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 - PubMed (original) (raw)

Randomized Controlled Trial

. 2009 Mar 1;27(7):1007-13.

doi: 10.1200/JCO.2007.13.8925. Epub 2009 Jan 26.

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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. 2009.

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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.

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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.

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