This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cheung, I. Y. Articles by Cheung, N.-K. V. Search for Related Content PubMed PubMed Citation Articles by Cheung, I. Y. Articles by Cheung, N.-K. V.

Early Molecular Response of Marrow Disease to Biologic Therapy Is Highly Prognostic in Neuroblastoma

Irene Y. Cheung, M. Serena Lo Piccolo, Brian H. Kushner, Nai-Kong V. Cheung

From the Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY.

Address reprint requests to Irene Y. Cheung, ScD, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; e-mail: cheungi{at}mskcc.org.

Purpose: A promising treatment strategy for stage 4 neuroblastoma patients is the repeated application of anti-GD2 immunotherapy after activating myeloid effectors with granulocyte-macrophage colony-stimulating factor (GM-CSF). To use early marrow response as a prognostic marker is particularly relevant for patients not likely to benefit from this therapy.

Patients and Methods: Eighty-six stage 4 neuroblastoma patients older than 1 year at diagnosis were classified in four clinical groups on protocol entry: complete remission or very good partial remission (n = 33), primary refractory (n = 33), secondary refractory (n = 10), and progressive disease (n = 10). Bone marrow samples collected before and following treatment were assayed for GD2 synthase mRNA by real-time reverse transcriptase polymerase chain reaction. Response and survival analyses were performed on posttreatment samples before the third cycle at 1.8 months from protocol entry.

Results: GD2 synthase mRNA was evident in pretreatment marrow samples of the four clinical groups (42%, 52%, 60%, and 80% of samples, respectively), with median transcript level of 10.0, 16.6, 26.5, and 87.2, respectively. This marker became negative following antibody plus GM-CSF in 77% of complete remission or very good partial remission, 45% of primary refractory, 25% of secondary refractory, and 0% of progressive disease group. Progression-free survival was statistically different between responder and nonresponder groups (P < .0001). Among patients with minimal residual disease, molecular responders had a significantly lower risk of disease progression at a median follow-up of 29.8 months (P = .0001).

Conclusion: GD2 synthase mRNA is a sensitive response marker of neuroblastoma in the bone marrow. It is particularly useful for minimal residual disease evaluation and may potentially be useful as an early predictor of resistance to antibody plus GM-CSF immunotherapy.

Supported in part by grants from the National Institutes of Health (CA095742) and the Robert Steel Foundation, Hope Street Kids, the Pediatric Cancer Foundation, and the Katie-Find-a-Cure Fund.

This article has been cited by other articles:

				I. Y. Cheung, Y. Feng, A. Vickers, W. Gerald, and N.-K. V. Cheung Cyclin D1, a Novel Molecular Marker of Minimal Residual Disease, in Metastatic Neuroblastoma J. Mol. Diagn., April 1, 2007; 9(2): 237 - 241. [Abstract] [Full Text] [PDF]

				M. V. Corrias, R. Haupt, B. Carlini, S. Parodi, L. Rivabella, A. Garaventa, V. Pistoia, and S. Dallorso Peripheral blood stem cell tumor cell contamination and survival of neuroblastoma patients. Clin. Cancer Res., October 1, 2006; 12(19): 5680 - 5685. [Abstract] [Full Text] [PDF]

				N.-K. V. Cheung, R. Sowers, A. J. Vickers, I. Y. Cheung, B. H. Kushner, and R. Gorlick FCGR2A Polymorphism Is Correlated With Clinical Outcome After Immunotherapy of Neuroblastoma With Anti-GD2 Antibody and Granulocyte Macrophage Colony-Stimulating Factor J. Clin. Oncol., June 20, 2006; 24(18): 2885 - 2890. [Abstract] [Full Text] [PDF]

				K. Swerts, B. De Moerloose, C. Dhooge, J. Vandesompele, C. Hoyoux, K. Beiske, Y. Benoit, G. Laureys, and J. Philippe Potential Application of ELAVL4 Real-Time Quantitative Reverse Transcription-PCR for Detection of Disseminated Neuroblastoma Cells Clin. Chem., March 1, 2006; 52(3): 438 - 445. [Abstract] [Full Text] [PDF]

				B. H. Kushner, K. Kramer, M. P. Laquaglia, S. Modak, K. Yataghene, and N.-K. V. Cheung In Reply: J. Clin. Oncol., September 1, 2005; 23(25): 6263 - 6263. [Full Text] [PDF]

				W. Janni, B. Rack, K. Lindemann, and N. Harbeck Detection of Micrometastatic Disease in Bone Marrow: Is It Ready for Prime Time? Oncologist, August 1, 2005; 10(7): 480 - 492. [Abstract] [Full Text] [PDF]

				T. Simon, B. Hero, A. Faldum, R. Handgretinger, M. Schrappe, D. Niethammer, and F. Berthold Consolidation Treatment With Chimeric Anti-GD2-Antibody ch14.18 in Children Older Than 1 Year With Metastatic Neuroblastoma J. Clin. Oncol., September 1, 2004; 22(17): 3549 - 3557. [Abstract] [Full Text] [PDF]