Department of Radiation Oncology, University of Tuebingen, Tuebingen, Germany.
Department of Paediatrics I, Hematology and Oncology, Tuebingen, Germany.
Int J Radiat Oncol Biol Phys. 2019 May 1;104(1):137-143. doi: 10.1016/j.ijrobp.2018.12.031. Epub 2018 Dec 26.
This retrospective analysis aimed to address the efficacy of total nodal irradiation (TNI)-based reconditioning regimens in pediatric patients with graft failure/rejection after allogeneic hematopoietic cell transplantation.
Thirty-three pediatric patients with malignant (n = 25) and nonmalignant diseases (n = 8) were treated with a TNI-based reconditioning regimen. All patients received a 7-Gy single dose combined with anti-T lymphocyte antibody OKT3 (n = 16), anti-thymocyte globulin (n = 24), fludarabine (n = 31), and/or thiotepa (n = 28), followed by an infusion of peripheral blood stem cells (n = 31) or bone marrow transplant (n = 2). Twenty-eight of 33 patients had haploidentical family donors.
After a median of 11 days, engraftment was seen in 32 of 33 children. Two children died 34 days after retransplantation because of either disease relapse or treatment-related multiple organ failure. Severe acute toxicity was reported in only 1 child (systemic inflammatory response syndrome-like reaction; recovery after cortisone treatment). The average follow-up was 60.2 months (range, 1.1-162.5 months). Event-free and overall survival rates at 2/5 years follow-up were 62.0%/58.6% and 65.1%/61.7%, respectively. Despite sustained engraftment, 12 patients died from disease relapse (n = 3), Moschkowitz syndrome (n = 1), or multiple organ failure (n = 8). Follow-up data were available for 18 of 21 survivors, with a median follow-up of 92.8 months (range, 3.6-162.5 months). Hypothyroidism was present in 78.6% of patients, and sex/growth hormonal insufficiencies were reported for 37.5%. Mean forced expiratory volume in 1 second after TNI was 84%; mean vital capacity was 79%. Severe growth failure (<3rd percentile) occurred in 28.6% (height) and 35.7% (weight) of patients. No secondary malignancies were reported.
In the high-risk group of patients with graft failure/rejection after allogeneic hematopoietic cell transplantation, the TNI-based reconditioning regimen seems to allow sustained engraftment combined with a favorable toxicity profile, leading to long-term event-free and overall survival. Late toxicity after a median follow-up of over 7.5 years includes growth failure, manageable hormonal deficiencies, and a low risk of decrease of lung function.
本回顾性分析旨在探讨在异基因造血细胞移植后发生移植物失败/排斥的患儿中，基于全淋巴结照射（TNI）的预处理方案的疗效。
33 例患有恶性疾病（n=25）和非恶性疾病（n=8）的儿科患者接受了基于 TNI 的预处理方案。所有患者均接受单次 7 Gy 剂量照射，联合抗 T 淋巴细胞抗体 OKT3（n=16）、抗胸腺细胞球蛋白（n=24）、氟达拉滨（n=31）和/或噻替哌（n=28），随后输注外周血干细胞（n=31）或骨髓移植（n=2）。33 例患者中有 28 例有单倍体家族供者。
中位时间 11 天后，33 例患儿中有 32 例出现植入。2 例患儿在移植后 34 天因疾病复发或治疗相关多器官衰竭而死亡。仅有 1 例患儿发生严重急性毒性（全身炎症反应综合征样反应；皮质激素治疗后恢复）。平均随访时间为 60.2 个月（范围，1.1-162.5 个月）。2/5 年的无事件生存率和总生存率分别为 62.0%/58.6%和 65.1%/61.7%。尽管持续植入，但 12 例患儿因疾病复发（n=3）、Moschkowitz 综合征（n=1）或多器官衰竭（n=8）而死亡。21 例幸存者中有 18 例可获得随访数据，中位随访时间为 92.8 个月（范围，3.6-162.5 个月）。78.6%的患者存在甲状腺功能减退，37.5%的患者存在性激素/生长激素不足。TNI 后用力呼气量 1 秒（FEV1）为 84%，肺活量为 79%。28.6%（身高）和 35.7%（体重）的患者发生严重生长不良（<第 3 百分位数）。无继发性恶性肿瘤报告。
在异基因造血细胞移植后发生移植物失败/排斥的高危患儿中，基于 TNI 的预处理方案似乎可实现持续植入，同时具有良好的毒性特征，从而获得长期无事件生存率和总生存率。在中位随访超过 7.5 年后，晚期毒性包括生长不良、可管理的激素缺乏以及肺功能下降的风险较低。
