Quantitation of GD2 synthase mRNA by real-time reverse transcriptase polymerase chain reaction: Clinical utility in evaluating adjuvant therapy in neuroblastoma Journal Article
| Authors: | Cheung, I. Y.; Lo Piccolo, M. S.; Kushner, B. H.; Kramer, K.; Cheung, N. K. V. |
| Article Title: | Quantitation of GD2 synthase mRNA by real-time reverse transcriptase polymerase chain reaction: Clinical utility in evaluating adjuvant therapy in neuroblastoma |
| Abstract: | Purpose: Minimal residual disease (MRD) is one of the final hurdles to cancer cure. Because therapy (myeloablation, immunotherapy, or differentiation) for MRD is applied at the time of clinical remission, objective surrogate markers are needed to gauge treatment efficacy. Patients and Methods: Using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) of GD2 synthase (β1,4-N-acetylgalactosaminyltransferase, EC 2.4.1.92) mRNA, we evaluated MRD response to anti-GD2 monoclonal antibody 3F8 adjuvant therapy, namely, one cycle of radio-immunotherapy using iodine-131 (131I)-3F8 plus one cycle of unlabeled 3F8 in 45 stage 4 neuroblastoma patients (newly diagnosed or without prior relapse) on the N7 protocol at Memorial Sloan-Kettering Cancer Center. The prognostic effect of MRD in their bone marrows before and after this phase of adjuvant therapy on progression-free survival (PFS) and overall survival (OS) was also analyzed. Results: Before 3F8 treatment, 24 of 45 patients were in complete remission (CR), 12 were in very good partial remission (VGPR), and nine were in partial remission (PR), according to criteria from International Neuroblastoma Staging System plus 131I-3F8 scan; 71% had detectable tumor cells in marrow by real-time RT-PCR. Of the 32 positive patients, 20 became negative after therapy, with a 63% efficacy. When patients were stratified by CR/VGPR versus PR, GD2 synthase positivity was prognostic when detected before 3F8-targeted therapy (PFS, P = .045 and OS, P = .010). Persistent marker positivity was also predictive of PFS (P = .035) and OS (P = .027). Patients who succumbed to the disease had transcript levels four times higher than those who remain alive. Conclusion: GD2 synthase mRNA is a useful surrogate marker for evaluating adjuvant treatment efficacy in neuroblastoma with prognostic potential. © 2003 by American Society of Clinical Oncology. |
| Keywords: | survival; adult; cancer survival; clinical article; controlled study; treatment outcome; aged; middle aged; survival analysis; unclassified drug; overall survival; genetics; disease course; antineoplastic agents; disease marker; adjuvant therapy; cancer staging; methodology; antineoplastic agent; neoplasm staging; reverse transcription polymerase chain reaction; bone marrow; enzymology; pathology; radiation exposure; monoclonal antibody; cancer regression; immunology; antibodies, monoclonal; myeloablative conditioning; immunotherapy; immunoglobulin g; iodine 131; radioactive iodine; iodine radioisotopes; neuroblastoma; messenger rna; minimal residual disease; neoplasm, residual; reverse transcriptase polymerase chain reaction; rna, messenger; disease progression; prediction and forecasting; predictive value of tests; remission; remission induction; real time polymerase chain reaction; radioimmunotherapy; monoclonal antibody 3f8; 3f8 antibody; synthetase; n-acetylgalactosaminyltransferases; humans; prognosis; human; male; female; priority journal; article; (n acetylneuraminyl) galactosylglucosylceramide n acetylgalactosaminyltransferase; (n-acetylneuraminyl)-galactosylglucosylceramide n-acetylgalactosaminyltransferase; n acetylgalactosaminyltransferase; beta 1,4 n acetylgalactosaminyltransferase |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 21 |
| Issue: | 6 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2003-03-15 |
| Start Page: | 1087 |
| End Page: | 1093 |
| Language: | English |
| DOI: | 10.1200/jco.2003.02.055 |
| PUBMED: | 12637475 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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