Myelodysplastic neoplasms: a rare blood disorders

Myelodysplastic neoplasms or myeloproliferative neoplasms (MDS/MPN) are a group of rare blood disorders characterized by the abnormal production and functioning of blood cells. They represent a complex overlap between myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). The former involves

a disruption in the maturation process of blood stem cells,
decreasing the production of healthy red blood cells,
white blood cells, and
platelets.

In contrast, MPNs are characterized by an abnormal increase in the number of blood stem cells, resulting in the gradual accumulation of various types of blood cells. These disorders account for less than 1% of all hematological malignancies.

Types

The different types of MDS/MPN are –

Chronic myelomonocytic leukaemia (CMML) is a type of blood cancer characterized by increased monocytes and immature white blood cells. It typically affects older adults and causes symptoms like Fatigue, infections, and enlarged spleen.
Juvenile myelomonocytic leukaemia (JMML) is a rare form of leukaemia, mainly affecting children under four. JMML is characterized by the excess production of abnormal monocytes, leading to symptoms such as anaemia, bleeding, and infections.
Atypical chronic myelogenous leukaemia (CML) – This rare subtype of leukaemia shares similarities with CMML but lacks the specific genetic abnormality known as the Philadelphia chromosome. It is characterized by increased numbers of white blood cells, including granulocytes. It may cause symptoms like Fatigue, weight loss, and enlarged spleen.

Causes

The exact aetiology behind Myelodysplastic neoplasms (MDS/MPN) remains elusive. However, some significant risk factors for developing this disorder are –

Chemotherapy – Drugs like melphalan, cyclophosphamide, busulfan, and chlorambucil increase the risk of getting this syndrome.
Age – Older adults in their 70s and 80s are more susceptible to developing this syndrome than people younger than 50.
Sex – MDS is more common in men than women, which might be associated with occupational Exposure to certain chemicals.
Genetic syndromes – Some inherited syndromes like Shwachman-Diamond syndrome, Diamond-Blackfan anaemia, neurofibromatosis type-1, Fanconi anaemia, sideroblastic anaemia, and familial platelet disorder with a propensity to myeloid malignancy increases the risk.
Occupational Exposure – Exposure to certain chemicals like hydrocarbons, xylene, and benzene increases the risk of developing MDS.
Family history of MDS/MPN
Exposure to high-dose of radiation

Symptoms

People with MDS usually do not experience any signs and symptoms in the initial stages of the syndrome. When the disease progresses, some of the common symptoms seen are:

· Fatigue
· Loss of weight
· Leukopenia (low white blood cell counts)
· Frequent infections
· Pinpoint-sized red spots on the skin due to bleeding (petechiae)
· Pain or discomfort below the ribcage
· Skin rashes
· Swollen lymph nodes
· Thrombocytopenia (low platelet counts)
· Unusual paleness
· Easy bleeding and bruising
· Shortness of breath.

Screening tests for Myelodysplastic neoplasms

On noticing any abnormality, the physician will first conduct a complete physical exam to rule out other possibilities. If Myelodysplastic neoplasms (MDS/MPN) is suspected, additional screening tests are recommended to confirm it. These include:

Complete blood count (CBC) with differential – A blood sample is taken and examined for the number of blood cells, haemoglobin, and the portion of the blood sample making up the red blood cells.
Peripheral blood smear: A laboratory test involves spreading a thin layer of blood on a microscope slide for examination. It helps evaluate blood cell morphology and identify abnormalities like changes in size, shape, or staining patterns of the blood cells. It also helps detect if too much iron is in the red blood cells.
Cytogenetic analysis is used to study the structure and behaviour of chromosomes. It helps to identify chromosomal abnormalities, such as deletions, duplications, translocations, or rearrangements. Any changes in the chromosome can indicate the presence of cancer.
Blood chemistry studies: In this test, the blood sample is analyzed to detect any abnormally high levels of certain substances like vitamin B12 or folate in the blood. These substances are often released into the blood by the tissues or organs.
Bone marrow biopsy: A sample of the bone marrow is taken from the hipbone or breastbone via biopsy and tested for lymphoma.
Immunocytochemistry: In this test, antibodies linked to enzymes or fluorescent dyes detect specific antigens in a patient’s bone marrow sample. It aids in diagnosing cancer and distinguishing between myelodysplastic syndromes, leukemia, and other conditions.

Treatment for Myelodysplastic neoplasms

MDS/MPN are challenging to treat. The standard treatment options available for Myelodysplastic neoplasms are:

Supportive care – This protocol is used to treat the signs and symptoms experienced by the patients. It includes blood transfusion therapy, using erythropoiesis-stimulating agents (ESAs) or antibiotic therapy to fight infections.
Chemotherapy – Chemotherapeutic agents are used to destroy the tumor cells or hamper the disease progression. Commonly used chemotherapeutic drugs for treating MDS/MPN are hydroxyurea, azacytidine, and decitabine.
Chemotherapy with stem cell transplant – In this approach, stem cells from the patient or donor are infused back into the patient after Chemotherapy to replace the blood cells damaged by the treatment.
Radiation therapy is recommended for patients experiencing severe discomfort due to an enlarged spleen. Although radiation can help shrink the spleen and alleviate specific symptoms, it does not directly target the underlying myelodysplastic/myeloproliferative neoplasms.

References

United States: Bristol Myers Squibb Announces Positive Topline Results of Phase 3 COMMANDS Trial. (2022, November 5). MENA Report.
Blood Cancers (Leukemia and Lymphoma) | Sylvester Comprehensive Cancer Center | University of Miami Health System. https://umiamihealth.org/sylvester-comprehensive-cancer-center/treatments-and-services/pediatric-cancers/blood-cancers-(pediatrics)