High rates of relapse and toxicities among infants who undergo allogeneic hematopoietic cell transplant (allo-HCT) contribute to survival rates that have remained largely unchanged from 2000-2014, based on a retrospective study of almost 2,500 cases.
Although survival rates improved from 2000 to 2004 among children aged 1 and younger who underwent allo-HCT for nonmalignant conditions, rates plateaued thereafter, reported lead author Suhag H. Parikh, MD, of Duke University Medical Center in Durham, North Carolina, and his colleagues. Still more disappointing, survival rates for infants with malignant conditions remained relatively flat throughout the 15-year study period.
For adult patients, allo-HCT survival rates have improved over time, but data for infants are rare. This is a concerning blind spot because infants are a particularly vulnerable population in the transplant setting.
Courtesy Duke Health
Dr. Suhag H. Parikh
“Infants may be at higher risk for toxicities than adults,” the investigators wrote in JAMA Pediatrics. “Although children are considered to have better tolerance to high-intensity or myeloablative conditioning regimens and perhaps better immune reconstitution owing to a functional thymus, infants may be at higher risk of transplant-associated complications.”
The present study involved 2,498 infants,1 year old or younger (median age 7 months), who underwent allo-HCT for malignant or nonmalignant conditions between 2000 and 2014. Information was drawn from The Center for International Blood and Marrow Transplant Research (CIBMTR), which consists of data from more than 450 transplant centers across the world.
The investigators assessed overall survival trends among infants undergoing allo-HCT; in addition, they analyzed factors contributing to mortality and rates of two major organ toxicities: sinusoidal obstruction syndrome and idiopathic pneumonia syndrome. Cases were divided into 2 cohorts: malignant and nonmalignant. Time-analysis was divided into three periods: 2000-2004, 2005-2009, and 2010-2014.
Overall, the results were disheartening. Survival trends were generally flat during the 15-year study period, and some outcomes actually worsened over time. As a small highlight, infants with nonmalignant disease had improved survival when comparing the second and third time period with the first time period (HR, 0.77; P = .007); however, this trend fell flat after 2004. Three-year overall survival rates for infants with nonmalignant disease from least recent to most recent time period, were 65.0%, 72.0%, and 74.0%.
Survival was poorer with malignant conditions, with 3-year overall survival rates of 54.8%, 64.6%, and 58.9% from least recent to most recent time period. This trend was associated with a worsening relapse rate, which increased from 19% to 36% from 2000 to 2014.
Also, toxicities were relatively common. Sinusoidal obstruction syndrome occurred in 32% of infants with malignant disease and in 13% with nonmalignant conditions. The rate of interstitial pneumonia syndrome at 100 days post-transplant was 5% across all patients.
Optimal supportive care and donor/graft selection might improve outcomes, as could reduced-intensity/nonmyeloablative conditioning regimens rather than total body irradiation, according to the researchers.
Changes in practice for disease subgroups may be warranted, based on the improved survival rate seen for infants with nonmalignant disease, which was mostly driven by better outcomes in patients with severe combined immunodeficiency, a disease subgroup that has had newborn-screening programs since 2008. Judging by the trends, such programs are truly making a difference, the researchers wrote.
The study was funded by the National Cancer Institute (NCI); the National Heart, Lung and Blood Institute (NHLBI); Health Resources and Services Administration; the Office of Naval Research; and a number of private pharmaceutical companies. The investigators reported financial relationships with Sangamo Therapeutics, Mallinckrodt, Takeda, Jazz, and others.
SOURCE: Parikh et al. JAMA Peds. 2019 March 18. doi: 10.1001/jamapediatrics.2019.0081.