No abstract

Despite expectations that 2-chlorodeoxyadenosine (2-CdA) would prove active primarily in lymphoproliferative diseases, early reports suggested unexpected high activity of this drug in heavily pretreated children with acute myeloblastic leukemia (AML) at a maximally tolerated dose of 8.9 mg/m2/day for 5 days. In view of these findings, we conducted an escalating dose trial of 2-CdA in adult patients with relapsed or resistant AML. Thirty-six patients who had received extensive prior therapy were treated at 9 dose levels of 2-CdA at daily doses ranging from 5 to 21 mg/m2 for 5 days. 2-CdA eliminated leukemic blasts from the peripheral blood in 32 of 36 cases; however, bone marrow hypoplasia was seen only at daily dose levels > or = 15 mg/m2. We observed a total of 3 complete remissions: 1 at the 15 mg/m2/d dose level and 2 at the 21 mg/m2/d dose level; these responses persisted for 3, 2, and 3 months, respectively. Although prolonged myelosuppression would have been dose-limiting at 21 mg/m2/d for 5 days, the most important adverse effect was the development of a sensorimotor peripheral neuropathy. This reaction, whose onset was substantially delayed after completion of drug treatment, was observed in 2 of 5 patients at the 19 mg/m2/d level and in 4 of 4 evaluable patients at the 21 mg/m2/d level. Pathologically, this process was characterized by axonal degeneration and secondary demyelination. Other side effects included reactivation of a posttransplant Epstein-Barr virus-related lymphoma in 1 patient and tumor lysis syndrome. We conclude that the maximally tolerable dose of 2-CdA in adult patients (17 mg/m2/d for 5 days) in approximately twofold in excess of that previously reported in children and that the limiting toxic effect is a degenerative neuropathic disorder. We confirm that this drug has definite activity in AML, but the magnitude of this effect needs to be determined in larger numbers of patients who have received less extensive therapy. This agent deserves further evaluation in patients with both AML and acute lymphoblastic leukemia at these higher doses and perhaps as part of a preparative regimen for patients undergoing bone marrow transplantation.

No abstract

This study sought to identify major predictors of survival after second surgery. Methods: We collected clinical, pathological and radiographic data through a retrospective review of charts of 21 patients who underwent elective surgery for GBM recurrence at our institution in the past 6 years. Kaplan-Meier survival analysis and Cox proportional-hazards regression were employed to determine which variables significantly impacted survival time. Results Among variables examined, age, less than or equal to 50 (P equals 0.04), and chemotherapy treatment after second surgery (P equals 0.00057), were significant. Patients younger than 50, had a mean length of survival period of 14.7 months, while patients, age 50 or older, survived an average of 7.6 months. Patients who underwent chemotherapy after second resection survived an average of 12.6 months. Comparatively, mean survival period of patients who did not undergo chemotherapy was 3.7 months. The cumulative prognostic significance of age and post-reoperative chemotherapy treatment was determined to be 0.038 using Cox proportional-hazards regression modelling. Conclusion: The results confirm that younger patients survive longer after second surgery and that a second round of chemotherapy can prolong survival. Data from larger cohorts of patients is required to identify other important predictors.

Suppl 2-S14 confirmed GMFb:actin complexes. Subcellular localization of GMFb only changed with cytochalasin D. In primary embryonic forebrain cultures and RA treated cells, GMFb localized to axons and growth cones. Transfection of wild-type GMFb but not a Cterminal deletion mutant promoted process outgrowth. Phosphorylated GMFb (pGMFb) expression was found in adult brain and low grade gliomas, but not in embryonic brain or glioblastoma. Conclusions: GMFb binds directly to the actin cytoskeleton and is an ADF. GMFb''s phosphorylated form is highly expressed in the differentiated nervous system and low grade gliomas. Future studies will determine whether GMFb or pGMFb expression correlates with patient survival. Using the GMFb knockout mouse, the role of GMFb in glioma tumor invasion and signaling will be addressed in vivo.