Burkitt lymphoma in adolescents and young adults: management challenges

Abstract

About one-half of all Burkitt lymphoma (BL) patients are younger than 40 years, and one-third belong to the adolescent and young adult (AYA) subset, defined by an age between 15 and 25-40 years, based on selection criteria used in different reports. BL is an aggressive B-cell neoplasm displaying highly characteristic clinico-diagnostic features, the biologic hallmark of which is a translocation involving immunoglobulin and c-MYC genes. It presents as sporadic, endemic, or epidemic disease. Endemicity is pathogenetically linked to an imbalance of the immune system which occurs in African children infected by malaria parasites and Epstein-Barr virus, while the epidemic form strictly follows the pattern of infection by HIV. BL shows propensity to extranodal involvement of abdominal organs, bone marrow, and central nervous system, and can cause severe metabolic and renal impairment. Nevertheless, BL is highly responsive to specifically designed short-intensive, rotational multiagent chemotherapy programs, empowered by the anti-CD20 monoclonal antibody rituximab. When carefully applied with appropriate supportive measures, these modern programs achieve a cure rate of approximately 90% in the average AYA patient, irrespective of clinical stage, which is the best result achievable in any aggressive lymphoid malignancy to date. The challenges ahead concern the following: optimization of management in underdeveloped countries, with reduction of diagnostic and referral-for-care intervals, and the applicability of currently curative regimens; the development of lower intensity but equally effective treatments for frail or immunocompromised patients at risk of death by complications; the identification of very high-risk patients through positron-emission tomography and minimal residual disease assays; and the assessment in these and the few refractory/relapsed ones of new monoclonals (ofatumumab, blinatumomab, inotuzumab ozogamicin) and new molecules targeting c-MYC and key proliferative steps of B-cell malignancies.

Keywords: Burkitt lymphoma; adolescents; outcome; treatment; young adults.

Figure 1

Typical case of endemic BL involving the facial bones in an African child (picture courtesy of RB, taken at Ocean Road Cancer Institute, Dar-es-Salaam, Tanzania, 2007).

Figure 2

Diagnostic pathology of BL: low magnification (×10, ×40) hematoxylin/eosin staining of BL sample involving the gastrointestinal tract, showing monotonous proliferation of medium-sized basophilic lymphoid cells punctuated by lightly colored macrophages (“starry sky” pattern) (A and B); immunohistochemistry, demonstrating staining for B-cell antigens including CD20 and the early CD10 antigen, with concurrent c-MYC and BCL6 expression and high proliferative rate (Ki67) (C–H).