Understanding Prognosis in MDS | Aplastic Anemia and MDS International Foundation

Understanding Prognosis in MDS

Richard Stone, MD is Director of the Adult Acute Leukemia Program at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, both in Boston, Massachusetts. He also serves as Chairman of the AA&MDSIF Medical Advisory Board. In this May 2011 interview, Dr. Stone responds to questions about prognosis in MDS -- what it is, what MDS prognosis means, what prognostic tools are used, and how prognosis is used to predict and plan for potential outcomes.

Can you explain what myelodysplastic syndromes (MDS) are?

Myelodysplastic syndromes are a group of diseases that affect bone marrow output. It’s a heterogeneous group of diseases, meaning that one patient’s MDS is often different from another patient’s MDS. Some types are relatively mild, where a patient can live for years, and others are quite severe and dangerous, such that prospects for long-term survival can be poor. What they have in common is ineffective bone marrow function, where the marrow is trying to make the correct amount of all blood cells as evidenced by the high degree of cellular activity—red blood cells, white blood cells, and platelets—but is unable to do so.

What does prognosis mean?

Prognosis means a guess as to how a patient is going to fare in the future based on present conditions. Predicting the future is always difficult, but it is important to try to do this for patients with potentially serious diseases like MDS. We want to be able to tell patients what they may be able to in terms of upcoming problems as well as estimating survival duration. So-called prognostic features or ‘prognostic index’ represents a tool that doctors use to relatively accurately inform patients about expectations. The prognosis is also used to develop a treatment plan. For example, a poor prognosis may suggest a more risky therapy, such as a stem cell transplant, be tried. A better prognosis that indicates a longer life expectancy may influence a decision to stay with a safer approach.

Can you discuss the International Prognostic Scoring System (IPSS)? How do doctors use it?

The IPSS was devised in 1998—after review of a large panel of MDS patients—which determined which specifi c disease features were important for prognosis The developers of the IPSS determined there were three things needed to help determine prognosis—the percentage of bone marrow blasts (immature white blood cells), the number of cytopenias (low blood counts), and the bone marrow karyotype (the chromosomal analysis of bone marrow that is made at the time of diagnosis). From these, a score is formulated that estimates the likelihood of disease and survival.

Can you discuss the International Prognostic Scoring System (IPSS)? How do doctors use it?

The IPSS was devised in 1998—after review of a large panel of MDS patients—which determined which specifi c disease features were important for prognosis The developers of the IPSS determined there were three things needed to help determine prognosis—the percentage of bone marrow blasts (immature white blood cells), the number of cytopenias (low blood counts), and the bone marrow karyotype (the chromosomal analysis of bone marrow that is made at the time of diagnosis). From these, a score is formulated that estimates the likelihood of disease and survival.

What are bone marrow blasts?

These are young cells that are immature, but have the capacity to eventually give rise to the functional blood cells—red, white, and platelets. It’s difficult to tell a cancerous immature cell or blast from a healthy normal one. So if there are too many immature cells in the bone marrow, that indicates a problem. Ideally, blasts should comprise less than 5% of all marrow cells.

Are there any problems with the IPSS?

There are a few problems. One is that it is relatively old, given the development of new more effective therapies since 1998 when it was introduced. It was developed based on patients in the 1980s and 1990s. New drug treatments have been introduced since then, like lenalidomide (Revlimid®) and the hypomethylating agents—azacitidine (Vidaza®) and decitabine (Dacogen®)—and IPSS doesn’t take the effect of these into account. Another drawback is that it is not dynamic; that is, it is determined at diagnosis and doesn’t take into account events and treatments that subsequently occur. Also, it doesn’t apply to patients with prior hematologic abnormalities or prior treatment for other cancers. Finally, it doesn’t include an assessment of overall health, marrow functional status, or other non-MDS diseases beyond the three defining criteria I mentioned earlier. For example, the need for red cells could influence prognosis for patients with a particular IPSS score.

What are some of the newer prognostic tools?

There are some newer, improved prognostic scoring systems that have been developed, including the World Health Organization Prognostic Scoring System (WPSS). The WPSS takes advantage of the fact that the classifi cation categories of MDS have changed. There have been refi nements in the different MDS subtypes based on the way the bone marrow looks—how many cell lines are dysplastic, that is, how odd they appear under the microscope. WPSS also takes into account whether the patient is having red cell transfusions, and the IPSS did not. A transfusion is an independent prognostic factor that matters— patients not needing transfusions are a little better off than those who do, even controlling for other known prognostic factors. Pathology, morphology, and the significance of transfusions are all part of the changes in the WPSS. It may be able to deliver a more accurate estimate of prognosis than the IPSS. The IPSS has recently been refi ned as well to take into account a wider range of chromosomal abnormalities. Also, the MD Anderson Cancer Center has a prognostic scoring system that recently is becoming more widely used because it takes into account the patient’s performance status (overall health) that sometimes trumps the hematological issues.

When a patient gets diagnosed with MDS, what should they be asking their doctor about their prognosis?

Patients should take into account the best possible prognosis, perhaps employing several classifi cation systems. Such an effort could aid a patient’s understanding of their particular disease state. This is a good opportunity for the doctor to remind the patient that these prognostic scoring systems are just a gross estimate of how a patient will do. A patient with a higher risk presentation of MDS and an adverse prognosis can still live a long time, since estimates are just that.

Compared to what may eventually exist in assessing MDS prognosis, what we have now is very rudimentary. Our increased understanding of the genetic underpinnings of MDS may allow a more accurate prognostic scoring system to be developed. While patients will understandably be concerned at the prospect of a shortened life expectancy, they should realize everyone’s situation will be different, especially given the heterogeneity of MDS. They should focus on learning everything they can about the disease, establish a good relationship with their doctor, and try to stay abreast of new developments in this disease. The AA&MDSIF Web site can be an excellent source of information.

Interviewee: 

Richard M. Stone, MD

Lead Photo
Position / Title: 
Professor of Medicine, Harvard Medical School
Institution: 
Dana-Farber Cancer Institute

Dr. Stone received his MD in 1981 from Harvard Medical School, his internal medicine residency training at Brigham and Women's Hospital, and his hematology-oncology fellowship at DFCI. He has performed numerous laboratory and clinical studies on acute leukemia and related disorders, and frequently participates in grand rounds worldwide. He is currently the Director of the Adult Acute Leukemia Program at DFCI, serves on the Medical Oncology Board of the American Board of Internal Medicine, and is vice chair of the Leukemia Core Committee for the national cooperative trials group Cancer and Leukemia Group B.