Myelodysplastic syndromes and cancer
Myelodysplastic syndromes (MDS) are a group of hematological disorders characterized by ineffective blood cell production in the bone marrow, leading to insufficient healthy red and white blood cells. This can result in severe health complications, including a higher likelihood of developing acute myeloid leukemia. MDS primarily affects older adults, with a majority of diagnoses occurring in individuals over seventy, although certain inherited conditions can predispose younger individuals to the syndrome. Risk factors include prior exposure to chemotherapy, genetic mutations, and environmental toxins such as benzene, which can be found in common substances like gasoline and cigarette smoke.
Symptoms of MDS often include anemia, fatigue, easy bruising, and a vulnerability to infections, with some individuals remaining asymptomatic until routine blood tests reveal abnormalities. Diagnosis typically involves blood tests and bone marrow analysis to classify the specific subtype of MDS, which can influence treatment options. While treatment may include blood transfusions and medications like azacitidine or lenalidomide, allogeneic stem-cell transplantation remains the only potential cure, albeit with significant risks. Prognosis varies widely, with factors such as the type of MDS and cytogenetic profile playing crucial roles in determining survival outcomes.
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Subject Terms
Myelodysplastic syndromes and cancer
ALSO KNOWN AS: Myelodysplasia
RELATED CONDITIONS: Acute myeloid leukemia
DEFINITION: Myelodysplastic syndromes characterize a range of hematological disorders in which the bone marrow stem cells either do not mature into red or white blood cells or do not function properly. This lack of healthy blood cells can lead to life-threatening conditions.
Risk factors: Certain MDS subtypes have been linked to various risk factors, such as prior therapy for cancer, inherited genetic mutations, and exposure to environmental toxins. People who have been exposed to benzene and ionizing radiation appear to be susceptible to MDS. Benzene is found in gasoline, detergents, rubber, furniture polish, and cigarette smoke. Long-term exposure to certain agricultural chemicals and heavy metals may also contribute to MDS.
Secondary MDS or treatment-related MDS most often appears after treatment for acute lymphocytic leukemia, Hodgkin disease, and non-Hodgkin lymphoma. Still, they can also arise after treatment for some autoimmune diseases or chemotherapy for cancer of the breast, lung, testis, or intestinal tract. The most commonly associated chemotherapy drugs include Mechlorethamine, Procarbazine, Chlorambucil, Cyclophosphamide, Ifosfamide, Etoposide, Teniposide, and Doxorubicin. The risk of secondary MDS increases when these drugs are used in combination with certain forms of radiation therapy.
Other risk factors for myelodysplastic syndromes include inherited syndromes such as Fanconi anemia, Shwachman-Diamond syndrome, diamond blackfan anemia, familial platelet disorder with a propensity to myeloid malignancy, severe congenital neutropenia, and dyskeratosis congenita. People who smoke cigarettes, which contain benzene and other cancer-causing substances, are also at an increased risk for myelodysplastic syndromes.
Etiology and the disease process: Myelodysplastic syndromes rarely occur in people younger than sixty, other than children and adults who survive regimens for cancer treatment. Myelodysplasia is diagnosed more often in men than women. Several inherited conditions, including Blackfan-Diamond anemia, familial platelet disorder, and severe congenital neutropenia, make a person more likely to develop myelodysplastic syndromes.
Incidence: Approximately ten thousand Americans are diagnosed with myelodysplastic syndromes each year. Most of those who receive a myelodysplastic syndrome diagnosis are over seventy, and it is uncommon in individuals under fifty.
Symptoms: The early stages of myelodysplastic syndromes may be uneventful and indistinct from other diseases. Myelodysplastic syndromes are often marked by anemia, which leads to shortness of breath and fatigue during light exertion. Other symptoms may include unusually pale skin, easy bleeding or bruising, tiny red spots (petechiae) just beneath the skin, weight loss, and frequent infections. About 20 percent of patients with myelodysplastic syndromes exhibit infections or bleeding, and about 20 percent of patients have no symptoms and are diagnosed during routine blood tests.
Screening and diagnosis: A complete blood count will help determine the number of platelets and red and white blood cells and the hemoglobin levels in red cells. A peripheral blood smear may help determine the shape, size, and appearance of blood cells. Myelodysplastic syndromes are usually diagnosed after other diseases, such as leukemia, have been excluded. Bone marrow tests help confirm a diagnosis of myelodysplastic syndrome. These include and to obtain bone and marrow tissues, which are then analyzed using cytochemistry, flow cytometry, immunocytochemistry, and cytogenetic profiles.
Physicians originally used the French-American-British (FAB) system to classify myelodysplastic syndromes into five subtypes. In the 1990s, the World Health Organization (WHO) expanded the FAB into seven subtypes based on factors such as circulating blood counts or changes in the bone marrowrefractory anemia with ringed sideroblasts (RARS), refractory cytopenia with unilineage dysplasia (RCUD), refractory cytopenia with multilineage dysplasia (RCMD), refractory anemia with excess blasts-1 (RAEB-1), refractory anemia with excess blasts-2 (RAEB-2), unclassified myelodysplastic syndrome (MDS-U), and myelodysplastic syndrome associated with isolated del(5q) chromosome abnormality.
Medical professionals may assess a patient's health using the WHO Prognostic Scoring System (WPSS) based on the classifications above. In addition to the MDS type, the system considers the degree of cellular chromosomal abnormalities and whether the patient needs blood transfusions. Some medical professionals use the Revised International Prognostic Scoring System (IPSS-R) instead of or combined with the WPSS. The IPSS-R considers the percentage of blasts in bone marrow, the type and number of chromosome abnormalities in the sampled cells, and the level of red blood cells, platelets, and neutrophils in the patient's blood. These factors are scored to determine the risk level on a five-category scale from very low to very high. Because IPSS-R was developed before most modern MDS treatments, its use is limited. Additionally, IPSS-R and WPSS fail to include individuals who develop MDS following chemotherapy. To better assess prognosis and determine appropriate treatment, a combination of these scales is often used with consideration of the patient's age, performance status, gene or chromosome changes, ferritin level, and other factors.
Treatment and therapy: Most patients require a transfusion of red blood cells to help relieve anemia. Drugs such as darbepoetin and erythropoietin may help the body produce more red blood cells and thus reduce the need for transfusions.
The US Food and Drug Administration has approved three drugs specifically for the treatment of myelodysplastic syndromes. Azacitidine (Vidaza, approved 2004) and decitabine (Dacogen, approved 2006) are administered to stimulate blast cells to mature into healthy blood cells, and lenalidomide (Revlimid, approved 2005), a derivative of thalidomide, has been shown to eliminate transfusion dependence in some lower-risk patients with the del(5q) abnormality. However, these drugs are ineffective in some people and may cause additional problems. Other treatments include Imetelstat, a telomerase inhibitor approved in 2024, selinexor (XPOVIO), an XPO1 inhibitor approved in 2020, and glasdegib (DAURISMO), a smoothened inhibitor. Pevonedistat, a NEDD8-activating enzyme (NAE) inhibitor, also shows promise for treating MDS.
The only potential cure for myelodysplastic syndromes is allogeneic (donor) stem-cell transplantation, but few patients are eligible for the procedure because it poses severe risks.
Prognosis, prevention, and outcomes: Patients with fewer bone marrow blasts, more cells in the blood, and better cytogenetic profiles may demonstrate a longer median survival time, whereas patients with more blasts, fewer blood cells, and chromosome 7 abnormalities have a shorter survival time. WHO median survival times range from twelve years for those designated very low risk to nine months for those designated very high risk.
Bibliography
Deeg, H. Joachim, et al., eds. Myelodysplastic Syndromes. 2nd ed. Springer, 2013.
Hellström-Lindberg, Eva, and Luca Malcovati. “Supportive Care, Growth Factors, and New Therapies in Myelodysplastic Syndromes.” Blood Reviews, vol. 22, no. 2, 2008, pp. 75–91. doi:10.1016/j.blre.2007.10.003.
Dyer, Peter, and Martha L. Arellano. Myelodysplastic Syndromes. Karger, 2021.
López Corrales, Néstor L., and Vasco Ariston de Carvalho Azevedo. "Biomarkers in Myelodysplastic Syndrome." Cancer Biomarkers: Minimal and Noninvasive Early Diagnosis and Prognosis. Ed. Debmalya Barh et al. CRC, 2017. 783–812.
"Myelodysplastic Syndromes." American Cancer Society, www.cancer.org/cancer/types/myelodysplastic-syndrome.html. Accessed 20 June 2024.
"Myelodysplastic Syndromes Treatment (PDQ)–Patient Version." National Cancer Institute, 17 Nov. 2023, www.cancer.gov/types/myeloproliferative/patient/myelodysplastic-treatment-pdq. Accessed 20 June 2024.
Várkonyi, Judit, ed. The Myelodysplastic Syndromes. Springer, 2011.