High cure rates in Burkitt lymphoma and leukemia: a Northern Italy Leukemia Group study of the German short intensive rituximab-chemotherapy program

Abstract

We evaluate the long-term results of a prospective clinical study enrolling more than 100 adult patients with Burkitt lymphoma/leukemia. Depending on extent of disease, treatment consisted of six to eight rituximab infusions and four to six courses of intensive chemotherapy (attenuated in patients aged >55 years) with high-dose methotrexate, fractionated ifosfamide/cyclophosphamide, other drugs in rotation, and intrathecal chemoprophylaxis. One-hundred five patients were treated (median age 47 years, range 17-78 years); 48% had Burkitt leukemia, 25% were older than 60 years, 37% had an Eastern Cooperative Oncology Group performance score >1, and 14% were positive for human immunodeficiency virus. The complete response rate and 3-year overall and disease-free survival rates were 79%, 67% and 75%, respectively, ranging from 100% to 45% for survival (P=0.000) and from 100% to 60% for disease-free survival (P=0.01) in patients with low, intermediate and high adapted International Prognostic Index scores. In multivariate analysis, only age (≤ versus >60 years) and performance status (0-1 versus >1) retained prognostic significance, identifying three risk groups with overall and disease-free survival probabilities of 88% and 87.5%, 57% and 70.5%, 20% and 28.5% (P=0.0000 and P=0.0001), respectively. The relapse rate was only 7% in patients treated with an intercycle interval ≤ 25 days. This regimen achieved 100% curability in patients with low adapted International Prognostic Index scores (21% of total), and very close to 90% in patients aged ≤ 60 years with performance score 0-1 (48% of total). Rapid diagnosis of Burkitt lymphoma/leukemia with prompt referral of patients to prevent clinical deterioration, and careful supervision of treatment without chemotherapy delay can achieve outstanding therapeutic results. ClinicalTrials.gov ID, NCT01290120.

Figures

Figure 1.

Outline of the GMALL B-ALL/NHL2002 protocol (excluding prephase and rituximab administrations, the planned median intercycle time between chemotherapy day 1 of first and last A-B-C blocks was 23 and 22 days for the four and six cycle programs, respectively; other treatment details can be found in Online Supplementary Material S1B).

Figure 2.

Three-year probability of overall survival (OS) and disease-free survival (DFS). (A) OS: all patients, 0.67 (95% CI, 0.57 to 0.76). (B) DFS: all patients, 0.75 (95% CI, 0.63 to 0.84). (C) OS according to aIPI: low, 1.0; intermediate, 0.66 (95% CI, 0.51 to 0.77); high, 0.45 (95% CI, 0.26 to 0.62). (D) DFS according to aIPI: low, 1.0; intermediate, 0.69 (95% CI, 0.51 to 0.82); high, 0.60 (95% CI, 0.34 to 0.79).

Figure 3.

Three-year probability of overall survival (OS), disease-free survival (DFS), treatment-related mortality (TRM), and cumulative incidence of relapse (CIR) according to age and PS. (A) OS: age ≤60 and PS 0–1, 0.88 (95% CI, 0.75 to 0.94); age >60 or PS >1, 0.57 (95% CI, 0.42 to 0.70); age >60 and PS >1, 0.20 (95% CI, 0.03 to 0.47). (B) DFS: age ≤ 60 and PS 0–1, 0.875 (95% CI, 0.68 to 0.95); age > 60 or PS > 1, 0.705 (95% CI, 0.51 to 0.84); age > 60 and PS > 1, 0.285 (95% CI, 0.04 to 0.61). (C) TRM: age ≤ 60 and PS 0–1, 0.08 (95% CI, 0.03 to 0.20); age >60 or PS > 1, 0.25 (95% CI, 0.15 to 0.40); age > 60 and PS > 1, 0.40 (95% CI, 0.17 to 0.75). (D) CIR: age ≤ 60 and PS 0–1, 0.07 (95% CI, 0.02 to 0.21); age > 60 or PS > 1, 0.22 (95% CI, 0.10 to 0.43); age > 60 and PS > 1, 0.40 (95% CI, 0.12 to 0.87).