Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Myelodysplastic Syndromes
The French-American-British (FAB) and World Health Organization (WHO) classification systems of MDS and MPS have been difficult to apply to pediatric patients. Alternative classification systems for children have been proposed, but none have been uniformly adopted, with the exception of the modified WHO system.[14,15,16,17,18] The WHO system  has been modified for pediatrics.
Diagnostic Categories for Myelodysplastic and Myeloproliferative Disease in Children
- Down syndrome disease
- Transient myeloproliferative disorder.
- Myeloid leukemia of Down syndrome.
- Myelodysplastic/myeloproliferative disease
- Juvenile myelomonocytic leukemia (JMML).
- Myelodysplastic syndrome
- Refractory cytopenia (previously called refractory anemia)—peripheral blood blasts <2% and bone marrow blasts <5%.
- Refractory anemia with excess blasts—peripheral blood blasts 2% to 19% or bone marrow blasts 5% to 19%.
- Refractory anemia with excess blasts in transformation—peripheral blood or bone marrow blasts 20% to 29%. In the FAB classification, refractory anemia with excess blasts in transformation required evidence of dysplasia, particularly in the red blood cell lineage, and 21% to 30% myeloblasts in the bone marrow; if there was greater than 30% myeloblasts this was considered to be acute myeloid leukemia. In part because of the artificial designation of the percentage of blasts, the WHO classification system now simply considers these patients to have AML and the refractory anemia with excess blasts in transformation subtype has been eliminated.
The refractory cytopenia subtype represents approximately 50% of all childhood cases of MDS. The presence of an isolated monosomy 7 is the most common cytogenetic abnormality, although it does not appear to portend a poor prognosis compared with its presence in overt AML. However, the presence of monosomy 7 in combination with other cytogenetic abnormalities is associated with a poor prognosis.[20,21] The relatively common abnormalities of -Y, 20q- and 5q- in adults with MDS are rare in childhood MDS. The presence of cytogenetic abnormalities found in AML defines disease that should be treated as AML and not MDS. The International Prognostic Scoring System can help to distinguish low-risk from high-risk MDS, although its utility in children with MDS is more limited than in adults, in part because children often have more high-risk characteristics compared with adults, especially in terms of cytopenias.[22,23] Nevertheless, the median survival for children with high-risk MDS remains substantially better than adults.
The optimal therapy for childhood MDS has not been established. A key issue in thinking about therapy for pediatric patients with MDS is that these disorders usually involve a primitive hematopoietic stem cell. Thus, allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be the optimal approach to treatment for pediatric patients with advanced MDS. Unresolved issues include determining the best transplant preparative regimen and source of donor cells.[25,26] However, some data are important to consider when making decisions. For example, disease-free survival has been estimated to be between 50% to 70% for pediatric patients with advanced MDS using myeloablative transplant preparative regimens.[27,28,29,30,31] While using nonmyeloablative preparative transplant regimens are being tested in patients with MDS and AML, such regimens are still investigational for children with these disorders, but may be reasonable in the setting of a clinical trial or when a patient's organ function is compromised in such a way that they would not tolerate a myeloablative regimen.[32,33,34]