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Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma: A Randomized Clinical Trial.

Publication ,  Journal Article
Park, JR; Kreissman, SG; London, WB; Naranjo, A; Cohn, SL; Hogarty, MD; Tenney, SC; Haas-Kogan, D; Shaw, PJ; Kraveka, JM; Roberts, SS ...
Published in: Jama
August 27, 2019

IMPORTANCE: Induction chemotherapy followed by high-dose therapy with autologous stem cell transplant and subsequent antidisialoganglioside antibody immunotherapy is standard of care for patients with high-risk neuroblastoma, but survival rate among these patients remains low. OBJECTIVE: To determine if tandem autologous transplant improves event-free survival (EFS) compared with single transplant. DESIGN, SETTING, AND PARTICIPANTS: Patients were enrolled in this randomized clinical trial from November 2007 to February 2012 at 142 Children's Oncology Group centers in the United States, Canada, Switzerland, Australia, and New Zealand. A total of 652 eligible patients aged 30 years or younger with protocol-defined high-risk neuroblastoma were enrolled and 355 were randomized. The final date of follow-up was June 29, 2017, and the data analyses cut-off date was June 30, 2017. INTERVENTIONS: Patients were randomized to receive tandem transplant with thiotepa/cyclophosphamide followed by dose-reduced carboplatin/etoposide/melphalan (n = 176) or single transplant with carboplatin/etoposide/melphalan (n = 179). MAIN OUTCOMES AND MEASURES: The primary outcome was EFS from randomization to the occurrence of the first event (relapse, progression, secondary malignancy, or death from any cause). The study was designed to test the 1-sided hypothesis of superiority of tandem transplant compared with single transplant. RESULTS: Among the 652 eligible patients enrolled, 297 did not undergo randomization because they were nonrandomly assigned (n = 27), ineligible for randomization (n = 62), had no therapy (n = 1), or because of physician/parent preference (n = 207). Among 355 patients randomized (median diagnosis age, 36.1 months; 152 [42.8%] female), 297 patients (83.7%) completed the study and 21 (5.9%) were lost to follow-up after completing protocol therapy. Three-year EFS from the time of randomization was 61.6% (95% CI, 54.3%-68.9%) in the tandem transplant group and 48.4% (95% CI, 41.0%-55.7%) in the single transplant group (1-sided log-rank P=.006). The median (range) duration of follow-up after randomization for 181 patients without an event was 5.6 (0.6-8.9) years. The most common significant toxicities following tandem vs single transplant were mucosal (11.7% vs 15.4%) and infectious (17.9% vs 18.3%). CONCLUSIONS AND RELEVANCE: Among patients aged 30 years or younger with high-risk neuroblastoma, tandem transplant resulted in a significantly better EFS than single transplant. However, because of the low randomization rate, the findings may not be representative of all patients with high-risk neuroblastoma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00567567.

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Published In

Jama

DOI

EISSN

1538-3598

Publication Date

August 27, 2019

Volume

322

Issue

8

Start / End Page

746 / 755

Location

United States

Related Subject Headings

  • Young Adult
  • Transplantation, Autologous
  • Stem Cell Transplantation
  • Risk
  • Proportional Hazards Models
  • Neuroblastoma
  • Male
  • Intention to Treat Analysis
  • Infant
  • Induction Chemotherapy
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Park, J. R., Kreissman, S. G., London, W. B., Naranjo, A., Cohn, S. L., Hogarty, M. D., … Diller, L. (2019). Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma: A Randomized Clinical Trial. Jama, 322(8), 746–755. https://doi.org/10.1001/jama.2019.11642
Park, Julie R., Susan G. Kreissman, Wendy B. London, Arlene Naranjo, Susan Lerner Cohn, Michael D. Hogarty, Sheena C. Tenney, et al. “Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma: A Randomized Clinical Trial.Jama 322, no. 8 (August 27, 2019): 746–55. https://doi.org/10.1001/jama.2019.11642.
Park, Julie R., et al. “Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma: A Randomized Clinical Trial.Jama, vol. 322, no. 8, Aug. 2019, pp. 746–55. Pubmed, doi:10.1001/jama.2019.11642.
Park JR, Kreissman SG, London WB, Naranjo A, Cohn SL, Hogarty MD, Tenney SC, Haas-Kogan D, Shaw PJ, Kraveka JM, Roberts SS, Geiger JD, Doski JJ, Voss SD, Maris JM, Grupp SA, Diller L. Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma: A Randomized Clinical Trial. Jama. 2019 Aug 27;322(8):746–755.
Journal cover image

Published In

Jama

DOI

EISSN

1538-3598

Publication Date

August 27, 2019

Volume

322

Issue

8

Start / End Page

746 / 755

Location

United States

Related Subject Headings

  • Young Adult
  • Transplantation, Autologous
  • Stem Cell Transplantation
  • Risk
  • Proportional Hazards Models
  • Neuroblastoma
  • Male
  • Intention to Treat Analysis
  • Infant
  • Induction Chemotherapy