Pediatric Patients with Sickle Cell Disease at Harbor-UCLA & Early Experience of L-Glutamine Therapy

Background.Sickle cell disease (SCD) affects millions of people worldwide, including >100,000 Americans, and is often complicated by acute crises. Complex pathophysiology makes it challenging to ameliorate SCD severity, which can be influenced by hydration and disease-modifying agents such as hydroxyurea (HU). Due to the increased metabolic demands of chronic illness, optimal nutrition and presumably antioxidant L-glutamine (Gln) may further contribute to disease control. Thus, we hypothesized that better nutrition and Gln adherence may reduce occurrences of pain crises in SCD.

Methods.An IRB-approved retrospective review of pediatric patients with SCD ≥1 y of age was conducted at our institution, along with voluntary nutrition surveys. Evaluations were carried out for associations between disease severity and clinical/laboratory variables representing nutrition, growth, hematologic parameters [fetal hemoglobin (HbF), mean corpuscular volume (MCV)], and treatment compliance (with HU and/or Gln).

Results.Preliminary analyses included data from 50 SCD patients (25 F/25 M), with a mean age of 9.1 ±7 y and a mean BMI of 56.4 ±32.6% (±SDEV). Sixty percent of the patients had HbSS/Sß⁰ (32%-HbSC and 8%-HbSß⁺). The average number of annual pain crises (APC, 0.97 ±1.14) requiring hospital visits or admissions per patient rose with age. HbF expectedly dropped with age. HbF levels <10% in teenage and older patients were associated with a ≥2-fold higher APC, compared to younger patients (despite similar proportions of HbSS/Sß⁰). Proper hydration and nutrition were reported by 69% and 43% of 35 survey participants, respectively. APC values for 3 main groups were:

- 0.87 ±1.1 for well hydrated/well nourished (n=14, 3.1 ±2.3 y)

- 1.4 ±2 for well hydrated/poorly nourished (n=10, 11 ±6.4 y)

- 1.97 ±2 for poorly hydrated/poorly nourished (n=8, 13 ±5.4 y).

There were no correlations between caloric intake and BMI. However, 20% of surveyed patients (12 ±7.8 y) had Z-scores lower than -1 SD for both height and weight. Their mean APC was significantly higher (2.5 ±2.5vs.1 ±1.3,p=0.03 byt-test). Their prealbumin levels trended lower than normal for age, and were more diminished in older patients.

Nearly 60% of our patients were on HU (80% with HbSS/Sß⁰, age 10.8 ±7.4 y). Good HU adherence was reported by 22 patients, typically ≥90%, which was associated with higher MCVs (92 ±9.6 vs. 74 ±10 f/L,p<0.01), a trend toward higher HbF levels, and younger ages (15 vs. 9% and 9.7 ±7 vs. 14 ±7.7 y,p=NS). The majority (83%) of our patients 5 y of age or older were prescribed Gln, and 70% of the prescriptions were dispensed. Some refused Gln due to abdominal pain or taste, and a quarter of patients reported <50% Gln intake while on both HU and Gln. Thus, overall Gln compliance in 23-months was ≥70% in 12 patients. Patients were excluded while on chronic transfusion. Of 10 evaluable patients, 6 (8.8 ±2.2 y) had a significantly lower APC with Gln (mean APC decrease 0.9 to 0.2,p=0.016 by pairedt-test) coupled with a 12% rise in prealbumin (14.1 to 15.8 mg/dL;p=0.1).

Conclusions.Well-nourished/hydrated patients were younger and had a milder disease phenotype, whereas more severe disease was seen in poorly nourished older patients, often with suboptimal compliance. L-Glutamine can be a clinically meaningful addition to HU and should be further studied in pediatric SCD.