Clinicians may be able to change the way people with a blood disease called myelodysplastic syndrome are diagnosed and treated, potentially preventing it from turning into leukemia, according to research by two University of Florida medical students.
Their findings will be presented Saturday at the American Society of Hematology's annual meeting in Orlando.
Myelodysplastic syndrome, or MDS, is a rare disease in which bone marrow loses the ability to produce healthy blood cells, according to the Myelodysplastic Syndromes Foundation. In about 30 percent of people who have MDS, the disease can progress into acute myeloid leukemia, a type of leukemia that is difficult to treat.
UF medical student Cindy Medina found that a software program that interprets cancer gene mutations and tests for drug sensitivity was successful in predicting patient outcomes in an examination of three previously published clinical studies.
The software, which was created by a company called Cellworks, is currently being tested in UF Health cancer clinics by UF Health researcher Christopher R. Cogle, M.D. The new personalized medicine program, called iCare for Cancer Patients, reads the genes that make up an individual patient's cancer, creates a unique map of the inside of the patient's cancer cell using information from published medical literature and then screens for FDA-approved drugs with therapeutic potential.
Cogle recently received an $800,000 grant from the Gateway for Cancer Research Foundation to advance the iCare program into randomized clinical trials. The foundation supports both repurposing FDA-approved drugs and the mission to personalize therapy for patients with cancer. The grant will support a randomized clinical study looking at the effectiveness of using the Cellworks software to match patients with cancer therapies.
To test how well the iCare precision oncology method worked, Medina used the software to examine three previously published MDS studies to see if it could predict the outcomes of the patients included in those studies.
In the previously published studies, MDS patients were treated with three different kinds of medications, azacitidine, decitabine and lenalidomide.
In the first study Medina investigated, of the 37 patients who responded well to lenalidomide, the software predicted 35 patients would respond well. Of the nine patients that did not respond to lenalidomide, the software predicted four would not respond well.
In the second study, of seven patients who responded well to the chemotherapies azacitidine or decitabine, the software predicted all of them correctly. Of the eight patients who did not respond well to the medications, the software was correct in five cases.
In the final study, the software correctly predicted clinical outcomes in all 10 MDS patients treated with the combination of azacitidine and lenalidomide.
Medina thinks the software did a good job at predicting who would respond to treatment because the software relies on published studies available in PubMed to make an accurate prediction. If there were more publications on genes and proteins linking to improved clinical response, then the software would be stronger in predicting who will respond well. By incorporating new information as soon as it is published in PubMed, the software continually learns about MDS and provides better modeling results.
"In the long run, we really want to be more efficient in treatment selection, and spare patients from lengthy or toxic treatments that maybe they were not going to benefit from in the first place," Medina said. "Our modeling grants us a greater understanding of MDS biology and provides us with an opportunity to find more targeted and personalized therapies for our patients."
Another UF medical student, Shannon Stockton, discovered that 21 different gene mutations are recurrently found in patients with MDS and that some of the gene mutations link with particular blood count abnormalities. Stockton found these associations by combining traditional blood cell counting and chromosome staining with newer gene mutation technology called next-generation sequencing. In fact, Stockton said that although all MDS patients have blood count abnormalities, about half have chromosomes that appear normal. This "normal" result causes great confusion in the clinic, as doctors cannot confirm an MDS or leukemia diagnosis without a finding an abnormality in a person's DNA.
"Very few hematologists test their MDS patients for genetic mutations," Stockton said. "That's a problem because what our research shows is that gene mutations are present in all MDS patients and those gene mutations can give a lot of information about how patients will respond to different treatments."
Stockton's research showed that all MDS patients, no matter what their chromosomes looked like under the microscope, had one to four mutated genes out of the 21 genes she examined.
"Even if your chromosomes look normal, you can still have deeper gene mutations that can have implications for your diagnosis, prognosis and how well you respond to treatment," Stockton said.
Both Medina and Stockton earned $500 achievement awards from the American Society of Hematology for their research.
"I'm very proud and excited for our medical students who were selected to present their discoveries at a national meeting and received prestigious achievement awards," said Cogle, Medina and Stockton's mentor and an associate professor of medicine in the division of hematology and oncology in the UF College of Medicine. "It's a testament to their intellect, persistence and curiosity."