Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2009 Mar 1;27(7):1007-13.
doi: 10.1200/JCO.2007.13.8925. Epub 2009 Jan 26.

Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children's oncology group study

Katherine K Matthay  1 , C Patrick Reynolds, Robert C Seeger, Hiroyuki Shimada, E Stanton Adkins, Daphne Haas-Kogan, Robert B Gerbing, Wendy B London, Judith G Villablanca
Affiliations
Randomized Controlled Trial

Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children's oncology group study

Katherine K Matthay et al. J Clin Oncol. .

Erratum in

  • J Clin Oncol. 2014 Jun 10;32(17):1862-3

Abstract

PURPOSE We assessed the long-term outcome of patients enrolled on CCG-3891, a high-risk neuroblastoma study in which patients were randomly assigned to undergo autologous purged bone marrow transplantation (ABMT) or to receive chemotherapy, and subsequent treatment with 13-cis-retinoic acid (cis-RA). PATIENTS AND METHODS Patients received the same induction chemotherapy, with random assignment (N = 379) to consolidation with myeloablative chemotherapy, total-body irradiation, and ABMT versus three cycles of intensive chemotherapy. Patients who completed consolidation without disease progression were randomly assigned to receive no further therapy or cis-RA for 6 months. Results The event-free survival (EFS) for patients randomly assigned to ABMT was significantly higher than those randomly assigned to chemotherapy; the 5-year EFS (mean +/- SE) was 30% +/- 4% versus 19% +/- 3%, respectively (P = .04). The 5-year EFS (42% +/- 5% v 31% +/- 5%) from the time of second random assignment was higher for cis-RA than for no further therapy, though it was not significant. Overall survival (OS) was significantly higher for each random assignment by a test of the log(-log(.)) transformation of the survival estimates at 5 years (P < .01). The 5-year OS from the second random assignment of patients who underwent both random assignments and who were assigned to ABMT/cis-RA was 59% +/- 8%; for ABMT/no cis-RA, it was 41% +/- 8% [corrected]; for continuing chemotherapy/cis-RA, it was 38% +/- 7%; and for chemotherapy/no cis-RA, it was 36% +/- 7%.

Conclusion: Myeloablative therapy and autologous hematopoietic cell rescue result in significantly better 5-year EFS than nonmyeloablative chemo therapy; neither myeloablative therapy with [corrected] autologous hematopoietic cell rescue nor cis-RA given after consolidation therapy significantly improved OS.

PubMed Disclaimer

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
(A) Event-free survival (EFS) and overall survival (OS) for all patients (N = 539). (B) EFS and OS for patients with stage 4 disease (n = 466).
Fig 2.
Fig 2.
(A) Event-free survival for patients randomly assigned to continuing chemotherapy (CC; n = 190) versus autologous bone marrow transplantation (BMT; n = 189). P = .0434. (B) Overall survival for patients randomly assigned to CC (n = 190) versus BMT (n = 189). P = .3917 by log-rank test; P < .0001 by test of the log(−log(.)) transformation of the survival estimates at 5 years.
Fig 3.
Fig 3.
(A) Event-free survival for patients randomly assigned to 13-cis-retinoic acid (cis-RA) (n = 130) versus no cis-RA (n = 128). P = .1219. (B) Overall survival for patients randomly asigned to cis-RA (n = 130) versus no cis-RA (n = 128). P = .1946 by log-rank test; P = .0006 by test of the log(−log(.)) transformation of the survival estimates at 5 years.
Fig 4.
Fig 4.
(A) Event-free survival for patients who participated in both the first and second random assignments (autologous bone marrow transplantation + 13-cis-retinoic acid [cis-RA] [n = 50] versus continuing chemotherapy (CC) + no cis-RA [n = 53]). P = .0038. (B) Overall survival for patients who participated in both the first and second random assignments (autologous bone marrow transportation + cis-RA versus CC + no cis-RA) P = .0540.
See this image and copyright information in PMC

Comment in

References

    1. Matthay KK, Yamashiro D. Neuroblastoma. In: Bast RC, Kufe DW, Pollock RE, et al., editors. Cancer Medicine. London, United Kingdom, B.C.: Decker; 2000. pp. 2185–2197. in. pp.
    1. Dini G, Philip T, Hartmann O, et al. Bone marrow transplantation for neuroblastoma: A review of 509 cases—EBMT Group. Bone Marrow Transplant. 1989;4(suppl 4):42–46. - PubMed
    1. Philip T, Zucker JM, Bernard JL, et al. Improved survival at 2 and 5 years in the LMCE1 unselected group of 72 children with stage IV neuroblastoma older than 1 year of age at diagnosis: Is cure possible in a small subgroup? J Clin Oncol. 1991;9:1037–1044. - PubMed
    1. Stram DO, Matthay KK, O'Leary M, et al. Consolidation chemoradiotherapy and autologous bone marrow transplantation versus continued chemotherapy for metastatic neuroblastoma: A report of two concurrent Children's Cancer Group studies. J Clin Oncol. 1996;14:2417–2426. - PubMed
    1. Reynolds CP, Kane DJ, Einhorn PA, et al. Response of neuroblastoma to retinoic acid in vitro and in vivo. Prog Clin Biol Res. 1991;366:203–211. - PubMed

Publication types