Association of primary mediastinal B-cell lymphoma (PMBL) in children (C) and adolescents (A) with a significantly inferior prognosis: Final results of the FAB/LMB 96 trial

Abstract

10001 Background: Single pediatric cooperative group studies have demonstrated an EFS ranging from 65 - 75% in C & A with large cell lymphomas arising in the mediastinum (Lones/Cairo et al, J Clin Oncol, 2000; Burkhardt/Reiter et al, Br J Haematol, 2005; Seidman/Reiter et al, J Clin Oncol, 2003). Recently, Staudt and Shipp have independently demonstrated that following gene expression profiling by oligonucleotide microarray that PMBL resembles more like classical Hodgkin lymphoma than diffuse large B-cell lymphoma with enhanced NF-κB pathway gene expression (Rosenwald et al, J Exp Med, 2003; Abramson et al, Blood, 2005). It remains to be determined what the optimal therapy for C & A with PMBL is and if poor outcome subgroups can be identified. Methods: We analyzed the results of C & A with PMBL treated with group B therapy on FAB/LMB 96 (Patte/Cairo et al, Blood, 2007). Results: There were 528 patients with stage III/IV disease treated on group B therapy on FAB/LMB 96 resulting in a 2 yr EFS of 84% (CI95: 82–86%). Forty-two of these patients had PMBL; M/F: 26/16; 10 - 14 vs 15 -19 yrs: 28/14; and LDH < 2 vs ≥ 2 upper normal: 20/22. Response to COP reduction: 1 CR (100%), 33 IR (20–99%) and 7 NR (< 20%). There was no significant difference in EFS with respect to age, gender, COP response and initial LDH. 5 yr EFS and OS were 54% (CI95: 38–68%) and 73% (CI95: 56–84%), respectively. 5 yr EFS was significantly inferior compared to the remainder of the other patients with stage III disease treated on group B therapy (54%: CI95 38–68% vs 85%: CI95 81–88%) (p < 0.001). Conclusions: PMBL in C & A is associated with a significantly inferior EFS compared to other histological forms of stage III/IV mature B-NHL. Alternate treatment strategies including consideration of underlying biological differences need to be developed to improve EFS in C & A with this poor-risk sub-group of mature B-NHL. No significant financial relationships to disclose.