Advanced stage, increased lactate dehydrogenase, and primary site, but not adolescent age (≥ 15 years), are associated with an increased risk of treatment failure in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB LMB 96 study

Abstract

Purpose: Adolescents (age 15 to 21 years) compared with younger children with mature B-cell non-Hodgkin's lymphoma (NHL) have been historically considered to have an inferior prognosis. We therefore analyzed the impact of age and other diagnostic factors on the risk of treatment failure in children and adolescents treated on the French-American-British Mature B-Cell Lymphoma 96 (FAB LMB 96) trial.

Patients and methods: Patients were divided by risk: group A (limited), group B (intermediate), and group C (advanced), as previously described. Prognostic factors analyzed for event-free survival (EFS) included age (< 15 v ≥ 15 years), stage (I/II v III/IV), primary site, lactate dehydrogenase (LDH), bone marrow/CNS (BM/CNS) involvement, and histology (diffuse large B-cell lymphoma v mediastinal B-cell lymphoma v Burkitt lymphoma or Burkitt-like lymphoma).

Results: The 3-year EFS for the whole cohort was 88% ± 1%. Age was not associated as a risk factor for increased treatment failure in either univariate analysis (P = .15) or multivariate analysis (P = .58). Increased LDH (≥ 2 × upper limit of normal [ULN] v < 2 × ULN), primary site, and BM-positive/CNS-positive disease were all independent risk factors associated with a significant increase in treatment failure rate (relative risk, 2.0; P < .001, P < .012, and P < .001, respectively).

Conclusion: LDH level at diagnosis, mediastinal disease, and combined BM-positive/CNS-positive involvement are independent risk factors in children with mature B-cell NHL. Future studies should be developed to identify specific therapeutic strategies (immunotherapy) to overcome these risk factors and to identify the biologic basis associated with these prognostic factors in children with mature B-cell NHL.

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.

Overall experimental design of (A) group A therapy, (B) group B therapy, (C) group C therapy for CNS-positive patients, (D) group C therapy for CNS-negative patients. The number after the regimen name indicates the cycle number. ADR, doxorubicin; ARA C, cytarabine; COP, cyclophosphamide, vincristine, and prednisone; COPAD, cyclophosphamide, vincristine, prednisone, and doxorubicin; COPADM, COPAD with high-dose methotrexate (HD-MTX; 8 g/m2); CPM, cyclophosphamide; CYM, cytarabine and HD-MTX; CYVE, cytarabine 2 g/m2 and etoposide 100 mg/m2; IT, intrathecal; M1, maintenance cycle 1; M2, maintenance cycle 2; M3, maintenance cycle 3; M4, maintenance cycle 4; VP-16, etoposide.

Fig 2.

(A) Probability of overall survival and event-free survival of entire cohort. (B) Probability of event-free survival in patients treated with group A, group B, or group C therapy.

Fig 3.

Probability of event-free survival in patients treated in the French-American-British Mature B-Cell Lymphoma 96 (FAB LMB 96) study, grouped by age.

Fig 4.

Probability of event-free survival in patients treated in the French-American-British Mature B-Cell Lymphoma 96 (FAB LMB 96) study, stratified by (A) lactate dehydrogenase (LDH) at diagnosis (v ≥ 2 × institutional ULN), (B) bone marrow (BM)/CNS involvement, and (C) primary site. Abd/retro, abdominal/retroperitoneal; H&N, head and neck; Med, mediastinal; PN, peripheral node.