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Resources for Hematology Fellows

Sickle Cell Disease in the Adult Population

Sickle cell disease (SCD) in the adult population has been an understudied and underappreciated topic compared to other hematologic conditions. Lack of awareness of gaps in the SCD field stems largely from the fact that SCD is frequently considered a primarily pediatric condition. However, 95 percent of patients with SCD in the United States now survive into adulthood, meaning they will require ongoing specialized care at adult treatment centers. It is therefore critical to enhance our understanding and care approach.

Major gaps in patients’ understanding about SCD or sickle cell trait (SCT) in both the United States and worldwide have been increasingly recognized. Patient misinformation and/or a lack of information are frequent problems among young adults, as shown recently in a large study of patients with SCT.1 Pregnant women also face knowledge deficits regarding SCD and SCT.2 The transition from pediatric to adult care in patients with SCD presents a unique challenge.3 Within adult hematology, SCD has been underaddressed due the relatively low absolute number of hospitalizations in most centers compared to other adult hematologic diagnoses. In many cases, upon transitioning care centers, patients between ages 18 and 25 years of age encounter practitioners who are poorly equipped to take care of complex adolescent and young adult (AYA) populations in many specialties, and this is associated with increased morbidity and mortality. It has been shown that one-quarter of patients with SCD in this age group develop increasing complications of disease, leading to higher health-care resource utilization, and this progression doesn’t necessarily plateau with age.3 These findings highlight the need for research foci and improved clinical care targeted to these growing patient subgroups.

There have been recent pushes to amplify adult SCD research, especially for antisickling agents to decrease pain crises. We have seen a major resurgence in published studies in 2016. Dr. Kenneth I. Ataga and colleagues studied the efficacy of the P-selectin inhibitor crizanlizumab in patients between ages 16 and 65 years. In a randomized phase II study, crizanlizumab decreased the rate of vaso-occlusive crises (VOC) compared to placebo.4 This endpoint is highly important as it is a surrogate of quality of life in these patients. Other previously studied agents include the hemoglobin modifier and HbS polymerization inhibitor voxelotor (GBT440), nitric oxide donors, arginine, rheologic targeted agents for improving microvascular blood flow like vepoloxamer (MST-188), and the pan-selectin inhibitor rivipansel for the treatment of VOC. Of note, some of these agents have not shown efficacy in trials, but studies are ongoing. There is currently limited data for the microvascular blood flow enhancer sevuparin, the HbF inducer pomalidomide (FDA-approved therapy for multiple myeloma), the PDE9A inhibitor IMR-687, and the natural HbS polymerization inhibitor SCD-101. A major limitation to the development of novel antisickling agents is an underestimation of the potential benefit. SCD requires more attention from funding agencies.

While these represent disease-modifying therapies, there has been promising pre-clinical data for curative options like gene therapy for SCD. Bone marrow transplantation has been the only curative option to date but carries significant risks. Gene therapy strategies involve CRISPR-based methods for genomic editing to target the β-globin locus.5 Such methods make use of the ability to design single-guide RNAs to correct the Glu6Val amino acid substitution ex vivo in hematopoietic stem and progenitor cells, which are subsequently delivered back to patients. Soon, we may see the approval of this therapeutic modality, especially as cell-based therapy protocols gain momentum. As funding frequently relies on the large-scale clinical relevance of potential new therapies on broad populations, it will be paramount for academic hematologists to emphasize the importance of these adult SCD research efforts to improve quality of life and offer curative options.

1Harrison SE, Walcott CM, Warner TD. Knowledge and awareness of sickle cell trait among young African American adults. West J Nurs Res. 2017;39:1222-1239.

2Obed SA, Asah-Opoku K, Aboagye S, et al. Awareness of sickle cell trait status: a cross-sectional survey of antenatal women in Ghana. West J Nurs Res. Am J Trop Med Hyg. 2017;96:735-740.

3Kayle M, Docherty SL, Sloane R, et al. Transition to adult care in sickle cell disease: A longitudinal study of clinical characteristics and disease severity. Pediatr Blood Cancer. 2018;doi: 10.1002/pbc.27463. [Epub ahead of print].

4Ataga KI, Kutlar A, Kanter J, et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017;376:429-439.

5Dever DP, Bak RO, Reinisch A, et al. CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells. Nature. 2016;539:384-389.