Prognostic significance of GAGE detection in bone marrows on survival of patients with metastatic neuroblastoma

Background. Previously, we reported the utility of GAGE as a molecular mark er for neuroblastoma (NB) and malignant melanoma in blood and bone marrow ( BM). Among patients with stage III melanoma rendered disease-free by surger y, GAGE expression was a strong prognostic factor for patient survival. Pro cedure. All patients with advanced NB diagnosed at > 1 year of age initiall y treated with protocol Nb (n = 24) and N7 (n = 38) at Memorial Sloan-Kette ring Cancer Center were included in this study. Their BM cells at 12, 18, a nd 24 months (median time after diagnosis) were evaluated for the presence of GAGE Results. GAGE positivity at 12 months (25%), when patients were sti ll on treatment, did not predict progression-free survival(PFS) and overall survival tram the time of sampling. Positivity at 18 months (29%) was asso ciated with poorer PFS and survival (but P > 0.05). By 24 months, the prese nce of GAGE (26%) was a very strong predictor of outcome (P < 0.001). When only remission marrows at 24 months were analyzed, PFS was 4.7-fold lower a mong GAGE-positive patients. Thirty-seven percent of N6 patients were posit ive for CAGE, in contrast to 17% of the patients in the more current regime n N7. Conclusions, The detection of GAGE by RT-PCR in marrow may have utili ty in molecular staging of patients in clinical remission. It may allow ear lier identification of patients at risk, such that appropriate intervention can be given before clinical relapse. CAGE may also serve as a surrogate e ndpoint for adjuvant treatment strategies, and to determine the duration of therapy. Med. Pediatr. Oncol. 35:632-634, 2000. (C) 2000 Wiley-Liss. Inc.