mL (all P < .05). We conclude that peritransplant alemtuzumab levels impact acute GVHD, mixed chimerism, and lymphocyte recovery following RIC HCT with alemtuzumab, fludarabine, and melphalan. Precision dosing trials are warranted. We recommend a day 0 therapeutic range of 0.2 to 0.4 μg/mL.
降低强度的条件（RIC）异基因造血细胞移植（HCT）用阿仑单抗、氟达拉滨和马法兰是治疗非恶性疾病患者的有效方法。混合嵌合体和移植物抗宿主病（GVHD）仍然是成功的限制因素。我们假设在第 0 天更高水平的阿仑单抗会导致急性 GVHD 的风险较低，混合嵌合体的风险较高，以及早期淋巴细胞恢复延迟，并且可以确定阿仑单抗水平阈值增加这些结果的风险。我们从 105 例患者中收集数据，以检查移植前阿仑单抗水平对急性 GVHD、混合嵌合体和淋巴细胞恢复的影响。阿仑单抗水平≤0.15μg/mL 与≥0.16μg/mL 的患者中初始 I-IV、II-IV 和 III-IV 级急性 GVHD 的累积发生率分别为 68% vs 18%（P<0.0001）、47% vs 13%（P=0.0002）和 32% vs 8%（P=0.005）。阿仑单抗水平≤0.15μg/mL 的患者混合嵌合体的累积发生率为 21%，0.16-4.35μg/mL 的为 42%，>4.35μg/mL 的为 100%（P=0.003）。阿仑单抗水平≤0.15μg/mL 或 0.16-0.56μg/mL 的患者在第+30 天的淋巴细胞计数较高，在第+100 天的 T 细胞计数较高，与水平≥0.57μg/mL 的患者相比（均 P<0.05）。我们得出结论，移植前阿仑单抗水平影响 RIC HCT 用阿仑单抗、氟达拉滨和马法兰后的急性 GVHD、混合嵌合体和淋巴细胞恢复。需要进行精确剂量试验。我们建议第 0 天的治疗范围为 0.2-0.4μg/mL。
