Stopping the Sickle Cycle

by Allan Platt, PA-C, MMSc, DFAAPA

When I was in PA school  in 1977 I was taught that the life expectancy for a sickle cell disease patient was mid teens. I knew this was a genetic hemoglobin issue, one amino acid out of place in the beta globin protein chain, but I had no idea how far we come in 40 years. Life expectancy has grown with identification of patients with newborn screening programs, prophylactic penicillin from birth to age six, the advent of the pneumococcal vaccine, transcranial doppler ultrasound screening and transfusions to prevent stroke. In 1982, a patient at St. Jude Children’s Research Hospital in Memphis TN had leukemia and sickle cell disease. A St. Jude doctor performed the transplant using bone marrow donated from the patient’s brother.  The patient was cured of both leukemia and sickle cell disease. Many stem cell transplants have been curative with a 90% survival but only 18% of patients have an acceptable match. The advent of hydroxyurea in the 1980s as a preventive therapy reduced the need for blood transfusions, pain events and hospitalizations. It was found to prolong lives. By the early 1990s, the Cooperative Study of Sickle Cell Disease estimated a median life expectancy of those with sickle cell anemia, the most severe form of the disease, of 42 years of age for males and 48 years of age for females. In 2005 Lanzkron et al confirmed these findings of a significant decrease in mortality for children with SCD, but mortality for adults increased during the same time period. This may reflect a lack of access to high-quality comprehensive care for adults with SCD in the US.

In 2017 two notable advances happened: In July the FDA approved Endari or L-glutamine oral powder to Emmaus Medical Inc for use as a preventative in sickle cell patients 5 years and older. The safety and efficacy of Endari were studied in a randomized trial of patients ages five to 58 years old with sickle cell disease who had two or more painful crises within the 12 months prior to enrollment in the trial. Patients were assigned randomly to treatment with Endari or placebo, and the effect of treatment was evaluated over 48 weeks. Patients who were treated with Endari experienced fewer hospital visits for pain treated with a parenterally administered narcotic or ketorolac, on average, compared to patients who received a placebo, fewer hospitalizations for sickle cell pain (median 2 vs. median 3), and fewer days in the hospital (median 6.5 days vs. median 11 days).  Patients who received Endari also had fewer occurrences of acute chest syndrome compared with patients who received a placebo (8.6 percent vs. 23.1 percent).

The March 2nd issue of the New England Journal of Medicine published Gene Therapy in a Patient with Sickle Cell Disease, a report of the first successful case of using gene therapy in a patient with sickle cell disease in Paris, France. Gene therapy that delivered an antisickling variant of hemoglobin in an autologous hematopoietic stem cell (HSC) transplant had ameliorated all the symptoms of severe sickle cell disease (SCD) in a 15-year-old boy 2 years out from the procedure.

These two major events bring hope to all those battling the sickle cycle of recurrent pain and complications. We have come a long way in 40 years.

 

References

Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994;330:1639–44.

Lanzkron S, Carroll CP, Haywood C. Mortality Rates and Age at Death from Sickle Cell Disease: U.S., 1979–2005. Public Health Reports. 2013;128(2):110-116.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560868/

L-glutamine oral powder https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm566097.htm

N Engl J Med 2017; 376:848-855 March 2, 2017

http://www.nejm.org/doi/full/10.1056/NEJMoa1609677?query=featured_home

 

 

See Allan Platt, PA-C, MMSc, DFAAPA speak in 2018 at the Georgia Association of Physician Assistants Summer Conference July 15-19.

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