Meylodysplasia or Myelodysplastic Syndrome (MDS) is a disease of the bone marrow where abnormal bone marrow stem cells fail to develop and mature into normal red blood cells, white blood cells, and/or platelets. The abnormal stem cells, having been damaged by mutations or from prior chemotherapy or radiation therapy, give rise to the development of polyclonal or eventually monoclonal cells in the bone marrow that result in low numbers of mature blood cells in the circulation. Therefore, when a complete blood count (CBC) is performed on peripheral blood, the white blood cell count may be low (leukopenia or granulocytopenia), the red blood cell count may be low (low hemoglobin or hematocrit), and the platelet count may be low (thrombocytopenia).
Because there are monoclonal cells in the bone marrow, MDS is considered a slowly progressive bone marrow cancer.
Cause of MDS
The cause of MDS is not known, although toxic chemicals and prior chemotherapy or radiation therapy in a small minority of patients are known to injure the stem cells in the bone marrow and give rise to MDS. Age, with a gradually increasing accumulation of mutations in bone marrow stem cells, is probably the major risk factor for developing MDS. At diagnosis, 86% of patients are >60 years of age.
Symptoms of MDS
There may be no symptoms in early or mild cases. However,if the red blood cell count drops and anemia develops (which is the most common manifestations of MDS), the anemia may lead to pallor, fatigue, tiredness, loss of stamina, dizziness, and shortness of breath. If the white blood cell count drops, then this increases the risk of developing infections (e.g., pneumonia), which may be life-endangering. If the platelet count drops, then excessive bleeding, bruising, and petechia may occur.The most common symptoms of MDS are fatigue, weakness, easy bruising or bleeding, fever, bone pain, shortness of breath, and frequent infections.In 25% of cases,
MDS can develop into acute myelogenous leukemia (AML), which is a serious leukemia that can sometimes be fatal in 1-2 years.
A bone marrow biopsy is typically how the diagnosis of MDS is established. The bone marrow is examined under the microscope for abnormal ("dysplastic") blood cells, very immature cells ("blasts"), and abnormal chromoscomes and genes by molecular testing, cytogenetic (chromosomal) analysis, and immunophenotyping.
Sub-Types of Myelodysplasia
There are several MDS subtypes. They include:
Unilineage dysplasia. One blood cell type, either white blood cells, red blood cells or platelets, is low in number and may appear abnormal under the microscope.
Multilineage dysplasia. Two or three blood cell types are abnormal.
Ring sideroblasts. The red blood cells in the bone marrow contain a ring of excess iron called ring sideroblasts.
Chromosomal deletions/abnormalities. There are specific mutations in the DNA that are characteristic of MDS..
Excessive "blasts." Very immature blood cells (blasts) are found in the blood and bone marrow.
The Revised International Prognostic Scoring System (IPSS-R)
The IPSS-R is a set of criteria that classifies MDS into five risk groups: very low, low, intermediate, high, and very high risk. It helps to determine a patient's treatment and his/her prognosis by applying these criteria and assigning patients to one of these risk groups. Low risk persons may live for many years and require little or no treatment, while high and very high risk individuals may require imediate and high-intensity treatment. http://www.bloodjournal.org/content/120/12/2454?sso-checked=true
There are certain criteria used in the IPSS-R that confer favorable or unfavorable risk. For example, cytogenetic factors that confer favorable risk include a normal karyotype or chromosomal deletions at 20q, 5q or 12p. The absence of "blasts" in the bone marrow is a favorable, while >10 "blasts" is unfavorable. A hemoglobin of >10 is favorable, while <8 is unfavorable. Platelet counts >100,000 are favorable, while <50,000 is unfavorable. An absolute neutrophil count (ANC) >0.8 is favorable, while <0.8 is unfavorable.
An on-line "calculator" to assess MDS risk may be found at: https://www.mdcalc.com/revised-international-prognostic-scoring-system-ipss-r-myelodysplastic-syndrome-mds
If MDS is relatively mild, no specific treatment is required and active surveillance (watchful waiting), by checking the CBC every few months, is all that may be needed. However, if the MDS appears to be progressive, then supporting care, including blood transfusions and medications to stimulate the bone marrow to produce more white blood cells (GM-CSF, Neupogen, Neulasta) or red blood cells (Procrit), can be used.
Vaccinations, to help prevent infection, are recommended. MDS patients should get an annual flu shot and the pneumococcal "pneumonia" vaccine. However, vaccines that are "live attenuated" vaccines, which are weakend copies of a live virus, must not be administered. They can be dangerous to MDS patients because of their weakend immune system. Timely treatment of infections with antibiotics is obviously important.
Disease-modifying therapy, such as azacitidine (Vidaza) or decitabine (Dacogen), help bone marrow cells to develop in a more normal manner and become mature, functioning cells. Lenalidomine (Revlimid), which is a thalidomide-like medicine, is another medication that can be effective, particularly in MDS patients who have anemia and abnormalities of chromosome 5 ("5q minus").
Immunosuppressive drugs may be effective in MDS patients who have a hypoplastic bone marrow, where the production of hematopoietic precursor cells is markedly diminished. Examples include antithymocyte globulin (ATG), methotrexate, cyclophosphamide, and cyclosporine.
Stem cell transplantation (SCT) is a formidable treatment, with significant risks, but if a matched donor can be found and the SCT ‘takes", then it can be curative. The best donoros are usually a biologic brother or sister, but unrelated donors are sometimes a good match. SCT is usually offered to MDS patients who are <75 years of age, but patient selection depends on an overall assessment of health and on the application of an hematopoietic cell transplantation co-morbidity index (HCT-CI), which is a tool that has been developed for assesssing the risks of SCT in individual patients. For some patients, there is a "reduced intensity" chemotherapy/radiation option before transplantation with stem cells.
SCT is typically not recommended for low risk MDS patients, because the risks of SCT usualy outweigh the benefits. While there is an approximately 60% chance of cure with SCT, there is a 40% risk of death or relapse at 5 years.
When death occurs in patients with MDS, it is usually from bone marrow failure, infection or bleeding, or from the development of acute myelogenous leukemia (AML).
Reduced-intensity stem cell transplant (Mini-SCT)
An alternative option for older individuals that may not be able to tolerate the intensive pre-treatment with radiation and chemotherapy that a conventional SCT requires, is what has been called a "mini"-SCT. Mini-transplant patients are pre-treated with lower doses of chemotherapy, generally without radiation therapy, which they tolerate better. They then receive an infusion of donor stem cells from a compatible donor, which reconstitute the bone marrow with healthy stem cells that give rise to normal red blood cells, white blood cells, and platelets.
Mini-SCT has been successfully used to treat aplastic anemia, leukemia, myelodysplasia, myeloproliferative diseases, lymphoma, and multiple myeloma. Unlike conventional SCT, which essentially eliminates all lthe stem cells in the bone marrow, mini-SCT suppresses the bone marrow to allow healthy donor stem cells to reconstitute the bone marrow.
While there are still significant risks with the mini-SCT, it is an option for older patients that may not tolerate conventional bone marrow therapy.
The median length of survival for patients with MDS depends on their IPSS-R risk category, other medical problems (co-morbid features), and age. However, statistics are only guesses at prognosis, and there is a wide variability from patient to patient that you should discuss with your doctor.
Disability Benefits with MDS
Whether you are eligible for long-term disability benefits under the Social Security Act (SSDI) and/or in accordance with an employer-based disability plan (ERISA), will depend on the stage of your MDS, the symptoms and functional limitations that you have, and the adequacy of the medical documentation in your medical record.
If you have MDS and suffer from chronic anemia, with a hemoglobin level <10, and have tiredness, severe fatigue, weakness, light-headedness, and other related symptoms, your functional capacity may be "less than sedentary" (meaning you are unable to perform even a "desk job"), and your chances of a long-term disability benefit award should be favorable. If you are prone to repeated infections, by virtue of a low white blood cell count, then certain working environments (crowds, multiple-person offices) may be medically contraindicated, because of the risk of exposure to infection. If you require treatment with immunosupressive drugs or chemotherapy, side effects from those drugs may also restrict your ability to work.