Systematic Review of l‐glutamine for Prevention of Vaso‐occlusive Pain Crisis in Patients with Sickle Cell Disease

Abstract

l‐glutamine was approved by the U.S. Food and Drug Administration (FDA) for sickle cell disease (SCD) in 2017. A vaso‐occlusive crisis (VOC) occurs in persons with SCD and is associated with acute pain episodes. This systematic review summarizes the evidence for l‐glutamine in the prevention of VOC and associated pain in patients with SCD. Medline, Embase, and International Pharmaceutical Abstracts were searched for records reporting on l‐glutamine use in persons with SCD. Eligibility criteria identified primary reports of investigations conducted in humans who were administered l‐glutamine, reported on outcomes related to VOC or associated pain, published in English, and were available as full text. All relevant efficacy, safety, participant demographic data, and study method characteristics were extracted and documented. Risk‐of‐bias assessments were conducted using the Risk of Bias in Non‐Randomized Studies‐of Interventions (ROBINS‐I) tool and the revised Cochrane risk‐of‐bias tool for randomized studies. Three studies assessing the effect of exogenous l‐glutamine administration in patients with SCD met eligibility criteria: one prospective nonrandomized controlled study and two prospective randomized controlled trials. Rate of VOC and related hospitalizations were reduced in patients receiving l‐glutamine, although some conflicting results were noted between studies. l‐glutamine was generally well tolerated. Limitations of one or more of the eligible studies included small sample size, nonblinding, and study groups that differed at baseline. l‐glutamine has limited high‐quality evidence supporting its use. Although l‐glutamine is FDA approved for the prevention of frequent episodes of VOC pain, only one randomized controlled trial has strong evidence to support this indication. Based on the results of a systematic review, l‐glutamine may be considered for patients unable to receive hydroxyurea or in addition to hydroxyurea for reduction in VOC and associated pain.

Blood rheology biomarkers in sickle cell disease

“…Both of these drugs have been shown to decrease VOC in patients in clinical trials. 63,64 HU ameliorates the complications of SCD by inducing HbF, reducing the WBC count, reducing the number of adhesive reticulocytes, and reducing inflammation. 65,66 The HU-induced rise in HbF helps reduce polymerization of HbS, allowing sickle RBCs to survive longer in the circulation.…”

Hematopoietic Cell Transplantation for Sickle Cell Disease

“…SCD is a major public health problem in the United States affecting more than 100,000 individuals (5), predominantly African Americans, and is associated with substantial healthcare costs. Hydroxyurea, L-glutamine (6), voxelotor (7), and crizanlizumab (8) offer the possibility of the modification and amelioration of the disorder. Patients have to take these medications indefinitely, and access to care, health disparities, and other sociodemographic factors may influence uptake, usage, and effectiveness of long-term disease modification therapy.…”

A Decision Support Tool for Allogeneic Hematopoietic Stem Cell Transplantation for Children With Sickle Cell Disease: Acceptability and Usability Study

“…Complications of SCD include painful vaso-occlusive episodes, acute chest syndrome, stroke, splenic sequestration, progressive organ dysfunction, and premature mortality [ 2 - 5 ]. Disease-modifying therapies, such as hydroxyurea, L-glutamine [ 6 ], voxelotor [ 7 ], and crizanlizumab [ 8 ], offer the possibility of long-term amelioration of the disorder. Despite undergoing these therapies, patients with SCD have a diminished quality of life (QoL) and life expectancy, which may be 20 years less than that of the general African-American population in which SCD is most prevalent [ 4 ].…”