Etiology and Epidemiology. In a child with aplastic anemia, pancytopenia evolves as the hematopoietic elements of the bone marrow disappear and the marrow is replaced by fat. In developed countries, aplastic anemia is most often idiopathic. The disorder may be induced by drugs such as chloramphenicol and felbamate or by toxins such as benzene. Aplastic anemia also may follow infections, particularly hepatitis and infectious mononucleosis (see Table 150-6). Immunosuppression of hematopoiesis is postulated to be an important mechanism in patients with postinfectious and idiopathic aplastic anemia.
Laboratory Studies. A bone marrow biopsy is crucial to determine cellularity or the extent of depletion of the hematopoietic elements.
Treatment. Survival rate is about 20% in severe aplastic anemia with supportive care alone, although the duration of survival may be years when vigorous blood product and antibiotic support is provided. For children with severe aplastic anemia—defined by an absolute reticulocyte count less than 50,000/μL, absolute neutrophil count less than 500/mm3, platelet count less than 20,000/mm3, and bone marrow cellularity on biopsy specimen less than 25% of normal—the treatment of choice is hematopoietic stem cell transplantation (HSCT) from a sibling with identical HLA and compatible mixed lymphocytes. When HSCT occurs before the recipient is sensitized to blood products, survival rate is greater than 80%. The treatment of aplastic anemia without an HLA-matched donor for HSCT is evolving, with two major options: potent immunosuppressive therapy or unrelated or partially matched HSCT. Results of trials using immunosuppressive therapy with antithymocyte globulin, cyclosporine, and corticosteroids in combination with hematopoietic growth factors have been encouraging. Such therapy is often toxic, and relapses often occur when therapy is stopped.
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Etiology and Epidemiology. Fanconi anemia is a constitutional form of aplastic anemia that usually presents in the latter half of the first decade of life and may evolve over years. A group of genetic defects in proteins involved in DNA repairhave been identified in Fanconi anemia, which is inherited in an autosomal recessive manner. The diagnosis is based on demonstration of increased chromosomal breakage after exposure to agents that damage DNA. The repair mechanism for DNA damage is abnormal in all cells in Fanconi anemia, which may contribute to the increased risk of malignancies. Terminal acute leukemia develops in 10% of cases. Other malignancies include solid tumors of the head and neck, gastrointestinal tumors, and gynecologic tumors.
Clinical Manifestations. Patients with Fanconi anemia have numerous characteristic clinical findings (see Table 150-6).
Treatment. Hematopoietic stem cell transplantation can cure the pancytopenia caused by bone marrow aplasia. Many patients with Fanconi anemia and about 20% of children with aplastic anemia seem to respond for a time to androgenic therapy, which induces masculinization and may cause liver injury and liver tumors. Androgenic therapy increases RBC synthesis and may diminish transfusion requirements. The effect on granulocytes, and especially the platelet count, is less impressive.
Marrow Replacement. Marrow replacement may occur as a result of leukemia, solid tumors (especially neuroblastoma), storage diseases, osteopetrosis in infants, and myelofibrosis, which is rare in childhood. The mechanisms by which malignant cells impair marrow synthesis of normal hematopoietic elements are complex and incompletely understood. Bone marrow aspirate and biopsy are needed for precise diagnosis of the etiology of marrow synthetic failure.