Pediatric Myelodysplastic Syndrome Workup

  • Author: Prasad Mathew, MBBS, DCh; Chief Editor: Robert J Arceci, MD, PhD   more...
 
Updated: Nov 4, 2011
 

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.

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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.[18] Loss of the long arm of chromosome 5 (5q-), the most frequent chromosomal aberration in adults with RA, is rare in childhood.

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Contributor Information and Disclosures
Author

Prasad Mathew, MBBS, DCh  Director, Hemostasis and Hematology Program, Professor of Clinical Pediatrics, University of New Mexico School of Medicine

Prasad Mathew, MBBS, DCh is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Coauthor(s)

Franklin O Smith III, MD  Marjory J Johnson Endowed Chair in Pediatric Hematology/Oncology, Professor of Pediatrics and Medicine, Division of Hematology/Oncology, University of Cincinnati Cancer Institute; Attending Physician, Blood and Marrow Transplant Program, Cincinnati Children's Hospital Medical Center

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

Disclosure: Wyeth Research Consulting fee Consulting; Seattle Genetics Other

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, Harris County Medical Society, Minnesota Medical Association, National Association of EMS Physicians, and Texas Pediatric Society

Disclosure: Draeger Honoraria Review panel membership

Chief Editor

Robert J Arceci, MD, PhD  King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine

Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Additional Contributors

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.

References

  1. Bennett JM, Catovsky D, Daniel MT, et al. The chronic myeloid leukaemias: guidelines for distinguishing chronic granulocytic, atypical chronic myeloid, and chronic myelomonocytic leukaemia. Proposals by the French-American-British Cooperative Leukaemia Group. Br J Haematol. 87(4):746-54. [Medline].

  2. Hasle H, Niemeyer CM, Chessells JM, Baumann I, Bennett JM, Kerndrup G. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia. Feb 2003;17(2):277-82. [Medline].

  3. Steliarova-Foucher E, Stiller C, Lacour B, Kaatsch P. International Classification of Childhood Cancer, third edition. Cancer. Apr 1 2005;103(7):1457-67. [Medline].

  4. Dokal I. Dyskeratosis congenita in all its forms. Br J Haematol. Sep 2000;110(4):768-79. [Medline].

  5. Lange BJ, Kobrinsky N, Barnard DR, et al. Distinctive demography, biology, and outcome of acute myeloid leukemia and myelodysplastic syndrome in children with Down syndrome: Children's Cancer Group Studies 2861 and 2891. Blood. Jan 15 1998;91(2):608-15. [Medline].

  6. Smith OP. Shwachman-Diamond syndrome. Semin Hematol. Apr 2002;39(2):95-102. [Medline].

  7. Butturini A, Gale RP, Verlander PC, et al. Hematologic abnormalities in Fanconi anemia: an International Fanconi Anemia Registry study. Blood. 84(5):1650-5. [Medline].

  8. Freedman MH, Bonilla MA, Fier C, et al. Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy. Blood. Jul 15 2000;96(2):429-36. [Medline].

  9. Willig TN, Niemeyer CM, Leblanc T, et al. Identification of new prognosis factors from the clinical and epidemiologic analysis of a registry of 229 Diamond-Blackfan anemia patients. Pediatr Res. Nov 1999;46(5):553-61. [Medline].

  10. Ohara A, Kojima S, Okamura J, et al. Evolution of myelodysplastic syndrome and acute myelogenous leukaemia in children with hepatitis-associated aplastic anaemia. Br J Haematol. Jan 2002;116(1):151-4. [Medline].

  11. Ohara A, Kojima S, Hamajima N, et al. Myelodysplastic syndrome and acute myelogenous leukemia as a late clonal complication in children with acquired aplastic anemia. Blood. Aug 1 1997;90(3):1009-13. [Medline].

  12. Blank J, Lange B. Preleukemia in children. J Pediatr. Apr 1981;98(4):565-8. [Medline].

  13. Greenberg PL, Mara B. The preleukemic syndrome: correlation of in vitro parameters of granulopoiesis with clinical features. Am J Med. Jun 1979;66(6):951-8. [Medline].

  14. Hasle H, Kerndrup G, Jacobsen BB. Childhood myelodysplastic syndrome in Denmark: incidence and predisposing conditions. Leukemia. Sep 1995;9(9):1569-72. [Medline].

  15. Luna-Fineman S, Shannon KM, Atwater SK, et al. Myelodysplastic and myeloproliferative disorders of childhood: a study of 167 patients. Blood. 93(2):459-66. [Medline].

  16. Malcovati L, Della Porta MG, Cazzola M. Predicting survival and leukemic evolution in patients with myelodysplastic syndrome. Haematologica. Dec 2006;91(12):1588-90. [Medline].

  17. Bejar R, Stevenson K, Abdel-Wahab O, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. Jun 30 2011;364(26):2496-506. [Medline].

  18. Hasle H, Arico M, Basso G, et al. Myelodysplastic syndrome, juvenile myelomonocytic leukemia, and acute myeloid leukemia associated with complete or partial monosomy 7. European Working Group on MDS in Childhood (EWOG-MDS). Leukemia. 13(3):376-85. [Medline].

  19. Yoshimi A, Baumann I, Fuhrer M, et al. Immunosuppressive therapy with anti-thymocyte globulin and cyclosporine A in selected children with hypoplastic refractory cytopenia. Haematologica. Mar 2007;92(3):397-400. [Medline].

  20. Lang P, Greil J, Bader P, et al. Long-term outcome after haploidentical stem cell transplantation in children. Blood Cells Mol Dis. Nov-Dec 2004;33(3):281-7. [Medline].

  21. Yusuf U, Frangoul HA, Gooley TA, et al. Allogeneic bone marrow transplantation in children with myelodysplastic syndrome or juvenile myelomonocytic leukemia: the Seattle experience. Bone Marrow Transplant. Apr 2004;33(8):805-14. [Medline].

  22. Strahm B, Locatelli F, Bader P, et al. Reduced intensity conditioning in unrelated donor transplantation for refractory cytopenia in childhood. Bone Marrow Transplant. Aug 2007;40(4):329-33. [Medline].

  23. Williamson PJ, Kruger AR, Reynolds PJ, et al. Establishing the incidence of myelodysplastic syndrome. Br J Haematol. 87(4):743-5. [Medline].

  24. Hasle H, Kerndrup G, Yssing M, et al. Intensive chemotherapy in childhood myelodysplastic syndrome. A comparison with results in acute myeloid leukemia. Leukemia. Aug 1996;10(8):1269-73. [Medline].

  25. List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. Oct 5 2006;355(14):1456-65. [Medline].

  26. Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. May 15 2002;20(10):2429-40. [Medline].

  27. Kantarjian H, Issa JP, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. Apr 15 2006;106(8):1794-803. [Medline].

  28. Miller K, Haesook K, Greenberg P, et al. Phase III prospective randomized trial of EPO with or without G-CSF versus supportive care in the treatment of MDS: results of the ECOG-CLSG trial. Blood. 2004;104:70.

 
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