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This study was designed to determine the prognostic significance of multidrug resistance, mediated by P-glycoprotein (Pgp) expression, in Ewing sarcoma. The clinical and laboratory features, treatment protocol, and outcome of 75 patients with Ewing sarcoma or peripheral neuroectodermal tumor treated between 1972 and 1997 were reviewed. Pgp expression was tested with the monoclonal antibody JSB-1. Thirty-four (64%) of the 53 tissue samples from untreated patients stained positive for Pgp. Progression-free and overall survival were 44 and 59%, respectively, in patients with negative findings, and 28 and 41% in those with positive findings; neither difference was significant. Of the 12 relapsed patients, 6 (50%) expressed more Pgp after chemotherapy than at diagnosis and 4 (33%) expressed less. Within these subgroups, 5 out of 6 and 3 out of 4 died from the disease. No correlation was found between Pgp and known prognostic factors of Ewing tumors. Pgp expression is probably an intrinsic factor of Ewing tumors but has no correlation to prognosis.

Insulin-like growth factor-I (IGF-I) is a known mitogen for various cell types, including those of the hematopoietic cell system. To study the role of IGF-I in the neoplastic process of leukemia in children, the authors have determined the number of IGF-I binding sites on circulating mononuclear cells of children with acute leukemia as compared to normal children, using binding assays. The IGF-I binding sites per cell on peripheral mononuclear cells of children with leukemia decreased compared to those of the control group (411 +/- 73 and 1334 +/- 227, respectively, p < .001), while their affinity increased (Kd = 0.14 +/- 0.04 and 0.43 +/- 0.16, respectively, p = .05). Furthermore, in the patients, the number of the IGF-I binding sites was significantly lower in the subgroup of the peripheral mononuclear cells, which included lymphocytes and monocytes, as compared to their number in the peripheral blast cells (254 +/- 43.6 and 536 +/- 98.6, respectively, p = .02). A significant reduction was found in serum GHBP levels in the patients as compared to the controls (28.21 +/- 1.93 and 35.83 +/- 2.90, respectively, p = .02), while serum IGF-I and growth hormone levels were similar in patient and control groups. These results suggest a possible involvement of IGF-I in childhood acute leukemia, but further studies are needed to establish whether IGF-I plays a role in this disease.

The aim of the study was to delineate the clinical characteristics of visual pathway tumor in children without neurofibromatosis-I. The authors reviewed the charts of all patients meeting these criteria (n = 12) who were followed in their center over a 13-year period. In 8 patients the disease was relentlessly progressive, and imaging showed a chiasmatic/hypothalamic, exophytic globular lesion. The remainder had a benign course with long periods of tumor stability; one showed some spontaneous visual improvement. The lesions of the latter subgroup were multilobular, with elongated posterior extension into the optic tract. This differentiation, according to the imaging findings, may have significant therapeutic implications. In the first type, every effort should be made to arrest the disease and decrease the size of the lesion, whereas in the second, despite decreased visual ability, careful observation in the appropriate approach. There are as yet no known biological markers to better delineate these two types of tumor behavior.

Congenital dyserythropoietic anemia (CDA) type I is a rare inherited bone marrow disorder characterized by moderate to severe macrocytic anemia with pathognomonic cytopathology of nucleated red blood cells. Previous studies have suggested that serum erythropoietin levels in affected patients are lower than expected for the degree of anemia. An earlier study demonstrated a substantial increase in the number of CFU-E in CDA type I pattern on addition of exogenous erythropoietin. The present study reports on the response to recombinant human erythropoietin in 8 patients with CDA type I. Eighteen weeks of treatment, starting at 300 IU/kg twice a week and gradually increasing to 500 IU/kg three times a week, did not have a substantial effect on the mean hemoglobin value. These results indicate that recombinant human erythropoietin (rHuEpo) is not beneficial to patients with CDA type I and that the relatively low levels of serum erythropoietin probably play no major role in the pathogenesis of the disease.

We have identified a 16 bp deletion in the 3' untranslated region of the alpha 2-globin gene, including the first nucleotide of the polyadenylation signal sequence. The propositus, her mother and one of her brothers, all heterozygotes for the above deletion, have mild microcytic anemia. This is the first description of a deletion in the alpha gene involving both the 3' untranslated region and the polyadenylation signal sequence, causing alpha-thalassemia.

A 7-month-old infant with typical features of diencephalic syndrome (DES) associated with a hypothalamic mass, most probably a glioma, was treated with chemotherapy. The tumor showed clear shrinkage, but after more than 2 years regrowth was noted. During the treatment period the child regained normal growth and became free of symptoms. As radiation therapy, especially at a young age, has significant adverse effects and a neurosurgical approach to the diencephalic region also has the potential to cause significant sequelae, a chemotherapeutic option, when it exists, is preferred. Thus, in an infant in whom a glioma is suspected to be the cause of the DES, based on the clinical picture and the neuroimaging appearance, chemotherapy should be considered the primary therapeutic modality. Even if its effect is temporary, its use is well justified. The most appropriate treatment protocol still needs to be determined.

One hundred children with non-central nervous system malignancies received ondansetron at initiation of chemotherapy and every 8 hours for 5 days after cisplatin-containing therapy and for 3 days after other chemotherapy. Ondansetron was administered orally except with the intravenous chemotherapy. For the chemotherapy days, 72 of 93 children (76%) had complete or major control of vomiting on their worst day, 25% with cisplatin-containing protocols, 60% with ifosfamide-containing protocols, and 82% with other protocols. For the overall period, 71 of 93 children (76%) reported complete or major control of vomiting on the worst day, 14% with cisplatin, 60% with ifosfamide, and 83% with other chemotherapy. All had mild or no nausea. Of the 355 chemotherapy days, 228 children (64%) were emesis free, 40% with cisplatin, 60% with ifosfamide, and 68% with other regimens. Of the overall period (541 days), 393 days were emesis free, 45% with cisplatin, 71% with ifosfamide, and 86% with other regimes. Sixty-nine patients were not hospitalized, and oral ondansetron was given when chemotherapy was completed. Of the 241 ambulatory chemotherapy days, 178 (74%) were emesis free. No significant toxicity was encountered. Oral ondansetron reduced hospitalization without reducing antiemetic efficiency in children.

Malignant thymomas are among the least common mediastinal tumors in the pediatric age group. Thymomas are considered malignant on the basis of macroscopic and microscopic invasiveness. As only 20 well-documented cases involving children have been reported in the literature, the pattern of responsiveness to therapy and the value of prognostic signs is obscure. Two cases of malignant pediatric thymomas are reported with pathognomonic histoimmunological features of aggressive thymoma. One was cured, with a follow-up of 70 months, and one died while on therapy. Analysis of the histological features and the immunoperoxidase staining displays the complexity of pediatric thymomas and the inability to prognosticate the outcome, respectively.

No mention of dactinomycin potentiation of pulmonary radiation was found in a review of the literature of the past 12 years. Before that, this complication was well described and investigators had calculated that dactinomycin increased the toxic effect of lung radiation by a factor of 1.3 and reduced the radiation tolerance of the lung by at least 20%. An example of such a toxic effect is described in the treatment of a 7-year-old girl with lung metastases from Ewing's sarcoma. The chemotherapy protocol followed contained cyclophosphamide, vincristine, dactinomycin, adriamycin, cisplatinum, VP16, and radiotherapy. The treatment was associated with fatal pulmonary fibrosis following the reintroduction of dactinomycin after radiotherapy. Our experience suggests that there is clinical significance to this complication in sarcoma therapy when dactinomycin-containing protocols are used with radiation in the treatment of pulmonary metastases.

An episode of leukoencephalopathy is reported in a 13-year-old girl who, after standard radiotherapy for a posterior fossa medulloblastoma, received 8 treatments with a protocol containing a 4-hour infusion of 500 mg/m2 methotrexate and 12 mg intrathecal methotrexate. The leukoencephalopathy, documented clinically and by CT and EEG, cleared after 2350 mg of leucovorin (citrovorum factor, folinic acid) was given in addition to the 135 mg given as part of the therapy. A review of the literature suggests that leukoencephalopathy may be prevented by high doses of leucovorin and can be treated by high doses, if lower doses were used initially. When high dose leucovorin was not used, residual neurological damage is not unusual.

A 4-year-old girl with juvenile chronic myeloid leukemia relapsed after an allogeneic bone marrow transplantation (BMT) and became refractory to conventional chemotherapy. Treatment with two courses of high-dose deferoxamine, an iron chelator (130-180 mg/kg/day), along with low-dose ARA-c (5 mg/kg/day) caused a remarkable decrease of the WBC and fetal Hb. Three days following the last dose of deferoxamine, the patient experienced an acute visual loss, confirmed by electroretinogram (ERG) and visual evoked response (VER). Slight improvement occurred a few days later, but the patient developed severe pancytopenia and died of Klebsiella septic shock. The ocular manifestations were attributed to deferoxamine toxicity in light of the rapid onset after first exposure, the electrophysiological pattern of metabolic damage in the ERG and VER, and the long interval between the last chemotherapy and BMT. The pathogenesis of deferoxamine toxicity is discussed.

A child with a B-cell lymphoma with extensive abdominal disease responded to high doses of chemotherapy. One month later, eye and central nervous system recurrence developed. Intraocular involvement was documented by diagnostic vitrectomy. Differential diagnosis and therapy are discussed.

After 3 years of treatment with azathioprine and prednisone, immunoblastic lymphoma appeared in a patient with systemic lupus erythematosus. An increased incidence of immunological aberrations and malignancies was found in her family and their relation to the pathogenesis of this patient's diseases is discussed.