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Myelodysplastic Syndromes

Clinicians attempt to diagnose and treat otherwise healthy patients before a stem cell transplant is necessary

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As the primary source of diagnostic information, not only do many healthcare professionals rely on the results provided by clinical laboratories, but so do the patients being treated accordingly. In the case of stem cell disorders like myelodysplactic syndrome, the information provided by the laboratory is as vital as ever. From established standards to new trends in technology, the ability to diagnose early and prevent potential risks is key before the condition worsens, eventually progressing towards acute leukemia. ADVANCE recently spoke with myelodysplastic syndrome guru, Steven Gore, MD, director of hematologic malignancies at Yale School of Medicine, who discussed the various measures available to combat the disease and provided a glimpse into the future of testing and treatment.

"Myelodysplastic syndrome is kind of a chronic leukemia -- is the way I would look at it," explained Gore. "It's a stem cell disorder. The abnormal stem cells try to make the normal compliment of different kinds of blood cells, but they are abnormal as they develop and tend to die off in the bone marrow."

According to Gore, there is a cure, but it's risky and not always necessary -- especially if patients are early in their diagnosis. While a stem cell transplant can potentially cure myelodysplastic syndromes, the side effects can be severe and sometimes fatal, so treating physicians and clinicians prefer to utilize that option in patients who are more high-risk rather than potentially endanger a relatively healthy person. Additionally, employing other treatments and therapies to reduce the percentage of blast cells, or immature cells, in the bone marrow increases the odds of success in transplants.

"We don't want to put people at risk of death if they otherwise have a reasonable prognosis," said Gore. "On the other hand, we'd like to offer transplants appropriately to patients with higher risk of disease."

Bone Marrow Aspirates
In terms of current clinical standards, there are several options for identifying and diagnosing myelodysplastic syndromes through bone marrow aspirate biopsies. In this case, the blast percentage can be quantified using flow cytometry or counted under a microscope. By running an iron stain on the bone marrow, clinicians can identify the specific abnormality in the cells known as ringed sideroblasts. Additionally, Gore emphasized the use of karyotyping to examine potential chromosomal aberrations that can be found in specific types of myelodysplastic syndromes.

"There are two current clinical prognostic scoring systems that are commonly used -- the most commonly used now is called the IPSS-R -- Revised International Prognostic Scoring System -- the other is WPSS, or WHO-based Prognostic Scoring System," continued Gore. "I calculate both of these on all my patients and the two tend to agree with each other a hundred percent, so I think they're probably pretty interchangeable."

On top of more traditional methods like the IPSS-R and WPSS evaluations, the emergence of genetic testing has also made a substantial imprint in both clinical and research-based testing. Although mutational analysis is not yet considered standard-of-care, it is becoming increasingly available. Along with methods like karyotyping, Gore also pointed out the resurgence of colony forming tests -- which culture tissue to look for BFU-E, a precursor to red blood cells that can help distinguish between myelodysplastic syndrome and autoimmune bone marrow failure states -- as well as the measuring of telomere lengths and function in the replication process -- which has also been linked to the disease.

"We know that certain gene mutations have prognostic information about myelodysplastic syndromes, and so there are companies which have jumped on this to promote panels -- which are done in CLIA certified labs now," said Gore.

Time to Take Action
Despite being a promising potential technique, Gore mentioned that DNA testing does not appear to supersede the results of current clinical prognostic scoring. The information provided by IPSS-R and WPSS systems has proven to be a reliable source in diagnosis and, as it stands, there is not yet anything to be substantially gained in the switch to more molecular-based processes. Because of this, Gore prefers to utilize genetic assays mainly in research setting, while depending on more established procedures in his own clinical practices.

When it comes to treating -- and possibly curing -- patients with myelodysplastic syndrome, the importance of testing comes down to the ability to monitor and reduce the number of blast cells collecting in a patient's bone marrow. In high-risk patients, a larger decrease corresponds to a better outcome in the case of a stem cell transplant. For low-risk patients, the capacity to monitor those cells and have the foresight to know when it's time to take action is invaluable in offering treatment while providing the best chance to maintain their well-being.

Michael Jones is on staff at ADVANCE.




     

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