A study appearing in the Journal of Pediatric Hematology/Oncology suggests that stem cell transplantation may provide severe sickle cell patients with the greatest quality of life, but more data is needed before a “gold standard” treatment can be identified.
Patients with sickle cell disease, an inherited blood disorder that affects red blood cells, need ongoing treatment, even when they are not experiencing pain. Three interventional treatments have been shown to be effective in decreasing the acute and long-term complications of sickle cell disease: hydroxyurea therapy, chronic transfusions and hematopoietic stem cell transplantation. “Because each of these therapies involve different risks and benefits there is little consensus among sickle cell clinicians when recommending a therapy,” said Sarah O’Brien, MD, MSc, pediatric hematologist and principal investigator in the Center for Innovation in Pediatric Practice at The Research Institute at Nationwide Children’s Hospital and lead study author. No randomized studies have been conducted to compare the three treatment strategies directly.
When clinical trial data are not available, decision analysis can be used as a tool in medical decision making. In this simulation model-based technique, an investigator combines information from a variety of sources to create a mathematical model representing a clinical decision. Data are collected to estimate the probability of each event, as well as expected risks, benefits, and cost of each strategy. The decision tree is then analyzed to identify which strategy has the highest expected value and is therefore the preferred course of action.
Dr. O'Brien and Jane S. Hankins, MD, MS, pediatric hematologist from St. Jude Children’s Research Hospital, designed a decision analysis model to compare treatment strategies in children with clinically severe sickle cell disease. The investigators took into account current knowledge of treatment risks and benefits for the three available treatments and estimated patient preferences for health states. The model’s study population was comprised of patients with clinically severe sickle cell disease followed over a 5-year time period. Five-year probabilities for survival, treatment efficacies and complications were extracted from published pediatric studies. The health outcome of interest included both the quality and quantity of life lived. This is the first time decision analysis has been used to compare treatment strategies in children with clinically severe sickle cell disease.
Findings from this model showed that stem cell transplantation was associated with the highest average quality of life, followed by hydroxyurea therapy and chronic transfusions. “Even in patients with HLA-matched sibling donors, which account for less than 10 percent of sickle cell patients, recommending stem cell transplantation over hydroxyurea therapy remains a difficult decision for clinicians since transplant is associated with additional risks,” said Dr. O’Brien. “The results of our model demonstrate that quality of life is also an important factor to consider in this decision.”
Dr. O’Brien says that the model is limited in the fact that it only follows patients for five years, but she considers this model as a place to start in decision making for patients with severe sickle cell disease. “More data is needed on the use of hydroxyurea therapy and stem cell transplantation in sickle cell disease, in particular, data on the long-term outcomes of these patients,” said Dr. O’Brien. “Importantly, our model demonstrates the necessity of eliciting quality-of-life data from children with sickle cell disease who undergo these therapies.”