Doernbecher Children's Hospital, Oregon Health & Science University, Portland, Oregon.
West German Cancer Center, University Hospital Essen, University Duisburg Essen, Essen, Germany.
Biol Blood Marrow Transplant. 2018 Aug;24(8):1651-1656. doi: 10.1016/j.bbmt.2018.04.025. Epub 2018 May 9.
This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (range, 1 to 19) underwent allogeneic HCT for AML in first (n = 18), second (n = 11), and third or greater remission (n = 3) or MDS (n = 8) using bone marrow (n = 25), peripheral blood stem cells (n = 5), or cord blood (n = 9). The regimen consisted of body surface area (BSA)-based treosulfan 10 g/m/day (BSA ≤ .5 m), 12 g/m/day (BSA > .5 to 1.0 m), or 14 g/m/day (BSA > 1.0 m) on days -6 to -4; fludarabine 30 mg/m/day on days -6 to -2; and a single fraction of 200 cGy total body irradiation on day -1. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and methotrexate for marrow and peripheral blood stem cell and cyclosporine/mycophenolate mofetil for cord blood. One-year overall survival, disease-free survival, and nonrelapse mortality were 80%, 73%, and 3%, respectively. One-year relapse was 38% for AML and 13% for MDS. No serious organ toxicities were observed. All 37 assessable patients engrafted. Cumulative incidences of grades II to IV acute GVHD and chronic GVHD were 22% and 40%, respectively. BSA-based treosulfan dosing resulted in predictable area under the curve and maximum concentration, which is required for dosing without measuring individual pharmacokinetic parameters. Observed differences in pharmacokinetics did not impact disease control or regimen toxicity. This BSA-based treosulfan regimen resulted in excellent engraftment and disease-free survival and minimal toxicity and transplant-related mortality (3%) in children and young adults with AML and MDS.
这项多中心研究评估了一种以三氟尿苷为基础的方案在接受异基因造血细胞移植（HCT）的儿童和年轻成人中的急性髓性白血病（AML）或骨髓增生异常综合征（MDS）中的疗效。40 名中位年龄为 11 岁（范围为 1 至 19 岁）的患者因 AML（n=18）、第 2 次（n=11）、第 3 次或以上缓解（n=3）或 MDS（n=8）接受异基因 HCT，采用骨髓（n=25）、外周血干细胞（n=5）或脐带血（n=9）。方案包括基于体表面积（BSA）的三氟尿苷 10g/m/天（BSA≤0.5m）、12g/m/天（BSA＞0.5 至 1.0m）或 14g/m/天（BSA＞1.0m），在-6 天至-4 天；氟达拉滨 30mg/m/天，在-6 天至-2 天；和 1 次 200cGy 全身照射在-1 天。移植物抗宿主病（GVHD）预防包括骨髓和外周血干细胞的他克莫司和甲氨蝶呤以及脐带血的环孢素/霉酚酸酯。1 年总生存率、无病生存率和非复发死亡率分别为 80%、73%和 3%。AML 的 1 年复发率为 38%，MDS 的复发率为 13%。未观察到严重的器官毒性。37 例可评估的患者均植入。2 级至 4 级急性 GVHD 和慢性 GVHD 的累积发生率分别为 22%和 40%。基于 BSA 的三氟尿苷剂量导致可预测的曲线下面积和最大浓度，这是无需测量个体药代动力学参数进行剂量的必要条件。观察到的药代动力学差异并未影响疾病控制或方案毒性。该基于 BSA 的三氟尿苷方案在 AML 和 MDS 儿童和年轻成人中导致了极好的植入和无病生存率，以及最小的毒性和与移植相关的死亡率（3%）。
