Bone Marrow Transplantation Unit, Tel Aviv Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Department I of Internal Medicine, University of Cologne, Cologne, Germany.
Haematologica. 2019 Sep;104(9):1798-1803. doi: 10.3324/haematol.2018.203869. Epub 2019 Feb 7.
Primary refractory acute myeloid leukemia (AML) is associated with a dismal prognosis. The FLAMSA-reduced intensity conditioning protocol (total body irradiation or treosulfan-based) has been described as an effective approach in patients with refractory leukemia undergoing allogeneic hematopoietic cell transplantation. A modified protocol (without amsacrine) has also recently been used. We retrospectively analyzed the transplantation characteristics and outcomes of all consecutive patients between the years 2003 and 2017 (n=51) diagnosed with primary refractory AML who underwent transplantation at the University of Cologne and the Tel Aviv Medical Center. Median age was 54 years and median follow up was 37 months. Median time to neutrophil and platelet engraftment was 13 (range, 8-19) and 13 (range, 7-30) days, respectively. None of the patients had primary graft failure. Incidences of grade 2-4 and grade 3-4 acute graft-v-host disease (GvHD), overall and moderate-severe chronic GvHD were 50% (95%CI: 41-67%), 12% (95%CI: 3-25%), 61% (95%CI: 47-72%), and 42% (95%CI: 34-51%), respectively. Anti-thymocyte globulin administration was associated with lower incidence of acute GvHD (HR: 0.327; =0.02). Non-relapse mortality at three months and three years were 6% and 16%, respectively. Relapse incidences were 6% and 29%, respectively. Overall survival rates at three months, three and five years were 90%, 61%, and 53%, respectively. Chronic GvHD disease was associated with a decreased mortality rate (HR: 0.397; =0.045). We conclude that sequential therapy in patients with primary refractory acute myeloid leukemia is safe and provides a remarkable anti-leukemic effect with durable survival and should be considered for every patient with primary refractory disease.
原发性难治性急性髓系白血病（AML）预后不良。FLAMSA 减少强度的预处理方案（全身照射或依托泊苷为基础）已被描述为接受异基因造血细胞移植的难治性白血病患者的有效方法。最近还使用了改良方案（不含安吖啶）。我们回顾性分析了 2003 年至 2017 年间（n=51）在科隆大学和特拉维夫医疗中心接受移植的原发性难治性 AML 患者的移植特征和结果。中位年龄为 54 岁，中位随访时间为 37 个月。中性粒细胞和血小板植入的中位时间分别为 13 天（范围 8-19 天）和 13 天（范围 7-30 天）。没有患者发生原发性移植物失败。2-4 级和 3-4 级急性移植物抗宿主病（GvHD）、总发生率和中重度慢性 GvHD 的发生率分别为 50%（95%CI：41-67%）、12%（95%CI：3-25%）、61%（95%CI：47-72%）和 42%（95%CI：34-51%）。使用抗胸腺细胞球蛋白与较低的急性 GvHD 发生率相关（HR：0.327；=0.02）。3 个月和 3 年的非复发死亡率分别为 6%和 16%。复发率分别为 6%和 29%。3 个月、3 年和 5 年的总生存率分别为 90%、61%和 53%。慢性 GvHD 与死亡率降低相关（HR：0.397；=0.045）。我们得出结论，原发性难治性急性髓系白血病患者的序贯治疗是安全的，具有显著的抗白血病作用，可实现持久的生存，应考虑用于每一位原发性难治性疾病患者。
