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.
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11 comments:
I'm glad you pointed out that radiation can also be a causal factor in this disease. My 70-year-old brother-in-law was affected by myelodysplastic syndrome (MDS) after being treated for local prostate cancer with radiation pellets. Treatment-related MDS or secondary MDS is often more severe and difficult to treat than de novo MDS (unknown changes to the bone marrow). He lasted about six months.
My understanding is that MDS is characterized by an excess of blasts in the bone marrow 5-20%. The only difference between MDS and leukemia is that the term "leukemia" is only used when the number of blasts reaches 20% or more. Do I have it right doc? But the end result is just the same.
Thank you for the posts on cancer. Will you do a post on findings from ASCO. I would also be interested in your views on the potential for a cure for cancer or the ability to manage the sickness like a chronic disease.
Thank you
Yes MDS is characterized by excess blasts (i.e. early forms of cells) but even before this, the cells can look peculiar. Where I practiced, the pathologists would sometimes diagnose the disease from the appearance of cells called megakaryocytes.
As for results from ASCO, I would be hesitant to use them for treatment. It is rare that the results hold up. I don't see a cure for cancer at anytime any more than I see a cure for aging. Our DNA is too fragile and susceptible to changes that make cancer almost inevitable.
The SEER (Surveillance Epidemiology and End Results) seems to support your comment about simple aging is enough. Until recently, we did not have access to SEER data in MDS (Myelodysplastic Syndromes). This data is now starting to be developed and is confirming that MDS differentially affects older patients. As the current generation's age and life expectation lengthens, MDS may become a significant health issue world wide.
Thank you sharing this information. The writings are very accessible and insightful. In particular, I'm thankful for your feedback on ASCO. I heard a similar view from an oncologist, but he didn't say it very clearly. My brother is finishing up treatment for nasal cancer. He's being treated by a top team, but I was hoping that ASCO would reveal some major advance, and it's just not the case
I'm saddened to hear your views about the timing for a cure. The same oncologist also said that personalized treatment therapies are far off, despite all of the chatter
Do you have any views on diet for cancer survivors? Who is doing promising research in this area -- something beyond not drinking and smoking
I didn't know that SEER is looking at MDS. I'll check it out. As for diet - my only advice is keep fit - and not overweight.The best you can do for yourself.
I'm a 59 year old female whose blood was found to have possible myelodysplastic signs ten years ago after a bone marrow aspiration and biopsy showed abnormal cells in this context. My bone marrow was examined because, prior to having chemo for breast cancer, I was found to have neutropenia during a routine blood test. Now, ten years on, I am being referred back for further bone marrow testing due to having been unwell lately with breathlessness and really severe tiredness. Also a tendency to bruising, which I've had several years, and low iron stores (4.7) which was found a couple of months ago during blood tests done when I complained of feeling unwell. Are you please able to give me some idea as to the likelihood that myelodysplasia has actually now developed? Or is there any other condition that could cause these symptoms?
A low iron level may mean bleeding - you need to be evaluated.
I doubt too many laypersons in this nation have more knowledge about MDS than I do. Being an unoffical advocate for fellow Vietnam veterans, widows and myself, I have been in an ongoing battle with Veterans' Affairs for eight years to have MDS claaified as cancer / leukemia.
In their own words the VA responded to my US Senator "We don't look at diseases the same as the medical community does." The VA considers MDS to be anemia. When it turns to AML they promise to review your case -- 3.5 years being the average time required.
Vietnam veterans are 14,000% more likely to have MDS / AML than the general population. That is data gather from a FOIA request I made.
Do you think their might be a linkage between our service and our disease?
I testified before the Institute of Medicine Agent Orange Committee on November 4, 2010. We are hopeful that they will do the horonable thing and recommend that MDS / AML be put on the Agent Orange presumptive list.
For sure I asked them to tell the VA that it is not just a form of anemia.
Thank you doctor for calling it what it is!
Thank you Dr for your succinct explanation. My husband (aged 48) was diagnosed 10 months ago with refractory cytopenia with multilineage dysplasis. His karyotype is normal. We have a wonderful specialist who my husband sees every 3 months, however he is always quite vague in terms of providing us with a prognosis! He has set the ball rolling in terms of running bone marrow tests on close family members in order to find a compatible donor (thankfully we have a match!), however he still tells us it is a matter of 'wait and see'. This is so frustrating! My question is, do you have any experience with ýoung'sufferers of MDS; specifically those with the same type my husband has? If so, I would be so grateful for some info on how their disease'progressed?
Thank you so much
The only young people I ever saw with myelodysplasia had received chemotherapy in the past and their disease was devastating. I think looking at bone marrow transplant is a good thing to do, The big problem is when and if to do it; that is a clinical decision that needs to be made by experts who know your husbands clinical situation.
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