Paediatric Haemato-Oncology Department, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, United Kingdom; Division of Clinical Studies, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, United Kingdom.
Paediatric Haemato-Oncology Department, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, United Kingdom; Division of Clinical Studies, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, United Kingdom; Hopp Children's Cancer Center (KiTZ) Heidelberg, University Medical Center for Children and Adolescents Angelika Lautenschläger Children's Hospital, Im Neuenheimer Feld 430 D, 69120, Heidelberg, Germany; Institute of Human Genetics, University Hospital Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
Leuk Res. 2019 Oct;85:106217. doi: 10.1016/j.leukres.2019.106217. Epub 2019 Aug 13.
For patients with primary refractory and relapsed acute leukaemias allogeneic stem cell transplantation is the only hope for cure, but morphological remission is not always achieved after standard salvage regimens. Here we review the experience with high-dose etoposide and cyclophosphamide (HD-Et/Cy) in relapsed/refractory acute leukaemias at the Royal Marsden Hospital.
Twenty-three patients (15 adults, 8 children) with refractory/relapsed acute myeloblastic (n = 18; 78%), lymphoblastic (n = 4; 17%) or biphenotypic (n = 1; 4%) leukaemia who had failed to respond to at least one previous line of chemotherapy received HD-Et/Cy at our institution between 2006 and 2015.
Overall response rate was 21.7% (95%CI 4.0-40.0). Median overall survival was 14.8 months (95%CI 9.1-49.1). Eight (35%) patients (7 AML, 1 biphenotypic leukaemia) proceeded to allogeneic transplant after one cycle of HD-Et/Cy: four of them (50%; 3 adults, 1 child) in complete remission and another four children (50%) with aplastic bone marrow with scattered blasts. Among the transplant recipients, three with AML (38%), ie. one adult (responder) and two children with aplastic bone marrow with scattered blasts, became long-term survivors 9.8, 4.4 and 2.5 years post-HD-Et/Cy, respectively. Toxicity profile was comparable to similar regimens with no treatment-related deaths. The most common grade 3-4 toxicity was febrile neutropenia (96%).
HD-Et/Cy can salvage patients with refractory/relapsed AML who remain candidates for allogeneic stem cell transplantation after failure of standard salvage regimens and do not have access to clinical trials.
对于原发性难治和复发的急性白血病患者，异体干细胞移植是治愈的唯一希望，但标准挽救方案后并非总能达到形态缓解。在此，我们回顾了皇家马斯登医院难治/复发急性白血病患者使用高剂量依托泊苷和环磷酰胺（HD-Et/Cy）的经验。
2006 年至 2015 年间，23 例难治/复发急性髓系白血病（n=18；78%）、急性淋巴细胞白血病（n=4；17%）或双表型白血病（n=1；4%）患者在我院接受 HD-Et/Cy 治疗，这些患者至少对一线化疗无反应。
总缓解率为 21.7%（95%CI 4.0-40.0）。中位总生存期为 14.8 个月（95%CI 9.1-49.1）。8 例（35%）患者（7 例 AML，1 例双表型白血病）在接受一个周期的 HD-Et/Cy 后进行了异体移植：其中 4 例（50%；3 例成人，1 例儿童）处于完全缓解，另外 4 例儿童（50%）骨髓再生不良伴散在的白血病细胞。在移植受者中，3 例 AML（38%），即 1 例成人（应答者）和 2 例骨髓再生不良伴散在的白血病细胞的儿童，分别在接受 HD-Et/Cy 后 9.8、4.4 和 2.5 年成为长期幸存者。毒性谱与类似方案相当，无治疗相关死亡。最常见的 3-4 级毒性是发热性中性粒细胞减少症（96%）。
在标准挽救方案失败后仍有资格进行异体干细胞移植且无法参加临床试验的难治/复发 AML 患者，HD-Et/Cy 可挽救这些患者。
