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•For pediatric and young adult patients with metastatic/recurrent Ewing sarcoma, 10- and 15-year survival data provide a strong rationale for treatment with high-dose chemotherapy followed by autologous stem cell transplantation.•Most transplant recipients without relapse within 5 years after transplant may achieve long-term disease cure.•Patients received a novel, uniform alkylating agent-based conditioning regimen: busulfan, melphalan, and topotecan.•Conditioning and transplant regimens were tolerated with prompt engraftment and minimal adverse effects (primarily mucositis, noninfectious diarrhea, and bacteremia).•Prognostic factors were identified for improving overall and disease-free survival for metastatic/recurrent disease: (1) disease status at transplant and (2) a late relapse occurring ≥2 years from diagnosis.

•For pediatric and young adult patients with metastatic/recurrent Ewing sarcoma, 10- and 15-year survival data provide a strong rationale for treatment with high-dose chemotherapy followed by autologous stem cell transplantation.•Most transplant recipients without relapse within 5 years after transplant may achieve long-term disease cure.•Patients received a novel, uniform alkylating agent-based conditioning regimen: busulfan, melphalan, and topotecan.•Conditioning and transplant regimens were tolerated with prompt engraftment and minimal adverse effects (primarily mucositis, noninfectious diarrhea, and bacteremia).•Prognostic factors were identified for improving overall and disease-free survival for metastatic/recurrent disease: (1) disease status at transplant and (2) a late relapse occurring ≥2 years from diagnosis.

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The objectives of this study were 1) to compare the time to hematologic recovery (absolute neutrophil count ANC =1,000/mm3and platelet count =100,000/mm3) in a randomized prospective study of two doses of granulocyte colony-stimulating factor (G-CSF) (5.0 vs. 10.0 g/kg per day) after ifosfamide, carboplatin, and etoposide (ICE) chemotherapy; and 2) to determine the response rate (complete response CR partial response PR) of ICE in children with refractory or recurrent solid tumors.

The activity of the drug combination ifosfamide and etoposide (VP16) in refractory and relapsed childhood acute lymphoblastic leukemia (ALL) was assessed in a phase II study.

OBJECTIVE: To describe platinum-based chemotherapy combined with local treatment modalities as an alternative to external beam radiotherapy for intraocular retinoblastoma. DESIGN: Platinum levels were measured by atomic absorption analysis in the tumors of 2 patients with retinoblastoma given carboplatin 5 or 2.5 hours before enucleation. Platinum levels in heated vs nonheated Greene melanoma tumors in rabbits were compared. A retrospective review of 172 affected eyes in 136 consecutive patients treated for retinoblastoma between January 1990 and December 1995 was performed. From 1990 to 1992, all treatable eyes initially received systemic carboplatin, 560 mg/m2, followed by 15 to 30 minutes of continuous diode laser hyperthermia (thermochemotherapy). Since 1992, larger tumors were treated initially with 3 monthly cycles of carboplatin, etoposide, and vincristine sulfate to reduce tumor volume (chemoreduction) followed by sequential aggressive local therapy (SALT) during examinations under anesthesia every 2 to 3 weeks. OUTCOME MEASURE: Treatment success was defined as eradication of tumor without enucleation or external beam radiotherapy. RESULTS: Significant therapeutic platinum levels were measured in the human tumors 2.5 and 5 hours after carboplatin administration. Increasing the temperature by 9°C for 15 minutes doubled platinum levels in the rabbit model. Of the 38 eyes with Reese-Ellsworth group 1 through 5b tumors that were treated primarily with thermochemotherapy, all 24 eyes with group 1 and 2 tumors were treated successfully and two of the 4 eyes with group 3 tumors and all 10 eyes with group 5b tumors were treated unsuccessfully. Chemoreduction plus SALT was the primary treatment in 35 eyes and was successful in all 10 eyes with group 1 through 4 tumors and unsuccessful in all 7 eyes with extensive subretinal seeding and all 18 eyes with group 5b tumors with vitreous seeding. Seventy patients received carboplatin or carboplatin, vincristine, and etoposide, with myelosuppression, occasionally associated with bacteremia, being the main side effect. Transfusions were required in 15% of patients. Radiation retinopathy occurred in all 6 eyes treated with iodine 125 plaques. CONCLUSIONS: Thermochemotherapy is successful primary treatment for Reese-Ellsworth group 1 and 2 retinoblastomas. For larger tumors in the absence of vitreous or extensive subretinal seeding, 3 cycles of chemoreduction followed by SALT eradicates residual viable tumor. Chemoreduction plus SALT was not successful in eyes with diffuse vitreous or extensive subretinal seeding. Prior chemotherapy increases the risk for radiation retinopathy following 125I plaque therapy. External beam radiotherapy can safely be avoided in the primary treatment of Reese-Ellsworth groups 1 through 4 nondispersed retinoblastoma.

A Phase II study of thioTEPA was performed by the Children's Cancer Group. ThioTEPA was administered intravenously every three weeks, at a dose of 65 mg/m2. Pediatric patients with recurrent sarcomas were targeted, but patients with other tumor diagnoses were also eligible. Toxicity was primarily hematopoietic, with thrombocytopenia being predominant. ThioTEPA did not demonstrate significant activity in the target tumor groups evaluated.

Dihydrofolate reuctase from human osteosarcoma cell lines resistant to Methotrexate (MTX) were examined. MTX resistance in TE85 osteosarcoma sublines was produced by exposing cells to gradually increasing concentrations of MTX. Cloned sublines of MTX-resistant cells are maintained in media containing 10-8(TE85/F.8), 10-7(TE85/R7), or 10-6M MTX (TE85/R6). Partial purification of human dihydrofolate reductase from both sensitive and resistant osteosarcoma cell lines was achieved using folate-sepharose affinity chromatography. Although the TE85/R6 cell line was 120-fold more resistant to MTX than the MTX-sensitive cells, the amplification of enzyme activity was only 3.3-fold. Monoclonal antibodies raised against dihydrofolate reductase from a MTX-resistant subline of L1210 murine leukemia cells (Proc. Am. Assoc. Cancer Res. 26:229, 1985) cross-reacted with reductases from human cells. Immunostaining with these antibodies was used to rapidly visualize elevated amounts of dihydrofolate reductase in MTX-resistant osteosarcoma cells. Further delineation of the exact mechanisms(s) accounting for the MTX resistance in these human osteosarcoma cells is currently under investigation.