Stage IV adult sporadic Burkitt lymphoma/leukemia with complex bone marrow cytogenetics is associated with a very poor outcome

To the editor:

Adult Burkitt lymphoma/leukemia (BLL) is a rare, aggressive B-cell neoplasm with typical morphologic appearances. It is characterized by rapid proliferation of mature B cells (Ki67/MIB-1 staining ≥ 99%) and overexpression of c-Myc, which most commonly results from the translocation t(8;14) and less frequently from t(2;8) and t(8;22). Based on shared genetic and molecular features, the World Health Organization (WHO) classification now recognizes a lymphomatous and leukemic phase of this disease as a single entity.¹ 

Overall improved outcomes with remission rates of 65% to 100% and long-term survival of 40% to 80% have been reported following introduction of intensive multidrug regimens such as CODOX-M/IVAC and Hyper-CVAD.^2-4  Furthermore, the addition of rituximab (RTX), a monoclonal anti-CD20 antibody, has further increased responses.⁵  Recognized prognostic factors in BLL are old age, raised level of lactate dehydrogenase, poor performance status, and advanced stage disease and are used in some protocols to distinguish between low-risk and high-risk disease. Thus adjusting treatment intensity accordingly has proven beneficial.^2,4  Nevertheless, the majority of patients with advanced-stage disease achieve durable remissions if treated with these chemotherapy regimens. Recently, Mead et al reported the results of the MRC/NCRI LY10 trial.⁶  They found a 2-year progression-free survival (PFS) of 64% (95% confidence interval, 51%-77%) following treatment with CODOX-M/IVAC in 58 patients with BLL and did not identify clinical differences relating to the disease sites involved at presentation.

In contrast, we have observed a very poor outcome of adult patients with sporadic BLL and bone marrow involvement. Between 1998 and 2008, 13 patients were diagnosed within the Greater Manchester area in the United Kingdom. All patients were HIV-negative and received treatment with alternating CODOX-M/IVAC as per LY06 or LY10, with or without RTX.^4,6  The median age was 42 years (range, 19-69 years). Patients were diagnosed by a specialist hematopathology service according to WHO criteria. Patient characteristics are summarized in Table 1. There were no treatment-related deaths. Four patients had refractory disease and subsequently died of disease progression; 4 patients underwent stem cell transplantation (SCT); patients 1 and 7 had an allogeneic sibling, patient 9 had a matched unrelated donor SCT, and patient 6 had an autologous SCT. All patients relapsed and died within 2 months of completing therapy. The median overall survival from diagnosis was 5 months (range, 4-17 months) and median progression-free survival was 3 months (range, 0-12 months). For those who achieved remission (n = 9), median time from completion of therapy to relapse was less than 1 month (range 0-12).

We believe that bone marrow involvement with complex cytogenetics is most important in determining prognosis in this subgroup of BLL and would like to emphasize this observation. It would therefore be useful for the authors of the recently reported LY10 trial to perform a subgroup analysis for those patients with bone marrow involvement, and assess outcome with respect to their karyotypes. Furthermore, alternative treatment strategies are required for this subgroup of patients, as salvage treatments are rarely, if ever, successful in refractory or relapsed disease.^2,7,8  Further trials are needed to re-evaluate the role of SCT as well as other experimental treatments such as radioimmunotherapy (Zevelin) or molecular therapies targeting c-Myc.