AABB24: Transfusion Independence for Patients with Sickle Cell Disease?

The most common inherited hematologic disorder is sickle cell disease (SCD). For years, chronic blood transfusion has been a cornerstone for management of these patients, who often experience lifelong complications. Stem cell transplantation and gene therapies are now offering possible curative options and enabling patients’ care teams to consider the potential for transfusion independence.

During the session “Sickle Cell Disease: Inching Toward Transfusion Independence,” attendees learned from speakers who related progress of treatment via chronic red cell transfusions to the use of novel biotherapeutics.
Understanding Sickle Cell Disease

Ruchika Goel, MD, MPH, CABP, from Vitalant in Scottsdale, Ariz., began with a quick review of SCD, including the disease physiology and its global impacts. She also noted statistics for SCD prevalence around the world, the number of infants born with the sickle cell trait, and expected increase in affected patients in the next 25 years.

Curative Approaches
Goel explored new Food and Drug Administration (FDA)-approved therapies that modify SCD progression and could result in transfusion independence. Examples included L-glutamine (modifies red cell shape for better flow), voxelotor (decreases hemolysis) and crizanlizumab (relieves pain crises). As she observed, the voluntary recall of voxelotor and discontinuation of clinical trials by the manufacturer less than a month ago illustrate the challenges of balancing the risks vs. benefits of novel therapies.

An alternative approach to the use of products that counteract the effects of sickling is the use of viral vectors to deliver disease-modifying genetic changes that may prevent the damage. Goel detailed newly approved therapies that may prove to be curative. Her discussion included the advantages and disadvantages of competing approaches.

Red Cell Transfusion Is Here to Stay
Ross Fasano, MD, from Emory University, Atlanta, Ga., recapped the current red cell transfusion therapies used in treating SCD. He observed that many studies comparing red cell therapy with gene therapy have been, and continue to be, conducted. So far, the results have shown that red cell therapy remains a mainstay of treatment for the complications of SCD. He described not only the traditional FDA-approved treatments for SCD, but also the complications of iron overload that often result from transfusion therapy without chelation.

Fasano also detailed different settings in which red cell transfusion should, and should not, be used for patients with SCD undergoing surgery for acute illness. He cautioned attendees that vascular access and maintaining an iron balance can prove to be challenges in some patient populations and that there are many unanswered questions, particularly concerning older patients with SCD.