Haematology/Oncology, Department of Medicine, University of Chicago Cancer Research Center, University of Chicago, 5841 S Maryland Avenue, Chicago, IL 60637, USA.
Bone Marrow Transplant. 2010 Dec;45(12):1692-8. doi: 10.1038/bmt.2010.32. Epub 2010 Mar 8.
To control disease before allogeneic hematopoietic cell transplantation (HCT) for relapsed/refractory AML, we used clofarabine cytoreduction. Seventeen patients received clofarabine 30-40 mg/m(2) i.v. daily for 5 days with plans to initiate conditioning during the nadir, 14 days later. Bone marrow biopsy 12 days after clofarabine showed effective cytoreduction (that is,<20% cellularity with <10% blasts) in 10 of 17 patients (59%). Ineffective cytoreduction correlated with lower PFS (3.8 vs 6.4 months; HR=2.7, 95% CI=1.10-14.29, P=0.035) and OS (5.1 vs 16.6 months; HR=2.5, 95% CI=0.98-12.17, P=0.053). Significant toxicities before HCT, attributable to clofarabine, were grade 1-2 hyperbilirubinemia (18%); grade 1-2 (59%) or grade 3-4 (18%) transaminitis; and grade 1-2 (18%) creatinine elevation. Sixteen patients proceeded to HCT infusion 22 days (median) after initiation of clofarabine. Day 100 and 2-year transplant-related mortality were 6 and 36%. Nine patients relapsed. One year PFS and OS were 25 and 38%, respectively. Two patients are alive in remission at 18 and 52 months. Clofarabine cytoreduction followed by immediate HCT is feasible with acceptable toxicity and TRM. Outcomes for this cohort of patients with refractory AML remain poor and we are studying this approach in a prospective manner.
为了在复发/难治性急性髓系白血病（AML）进行异基因造血细胞移植（HCT）之前控制疾病，我们使用氯法拉滨进行细胞减少治疗。17 名患者接受氯法拉滨 30-40mg/m(2)静脉滴注，每天一次，连续 5 天，计划在 14 天后（即第 14 天的最低点）开始预处理。在氯法拉滨治疗后 12 天进行骨髓活检，17 名患者中有 10 名（59%）显示出有效的细胞减少（即细胞含量<20%，原始细胞<10%）。无效的细胞减少与较短的无进展生存期（3.8 个月与 6.4 个月；HR=2.7，95%CI=1.10-14.29，P=0.035）和总生存期（5.1 个月与 16.6 个月；HR=2.5，95%CI=0.98-12.17，P=0.053）相关。HCT 前归因于氯法拉滨的显著毒性为 1-2 级高胆红素血症（18%）；1-2 级（59%）或 3-4 级（18%）转氨酶升高；以及 1-2 级（18%）肌酐升高。16 名患者在开始氯法拉滨治疗后 22 天（中位数）进行了 HCT 输注。第 100 天和 2 年移植相关死亡率分别为 6%和 36%。9 名患者复发。1 年无进展生存率和总生存率分别为 25%和 38%。2 名患者在缓解期分别存活 18 个月和 52 个月。立即进行 HCT 的氯法拉滨细胞减少是可行的，具有可接受的毒性和移植相关死亡率。对于难治性 AML 患者，这种方法的结果仍然很差，我们正在以前瞻性的方式研究这种方法。
