Troullioud Lucas Alexandre G, Boelens Jaap Jan, Prockop Susan E, Curran Kevin J, Bresters Dorine, Kollen Wouter, Versluys Birgitta, Bierings Marc B, Archer Anne, Davis Eric, Klein Elizabeth, Kernan Nancy A, Lindemans Caroline A, Scaradavou Andromachi
Department of Pediatrics, Transplantation and Cellular Therapies Service, MSK Kids, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Department of Stem Cell Transplantation, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.
Front Oncol. 2023 Aug 15;13:1221782. doi: 10.3389/fonc.2023.1221782. eCollection 2023.
Patients with leukemia relapse after allogeneic hematopoietic cell transplant (HCT) have poor survival due to toxicity and disease progression. A second HCT often offers the only curative treatment.
We retrospectively reviewed our bi-institutional experience (MSKCC-USA; Utrecht-NL) with unrelated cord blood transplantation (CBT) for treatment of post-transplant relapse. Overall survival (OS) and event-free survival (EFS) were evaluated using the Kaplan-Meier method, treatment-related mortality (TRM) and relapse were evaluated using the competing risk method by Fine-Gray.
Twenty-six patients age < 21 years received a second (n=24) or third (n=2) HCT with CB grafts during the period 2009-2021. Median age at first HCT (HCT1) was 11.5 (range: 0.9-17.7) years and all patients received myeloablative cytoreduction. Median time from HCT1 to relapse was 12.8 (range 5.5-189) months. At CBT, median patient age was 13.5 (range 1.4-19.1) years. Diagnoses were AML: 13; ALL: 4, MDS: 5, JMML: 2; CML: 1; mixed phenotype acute leukemia: 1. Sixteen patients (62%) were in advanced stage, either CR>2 or with active disease. Median time from HCT1 to CBT was 22.2 (range 7-63.2) months. All patients engrafted after CBT. Thirteen patients developed acute GvHD; 7 had grade III or IV. With a median survivor follow-up of 46.6 (range 17.4-155) months, 3-year OS was 69.2% (95% CI 53.6-89.5%) and 3-year EFS was 64.9% (95% CI 48.8-86.4%). Eight patients died, 3 of AML relapse and 5 due to toxicity (respiratory failure [n=4], GvHD [n=1]) at a median time of 7.7 (range 5.9-14.4) months after CBT. Cumulative incidence of TRM at 3 years was 19.2% (95% CI 4.1-34.4%). Notably, all TRM events occurred in patients transplanted up to 2015; no toxicity-related deaths were seen in the 16 patients who received CBT after 2015. Cumulative incidence of relapse was 15.9% (95% CI 1.6-30.2%) at 3 years, remarkably low for these very high-risk patients.
Survival was very encouraging following CB transplants in pediatric patients with recurrent leukemia after first HCT, and TRM has been low over the last decade. CBT needs to be strongly considered as a relatively safe salvage therapy option for post-transplant relapse.
异基因造血细胞移植（HCT）后复发的白血病患者因毒性和疾病进展，生存率较低。第二次HCT通常是唯一的治愈性治疗方法。
我们回顾性分析了我们在美斯凯癌症中心（美国）和乌得勒支大学医学中心（荷兰）进行的无关脐血移植（CBT）治疗移植后复发的双机构经验。采用Kaplan-Meier方法评估总生存期（OS）和无事件生存期（EFS），采用Fine-Gray竞争风险方法评估治疗相关死亡率（TRM）和复发情况。
2009年至2021年期间，26例年龄<21岁的患者接受了第二次（n=24）或第三次（n=2）HCT，移植的是脐血移植物。首次HCT（HCT1）时的中位年龄为11.5岁（范围：0.9-17.7岁），所有患者均接受了清髓性细胞减少治疗。从HCT1到复发的中位时间为12.8个月（范围5.5-189个月）。在进行CBT时，患者的中位年龄为13.5岁（范围1.4-19.1岁）。诊断结果为：急性髓系白血病（AML）：13例；急性淋巴细胞白血病（ALL）：4例；骨髓增生异常综合征（MDS）：5例；幼年型粒单核细胞白血病（JMML）：2例；慢性粒细胞白血病（CML）：1例；混合表型急性白血病：1例。16例患者（62%）处于晚期，即完全缓解>2期或患有活动性疾病。从HCT1到CBT的中位时间为22.2个月（范围7-63.2个月）。所有患者在CBT后均实现造血重建。13例患者发生了急性移植物抗宿主病（GvHD）；7例为III级或IV级。中位随访生存期为46.6个月（范围17.4-155个月），3年总生存率为69.2%（95%置信区间53.6-89.5%），3年无事件生存率为64.9%（95%置信区间48.8-86.4%）。8例患者死亡，3例死于AML复发，5例死于毒性反应（呼吸衰竭[n=4]，GvHD[n=1]），中位时间为CBT后7.7个月（范围5.9-14.4个月）。3年时TRM的累积发生率为19.2%（95%置信区间4.1-34.4%）。值得注意的是，所有TRM事件均发生在2015年之前接受移植的患者中；2015年之后接受CBT的16例患者中未出现与毒性相关的死亡。3年时复发的累积发生率为15.9%（95%置信区间1.6-30.2%），对于这些高危患者而言，这一发生率非常低。
首次HCT后复发的儿科白血病患者接受脐血移植后的生存率非常令人鼓舞，并且在过去十年中TRM一直较低。CBT应被视为移植后复发相对安全的挽救治疗选择。
