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

Abstract

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. Disclosures No relevant conflicts of interest to declare.

Recent Advances in Sickle-Cell Disease Therapies: A Review of Voxelotor, Crizanlizumab, and L-glutamine

“…The literature search retrieved 236 citations, with two further articles added through bibliographies review. A total of thirty-one articles [ 12 , 14 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ] met all inclusion criteria: six for L-glutamine [ 12 , 17 , 18 , 19 , 20 , 21 ], nine for crizanlizumab [ 14 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ], and sixteen for voxelotor [ 16 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ,…”

“…One case series ( n = 4, ages 9–24) was included evaluating opioid use in patients starting L-glutamine [ 19 ]. Two single-center retrospective studies were included, both ( n = 50 and n = 111) investigating prescribing data, compliance, and side effects of L-glutamine [ 20 , 21 ]. Table 1 summarizes the findings of these included studies.…”

“…About 2.7% of subjects discontinued therapy due to side effects [ 12 ]. In retrospective studies, since L-glutamine’s approval, most frequent side effects cited included abdominal pain, nausea, constipation, or taste of the medication [ 20 , 21 ]. When looking at l-glutamine prescribing data, at one pediatric center, 70% of prescriptions were dispensed, and 24% had good compliance (defined as ≥70%) [ 20 ].…”

“…In retrospective studies, since L-glutamine’s approval, most frequent side effects cited included abdominal pain, nausea, constipation, or taste of the medication [ 20 , 21 ]. When looking at l-glutamine prescribing data, at one pediatric center, 70% of prescriptions were dispensed, and 24% had good compliance (defined as ≥70%) [ 20 ]. At another adult center, at the end of a study period, 35% never filled the prescription, 42% discontinued, and only 19% were still actively taking L-glutamine.…”