ASH press briefing rundown: optimizing pediatric care

Epigenetic aging and neurocognitive function in Hodgkin lymphoma survivors

Long-term survivors of pediatric Hodgkin lymphoma (HL) are at elevated risk for cardiopulmonary morbidity, cognitive impairment, and premature mortality, considered a result of accelerated aging. At ASH, AnnaLynn Williams, PhD, of the Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, presented the results of a study examining the relationship between biological aging and neurocognitive function.

This study included 215 survivors of pediatric HL and 282 community controls of European ancestry from the St. Jude Lifetime Cohort. Survivors of HL had a significantly greater epigenetic age acceleration (EAA) compared to community controls (HL survivor mean EAA (95% confidence interval [CI]) = 64.2 (3.6, 4.8) versus control mean EAA (95%CI) = -3.5 (-4.1, -2.9)) mean difference b =7.7 years, 95% CI 6.8 to 8.5; p<0.001.

Among HL, EAA was associated with worse visual-motor processing speed, with those in the second and third tertile performing on average 0.42 and 0.55 standard deviations worse, respectively than HL survivors in the first tertile. Those in the second and third tertiles also performed worse on short-term memory compared to those in the first tertile (second b = -0.42, 95% CI -0.74 to -0.10, p=0.011; third b = -0.59, 95% CI -0.90 to -0.27, p<0.001). In addition, those in the second or third tertiles performed 0.4 standard deviations worse, on average, than the first tertile in verbal fluency (second b = -0.40 95%CI -0.76 to -0.03 p=0.035; third b = -0.39, 95%CI -0.75 to -0.03, p=0.036).

The investigators concluded that survivors of pediatric HL experience significant EAA associated with deficits in visual-motor processing speed, short- and long-term memory, and verbal fluency. As a result, EAA may be a useful biomarker to identify survivors at risk for accelerated cognitive aging and as a pre-clinical gauge for interventions designed to improve cognitive function.¹

Formula feeding and iron deficiency in very preterm infants

According to a retrospective population-based cohort study, presented by Grace Power of Dalhousie University, Halifax, Canada, formula feeding significantly increases risk of iron deficiency (ID) in very preterm infants during the first 4-6 months of life.

Preterm infants are considered at increased risk of developing ID, which is associated with adverse neurodevelopmental and behavioural outcomes later in life. Breast fed (BF) preterm infants are considered at particularly increased risk and therefore iron supplementation is routinely recommended for these infants.

The primary objective of the study was to investigate how feeding type influences the iron status of very preterm infants at 4-6-months corrected age. A secondary objective was to further explore the risk factors associated with ID in the formula fed (FF) group.

A total of 392 infants were studied (gestational age: 23-30 weeks; 55.75% male). Of these, 285 were exclusively FF with iron-rich formula and 107 were exclusively or partially BF. Mean birth weight, gestational age and neonatal variables were comparable between the two groups.

Mean iron intake from formula in the FF group was 1.66 mg/kg/day, below the 2mg/kg/day recommendation. An intake of ≥2mg/kg/day from formula alone was only achieved in 20.4% of FF infants. These infants were also less likely to receive additional iron supplements.

Despite FF infants having a higher mean total daily iron intake, 36.8% of infants in FF group developed ID versus 20.6% in BF group (p=0.002). A possible explanation may be that the bioavailability of iron from formula is lower than from breast milk, because breast milk contains lactoferrin, which aids iron absorption.
There were some differences in the characteristics of ID and non-ID FF infants; mean gestational age and birth weight were both lower in the ID group, which also had a higher percentage of infants born <1100g (p=0.01) and more infants receiving at least one blood transfusion.

As a result, the investigators suggest the international recommendations for iron supplementation in FF very preterm infants needs to be revisited, with optimal iron supplementation guided by a risk adapted strategy incorporating factors such as lower gestational age and birth weight, and need for blood transfusions.²

Alloantibody exchange for sickle cell disease alloimmunisation

Red blood cell (RBC) alloimmunization rates and consequently delayed hemolytic transfusion reaction (DHTR) mortality in patients with sickle cell disease (SCD) is particularly high, so there is interest in a blood bank information system alloantibody exchange in the United States. However, cost of implementation has been a concern. George Goshua, MD, MSc, of Yale University School of Medicine, New Haven, CT, presented the results of a study investigating the impact of an exchange that enables alloantibody data-sharing across hospitals. The study involved the simulation of alloimmunized patients with SCD to project lifetime cumulative DHTR-specific mortality without an alloantibody exchange (status quo) versus with a US-wide alloantibody exchange.

It was found that implementing an alloantibody exchange versus not yields a decrease in cumulative lifetime DHTR-specific mortality (2.4% versus 5.7%, respectively). The absolute peak probability decrease of having a history of incident DHTR and being alive at age 41 was 27.0% versus 10.6%, respectively. The strategy of alloantibody exchange implementation accrues 22.08 per-person lifetime discounted quality adjusted life years (QALYs; 95% credible interval 22.03-22.12) versus 21.72 without (95% credible interval 21.61-21.82).

The lifetime population benefit for an alloimmunized population living with SCD in the United States is up to 15,710 QALYs gained. Total lifetime costs accrue $1.0 billion with exchange as compared to $2.5 billion without. This yields population-level cost savings of $1.5 billion USD ($34,091 saved per alloimmunized patient registered in the exchange), with an accrued incremental net monetary benefits (NMB) of $3 billion.

The investigators suggest that by reducing DHTR-specific mortality, an alloantibody exchange is predicted to be a life- and cost-saving investment for alloimmunized people living with SCD.³