Salvaged single-unit cord blood transplantation for 26 patients with hematologic malignancies not in remission

Treatments for patients with hematologic malignancies not in remission are limited, but a few clinical studies have investigated the effects of salvaged unrelated cord blood transplantation (CBT). We retrospectively studied 19 patients with acute leukemia, 5 with myelodysplastic syndrome (MDS with refractory anemia with excess blasts [RAEB]), and 2 with non-Hodgkin's lymphoma who received 1 CBT unit ≤2 loci human leukocyte antigen (HLA)-mismatched after undergoing myeloablative conditioning regimens between July 2005 and July 2014. All of them were in non-remission before transplantation. The infused total nucleated cell (TNC) dose was 4.07 (range 2.76-6.02)×107/kg and that of CD34+ stem cells was 2.08 (range 0.99-8.65)×105/kg. All patients were engrafted with neutrophils that exceeded 0.5×109/L on median day +17 (range 14-37 days) and had platelet counts of >20×109/L on median day +35 (range 17-70 days). Sixteen patients (61.5%) experienced pre-engraftment syndrome (PES), and six (23.1%) patients progressed to acute graft-versus-host disease (GVHD). The cumulative incidence rates of II-IV acute GVHD and chronic GVHD were 50% and 26.9%, respectively. After a median follow-up of 27 months (range 5-74), 14 patients survived and 3 relapsed. The estimated 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) rates were 50.5%, 40.3%, and 35.2%, respectively. Salvaged CBT might be a promising modality for treating hematologic malignancies, even in patients with a high leukemia burden.

针对未获得缓解的血液系统恶性肿瘤患者，现有治疗手段十分有限，但已有少量临床研究探索了挽救性无关脐带血移植（salvaged unrelated cord blood transplantation, CBT）的应用效果。本研究回顾性分析了2005年7月至2014年7月期间，接受清髓性预处理方案后输注1份人类白细胞抗原（human leukocyte antigen, HLA）配型错配≤2个位点的脐带血单位的患者，其中急性白血病患者19例、骨髓增生异常综合征（myelodysplastic syndrome, MDS）伴原始细胞增多的难治性贫血（refractory anemia with excess blasts, RAEB）患者5例、非霍奇金淋巴瘤患者2例，所有患者移植前均未获得缓解。输注的有核细胞总数（total nucleated cell, TNC）中位数为4.07×10^7/kg（范围2.76~6.02×10^7/kg），CD34+干细胞剂量中位数为2.08×10^5/kg（范围0.99~8.65×10^5/kg）。所有患者均实现中性粒细胞植入，中性粒细胞计数≥0.5×10^9/L的中位时间为移植后+17天（范围14~37天）；血小板计数＞20×10^9/L的中位时间为移植后+35天（范围17~70天）。16例患者（61.5%）发生植入前综合征（pre-engraftment syndrome, PES），6例患者（23.1%）进展为急性移植物抗宿主病（acute graft-versus-host disease, GVHD）。Ⅱ~Ⅳ级急性GVHD与慢性GVHD的累积发生率分别为50%与26.9%。中位随访时间为27个月（范围5~74个月），14例患者存活，3例出现疾病复发。预估的2年总生存率（overall survival, OS）、无病生存率（disease-free survival, DFS）与非复发死亡率（non-relapse mortality, NRM）分别为50.5%、40.3%与35.2%。挽救性无关脐带血移植或可成为治疗血液系统恶性肿瘤的极具前景的手段，即便针对白血病负荷较高的患者亦具有应用价值。