childhood myelodysplastic syndrome

Overview

Childhood Myelodysplastic Syndrome (MDS) is a rare group of disorders in which the bone marrow, the tissue responsible for producing blood cells, does not function properly, resulting in abnormal development of blood cells. Unlike the more common adult form, childhood MDS has distinct biological and clinical characteristics. It often progresses to acute myeloid leukemia (AML) if left untreated. MDS in children can present as isolated cytopenias (low blood cell counts) or with multiple affected cell lines, making early diagnosis and intervention crucial.

Causes

In many cases, the exact cause of childhood MDS is unknown (idiopathic), but several known risk factors and conditions are associated with its development:

• Inherited bone marrow failure syndromes: Such as Fanconi anemia, Shwachman-Diamond syndrome, or Diamond-Blackfan anemia

• Germline genetic mutations: In genes like GATA2, RUNX1, or SAMD9/SAMD9L

• Previous cancer treatment: Chemotherapy or radiation therapy can increase the risk of secondary MDS

• Congenital disorders: Some children are born with conditions that predispose them to MDS

• Environmental exposures: Rare in children but possible in certain settings

Symptoms

Symptoms of childhood MDS are primarily related to decreased production of healthy blood cells and may include:

• Fatigue or weakness: Due to anemia (low red blood cell count)

• Increased infections: Resulting from neutropenia (low white blood cells)

• Easy bruising or bleeding: Caused by thrombocytopenia (low platelets)

• Pallor (pale skin)

• Fever or frequent illnesses

• Bone or joint pain: Occasionally present due to marrow dysfunction

• Enlarged spleen or liver: In some advanced or associated cases

Diagnosis

Diagnosis of childhood MDS involves a combination of blood tests, bone marrow analysis, and genetic studies. The diagnostic process typically includes:

• Complete blood count (CBC): Shows cytopenias (low levels of one or more blood cell types)

• Bone marrow aspiration and biopsy: Evaluates cellularity, dysplasia (abnormal cell appearance), and blast percentage

• Cytogenetic analysis: To identify chromosomal abnormalities commonly seen in MDS (e.g., monosomy 7)

• Genetic testing: Especially in suspected inherited or familial cases

• Flow cytometry: To assess abnormal patterns in blood or marrow cells

MDS in children is categorized based on the WHO (World Health Organization) classification system, including subtypes like refractory cytopenia of childhood (RCC) and MDS with excess blasts.

Treatment

Treatment for childhood MDS depends on the subtype, severity, and presence of genetic mutations. Common treatment options include:

• Hematopoietic stem cell transplantation (HSCT): Also known as bone marrow transplant, this is the only curative option for most children with MDS

• Supportive care: Includes red blood cell or platelet transfusions and antibiotics for infections

• Immunosuppressive therapy: In select cases, such as children with hypocellular MDS or those without a suitable donor

• Chemotherapy: Used if the disease progresses to AML or in high-risk MDS

• Genetic counseling and surveillance: For inherited MDS syndromes

Treatment decisions are best made by a pediatric hematologist-oncologist, often within a specialized cancer center.

Prognosis

The prognosis for childhood MDS varies widely based on the subtype, genetic abnormalities, and response to treatment. Children who undergo successful stem cell transplantation have a favorable long-term outcome. However, those with high-risk cytogenetics (such as monosomy 7) or progression to AML may face a more guarded prognosis. Early diagnosis and appropriate intervention are key to improving survival and quality of life. Lifelong follow-up is essential to monitor for complications or relapse.