Chronic Myeloproliferative Disorders



Chronic Myeloproliferative Disorders


C. Philip Steuber



The chronic myeloproliferative disorders in children are rare conditions accounting for 1% to 2% of all childhood malignancies and 3% to 5% of all childhood leukemias. As with the acute myeloid leukemias (AML), these disorders are the result of the uncontrolled clonal proliferation of one or more marrow-cell lineages. Each entity listed in Box 302.1 is designated according to the predominant type of cell involved. The term chronic is somewhat deceptive in that the prognosis for these disorders is generally worse than that for the acute leukemias.


JUVENILE MYELOMONOCYTIC LEUKEMIA

Juvenile myelomonocytic leukemia (JMML), formerly designated as juvenile chronic monomyelogenous leukemia (JCML), is a clonal panmyelopathy most often presenting in children younger than 2 years. Boys predominate (by more than 2:1). The children present with lymphadenopathy that is often suppurative and fever. They frequently exhibit a chronic
eczematoid facial rash and moderate organomegaly. Hematologic abnormalities include a mild anemia, symptomatic thrombocytopenia, and moderate leukocytosis (usually less than 100,000 cells per microliter). The leukocytosis is caused by circulating immature monocytes and myelocytes, which are identifiable histochemically and in cell culture. Circulating nucleated erythrocytes also can be seen. Fetal hemoglobin levels are markedly elevated. Bone marrow specimens are hypercellular, with elevated numbers of myeloid and monocytoid forms. Dyserythropoietic changes are observed, and megakaryocytes are diminished. Although erythroid, myeloid, and megakaryocytic cell lines are involved, abnormal monocyte forms usually predominate. Characteristically, marrow cultures are considered the diagnostic study, and demonstrate predominantly monocytic differentiation, with granulocyte-macrophage colony-forming unit growth occurring spontaneously in the absence of growth factors. Marrow cultures demonstrate a marked growth response when exposed to granulocyte-macrophage colony stimulating factor (GM-CSF). Polyclonal elevations of immunoglobulins have been described, and an association with chronic Epstein-Barr virus infection has been reported. Specific cytogenetic patterns have not been associated with JMML. When chromosomal abnormalities are detected, they most often involve chromosomes 7 and 8. However, most patients studied have normal karyotypes. Diagnostic criteria for JMML have been proposed; these are listed in Box 302.2.


Children with JMML respond poorly to therapy. Younger patients (less than 1 year of age) generally fare better. Transient responses have been reported with various low- and high-dose chemotherapy regimens. Radiation therapy and splenectomy usually are not helpful. The use of isotretinoin (13-cis-retinoic acid) alone or in combination with chemotherapy regimens to induce maturation of the monocytes and myelocytes is reported to be transiently effective. It has been suggested that aggressive therapy, similar to that effective in acute forms of myeloid and monocytic leukemia, should be used, and that subsequent allogeneic bone marrow transplantation should be considered as the primary therapeutic option. Improved survivals after transplantation have been reported. Most children with JMML die within 1 to 2 years of diagnosis, regardless of therapy.


ADULT CHRONIC MYELOGENOUS LEUKEMIA

The incidence of adult chronic myelogenous leukemia (ACML) in the pediatric age group is approximately twice that of JMML. ACML is uncommon before 3 years of age, and usually is diagnosed between the ages of 10 and 14. As with JMML, males predominate. Common chief complaints include fever, weakness, pain, weight loss, and increasing abdominal girth. Respiratory system complaints are common. Marked splenomegaly is evident.

Jul 24, 2016 | Posted by in ORTHOPEDIC | Comments Off on Chronic Myeloproliferative Disorders
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