By Ahmar U. Zaidi, MD, and Ayesha Zia, MD
Two roads diverged in a wood, and I—
I took the one less traveled by,
And that has made all the difference.
– Robert Frost
For individuals with sickle cell disease (SCD), the road from Walter Clement Noel’s “peculiar elongated cells” and uncertain diagnosis in 1910 to a multitude of novel therapies on the horizon in 2018 has been protracted and arduous. Only a few walk this path, and even fewer offer a helping hand along the way. On this dimly lit route, it is in the moments of illumination, through the work of committed researchers and patients, that our next step becomes clear. Researchers on this road less traveled have made all the difference for patients with SCD. At the 2018 annual meeting, the devotion of the scientific community in improving outcomes in SCD was brightly manifest.
Even before the meeting officially started, attendees hit the ground running with an exceptional session on the care of patients with SCD in advanced age, presented by Swee Lay Thien, MBBS, DSc, John Strouse, MD, PhD, Andrew Schamess, MD, and Payal Desai, MD. Theirs was a particularly imperative session in this new era in which the lifespan of patients with SCD is increasing. Another session on December 1, 2018, covered clinical complications and organ damage in SCD. Session highlights included the need for right-heart catheterization in individuals with elevated tricuspid regurgitant velocity by Pablo Bartolucci, MD, PhD, early hyperfiltration and its ability to predict albuminuria by Jeffrey Lebensburger, DO, MSPH; incidence of thrombotic events in patients with SCD and the potential role of thrombomodulin in this relationship, as detailed by Andrew Srisuwananukorn, MD; and incidence of bleeding events (particularly gastrointestinal bleeding) in patients with SCD by Nisha Hariharan, MD. Finally, Kenneth Ataga, MD, showed that low hemoglobin is associated with a more severe clinical phenotype, in an exhaustive and thorough meta-analysis, making increase in hemoglobin an attractive endpoint. The day concluded with the education session “Sickle Cell Disease: New Frontiers,” in which Rakhi Naik, MD, discussed the current landscape of sickle cell trait, Enrico Novelli, MD, summarized the biomarker development in SCD, and Deepa Manwani, MD, elaborated on the progress of current therapies and development in SCD.
On December 2, 2018, many translational and basic science presentations, ranging from anti-sickling mechanisms of low-molecular-weight heparin, to the contribution of mast cells in brain microvascular permeability, were well received. Further, an ASH-initiated effort ongoing since 2014 culminated in 50 recommendations from 75 experts across five SCD guideline panels presented at the “Special Education Session on ASH Clinical Practice Guidelines on Sickle Cell Disease.” Highlights of these new recommendations were shared in a meeting with members of the sickle cell community, and the final guidelines will be published in early 2019. Perhaps the sickle cell highlight of the meeting was a Plenary Scientific Session presentation by Léon Tshilolo, MD, PhD, in which he discussed data from the Realizing Effectiveness across Continents with Hydroxyurea (REACH) trial, providing the first prospective data on hydroxyurea treatment for children with SCD in sub-Saharan Africa. These results demonstrated the feasibility, safety, and benefits of daily oral hydroxyurea in the area of greatest global burden (see the December 3, 2018, issue of ASH News Daily).
The tremendous influx of data and knowledge continued on the meeting’s third day, when Elliott Vichinsky, MD, and Patrick McGann, MD, presented promising results from GBT440 and clinical pharmacokinetic dosing of hydroxyurea, respectively. We also learned of the benefits of L-arginine in pain episodes through improvement of mitochondrial function, from Claudia Morris, MD. Courtney Fitzhugh, MD, and Kim Smith-Whitley, MD, discussed new drugs and curative approaches in a special-interest session. Paula Tanabe, PhD, MSN, MPH, discussed current best practices in acute pain management, while Wally Smith, MD, highlighted the current best practices in the management of chronic pain. An interesting highlight was the oral presentation by Aithanh Nguyen, a high school student who presented data that demonstrated a novel role for α-1-anti-trypsin in reducing thermal sensitivity in SCD. These observations have the potential to develop therapeutic agents for treatment of pain in SCD following clinical trials.
The 2018 annual meeting was led by ASH President Alexis Thompson, MD, MPH, who is a key SCD opinion leader and advocate, and we were provided with many innovative advances in the science of SCD. So as we continue our walk on the road toward a global cure for SCD, this meeting will be a turning point – a light on the dimly lit road less traveled, showing us the direction in which we must continue.
Drs. Zaidi and Zia indicated no relevant conflicts of interest.