melphalan and Ependymoma

We treated 49 patients with recurrent or poor-prognosis CNS malignancies with high-dose chemotherapy regimens followed by autologous marrow rescue with or without peripheral-blood stem-cell augmentation to determine the toxicity of and event-free survival after these regimens.. Nineteen patients had medulloblastomas, 12 had glial tumors, seven had pineoblastomas, five had ependymomas, three had primitive neuroectodermal tumors, two had germ cell tumors, and one had fibrosarcoma. Thirty-seven received chemotherapy with cyclophosphamide 1.5 g/m2 daily x 4 and melphalan 25 to 60 mg/m2 daily x 3. Nine received busulfan 37.5 mg/m2 every 6 hours x 16 and melphalan 180 mg/m2 (n = 7) or 140 mg/m2 (n = 2). Three received carboplatin 700 mg/m2/d on days -7, -5, and -3 and etoposide 500 mg/m2/d on days -6, -4, and -2. All patients received standard supportive care.. Eighteen of 49 patients survive event-free 22+ to 55+ months (median, 33+) after transplantation, including nine of 16 treated before recurrence and nine of 33 treated after recurrence. There was one transplant-related death from pulmonary aspergillosis. Of five patients assessable for disease response, one had a partial remission (2 months), one has had stable disease (55+ months), and three showed progression 2, 5, and 8 months after transplantation.. The toxicity of these regimens was tolerable. Certain patients with high-risk CNS malignancies may benefit from such a treatment approach. Subsequent trials should attempt to determine which patients are most likely to benefit from high-dose chemotherapy with autologous stem-cell rescue.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Brain Neoplasms; Busulfan; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Ependymoma; Female; Fibrosarcoma; Glioblastoma; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Medulloblastoma; Melphalan; Neoplasm Recurrence, Local; Pinealoma; Transplantation, Autologous; Treatment Outcome

To determine the maximum-tolerated dose of cyclophosphamide (CTX) when administered sequentially with melphalan 60 mg/m2/d for 3 days, followed by autologous bone marrow rescue (ABMR), in children with recurrent or progressive malignant brain tumors, and to make preliminary observations on efficacy.. Nineteen patients between the ages of 2 and 21 years were enrolled and 18 were assessable for effects of therapy. CTX was administered to seven patients at 750 mg/m2/d for 4 days, to five patients at 975 mg/m2/d, to three patients at 1,200 mg/m2/d, and to three patients at 1,500 mg/m2/d. All patients received ABMR. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used in 15 patients. Toxicity, response to therapy, time to progression, and survival and monitored.. The median time to a granulocyte count more than 500/dL was 19 days (range, 11 to 39), and for a platelet count more than 50,000/dL was 33 days (range, 16 to 60). Four heavily pretreated patients (22%) died of transplant-related complications. No dose-limiting, non-hematologic toxicities were defined for the study. Seven of 18 patients (39%) had a complete response (CR) or a partial response (PR). These included four patients with medulloblastoma (CR and three PRs), two with germinomas (two CRs), and one with ependymoma (one CR). The estimated 1-year survival rate was 39% (SE 12%).. CTX, at a maximum total dose of 6,000 mg/m2, administered sequentially with melphalan and followed by ABMR was tolerable in children with recurrent brain tumors who had not been heavily pretreated. Responses were seen in patients with medulloblastoma and germinomas. Further trials in children with chemosensitive tumors, with minimal residual disease, are planned.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Brain Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Drug Administration Schedule; Ependymoma; Female; Germinoma; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Medulloblastoma; Melphalan; Pilot Projects; Survival Rate; Transplantation, Autologous

Topics: Animals; Antibodies; Antibodies, Neoplasm; Brain Neoplasms; Ependymoma; Injections, Intravenous; Melphalan; Mice; Mice, Inbred C3H; Neoplasm Transplantation; Rabbits

Topics: Animals; Antibody Formation; Ependymoma; Haptens; Injections, Intravenous; Leukemia, Experimental; Mammary Neoplasms, Experimental; Melphalan; Mice; Neoplasms, Experimental; Rabbits

Topics: Animals; Antibodies; Ependymoma; Freund's Adjuvant; gamma-Globulins; Immune Sera; Melphalan; Mice; Neoplasms, Experimental; Rabbits

Topics: Animals; Antibody Formation; Antigen-Antibody Reactions; Ependymoma; Leukemia, Experimental; Mammary Neoplasms, Experimental; Melphalan; Mice

Topics: Alkylating Agents; Animals; Antineoplastic Agents; Brain Neoplasms; Cyclophosphamide; Dactinomycin; Ependymoma; Mannitol; Melphalan; Mice; Neoplasms; Neoplasms, Experimental; Neuroectodermal Tumors, Primitive; Pharmacology; Research; Toxicology