Pediatric Myelodysplasia

Updated: May 17, 2023
Author: Natalia Dixon, MD; Chief Editor: Jennifer Reikes Willert, MD 


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.




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. Three quarters of patients with RCC have a platelet count of below 150,000, while anemia with a hemoglobin concentration of less than 10 g/dL is noted in about half of the affected children. Macrocytosis (defined by the patient’s age) is seen in most. The white blood cell count is decreased in many patients, and severe neutropenia is noted in about 25%.[21] The interval between onset of symptoms and diagnosis ranges from 0-23 months, with a median of 2 months.

Eliciting a prior history of malignancy or cytotoxic therapy is important to distinguish between de novo versus secondary myelodysplasia syndrome (MDS). Specifically, a history of previous exposure to alkylating agent chemotherapy, epidophyllotoxin, radiation therapy, or hematopoietic stem cell transplant is important as these are risk factors for therapy-related myelodysplasia syndrome.[22] A constitutional bone marrow failure syndrome (eg, Fanconi syndrome, Diamond-Blackfan anemia, Kostmann syndrome, Shwachman-Diamond syndrome) or aplastic anemia can also precede secondary myelodysplasia syndrome. Familial cases of myelodysplasia syndrome have also been reported; the history is usually that of a first-degree relative with myelodysplasia syndrome, AML, or both.


The physical examination often reveals the degree of cytopenia (eg, symptoms of pallor, bruising, petechiae). Splenomegaly and hepatomegaly are more common in childhood myelodysplasia syndrome and predominate in JMML. A pathognomonic erythematous maculopapular rash is seen in one third of children with JMML. Congenital anomalies and syndromic features are significant because of the association of myelodysplasia syndrome with several constitutional disorders, as described in Causes.


A feature unique to childhood myelodysplasia syndrome is that in about 25% of children there is an associated syndrome or congenital abnormality. Known inherited predispositions to the development of myelodysplasia syndrome include NF type 1 (NF-1), Fanconi anemia, severe congenital neutropenia (Kostmann syndrome), Down syndrome, Noonan syndrome, Shwachman-Diamond disease, Diamond-Blackfan anemia, dyskeratosis congenita, and Dubowitz syndrome. Bloom syndrome, Poland syndrome, and ataxia telangiectasia have also been associated with preleukemia.

A study by Zubovic et al found 291 differently expressed genes in patients with pediatric myelodysplasia syndrome, with these genes playing a role in the regulation of apoptosis and the cell cycle, ribosome biogenesis, inflammation, and adaptive immunity. The investigators suggested that the genes may provide new molecular biomarkers and treatment targets.[23]

The most recent pediatric classification systems for myelodysplasia syndrome have designated Down syndrome–related diseases (eg, transient myeloproliferative disorder, myeloid leukemia of Down syndrome) as unique and separate from myelodysplasia syndrome classification in other children.[24] This is based on the unique mutations, molecular phenotype, and therapy response seen in this population.

As the population of childhood cancer survivors increases, treatment-related myelodysplasia syndrome following cytotoxic chemotherapy is of more concern in the pediatric population.[25, 26] The most common association is with prior alkylator therapy, with or without concomitant radiation. The risk of myelodysplasia syndrome peaks 5-7 years after alkylator treatment and is related to cumulative dose. A strong association with monosomy 7 or del7q is recognized.



Differential Diagnoses



Laboratory Studies

CBC (differential and peripheral blood smear)

Peripheral blood count reveals anemia, neutropenia, and/or thrombocytopenia. The anemia is often macrocytic. Cytopenias can evolve and progress over a period of weeks to months.

The blood smear commonly reveals macrocytosis, hypogranular granulocytes, pseudo–Pelger-Huet anomaly (hypogranular and hypolobulated granulocytes), and giant platelets. Reticulocyte counts are low despite normal numbers of erythroid progenitors in the marrow. In JMML, marked monocytosis may be present.

Bone marrow aspirate and trephine core biopsy

See Procedures and Histologic Findings.

Quantitative hemoglobin electrophoresis

This may reveal elevated hemoglobin F levels, indicating reversion to fetal erythropoiesis due to bone marrow stress.

Cytogenetic studies (conventional karyotype, fluorescence in situ hybridization (FISH), polymerase chain reaction)

These studies reveal chromosomal abnormalities in 40-70% of pediatric cases of myelodysplasia syndrome (MDS).

Acquired chromosome abnormalities confirm the diagnosis when myelodysplasia syndrome is suspected.

The most commonly known abnormalities include monosomy 7 or 7q, monosomy 5 or 5q, or trisomy 8. myelodysplasia syndrome may also be associated with 20q, isochromosome 17, and abnormalities of 11q. Reciprocal translocations and inversions are uncommon.

Children who present with a peripheral blood and/or bone marrow disorder associated with t(8;21)(q22;q22), inv(16)(p13.1q22) or t(16;16)(p13.1;q22) or t(15;17)(q22;q12) should be considered to have AML regardless of the blast count.[4]

Fanconi anemia test

A Fanconi screen using diepoxybutane (DEB) or mitomycin C stimulation reveals abnormal chromosome breakage if this syndrome is present.

Paroxysmal nocturnal hemoglobinuria (PNH) test

Measurement of 2 complement regulatory proteins, CD55 (decay accelerating factor [DAF]) and CD59 (membrane inhibitor of reactive lysis [MIRL]) aids in diagnosis of PNH. The clinical picture of PNH is rare in childhood, although PNH clones in the absence of hemolysis or thrombosis may be observed in children with refractory cytopenia of childhood (RCC).

Human leukocyte antigen (HLA) typing

Human leukocyte antigen (HLA) typing of patient and family members should be performed at the outset, in anticipation of allogeneic hematopoietic stem cell transplantation (HSCT).

Additional laboratory studies

In most cases, myelodysplasia syndrome is diagnosed after a history and physical examination, followed by the laboratory workup described above. In some instances, additional tests may be warranted.

Viral serologies, especially human immunodeficiency virus (HIV), cytomegalovirus (CMV), EBV, and parvovirus, can be used to exclude viral etiologies of altered hematopoiesis.

The novo or primary form of myelodysplasia syndrome in children should be distinguished from cases of secondary myelodysplasia syndrome that follow congenital or acquired bone marrow failure syndromes[27] and from therapy-related myelodysplasia syndrome that follows cytotoxic therapy for a previous neoplastic or nonneoplastic condition.

Imaging Studies

Imaging studies do not contribute to establishing the diagnosis or prognosis of myelodysplasia syndrome.


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

Biopsy findings are needed to ascertain cellular architecture, cellularity, percentage of blasts, and the presence of fibrosis.

Bone marrow findings are reviewed under Histologic Findings.

As myelodysplasia has a varied temporal course, these procedures may need to be repeated at different time points if initial studies are not confirmatory and there is no alternate explanation for clinical/laboratory findings.

Histologic Findings

Bone marrow aspiration and biopsy are essential diagnostic tools.[28] The minimal morphologic criteria for the diagnosis of myelodysplasia syndrome remains similar in the most recent WHO classification system: In the appropriate clinical setting, at least 10% of the cells of at least 1 myeloid bone marrow lineage (erythroid, granulocytic, megaryocytic) must show unequivocal dysplasia for the lineage to be considered dysplastic.[4] Bone marrow biopsy should also be performed to assess cellularity and architecture because fibrosis can be a component of disease. The bone marrow of patients with myelodysplasia syndrome can be normocellular or hypocellular.[29] Hypocellularity of the bone marrow is more commonly observed in childhood myelodysplasia syndrome than in older patients.

Because the diagnosis of myelodysplasia syndrome relies heavily on marrow morphology, interobserver and intraobserver differences complicate disease classification. The FAB system, defined by a consensus of hematologists and hematopathologists, should be used in characterizing marrow results. The current FAB system is strictly based on morphology and does not take into account cytogenetics or predisposing abnormalities, which limits its use in children.[30] The changing classification schemes and continuing controversies underscore the fact that the understanding of myelodysplasia is evolving.[31, 32, 33]

As noted previously, the WHO classification system published in 2008 devotes a section to childhood myelodysplasia syndrome; a provisional entity, refractory cytopenia of childhood (RCC) is introduced in the classification for the first time. The category of RCC is reserved for childhood cases with less than 2% blasts in peripheral blood and less than 5% blasts in the bone marrow and persistent cytopenias associated with dysplasia in at least 2 cell lineages.[4, 34]

The morphological findings of RCC are illustrated in the following table.[4]

Morphological findings of refractory cytopenia of Morphological findings of refractory cytopenia of childhood.

Children with myelodysplasia syndrome and 2-19% blasts in peripheral blood and/or 5-19% blasts in the bone marrow are categorized using the same criteria as adults with myelodysplasia syndrome.[34] In contrast to adults, isolated refractory anemia is uncommon in children with myelodysplasia syndrome, who more commonly present with thrombocytopenia and/or neutropenia, often accompanied by a hypocellular bone marrow.[32]

The WHO classification includes some cytogenetic information; the most recently proposed WHO classification scheme for myelodysplasia syndrome is as follows:[4]

  • Refractory cytopenia with unilineage dysplasia - Refractory anemia, refractory neutropenia, refractory thrombocytopenia

  • Refractory anemia with ringed sideroblasts

  • Refractory anemia with multiple dysplasia

  • Refractory anemia with excess blasts

  • Myelodysplastic syndrome with isolated del(5q)

  • Myelodysplastic syndrome, unclassifiable

  • Childhood myelodysplastic syndrome - Provisional entity: Refractory cytopenia of childhood (RCC)

JMML is unique to the pediatric age group and hence categorized separately from myelodysplasia syndrome. This disease is characterized by the absence of t(9;22), an absolute peripheral monocyte count of higher than 450/mcL, elevated hemoglobin F levels, selective in vitro hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), and excessive proliferation of monocyte-macrophage colonies in clonogenic culture. In JMML, nearly 75% of patients demonstrate mutually exclusive mutations of PTPN11, NRAS or KRAS, or NF1, all of which encode signaling proteins in RAS-dependent pathways.

Diagnostic Challenges

Diagnostic problems arise when the clinical or laboratory findings suggest myelodysplasia syndrome but the morphologic findings are inconclusive; when secondary dysplasia is caused by nutritional deficiencies, medications, toxins, growth factor therapy, inflammation, or infection or when bone marrow hypocellularity or myelofibrosis obscures the underlying disease process.[35]

Per the most recent WHO classification system, if myelodysplasia syndrome has inconclusive morphologic features, a presumptive diagnosis of myelodysplasia syndrome can be made if a specific clonal abnormality is present. However, the list[4] is not fully inclusive (not included, but significant if found: del(20), trisomy 8 and –Y). These abnormalities, reported in some adult patients with aplastic anemia or other cytopenias are associated with favorable response to immunosuppressive therapy.[36] This emphasizes the variation in temporal evolution of the disease and should be kept in mind for clinical decision making.

Hypocellular myelodysplasia syndrome may be more common in children because of the relative prevalence of inherited marrow failure syndromes. Hence, if no MDS-related cytogenetic abnormalities are present, the distinction between childhood MDS and evolving aplastic anemia or congenital bone marrow failure syndrome can be very difficult. Therefore, at least 2 biopsies obtained at least 2 weeks apart are recommended to facilitate the detection of representative bone marrow spaces containing foci of erythropoiesis.[4]

The morphological changes in the bone marrow of children with hypoplastic RCC are compared with those with aplastic anemia in table 2.[4]

Morphological findings of hypoplastic refractory c Morphological findings of hypoplastic refractory cytopenia of childhood and aplastic anemia of childhood.


Medical Care

Once the diagnosis is established, management involves supportive care that includes transfusion, treatment of infections, and a search for an allogeneic stem cell donor. MDS 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. In a study of pediatric patients with myelodysplasia syndrome associated with germline mutation in the GATA2 gene (involved in hematopoiesis), Bortnick et al found that following HSCT, the probability of overall and disease-free survival at 5 years was 75% and 70%, respectively.[37]

A study by Sharma et al found that in pediatric patients with acute leukemia or myelodysplasia syndrome, who relapsed after an initial treatment with allogeneic hematopoietic cell transplantation (alloHCT), improved survival occurred in those who then underwent a second alloHCT or were treated with donor lymphocyte infusion, as well as in patients in whom a longer period of time passed between alloHCT and relapse. Survival was also improved in patients who underwent more recent transplantation, with the study involving cases from 1990 to 2018.[38]

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]

A study by Merli et al indicated that in pediatric patients with myelodysplasia syndrome who do not have a human leukocyte antigen (HLA)–matched donor, safe and effective management can be provided using an αβT-cell receptor– and CD19 B-cell–depleted HLA-haploidentical HSCT (TBdepl-haploHSCT). In patients who underwent this procedure, platelet and neutrophil recovery took a median of 11 and 15 days, respectively. The cumulative incidence of graft failure was about 14%, with a second TBdepl-haploHSCT used to rescue these patients. Grade I-IV and grade II-IV acute graft-versus-host disease (aGvHD) had cumulative incidences of 21.0% and 8.3%, respectively (in addition to a patient who developed aGvHD after a second TBdepl-haploHSCT). The cumulative incidence of chronic GvHD in patients at risk was almost 10%, with low-dose steroids and ruxolitinib resulting in complete resolution. The cumulative incidence of infectious complications was just over 50%, and the cumulative incidence of transplant-related mortality was about 4%. The patient group had a 5-year probability of overall survival of 88.6%, and of event-free survival, 76.2%.[39]

All patients, their parents, and siblings should have HLA typing. When an HLA-matched family donor is available, HSCT is the therapy of choice. In the absence of an HLA-matched family donor, transplant using a matched unrelated donor, cord blood, or a haploidentical parent should be considered.

Pediatric patients with no unfavorable cytogenetic features, mild cytopenias that do not cause symptoms, and few bone marrow blasts may enjoy a prolonged period without progressive disease; however, spontaneous resolution of MDS is rare, and most patients eventually progress. The optimal timing for transplant in such patients is controversial because the risk of MDS progression must be balanced against the risks of transplant-related mortality and morbidity. Patients with unfavorable features should undergo stem cell transplantation as soon as feasible, because the prognosis is significantly worse after progression to AML.

In the absence of transfusion requirements, severe cytopenias, or infections, an expectant approach with careful observation may be reasonable.

A consensus has not been reached regarding the approach to accelerating disease in the absence of a stem cell donor source. Intensive chemotherapy regimens are usually not successful and, at best, induce short-lived remissions. Furthermore, some studies suggest that patients who receive chemotherapy prior to myeloablative stem cell transplant fare worse than patients who proceed directly to transplant.

The use of hematopoietic growth factors has also been controversial. GM-CSFs have been avoided because of concerns that they may stimulate growth of the malignant clone. The use of erythropoietin has been shown to be helpful in patients who have symptomatic anemia and low erythropoietin levels. Responses in thrombopoiesis to interleukin-11 (Neumega) have been transient and modest in patients with myelodysplasia syndrome.

The role of azacitidine, decitabine, lenalidomide, and other new agents used in adults with myelodysplasia syndrome remains to be determined in children. Whether these agents can impact the quality of life while preparing for stem cell transplantation or can impact the probability of cure after transplantation is unknown.

Surgical Care

As cytopenia(s) progress, most children need central venous access for transfusions. This usually requires surgical placement of a double-lumen catheter. At least 2 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.


Once the diagnosis of myelodysplasia syndrome is considered, follow-up by a pediatric hematologist-oncologist is necessary.

Blood product and infectious disease support need to be managed aggressively at a tertiary care center where specialized blood banking procedures are available.

All pediatric patients should be evaluated at an institution with expertise in pediatric stem cell transplantation.

Children with monosomy 7 cytogenetics should have family members evaluated for familial monosomy 7 in consultation with a clinical geneticist.


Dietary restrictions pertain to periods of neutropenia and are similar to those used for immunocompromised patients with cancer. These include thoroughly cooking all meats and fish. No clinical trials have demonstrated the benefit of these dietary modifications to prevent infection.


Activity restrictions are based on the degree of thrombocytopenia and neutropenia. In general, children should remain as active as possible for both physical and psychological reasons. Strict hand washing and good general hygiene are important precautions. Patients with a Hickman line or port must avoid contact sports in which a direct impact to the line could cause it to break.

Thrombocytopenia precautions include avoiding contact sports and strict use of bike helmets and knee and elbow pads for any activity in which falling is a risk.

Neutropenia precautions include the avoidance of crowds and of anyone with symptoms of transmissible infection.



Medication Summary

Several aspects of the management of pediatric myelodysplasia syndrome (MDS) differ from adult myelodysplasia therapy. Most importantly, the treatment goal must be curative because prolonging life by 5-8 years is not considered successful therapy in a healthy 10-year-old patient as it might in a 90-year-old patient who has other health problems. Therefore, allogeneic HSCT should almost always be the goal for children with myelodysplasia syndrome. However, the timing of HSCT is variable in children depending on symptomatology, disease characteristics, donor availability, and weighing the risks and benefits of transplant with the child’s quality of life.

The relevance of immunomodulating agents in pediatrics is investigational and remains unclear.

Various agents have been used to slow the progression of myelodysplasia syndrome, including low-dose cytosine arabinoside, cladribine (2-CdA), growth factors (erythropoietin, granulocyte colony-stimulating factor [G-CSF]), amifostine, and hydroxyurea. These agents are temporizing at best, and their role has been limited to palliation of myelodysplasia syndrome while a donor search takes place. In adults, decitabine, azacitidine, and lenalidomide (used primarily for 5q-syndrome) can reduce the need for transfusion and, in some cases, delay progression to AML when used in the correct subsets of patients.

Patients who present with a high percentage of marrow blasts and rapidly progressive disease may require chemotherapy while preparing for transplant. Both de novo and therapy-related myelodysplasia syndrome are usually only transiently responsive to conventional chemotherapy, which can be used in an attempt to keep the patient in remission until allogeneic HSCT can be performed. Transplantation from an HLA-matched family donor is optimal, but alternative donors should be considered when an HLA-matched family donor is not available.[40, 41]

Therapy prior to transplant also involves the judicious use of blood products and aggressive infection control because patients are often agranulocytic.

DNA hypomethylating agents

Class Summary

These agents are indicated for myelodysplastic syndrome in adults.

Azacitidine (Vidaza)

Pyrimidine nucleoside analog of cytidine. Interferes with nucleic acid metabolism. Exerts antineoplastic effects by DNA hypomethylation and direct cytotoxicity on abnormal hematopoietic bone marrow cells. Hypomethylation may restore normal function to genes critical for cell differentiation and proliferation. Nonproliferative cells are largely insensitive to azacitidine. Indicated to treat MDS. FDA approved for all 5 MDS subtypes.

Decitabine (Dacogen)

Hypomethylating agent believed to exert antineoplastic effects by incorporating into DNA and inhibiting methyltransferase, resulting in hypomethylation. Hypomethylation in neoplastic cells may restore normal function to genes critical for cellular control of differentiation and proliferation. Indicated for treatment of MDS, including previously treated and untreated, de novo, and secondary MDS of all FAB subtypes (ie, RA, RARS, RAEB, RAEBT, CML) and IPSS groups intermediate-1 risk, intermediate-2 risk, and high risk.

Immunomodulating agents

Class Summary

These agents are indicated for myelodysplasia syndrome in adults.

Lenalidomide (Revlimid)

Indicated for transfusion-dependent MDS subtype of deletion 5q31 cytogenetic abnormality. Structurally similar to thalidomide. Elicits immunomodulatory and antiangiogenic properties. Inhibits proinflammatory cytokine secretion and increases anti-inflammatory cytokines from peripheral blood mononuclear cells. The drug is FDA approved for adult patients with low or intermediate-1 IPSS category who are unlikely to respond to erythropoietin



Further Outpatient Care

Outpatient follow-up care depends on the degree of anemia and thrombocytopenia. Close follow-up is warranted, as progression to frank AML can occur over weeks to months.

Transfusion support is now manageable in the outpatient setting. Packed RBCs and platelets need to be leukofiltered and irradiated. Donor exposure to platelets should be minimized with pheresis and single-donor products whenever possible. This minimizes the risk of development of alloimmunization and the risk of the patient becoming refractory to transfusions.

Further Inpatient Care

Inpatient admission for patients with myelodysplasia syndrome (MDS) is usually for treatment of fever during periods of neutropenia. These episodes require aggressive evaluation for a source of infection and empiric coverage with broad-spectrum antibiotics against gram-negative rods. Blood and urine should be cultured for bacteria and for fungus, depending on the duration of symptoms.

Inpatient care at a designated center is also needed for stem cell transplantation.

Inpatient & Outpatient Medications

Patients are often placed on Pneumocystis carinii pneumonia (PCP) prophylaxis because of their degree of immunosuppression. Trimethoprim-sulfamethoxazole (Bactrim, Septra) is commonly used on a 3-times-per-week schedule. In patients allergic to Bactrim or in cases of Bactrim-related myelosuppression, oral atovaquone or aerosolized pentamidine is effective on a monthly schedule.


Patients should be referred to centers with established stem cell transplant programs and experience in treating myelodysplasia syndrome and other hematologic malignancies.



Patients with myelodysplasia syndrome may have increased risk for infection due to depressed granulocyte number and function. Even in cases of normal neutrophil number, neutrophils may exhibit decreased myeloperoxidase and microbicidal activity. Granulocytes may exhibit poor adhesion, chemotaxis, phagocytosis, and decreased microbicidal activity. Patients are extremely susceptible to life-threatening gram-negative rod and fungal infections.


Patients often have thrombocytopenia and resultant hemorrhage. Platelet dysfunction may occur in myelodysplasia syndrome. Patients require frequent transfusions as the bone marrow becomes increasingly hypoplastic.


In rare circumstances, iron overload is a complication of chronic red blood cell transfusions and may necessitate iron chelation therapy.


Findings associated with a poorer prognosis in childhood myelodysplasia syndrome include refractory anemia with excess blasts (RAEB) and refractory anemia with excess blasts in transformation (RAEBT). Age younger than 2 years and hemoglobin F levels greater than 10% have proven in several series to be unfavorable features in patients. However, this is because most patients with these features have JMML, a disease that has proven refractory to all therapies tried to date, except for early allogeneic HSCT, which can be curative in some cases. Patients with myelodysplasia syndrome and major chromosomal abnormalities, such as monosomy 7, have a dismal prognosis unless they proceed to allogeneic HSCT.

Karyotype is the most important factor for progression to advanced myelodysplasia syndrome. Patients with monosomy 7 have significantly higher probability of progression than patients with other chromosomal abnormalities or normal karyotypes.[21] Spontaneous disappearance of monosomy 7 and cytopenia have been reported but remains a rare event.[42] In contrast, patients with trisomy 8, Down Syndrome or normal karyotype may experience a long stable course of their disease.

Patient Education

Patient education should relate to prevention and treatment of complications of thrombocytopenia and neutropenia, as outlined in Treatment. In cases in which patients have a central venous access device, parents must be educated with regard to its care.