Classification of Pediatric Myeloid Malignancies
RARS is rare in children. RA and RAEB are more common. The WHO classification schema has a subgroup that includes JMML (formerly juvenile chronic myeloid leukemia), CMML, and Ph chromosome-negative CML. This group can show mixed myeloproliferative and sometimes myelodysplastic features. JMML shares some characteristics with adult CMML [124,125,126] but is a distinct syndrome (see below). A subgroup of children younger than 4 years at diagnosis with myelodysplasia have monosomy 7. For this subset of children, their disease is best classified as a subtype of JMML. The International Prognostic Scoring System (IPSS) is used to determine the risk of progression to AML and the outcome in adult patients with MDS. When this system was applied to children with MDS or JMML, only a blast count of less than 5% and a platelet count of more than 100 x 109 /L were associated with a better survival in MDS, and a platelet count of more than 40 x 109 /L predicted a better outcome in JMML. These results suggest that MDS and JMML in children may be significantly different disorders than adult-type MDS. Older children with monosomy 7 and high-grade MDS, however, behave more like adults with MDS and are best classified that way and treated with allogeneic hematopoietic stem cell transplantation.[128,129] The risk group or grade of MDS is defined according to IPSS guidelines. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases was published in 2003; however, the usefulness of this classification has yet to be evaluated prospectively in clinical practice. A retrospective comparison of the WHO classification with the category, cytology, and cytogenetics system and a Pediatric WHO adaptation for MDS/MPD, has shown that the latter two systems are better able to effectively classify childhood MDS than the more general WHO system. A prospective study should be done to definitively determine the optimal classification scheme for childhood MDS/MPD.
Diagnostic Classification of Juvenile Myelomonocytic Leukemia
JMML is a rare leukemia that accounts for less than 1% of childhood leukemia cases. JMML typically presents in young children (a median age of approximately 1.8 years) and occurs more commonly in boys (male to female ratio approximately 2.5:1). Common clinical features at diagnosis include hepatosplenomegaly (97%), lymphadenopathy (76%), pallor (64%), fever (54%), and skin rash (36%). In children presenting with clinical features suggestive of JMML, a definitive diagnosis requires the following:
Table 3. Diagnostic Criteria for Juvenile Myelomonocytic Leukemia (JMML)
GM-CSF = Granulocyte-macrophage colony-stimulating factor.
|Minimal laboratory criteria (all 3 have to be fulfilled)
||1. Ph chromosome negative, no BCR/ABL rearrangement
|2. Peripheral blood monocyte count >1 x 109 /L
|3. Bone marrow blasts <20%
|Criteria for definite diagnosis (at least 2 must be fulfilled)
|| 1. Hemoglobin F increased for age
|2. Myeloid precursors on peripheral blood smear
|3. White blood count >10 x 109 /L
|4. Clonal abnormality (including monosomy 7)
|5. GM-CSF hypersensitivity of myeloid progenitors in vitro