5.5.2Natural History

Variable, although conversion to acute leukemia in children is not common.

5.5.3Management

•No standard therapy. When treatment is required for patients with significant complications or conversion to leukemia, stem cell transplantation is considered the only curative treatment

5.6Hypereosinophilic Syndrome

•Hypereosinophilic syndrome (HES) should be distinguished from molecularly defined and otherwise uncategorized chronic eosinophilic leukemia (CEL)

•The genes that are mutated in molecularly defined CEL include those encoding platelet-derived growth factor receptors A and B and fibroblast growth factor receptor 1

•Differentiation between clonal and nonclonal eosinophilia is difficult. The latter can be a result of abnormal cytokine production. Differentiation between chronic eosinophilic leukemia (CEL) and hypereosinophilic syndrome (HES) may be difficult (see WHO classification)

•CEL or HES can sometimes be a diagnosis of exclusion; infectious, inflamma- tory, and neoplastic disorders must be ruled out

•After exclusion of the above-mentioned disorders, HES or CEL may be differentiated based on presence of clonality or rearrangements of the receptor-encoding genes noted above

5.7Transient Myeloproliferative Syndrome Associated with Down Syndrome

Essentially mimics true leukemia clinically and in terms of laboratory findings.

•Occurs in approximately 10% of newborns with Down syndrome

•Spontaneous remission occurs within weeks to a few months in the majority of children

•Approximately 20% (i.e., 1 in 5 of children with Down syndrome) of children with spontaneous remission go on to develop AML, which is nearly always acute megakaryoblastic leukemia (AMKL) and develops usually within several months of the TMD

•Incidence of AMKL associated with Down syndrome is approximately 500 times higher than in children without Down syndrome

•AMKL exhibits differences between the two forms of AMKL in childhood:

–AMKL of infancy with t(1;22), with an aggressive evolving course associated with a poor response to chemotherapy

–AMKL in childhood without a long myelodysplastic phase, similar to AMKL associated with Down syndrome and also a poor response to chemotherapy

•Transient myeloproliferative syndrome (TMS) appears not to predispose children with Down syndrome to ALL, although incidence of ALL in children with Down syndrome is increased

•LeukemiccellsinAMKLandTMSexhibitmanysimilarities:morphology,cytochemistry, antigen expression pattern, and mutations of the GATA1 gene

•Treatment of infants with TMS is usually one of observation and supportive mea- sures, although some children may require, in part because of the complications associated with a high WBC, cytoreductive therapy with chemotherapy; low dose cytosine arabinoside is most commonly used

•Some infants with DS may also develop, even in the perinatal period, profound liver failure secondary to megakaryoblastic infiltration into the liver. This manifestation is associated with a high mortality

5.8Mast Cell Disease (Mastocytosis)

•Mast cells are derived from hematopoietic stem cells

•Heterogeneous group of disorders

•Abnormal growth and accumulation of mast cells in one or multiple organs

•Often associated with clonal proliferation

•Systemic forms are extremely rare in childhood

•Malignant forms are not observed in childhood

•Frequently associated with mutations in c-KIT, which encodes a tyrosine kinase receptor for stem cell factor

•The WHO classification is commonly used to distinguish different types of mastocytosis

•Particularly in children younger than 2 years, mastocytosis presents as solitary cutaneous lesion or with urticaria pigmentosa

•Often a self-limiting disorder in childhood

•Skin, bones and sometimes bone marrow can be affected

•Often pruritus caused by histamine release is evident and can be severe; thus treatment is symptomatic (antihistaminic agents)

WHO classification of mast cell disease (mastocytosis)

•Cutaneous mastocytosis

•Indolent systemic mastocytosis

•Systemic mastocytosis with associated clonal, hematological nonmast cell lineage disease

•Aggressive systemic mastocytosis

•Mast cell leukemia

•Mast cell sarcoma

•Extracutaneous mastocytoma

References

Niemeyer CM, Arico M, Basso G et al (1997) Chronic myelomonocytic leukemia in childhood: a retrospective analysis of 110 cases. European Working Group on Myelodysplastic Syndromes in Childhood (EWOG-MDS). Blood 89:3534–3543

Germing U et al (2008) Epidemiology, classification and prognosis of adults and children with myelodysplastic syndromes. Ann Hematol 87:691–699

Vardiman JW (2010) The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues: an overview with emphasis on the myeloid neoplasms.

Chem Biol Interact 184:16–20

Yin CC et al (2010) Recent advances in the diagnosis and classification of myeloid neoplasms – comments on the 2008 WHO classification. Int J Lab Hematol 32:461–476