Treatment outcomes in children with Burkitt lymphoma and L3 acute lymphoblastic leukemia treated using the lymphoma malignancy B protocol at a single institution

Abstract

Background: We compared the outcomes of patients with Burkitt lymphoma and French-American-British (FAB) L3 acute lymphoblastic leukemia treated using Lymphoma Malignancy B (LMB) or other treatment protocols.

Methods: Thirty-eight patients diagnosed between July 1996 and December 2007 were treated using LMB 96, and 22 patients diagnosed between January 1991 and May 1998 (defined as the early period) were treated using the D-COMP or CCG-106B protocols. We retrospectively reviewed their medical records and analyzed cumulative survival according to the treatment period by using Kaplan-Meier analysis.

Results: There were no intergroup differences in the distribution of age, disease stage, or risk group. The median follow-up period of the 33 live patients in the LMB group was 72 months (range, 36-170 months). Overall survival (OS) and event-free survival (EFS) of patients treated using LMB 96 were 86.8%±5.5% and 81.6%±6.3%, respectively, whereas OS and EFS of patients treated in the early period were 72.7%±9.6% and 68.2%±9.9%, respectively. In the LMB 96 group, OS of cases showing non-complete response (N=8) was 62.5%±17.1%, and OS of relapsed or primary refractory cases (N=6) was 33.3%±19.3%. Central nervous system (CNS) disease, high lactate dehydrogenase levels at diagnosis, and treatment response were significant prognostic factors.

Conclusion: Survival outcome has drastically improved over the last 2 decades with short-term, dose-intensive chemotherapy. However, CNS involvement or poor response to chemotherapy was worse prognostic factors; therefore, future studies addressing this therapeutic challenge are warranted.

Keywords: Burkitt lymphoma; L3 lymphocytic leukemia; Prognosis; Treatment outcome.

Fig. 1

LMB 96 protocol schedule [8]. Patients were stratified into 3 risk groups: A, B, and C, depending on stage, resection status, percentage of blasts in BM, and CNS involvement. Group A: Resected stage I and abdominal stage II. Group B: Patients not eligible for inclusion in group A or C. Group C: Patient with CNS involvement and more than 70% of blast in bone marrow. In the LMB 96 protocol, cranial irradiation was skipped and replaced with high-dose methotrexate (MTX) between consolidation phases in patients with CNS-positive disease.

Fig. 2

Outcome in patients treated using the LMB protocol. Three patients showed relapse (RL) after complete response (CR), and 2 of them responded to salvage therapy and are alive with no evidence of disease. Cases that did not show CR after the first consolidation chemotherapy included 5 cases of partial response (PR) and 3 refractory (ref) cases. One case of toxic death occurred during induction chemotherapy.

Fig. 3

Survival outcome of patients treated using LMB 89 (1996-2007) (A), and according to protocols used in the early period (1990-1998) (B).

Fig. 4

Event-free survival according to stage (A), treatment risk group (B), and LDH levels (C).

Fig. 5

Comparative analysis of event-free survival (EFS) according to the involvement of bone marrow. EFS of patients treated using the LMB protocol (A) and D-COMP or 106B protocols (B). In the early period, differences in EFS between groups with or without bone marrow involvement were significant (P=0.01). However, the differences between these groups were not significant in patients treated using the LMB protocol.

Fig. 6

Comparative analysis of event-free survival (EFS) according to the involvement of the central nervous system (CNS). EFS of patients treated using the LMB protocol (A) and D-COMP or 106B protocols (B). In either treatment group, there was no significant difference in EFS between groups with or without CNS involvement.