In patients with the condition, immature cells called blast cells make up more than 5 percent of the cells in the marrow. In normal conditions, these cells make up less than 5 percent of all cells in the marrow. The result is that the blast cells created do not develop into normal red cells, white cells and platelets, often causing more severe deficits in red blood cells, white blood cells and platelets.
Although this is classified as an acute leukemia, many patients continue to progress slowly. Therapies for such patients may be the same as used for patients with other types of high-risk MDS. Alternately, some may be treated using regimens more typically used to treat AML. MDS usually occurs in older people, typically starting after age 50, and is rarely inherited. It is more common in men. For many people, the condition develops without any known cause. In other people, secondary MDS may develop after being exposed to chemotherapy or radiation therapy, or exposure to industrial chemicals such as benzene, that damage the DNA of normal stem cells.
Cigarette smoke also may be associated with the condition. Symptoms of MDS include fatigue and shortness of breath during physical activity, which are common to many diseases. Some patients have no symptoms. A shortage of red blood cells anemia can lead to excessive tiredness, shortness of breath, and pale skin. A shortage of normal white blood cells leukopenia can lead to frequent or severe infections.
A shortage of blood platelets thrombocytopenia can lead to easy bruising and bleeding. Some people notice frequent or severe nosebleeds or bleeding from the gums. If doctors suspect you have MDS, they will need to examine cells from your blood and bone marrow to confirm the diagnosis. A blood test called a complete blood count CBC measures the amounts of different cells in the blood, such as the red blood cells, the white blood cells, and the platelets.
Patients with MDS often have too few red blood cells, and may also have shortages of white blood cells and platelets. This is abnormal and often signals a bone marrow problem. Blood cells from MDS patients may also have abnormal sizes, shapes, or other features that can be seen under the microscope.
Doctors also need to do a bone marrow aspiration or a bone marrow biopsy, two tests that involve taking a sample of cells or tissue from the bone marrow to examine for abnormalities under a microscope. For both procedures, you lie on an examining table. The doctors will look at the size and shape of the cells and determine the percentage of marrow cells that are blasts.
Different clinical features will help your physician classify your MDS and give some idea of the natural course of disease and how best to treat you. It rates three factors:. Each factor is given a score, with lower scores having a better outlook. The scores are added together to make the IPSS score, which places people with MDS into 4 groups: low risk, intermediate - 1 risk, intermediate - 2 risk, and high risk.
Doctors are still working on a cure for MDS, though there are many ways to manage the disease. Patients with very low risk who do not need blood transfusions may be able to go without treatment for years, as long as they are checked regularly by a doctor. Other patients need more aggressive therapies. These syndromes are caused by abnormal mutated genes that have been passed on from one or both parents.
Examples include:. In some families, MDS occurs more often than would be expected. Smoking increases the risk of MDS. Many people know that smoking can cause cancer of the lungs, but it can also cause cancer in other parts of the body that don't come into direct contact with smoke. No prospective combination study has ever demonstrated a survival advantage compared with hypomethylating agent monotherapy.
For patients who are refractory to or have relapsed after hypomethylating agent therapy, either because of limited numbers of treatment cycles, drug intolerance, or disease evolution caused by the development of abnormalities such as p53, SETBP1, or ASXL1, median survival is only 4.
A year-old man presented to his primary care provider with complaints of fatigue, oral mucosal bleeding when brushing his teeth, and easy bruisability.
Cytogenetics demonstrated a very complex karyotype, with 5 abnormalities. He was active and his only comorbidity was essential hypertension, for which he was taking a calcium-channel blocker.
Thus, whether HCT provides a survival advantage compared with disease-modifying agents for MDS patients has not been determined. However, 2 large prospective studies are being performed to address this question. All subjects initiate therapy with azacitidine. After 4 to 6 cycles, subjects are biologically assigned to HCT or no HCT based on the availability of a suitable donor. Those without a donor continue to receive azacitidine.
This trial asks the more fundamental question of whether HCT is of value at any time in the disease course. Single-arm studies that demonstrate improved outcome with early HCT or with transplantation at less advanced disease stages are inherently biased owing to patient selection. The decision analysis examined individuals aged 60 to 70 years a patient population increasingly being transplanted as commonly as younger adults and examined only reduced-intensity transplantation approaches, stratifying patients by MDS disease risk.
Another decision analysis examining younger patients undergoing myeloablative transplantation has previously been reported. For both decision models, early after entry there was a survival disadvantage for transplantation because of transplant-related morbidities, with a later plateau on the HCT survival curve providing the overall benefit for HCT in higher-risk MDS patients.
Because the intent of such decision analyses is to identify the decision strategy associated with superior outcomes, such as survival or quality-adjusted life years in a patient population, it is not possible to measure lives gained or lost, and decisions for individual patients will necessarily be modulated by a number of donor and recipient factors.
A second decision analysis strategy compared HCT with a cohort of patients who received best supportive care. The role of cytoreductive therapy before HCT is still unknown. The largest study included consecutive individuals who underwent HCT after azacitidine, after leukemia-type induction chemotherapy, or after both.
Although the entire cohort had higher-risk disease, it is impossible to retrospectively determine which factors were involved in choosing induction chemotherapy or azacitidine therapy first, and whether these factors eg, better performance status or fewer comorbidities influenced outcomes. Given these caveats, there were no differences in relapse rates, nonrelapse mortality, event-free survival, or overall survival comparing the azacitidine and induction chemotherapy groups, although the group that received both azacitidine and induction chemotherapy presumably because of disease progression before HCT fared significantly worse.
In retrospective analyses, when pre-HCT azacitidine was compared with no treatment, there was no benefit to azacitidine. As with other retrospective HCT analyses already discussed, these studies were affected by similar selection biases.
Patients with good-risk cytogenetics may enjoy durable remissions even without HCT. In older patients and those with unfavorable karyotypes, in whom complete response rates are low, pre-HCT induction chemotherapy is discouraged. The role of hypomethylating therapy after HCT to lessen relapse risk has also been addressed. Lenalidomide has been introduced with induction therapy in del 5q MDS patients before HCT but may trigger acute graft-vs-host disease in the post-HCT maintenance setting.
The logistics of performing HCT in the typically older, higher-risk MDS patient population are substantial, starting with identification of an appropriate donor. Older patients are more likely to have even older siblings who may be too elderly for stem cell donation or who may have medical comorbidities that preclude safe donation.
Every patient with higher-risk MDS should be well informed about the seriousness of the disease. Only then can a conversation occur about the role of hypomethylating agent—based therapy, clinical trials, and HCT, which remains the only curative option for MDS.
Ongoing randomized studies will help clarify the superiority of monotherapy or combinations of active drugs, and of hypomethylating agent—based therapy or HCT. Conflict-of-interest disclosure: M. Correspondence: Mikkael A. Sekeres, M. Sign In or Create an Account.
Sign In. Skip Nav Destination Content Menu. Close Abstract. Patient 1. What is the prognosis of higher-risk MDS? What is the recommended treatment for higher-risk MDS, and does treatment need to be started immediately? Can dosing of hypomethylating agents be interrupted nonconsecutive? Are there molecular markers of response?
Is there any advantage to hypomethylating agent—based combination therapy over monotherapy? What are the therapeutic options or investigational agents after failure of hypomethylating agents?
Disease overview: The myelodysplastic syndromes MDS are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia AML. Myelodysplastic syndromes occur more frequently in older males and in individuals with prior exposure to cytotoxic therapy. Diagnosis: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy.
Information obtained from additional studies such as karyotype, flow cytometry and molecular genetics is usually complementary and may help refine diagnosis.
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