A case of nonneurologic Gaucher's disease that biochemically resembles the neurologic types.

Systemic findings such as hepatosplenomegaly and typical Gaucher storage cells in a bone marrow aspirate led to the clinical diagnosis of Gaucher's disease in the seven-year old patient described in this report. On the basis of the lack of neurologic involvement the child was classified as having the Type 1, nonneurologic form of Gaucher's disease. After splenectomy glucocerebrosidase was extracted from her spleen for biochemical analysis. As expected, a marked deficiency of glucocerebrosidase activity was evident in the splenic extract, however her enzyme displayed anomalous behavior compared to other identical splenic preparations from documented Type 1 Gaucher's disease patients in that it failed to reconstitute with the acidic lipid phosphatidylserine. Using the polymerase chain reaction (PCR)-based color complementation assay and restriction endonuclease analysis, we compared the mutation genotype of this child with that of five other classical Type 1 patients. This analysis revealed that our patient alone was homoallelic for a T----C transition at position 1448 in the glucocerebrosidase cDNA that results in a 444Leu----Pro substitution in the glucocerebrosidase protein. The latter mutation genotype is normally associated with the neurologic phenotype, namely, the Types 2 and 3 forms of the disease. The relevance of the nature of polarity in clinical and biochemical analyses is discussed with regard to the phenotypic classification and the future clinical course of disease in the child.

Lymphocyte infusion for delayed extramedullary relapse of acute leukemia following bone marrow transplantation.

We report a case of extramedullary relapse of acute myelogenous leukemia twelve years after allogeneic bone marrow transplantation. Due to the localized nature of the relapse, we were able to eliminate a majority of the tumor burden, utilizing local irradiation. Destined with eventual systemic leukemia relapse, further therapy utilizing donor lymphocytes was given at a time of minimal disease burden. The patient remains in a state of complete remission.

Immunohistology, cytogenetics, and molecular studies of small round cell tumors of childhood. A review.

Malignancies of childhood include a well-defined spectrum of hematolymphoid, organ specific (adrenal, kidney, liver), soft tissue, bone, and nervous system (central and peripheral) neoplasms with variable biology. Small round cell neoplasms, a subset of childhood malignancies, are histologically similar but differ markedly in their histogenesis, therapy, and prognosis. Traditionally, clinical information and light microscopy, with the aid of histochemistry and ultrastructural evaluation, establish a diagnosis or at least narrow the differential diagnosis. Additionally, immunohistology, cytogenetics, and molecular studies have become important in diagnosis and in defining phenotype/genotype, patient treatment modalities, and prognosis in specific cases. The 11;22 chromosomal translocation typifies Ewing's sarcoma, primitive neuroectodermal tumor, and Askin's tumor, as does the resultant chimeric transcript, while expression and amplification of N-myc oncogene are predictive of the prognosis in neuroblastoma. Furthermore, studies of genes and gene products are elucidating mechanisms of oncogenesis and tumor progression.

Langerhans cell histiocytosis after therapy for a malignant germ cell tumor of the central nervous system.

Langerhans cell histiocytosis (LCH) is a clonal neoplastic disorder that results in a spectrum of clinical manifestations. Known to be associated with a variety of malignant diseases, LCH may precede, coincide with, or develop after the diagnosis of cancer. A child with a malignant germ cell tumor of the brain who subsequently experienced LCH is reported. The 8-year-old boy was treated for an immature teratoma of the posterior fossa with gross total resection and craniospinal irradiation preceding bleomycin, etoposide, and vinblastine chemotherapy for four cycles. Seven months after completion of therapy, he experienced multifocal bone disease with LCH.

Late echocardiographic findings following childhood chemotherapy with normal serial cardiac monitoring.

PURPOSE: Late development of myocardial dysfunction years following successful treatment of childhood malignancy with anthracyclines is well documented. There have been few studies of late cardiac performance in children in whom serial monitoring during treatment suggested normal cardiac performance, and those studies that do exist rely on the results of extensive evaluation. It was our purpose to determine whether findings consistent with known late cardiac changes could be discovered in these patients by echocardiographic monitoring similar to that routinely performed during treatment. PATIENTS AND METHODS: A total 28 consecutive asymptomatic patients who had completed anthracycline therapy at least 3 years previously, had been free of malignant disease since the completion of therapy, and who had had normal serial echocardiographic studies during and at completion of treatment were restudied by echocardiography. Of these 28, 12 had undergone mediastinal radiation as part of their acute treatment. RESULTS: Four patients (14%) of the study group were found to have abnormally low values for left ventricular shortening and ejection fractions. All four had also received mediastinal radiation. The remaining 24 patients, while having values for shortening fraction within the normal range, had, as a group, experienced a significant decrease in echocardiographic left ventricular shortening since completion of treatment. In these patients, left ventricular wall thickness had not increased commensurate with growth in body size and left ventricular cavity dimension. CONCLUSIONS: The known incidence of late asymptomatic cardiac dysfunction is confirmed despite the presence of persistently normal echocardiographic monitoring studies during and at completion of anthracycline treatment. Additionally, as a population, these patients show impaired myocardial growth over time, placing them at risk for future myocardial failure. Normal echocardiographic monitoring studies during antineoplastic treatment in children may not necessarily predict that patients will be free of the development of late cardiac dysfunction. Routine serial echocardiographic monitoring can, however, be helpful in the long-term management of these patients.