Department of Pediatric Blood and Marrow Transplant, Duke University Medical Center, Durham, North Carolina.
Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, Columbia University Medical Center, New York, New York.
JAMA Pediatr. 2019 May 1;173(5):e190081. doi: 10.1001/jamapediatrics.2019.0081. Epub 2019 May 6.
Studies demonstrating improved survival after allogeneic hematopoietic cell transplant generally exclude infants.
To analyze overall survival trends and other outcomes among infants who undergo allogeneic hematopoietic cell transplant.
DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, we used time-trend analysis to evaluate 3 periods: 2000 through 2004, 2005 through 2009, and 2010 through 2014. The study was conducted in a multicenter setting through the Center for International Blood and Marrow Transplant Research, which is made up of a voluntary working group of more than 450 transplant centers worldwide. Two groups of infants aged 1 year or younger in 2 cohorts were included: those with malignant conditions, such as leukemia, and those with nonmalignant disorders, including immunodeficiencies. Data analysis was conducted from July 2017 to December 2018.
Allogeneic hematopoietic cell transplant.
Survival trends, disease relapse, and toxicity.
A total of 2498 infants with a median age of 7 months (range, <1-12 months) were included. In the nonmalignant cohort (n = 472), survival rates improved from the first to the second period (hazard ratio, 0.77 [95% CI, 0.63-0.93]; P = .007) but did not change after 2004. Compared with infants with nonmalignant diseases (n = 2026; 3-year overall survival: 2000-2004, 375/577 [65.0%]; 2005-2009, 503/699 [72.0%]; and 2010-2014, 555/750 [74.0%]), those with malignant conditions had poorer survival rates, without improvement over time (3-year overall survival: 2000-2004, 109/199 [54.8%]; 2005-2009, 104/161 [64.6%]; and 2010-2014, 66/112 [58.9%]). From 2000 through 2014, relapse rates increased in infants with malignant conditions (3-year relapse rate: 2000-2004, 19% [95% CI, 14%-25%]; 2005-2009, 23% [95% CI, 17%-30%]; 2010-2014, 36% [95% CI, 27%-46%]; P = .01). Sinusoidal obstruction syndrome was frequent, occurring with a cumulative incidence of 13% (95% CI, 11%-16%) of infants with nonmalignant diseases and 32% (95% CI, 22%-42%) of those with malignant diseases. Generally, recipients of human leukocyte antigen-identical sibling bone marrow grafts had the best outcomes.
Survival rates have not improved for infants with malignant diseases over the 15-year study period. Infants with nonmalignant diseases had improved survival rates in the earlier but not the later study period. Higher relapses for the malignant cohort and toxicities for all infants remain significant challenges. Strategies to reduce relapse and toxicity and optimize donor and graft selection may improve outcomes in the future.
一般来说，显示异基因造血细胞移植后生存率提高的研究通常排除了婴儿。
分析接受异基因造血细胞移植的婴儿的总生存率趋势和其他结果。
设计、地点和参与者：在这项队列研究中，我们使用时间趋势分析评估了 3 个时期：2000 年至 2004 年、2005 年至 2009 年和 2010 年至 2014 年。该研究是在一个多中心环境中进行的，通过国际血液和骨髓移植研究中心进行，该中心由全球 450 多个移植中心的自愿工作组组成。两个队列中年龄为 1 岁或以下的婴儿分为两组：一组患有白血病等恶性疾病，另一组患有免疫缺陷等非恶性疾病。数据分析于 2017 年 7 月至 2018 年 12 月进行。
异基因造血细胞移植。
生存趋势、疾病复发和毒性。
共纳入 2498 名中位年龄为 7 个月（范围，<1-12 个月）的婴儿。在非恶性队列（n=472）中，生存率从第一期到第二期提高（风险比，0.77 [95%置信区间，0.63-0.93]；P=0.007），但 2004 年后未再改变。与患有非恶性疾病的婴儿（n=2026；3 年总生存率：2000-2004 年，375/577 [65.0%]；2005-2009 年，503/699 [72.0%]；2010-2014 年，555/750 [74.0%]）相比，患有恶性疾病的婴儿生存率较低，且随时间无改善（3 年总生存率：2000-2004 年，109/199 [54.8%]；2005-2009 年，104/161 [64.6%]；2010-2014 年，66/112 [58.9%]）。从 2000 年到 2014 年，恶性疾病婴儿的复发率增加（3 年复发率：2000-2004 年，19% [95%置信区间，14%-25%]；2005-2009 年，23% [95%置信区间，17%-30%]；2010-2014 年，36% [95%置信区间，27%-46%]；P=0.01）。窦状阻塞综合征很常见，发生率为非恶性疾病婴儿的 13%（95%置信区间，11%-16%）和恶性疾病婴儿的 32%（95%置信区间，22%-42%）。一般来说，接受人类白细胞抗原匹配的同胞骨髓移植的患者有最好的结果。
在 15 年的研究期间，患有恶性疾病的婴儿的生存率没有提高。患有非恶性疾病的婴儿在早期生存率有所提高，但在后期研究期间没有提高。恶性疾病婴儿的较高复发率和所有婴儿的毒性仍然是重大挑战。减少复发和毒性以及优化供体和移植物选择的策略可能会在未来改善结果。
