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Pediatric Myelodysplastic Syndrome Workup

  • Author: Prasad Mathew, MBBS, DCH, FAAP; Chief Editor: Jennifer Reikes Willert, MD  more...
Updated: Dec 10, 2015

Approach Considerations

Diagnostic studies for myelodysplastic syndrome center on a complete blood count (CBC) with differential, peripheral blood smears, bone marrow aspiration and biopsy. On the CBC, patients often have anemia with high mean cellular volume and RBC distribution width. Neutropenia and thrombocytopenia may be found.

In juvenile myelomonocytic leukemia (JMML), marked monocytosis may be present. Other diagnostic criteria for JMML include myeloid precursors in blood smears, clonal abnormality, granulocyte-macrophage colony-stimulating factor (GM-CSF) hypersensitivity of myeloid progenitors, and hemoglobin F levels above the reference range for age.

Other studies include the following:

  • Hemoglobin electrophoresis
  • Studies for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) to exclude marrow suppression due to a viral etiology
  • Folate and vitamin B-12 studies to evaluate for possible defects or deficiencies
  • Tissue typing of the patient and the family in anticipation of hematopoietic stem cell rescue
  • Testing for hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF)

Chromosomal analysis

Look for constitutional abnormalities if the patient has manifestations of Down syndrome (trisomy 21). Trisomy 21 with mosaicism occurs in 2-3% of cases in which 2 populations of cell types are present: a normal cell line with 46 chromosomes and a second cell line with trisomy 21. These children may appear phenotypically normal.

Order chromosomal fragility studies, including diepoxybutane (DEB) and mitomycin C (MCC) tests for Fanconi anemia.

Children with complex chromosomal aberrations combined with a low platelet count and/or elevated hemoglobin F levels have a notably worsened outcome.

The presence of monosomy 7 should prompt an evaluation of family members.

Bone marrow studies

Performing a bone marrow aspiration and biopsy is essential in establishing diagnosis and classification. In MDS, bone marrow findings reveal evidence of morphologic myelodysplasia in at least 2 different myeloid cell lines or dysplasia that exceeds 10% in one single cell line, with evidence of a clonal cytogenetic abnormality in hematopoietic cells. Dysplastic cells of various stages of differentiation with hypercellular findings may be evident.

Gene expression profile (GEP) analysis of bone marrow specimens has proved to be a powerful tool for the identification of gene signatures associated with distinct leukemia subtypes and has helped to stratify patients into different risk classes, as well as to identify deregulated genes involved in leukemia development. In 32 pediatric bone marrow specimens from MDS patients, GEP analysis was able to identify at diagnosis, patients with high risk to progress into AML. All MDS patients who evolved into AML showed AML-like signatures, while none of the MDS patients with a non AML-like signature showed evolution to AML.[20]


Histologic Findings

On peripheral smears, dysplastic shapes and cells with odd-appearing nuclear and cytoplasmic ratios (eg, anisocytosis, macrocytosis, microcytosis, poikilocytosis) are apparent. Although macrocytosis can indicate megaloblastic anemia (vitamin B-12 or folate deficiency), it is often observed in most bone marrow failure syndromes, including MDS. RBCs are often dimorphic (both hypochromic and normochromic). The number of reticulocytes is reduced in relation to the degree of anemia.

Depending on the class, variable granulocytic abnormalities are present. Pseudo–Pelger-Huët anomalies (eg, hyposegmented mature neutrophils, hypogranulation of cytoplasm) are characteristic of dysgranulopoiesis observed with MDS.

As additional immature elements are observed in periphery, these elements often appear bizarre with abnormal nucleus-to-cytoplasm ratios and are often oddly shaped. In addition, the number of eosinophils and basophils may increase in patients with adult-type MDS. On smears, platelets markedly vary in size.

Myelodysplasia most commonly presents with a hypercellular marrow. In refractory anemia (RA), the ratio of erythroid to myeloid cells is abnormal, and the marrow appears similar to that of patients with megaloblastic anemia due to folate or vitamin B-12 deficiency. Erythroblasts are often large, with clumped chromatin and a large nucleolus.

In refractory anemia with excess blasts (RAEB), the myeloid component of marrow increases. Small myeloblasts and promyelocytes predominate in the marrow. These cells are often dysmorphic with abnormal nucleus-to-cytoplasm ratios.

Abnormal megakaryocytes may appear small (micromegakaryocytes) or large. They may have a variable number of nuclei in the same marrow sample.

The minimal diagnostic criteria for MDS includes at least 2 of the following:

  • Sustained, unexplained cytopenia (neutropenia, thrombocytopenia, or anemia)
  • At least bilineage morphologic dysplasia
  • Acquired clonal cytogenetic abnormality in hematopoietic cells

In the prospective study of the European Working Group on MDS in Childhood, more than half of the patients with refractory cytopenia had a normal karyotype, followed in frequency by monosomy 7, trisomy 8, and other abnormalities.[21] Loss of the long arm of chromosome 5 (5q-), the most frequent chromosomal aberration in adults with RA, is rare in childhood.

Contributor Information and Disclosures

Prasad Mathew, MBBS, DCH, FAAP Professor of Pediatrics, Division of Hematology/Oncology, University of New Mexico School of Medicine

Prasad Mathew, MBBS, DCH, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society of Hematology, American Society of Pediatric Hematology/Oncology, International Society on Thrombosis and Haemostasis, American Society of Clinical Oncology, National Hemophilia Foundation, Hemophilia and Thrombosis Research Society, International Society of Paediatric Oncology, World Federation of Hemophilia

Disclosure: Received salary from Bayer HC for payment for services rendered.


Glenda H Grawe, MD Assistant Professor of Pediatrics, Baylor College of Medicine; Attending Physician, Department of Pediatrics, Section of Emergency Medicine, Texas Children's Hospital

Glenda H Grawe, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Emergency Physicians, Minnesota Medical Association, National Association of EMS Physicians, Texas Pediatric Society, Harris County Medical Society

Disclosure: Received honoraria from Draeger for review panel membership.

Franklin O Smith, III, MD Clinical Director, University of Cincinnati Cancer Institute, Professor of Medicine, Associate Director, Hematology/Oncology Fellowship Training Program, Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine; Professor of Pediatrics With Tenure, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine

Franklin O Smith, III, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Pediatric Society, American Society of Gene and Cell Therapy, American Society of Hematology, American Society of Pediatric Hematology/Oncology, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, International Society of Paediatric Oncology

Disclosure: Received consulting fee from Wyeth Research for consulting; Received from Seattle Genetics for other.

Chief Editor

Jennifer Reikes Willert, MD Associate Clinical Professor, Department of Pediatrics, Division of Pediatric Hematology/Oncology, Section of Stem Cell Transplantation, Stanford University Medical Center, Lucile Packard Children's Hospital

Jennifer Reikes Willert, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society for Blood and Marrow Transplantation, Children's Oncology Group, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.


Timothy P Cripe, MD, PhD Professor of Pediatrics, Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center; Clinical Director, Musculoskeletal Tumor Program, Co-Medical Director, Office for Clinical and Translational Research, Cincinnati Children's Hospital Medical Center; Director of Pilot and Collaborative Clinical and Translational Studies Core, Center for Clinical and Translational Science and Training, University of Cincinnati College of Medicine

Timothy P Cripe, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Kathleen M Sakamoto, MD, PhD Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Co-Associate Program Director of the Signal Transduction Program Area, Jonsson Comprehensive Cancer Center, California Nanosystems Institute and Molecular Biology Institute, University of California, Los Angeles, David Geffen School of Medicine

Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, International Society for Experimental Hematology, Society for Pediatric Research, and Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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