Myelodysplastic Syndrome

•Childhood MDS differs from that of adults in pathogenetic and biological features. In the 2008 WHO classification of hematopoietic and lymphoid neoplasms, there is a pediatric entity “childhood myelodysplastic syndrome” and a subgroup “Refractory cytopenia of childhood.” Additionally, there is a “new” entity “Myelodysplastic syndrome associated with isolated del(5q).”

•The FAB classification (see below) was developed and accepted in the late 1970s for adult patients; however, its use in pediatrics is impractical

•The lack of an adequate pediatric classification deters from appropriate disease interpretation and systematic clinical research into MDS

4.2Definition

•MDS is a heterogeneous group of clonal bone marrow disorders characterized by ineffective hematopoiesis with normo – or hypercellular bone marrow, resulting in different degrees of peripheral cytopenia and a variable risk of transformation to acute leukemia, frequently – but not always – acute myelogenous leukemia (AML)

•The disease duration varies from months to years, but there is also a more rapid form, with transformation into leukemia; this more rapidly transforming type of MDS may be more common among children

•Myeloproliferative syndrome neoplasms (MPS MPNs) or chronic myeloproliferative disorders have predominantly proliferative features with minor or absent dysplastic characteristics. There are mature cells with effective proliferation. They are comprised of a disease entity described in the 1950s with a clonal proliferative pattern of hematopoietic precursor cells that have a tendency to transform to acute leukemia

4.3Classification

•Concepts and definitions of the FAB classification include morphological aspects of bone marrow cells and the percentage of blasts in peripheral blood and bone marrow with five diagnostic categories (see table below). This system is based on data from adult patients

•Not all children with MDS fit into this classification

•Although generally accepted, the FAB classification and its modifications, which differentiate MDS from acute leukemia and define risk groups among MDS patients, exhibit weaknesses also for adult patients

•A new classification system that is currently used is the WHO classification, which has resolved many problems encountered with the FAB classification. However, pediatric MDS remains a problem and is not adequately defined by the WHO classification

•The WHO classification differentiates MDS from MPS, and a new category, “myelodysplastic/myeloproliferative diseases,” is proposed

•Problems associated with the WHO classification include the omission of constitutional disorders and bone marrow failure syndromes; unclear definition of hypocellular MDS in children; the significance of secondary MDS; and the prognostic relevance of the system for children

Pediatric MDS based on the original FAB criteria

Bennett et al. (1976, 1994); Hasle (1994)

WHO classification and criteria for the myelodysplastic syndromes and mixed myelodysplastic/ myeloproliferative neoplasms

WHO classification of the myelodysplastic/myeloproliferative neoplasms

•Chronic myelomonocytic leukemia (CMML)

•Atypical chronic myeloid leukemia (aCML), BCR-ABL1 negative

•Juvenile myelomonocytic leukemia (JMML)

•Myelodysplastic/myeloproliferative disease neoplasm, unclassifiable

•Refractory anemia with ring sideroblasts associated with marked thrombocytosis

Jaffe et al. (2001)