Advanced Stage, Elevated Ldh, Primary Sites, But Not Adolescent (A) Age (>= 15 Years) As Risk Factors For Disease Progression In Childhood (C) And Adolescent (A) Mature B-Nhl: Report Of The Fab/Lmb 96 International Trial

JOURNAL OF CLINICAL ONCOLOGY(2009)

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10032 Background: We recently reported the results in C & A with low risk (group A), intermediate risk (group B) and high risk (group C) mature B-NHL treated on FAB/LMB 96 (Gerrard et al, Br J Haematol, 2008; Patte et al, Blood, 2007; Cairo et al, Blood, 2007, respectively). Adolescent age (15–21 yrs) has historically been considered to be an independent risk factor for poor outcome in subsets of mature B-NHL (Hochberg/Cairo et al, Br J Haematol, 2008; Burkhardt et al, Br J Haematol 2005; Cairo et al, Br J Haematol, 2003). Methods: We analyzed the EFS of all pts treated on FAB/LMB 96 and the following risk factors were significant in a univariate and Cox multivariate analysis: age (<15 vs ≥15 yrs), stage I/II vs III/IV, primary sites, LDH <2 vs ≥2 NL and histology (DLBCL vs BL/BLL). Results: 1111 pts (15%, 15–21 years) were treated with group A (N = 132), group B (N = 744), and group C (N = 235) therapy. Five year EFS (CI95) for all, A, B, C pts was 86% (84%,88%), 98% (93%, 100%), 87%% (84%, 89%), and 79%% (73%,84%), respectively. Age (≥15 yrs), LDH ≥2NL, stage III/IV, and BM+/CNS+ and histology were significant univariate risk factors for decreased EFS (P<0.045, <0.0001, <0.0001, <0.0001, and <0.0001 respectively). Multivariate analysis demonstrated age ≥15 yrs and DLBCL histology were no longer independent significant risk factors (p = .82 and 0.08, respectively), but LDH (RR 2.0, p = .001), stage III/IV (RR 3.8, p<0.001), and primary sites including PMBL (RR 4.0, p<.001) and BM+/CNS+ (RR 2.8, p<0.001) were independent significant risk factors for poorer outcome. Conclusions: With the use of modern short but intense FAB-LMB 96 therapy, adolescent age is no longer a poor risk factor in children with mature B-NHL. The independent risk factors identified in this study (stage, LDH, primary site) for decreased EFS in C & A mature B-NHL will form the basis of the next risk adapted international pediatric mature B-NHL trial. No significant financial relationships to disclose.
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