One of the major and most devastating disappointments in my practice was to see patients who were cured of their cancer – usually lymphoma – who would then develop this devastating and largely untreatable disease.
What is myelodysplasia? It is a disease of the bone marrow cells where they become dysfunctional. The early stem cells don’t make enough red cell, white cells and platelets. When I would look at the bone marrow cells, I would see enough of these early cells. They would just look peculiar. They would be misshapen or too big or the nuclei of the cells would be too big.
How does this happen? We think is results from abnormalities of the genes. I would see it in patients who have had lots of serious chemotherapy along with radiation therapy. Certain drugs were particularly good at causing this. These were the alkylating agents that directly damage a cell’s DNA (as does radiation by the way). The most commonly used drug is called cytoxan (cyclophosphamide). It is still used to treat lymphomas and some cancers. So in my patients with lymphomas, who were often cured by aggressive treatment with these alkylating drugs and radiation, the DNA of their bone marrow would be disrupted enough so that myelodysplasia would develop. It didn’t happen very often – perhaps just a few times in my practice, but always a terrible event.
But, you don’t have to receive chemotherapy and/or radiation to get this disease. Simple aging is enough. I guess we are exposed to enough radiation through natural means to disrupt our DNA or, perhaps our DNA just falls apart on its own. Most patients with myelodysplasia who have not received anti-cancer treatment are in their 70’s and 80’s.
There are different varieties of this disease and doctors can distinguish them by looking at the appearance of the bone marrow cells as well as testing their DNA for mutations. People with the most peculiar cells have the shortest life span after diagnosis, about a year or two, although a few can last as long as ten years. Others with good-looking cells can live anywhere from five to fifteen years or even longer. The same holds for genetic changes. Certain ones are associated with very short survivals and others, with much longer life spans.
When people die from this, it is usually because they can’t make enough infection fighting cells and get overwhelming infections such as pneumonia. Or, they develop acute leukemia. This type of leukemia that develops in people with myelodysplasia is virtually untreatable – different from other kinds of leukemia. Also, remember that the patients are generally elderly so that they can’t handle aggressive treatment or the stress of not enough blood cells.
There are treatments that can help if they are given before acute leukemia develops. Drugs such as 5-aza-cytidine or its cousin decitabine can delay both death and transformation into leukemia and patients will feel better. Another drug called lenalidomide can also help. Also, there are drugs that stimulate the bone marrow to make its cells and these can be effective. Transfusions are always helpful.
For younger patients, the best hope is a stem cell transplant from someone else’s bone marrow. But, aside from transplant, there are no magic bullets. This is a bad disease that affects mainly old people and those that have received anti-cancer treatment.
Is it cancer? I think it is and so do most cancer specialists. It just acts differently, but, the end result – incurable -, is just the same.