Pediatric Myelodysplasia

Updated: May 17, 2023
  • Author: Natalia Dixon, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
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Practice Essentials

Myelodysplasia encompasses a heterogenous group of disorders that result in ineffective hematopoiesis. Historically, a wide variety of terms have been used to describe these syndromes, including preleukemia, refractory anemia with excess of myeloblasts, subacute myeloid leukemia, oligoleukemia, [1] odoleukemia, and dysmyelopoietic syndromes.

The myelodysplasia syndromes (MDSs) are clonal stem cell disorders characterized by progressive cytopenia or cytopenias, usually in the presence of a hypercellular bone marrow and multilineage dysplasia. Usually, all 3 cell lines (myeloid/monocyte, erythroid, megakaryocyte) are involved. Myelodysplasia syndrome is rare in childhood, and most children have a rapidly progressive course. Myelodysplasia disorders have been defined by their predilection to evolve into acute myeloid leukemias (AML), yet not all cases terminate in leukemia.

The 2001 World Health Organization (WHO) classification system incorporated cytogenetics into the the French-American-British (FAB) cooperative group morphologic classification system for adult myelodysplasia syndrome. [2] The FAB system, based on peripheral blood and bone marrow morphology, defined 5 morphologic categories that represent a transition between myelodysplasia syndrome and AML. [3]

Although many of the features observed in childhood myelodysplasia syndrome are similar to those in the adult form of the disease, unique differences are also noted, especially when children lack blasts in the peripheral blood or bone marrow. The 2008 World Health Organization (WHO) classification system has now formally recognized the unique nature of childhood myelodysplasia syndrome with the inclusion of a provisional entity, refractory cytopenia of childhood (RCC) (ICD-O code 9985/3). [4] Down syndrome–associated myelodysplasia syndrome is also categorized separately by the WHO as "myeloid proliferations related to Down syndrome."

Signs and symptoms of pediatric myelodysplasia

Patients with myelodysplasia may present with symptoms of hematopoietic failure, including infection, bleeding, bruising, fatigue, weight loss, and dyspnea upon exertion. However, no clinical symptoms are reported in up to 20% of children with RCC, in whom cytopenia(s) or isolated splenomegaly is discovered during routine evaluation for an unrelated symptom.

Splenomegaly and hepatomegaly are more common in childhood myelodysplasia syndrome and predominate in juvenile myelomonocytic leukemia (JMML).

Workup in pediatric myelodysplasia

Bone marrow aspiration and biopsy are essential to establish the diagnosis and to classify the myelodysplasia syndrome.

Laboratory studies include the following:

  • Complete blood count (CBC)
  • Quantitative hemoglobin electrophoresis
  • Cytogenetic studies
  • Fanconi anemia test
  • Paroxysmal nocturnal hemoglobinuria (PNH) test
  • Human leukocyte antigen (HLA) typing

Management of pediatric myelodysplasia

Once the diagnosis is established, management involves supportive care that includes transfusion, treatment of infections, and a search for an allogeneic stem cell donor. Myelodysplasia syndrome is an incurable disease without hematopoietic stem cell transplantation (HSCT). [5] Allogeneic HSCT regimens are associated with a 30-50% event-free survival rate at 3 years. Stem cell transplant timing is determined on a case-by-case basis because the temporal course of the disease is highly variable. The optimal conditioning regimen has not been determined. [6]

As cytopenia(s) progress, most children need central venous access for transfusions. This usually requires surgical placement of a double-lumen catheter. At least two lumens are necessary because most children proceed to stem cell transplantation, in which intensity of treatment and blood product support necessitate multilumen vascular access.

Splenectomy is restricted to patients with severe hypersplenism and disease that is unresponsive to other treatment modalities.



The cellular elements of blood originate from the pluripotent hematopoietic stem cell. Stem cells have extensive regenerative and differentiating capacity and generate lymphoid and myeloid precursors, which then produce lymphocytes, neutrophils, monocytes, eosinophils, basophils, erythrocytes, and platelets.

In myelodysplasia syndrome, a dysregulation occurs in the differentiation process. The point of dysregulation varies with each disorder and by associated cytogenetic abnormality. Bone marrow failure in myelodysplasia syndrome is due to ineffective hematopoiesis (related to excessive apoptosis) rather than a lack of hematopoiesis. Clinically, ineffective hematopoiesis manifests as isolated anemia, neutropenia, or thrombocytopenia, or as multiple cytopenias. Often, an isolated cytopenia progresses to pancytopenia over a period of weeks to months.

The biologic mechanisms implicated in the pathophysiology of myelodysplasia syndrome include genomic instability, epigenetic changes, abnormal apoptosis machinery, abnormal signal-transduction pathways, immune dysregulation, and the role of the bone marrow microenvironment.

Chromosomal abnormalities are frequently found in myelodysplasia syndrome, but their causal relationship to the disease remains unclear. The most common chromosome abnormalities involve chromosomes 5, 7, and 8. The association of monosomy 7 or deletion of 7 (del7q) in de novo, secondary, and constitutional forms of myelodysplasia syndrome has implicated chromosome 7 loss as a secondary genetic event in leukemogenesis. Cytogenetic studies and deletion mapping suggest loss of function of a tumor suppressor gene within the deleted segment of chromosome 7. Chromosome loss may occur as a germline mutation or may be acquired as a consequence of prior cytotoxic exposure. Favorable cytogenetic aberrations in adults involving chromosome Y and chromosome arms 20q- and 5q- are rare in children.

The risk of both myelodysplasia syndrome and AML is increased in certain genetic syndromes: the Shwachman-Diamond syndrome, Diamond-Blackfan syndrome, dyskeratosis congenita, Fanconi anemia, neurofibromatosis (NF), and severe congenital neutropenia (Kostmann syndrome). [7, 8]

Mutations in the ras oncogene are observed in 20-30% of childhood myelodysplasia syndrome cases. Increasing evidence suggests that, in the absence of a mutation in Ras protein itself, upstream effector proteins could contribute to the development of myelodysplasia syndrome. In patients with neurofibromatosis (NF), NF-1 gene product loss leads to a loss of negative feedback via guanosine 5'triphosphate (GTP) of oncogenic N-ras. This results in unregulated proliferation of an abnormal clone. This is one mechanism thought to be responsible for the increased incidence of myelodysplasia syndrome in children with NF. [9, 10]

Mutations in the telomerase component TERC, which are observed in patients with dyskeratosis congenita, are occasionally seen in pediatric myelodysplasia syndrome without the typical phenotypic features. [11, 12] Aberrant methylation of genes has been reported in pediatric myelodysplasia syndrome and is under continued investigation. [13]





The annual incidence is 0.5-4 per million population, [14] and myelodysplasia syndrome accounts for about 3-9% of hematologic malignancies in children. [15, 16] The exact incidence of myelodysplasia syndrome in childhood has been difficult to estimate because of unclear classification, heterogeneity of presentation, and heterogeneity of risk factors in the population.

Refractory cytopenia of childhood (RCC) is the most common subtype of myelodysplasia syndrome in childhood, accounting for about 50% of the cases. [17, 18]


Mortality in myelodysplasia syndrome results from bleeding, recurrent infection, and leukemic transformation. In the absence of treatment, myelodysplasia syndrome can be rapidly fatal, with or without the transformation to AML. An estimated 20-40% of adults with myelodysplasia syndrome develop leukemia, and 30-40% of patients with myelodysplasia syndrome experience infection, bleeding, or both.

Treatment-related morbidity and mortality in childhood myelodysplasia syndrome are usually related to complications of bone marrow transplant therapy. This includes graft failure with subsequent aplasia, transfusion-related diseases, infection, iatrogenic immunosuppression, graft versus host disease, and graft rejection.


No racial predilection has been observed in myelodysplasia syndrome.


The male-to-female ratio varies from 1.7-4.8:1 in different series. [19] The significance of this male predominance is unclear but is attributed, in part, to the increased prevalence of juvenile myelomonocytic leukemia (JMML), previously termed juvenile chronic myelogenous leukemia (JCML), as well as monosomy 7 syndrome in males. [20]


Myelodysplasia syndrome is uncommon in childhood; 50% of cases occur in persons older than 60 years. [19] Monosomy 7 syndrome and JMML occur almost exclusively in children younger than 4 years. Children treated with radiation or intensive chemotherapy for another malignancy are more likely to develop myelodysplasia syndrome as a secondary adverse event.