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J B Belasco

Publications and source records attributed to J B Belasco.

16 recordsLinked to original sources

Primary follicular lymphoma of the testis in childhood.

BACKGROUND: Follicular lymphoma in childhood is rare. The authors present four unusual primary follicular lymphomas of the testis in children. METHODS: Tumor tissue was evaluated using light microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction (PCR) for immunoglobulin heavy chain (IgH) and bcl-2 gene rearrangements. Southern blot and immunohistochemical analyses were used to detect bcl-6 gene rearrangements and protein expression, respectively. RESULTS: Four young boys ranging in age from 3 to 10 years were diagnosed with Stage IE follicular large cell lymphoma (Grade 3). A B-cell phenotype was documented in all four cases; monoclonality was confirmed in three cases by demonstration of light chain restriction or clonal IgH gene rearrangement. None of the lymphomas expressed Bcl-2 or p53 protein, and bcl-2 gene rearrangements were not found in the three lymphomas studied. In contrast, Bcl-6 protein was expressed by all three lymphomas studied, and a bcl-6 gene rearrangement was detected in the one case analyzed by Southern blot. All four boys were treated by orchiectomy and combination chemotherapy and are alive with no evidence of disease 18-44 months following their initial diagnoses. CONCLUSIONS: Follicular lymphomas may rarely occur as primary testicular tumors in prepubertal boys and, when localized, appear to be associated with a favorable prognosis. In contrast to follicular lymphoma in adults, pediatric follicular lymphomas of the testis are usually of large cell type (Grade 3) and lack bcl-2 or p53 abnormalities. The identification, in one case, of a bcl-6 gene rearrangement suggests an alternate molecular pathogenesis for pediatric follicular lymphoma.

Child

Phase II study of daily oral etoposide in children with recurrent brain tumors and other solid tumors.

Pre-clinical data and adult experience suggests that topoisomerase targeted anti-cancer agents may be highly schedule dependent, and efficacy may improve with prolonged exposure. To investigate this hypothesis, 28 children with recurrent brain and solid tumors were enrolled in a phase II study of oral etoposide (ETP). Patients were prescribed ETP at 50 mg/m2/ day for 21 consecutive days. Courses were repeated every 28 days pending bone marrow recovery. Evaluation of response was initially performed after 8 weeks and then every 12 weeks either by CT or MRI. Three of 4 patients with PNET (primitive neuroectodermal tumor)/medulloblastora achieved a partial response (PR). Two of 5 with ependymoma responded, one with a complete response and one with a PR. Toxicity was manageable with only 1 admission for fever and neutropenia in 120 cycles of therapy. Five patients had grade 3 or 4 neutropenia. One had grade 4 thrombocytopenia and one grade 2 mucositis and withdrew as a result. One patient had grade 2 diarrhea. Two patients who achieved a PR had received ETP as part of prior combination chemotherapy regimens. Daily oral etoposide is active in recurrent PNET/medulloblastoma and ependymoma. Toxicity is manageable and rarely requires intervention. Daily oral etoposide in combination with crosslinking agents should be considered in future phase III trials. Determination of activity in glioma and solid tumors is not complete.

Administration, Oral

Pulmonary metastases and bone sarcomas. Surgical removal of lesions appearing after adjuvant chemotherapy.

Pulmonary metastasis is the leading cause of death in pediatric patients with bone tumors. Multiple thoracotomies for surgical removal of individual lesions are performed at many centers. To explore the efficacy of this procedure and establish guidelines for an appropriate choice of patients, the experience with 43 thoracotomies in 24 children was reviewed. The appearance of first metastasis later than one year after diagnosis, presence of fewer than five nodules, and completeness of surgical resection were favorable predictors of postthoractomy survival. Early or multiple metastases, unresectable disease, and hilar, nodal, or pleural lesions conferred an unfavorable prognosis. With careful patient selection, pulmonary metastecotomy is a safe procedure that has few operative or long-term complications. It must be emphasized that although surgical removal of pulmonary metastases prolongs survival with good quality of life, the majority of patients with bone sarcomas ultimately succumb to their disease after thoracotomy. Follow-up time of greater than eight years is necessary to adequately assess the effectiveness of pulmonary resection in eradicating all disease in these patients.

Adolescent

Multiagent chemotherapy in relapsed acute lymphoblastic leukemia in children.

Twenty-seven evaluable children with early first bone marrow relapse of acute lymphoblastic leukemia were treated with an intensive induction/consolidation and ongoing maintenance therapy. Induction therapy consisted of a 35-day course of daunomycin, vincristine, and prednisone, immediately followed by teniposide, cytosine arabinoside (Ara-C), and L-asparaginase. Intrathecal methotrexate, hydrocortisone, and Ara-C were given through the induction/consolidation phase. Twenty-three of 27 patients achieved remission by the end of induction/consolidation. Maintenance with the same drugs in a modified dosage schedule continued for approximately 2 years. A small subgroup of patients who were M3 at day 35 but M1 at day 56 (end of induction/consolidation) and had a cumulative event-free survival (EFS) of only 0.40 at 6 months, all had relapsed by 15 months. However, the EFS for M1 patients by day 35 and maintained on chemotherapy was 0.64 at 12 months and 0.32 at 30, 36, and 48 months, respectively. Although good reinduction and remission duration rates at 12 to 24 months were achieved and an apparent plateau in survival occurs at 30 months, fall-off in survival would not be unexpected with probably less than 20% alive after 5 years.

Adolescent

IV melphalan in children.

Forty children with multiply relapsed cancers received iv melphalan at three doses: 30 mg/m2, 45 mg/m2, and 60 mg/m2. The hematologic toxicity was severe and protracted at all dose levels, whether or not the bone marrow was involved with tumor. Of 39 evaluable patients, 37 had grade 3 or 4 hematologic toxicity. Nonhematologic toxic effects were infrequent and not severe. Two complete responses (Hodgkin's disease, rhabdomyosarcoma), eight partial responses, and 30 failures were seen. There appeared to be a very narrow margin between efficacy and toxicity. Further study of melphalan in pediatric tumors may be warranted in special circumstances: in higher doses (greater than 100 mg/m2) as cytoreduction therapy for specific cancers with marrow rescue, or as part of combination therapy in certain cancers (eg, lymphoma, sarcoma), possibly at doses of 20 to 30 mg/m2 every 4 weeks.

Child

The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity.

We conducted a randomized controlled trial to determine whether intensive multi-agent adjuvant chemotherapy improves the chances of relapse-free survival in patients with nonmetastatic high-grade osteosarcoma of the extremity, as compared with concurrent controls. After undergoing definitive surgery, 36 patients were randomly assigned to adjuvant chemotherapy or to observation without adjuvant treatment. At two years the actuarial relapse-free survival was 17 percent in the control group, similar to that found in studies before 1970, and 66 percent in the adjuvant-chemotherapy group (P less than 0.001). Similar results were observed among 77 additional patients who declined to undergo randomization but who elected observation or chemotherapy. We conclude that the natural history of osteosarcoma of the extremity has remained stable over the past two decades, that adjuvant chemotherapy increases the chances of relapse-free survival of patients with high-grade osteosarcoma, and that it should be given to all such patients.

Antineoplastic Combined Chemotherapy Protocols

Syndrome of inappropriate antidiuretic hormone secretion. A complication of high-dose intravenous melphalan.

Melphalan is now being investigated as an intravenous (IV) bolus chemotherapeutic agent in children with resistant tumors involving the bone marrow. Two patients received 2 mg/kg melphalan, IV bolus; 10 patients received 1 mg/kg. Seven of the ten patients receiving 1 mg/kg had noticeable downward trends in the serum sodium concentrations, whereas both patients receiving 2 mg/kg developed hyponatremia (serum sodium concentration [SNa], mEq/l = 124-125) and inappropriate urinary sodium losses. Syndrome of inappropriate antidiuretic hormone (SiADH) is a previously unreported complication of high dose bolus melphalan therapy.

Adolescent

The breakpoint in 22q11 in a case of Ph-positive acute lymphocytic leukemia interrupts the immunoglobulin light chain gene cluster.

With a constant region probe (c-lambda) from the immunoglobulin light chain gene cluster, we performed in situ hybridization to bone marrow chromosome preparations from a patient with a Ph-positive form of acute lymphocytic leukemia. Results in this patient indicate that the immunoglobulin chain genes were involved in the 9;22 chromosome rearrangement.

Chromosome Mapping

Phase I clinical evaluation of diaziquone in childhood cancer.

Diaziquone (AZQ), a new lipid-soluble antitumor agent, was given by 15-30-minute infusion on a daily X 5 schedule to 47 children with refractory solid tumors and leukemia. The starting daily dose of 6 mg/m2 was escalated to 10 and 35 mg/m2 in patients with solid tumors and leukemia, respectively. In patients with solid tumors, myelosuppression was dose-limiting at a daily dose of 10 mg/m2. In patients with leukemia, prolonged pancytopenia and bone marrow hypoplasia were observed at daily doses greater than or equal to 25 mg/m2. At these higher doses, significant hyperbilirubinemia associated with sepsis was also seen. Corresponding increases of transaminases or alkaline phosphatase and significant hemolysis were not noted. The maximum tolerated dose for this daily dose schedule was 9 mg/m2 in children with solid tumors and 25 mg/m2 in children with relapsed leukemia. Responses to AZQ included stabilization of disease in osteosarcoma, neurofibrosarcoma, pinealoma, and ependymoma. A patient with juvenile chronic myelocytic leukemia in blast crisis converted back to the chronic phase. A patient with acute lymphoblastic leukemia had a substantial decrease in cerebrospinal fluid blast count. Bone marrow aplasia was achieved in children with acute lymphoblastic leukemia and acute nonlymphoblastic leukemia; however, remissions were not achieved. A phase II study of AZQ in children with refractory malignancies is now being performed by the Childrens Cancer Study Group.

Adolescent

High dose systemic methotrexate-associated acute neurologic dysfunction.

Two patients treated with high dose methotrexate otrexate with citrovorum rescue (HDMTX-CF) for osteogenic sarcoma developed the acute onset of neurologic deficits. Prior to the onset of symptoms, one child suffered brief episodes of altered consciousness. Both patients developed hemiparesis and then steadily improved over 72 hours. Laboratory evaluations disclosed normal coagulation parameters and nontoxic serum methotrexate levels at onset of symptoms. Computed tomography in one child disclosed a large low absorption abnormality. This patient represents the first reported case of positive radiologic findings associated with this syndrome. The two patients recovered completely and received further HDMTX-CF without sequelae. This condition may result from transient demyelination or embolic cerebrovascular disease.

Adolescent

Extraskeletal osteogenic sarcoma after treatment for Wilms' tumor.

A large proportion of children with Wilms' tumor will become long-term disease-free survivors. A small number of these children are at risk of developing second malignant neoplasms. There have been no previous reports of osteogenic sarcoma of the chest wall following treatment of Wilms' tumor. Our patient was age seven years when he received surgery, radiation therapy and chemotherapy for Wilms' tumor, eight years when he received radiation and chemotherapy for pulmonary metastases of Wilms' tumor, and 13 years when he developed osteogenic sarcoma of the chest wall.

Child

Acute promyelocytic leukemia presenting as a pelvic mass.

The case history of a child with acute promyelocytic leukemia (APL) is reported to illustrate both an unusual presentation of APL as a pelvic mass and to review the pathophysiology and treatment of the disease. Therapy of APL consists of chemotherapy, namely adriamycin/daunomycin for remission induction, and of control of disseminated intravascular coagulation. A chloroma, if present, may require local irradiation in addition to chemotherapy. With aggressive management, the number of prolonged remissions may be greater for APL than for any other form of acute myelogenous leukemia (AML), with significant numbers of patients achieving five-year survival.

Antineoplastic Agents