Treatment

The treatment of BL is largely based upon the use of dose-intensive, multiagent chemotherapy regimens, which incorporate high-dose systemic methotrexate and cytosine arabinoside for control of potential CNS as well as systemic disease. Most of the regimens developed in the last 5-10 years have initially been used in pediatric populations, and subsequently adapted for treatment of adults. Overall, modern regimens have been highly effective, with long-term remissions reported in over 90% of the patients, even with advanced and apparently poor risk disease. Risk stratification has gained increasing importance in terms of determining therapy of appropriate intensity.

Several models for risk stratification have been developed in recent years. These are summarized in Table 56.5. For adults with BL, the risk factors described for patients entered into the NCI-89-C-41 protocol have been most widely applied.58 In the original description of this regimen in adults, patients with high-risk disease received alternating cycles of cyclophosphamide, vincristine, dox-orubicin, methotrexate (CODOX-M) and ifosfamide, etoposide, cytosine, arabinoside (IVAC) therapy (see below) whereas those with low-risk disease received a less intensive treatment protocol including CODOX-M chemotherapy only. In a subsequent European trial of a modified version of this protocol, similar risk stratification was used, in which low-risk patients were defined as having a normal LDH level, WHO performance status of 0 or 1, Ann Arbor stage I or II, and no residual tumor masses >10 cm in diameter.59 All other patients were regarded as high risk. The most widely used regimens for BL have initially been introduced in pediatric populations, and subsequently adapted for adults, usually with comparable results. Details of reports of some of these regimens are summarized in Table 56.6. Most of these regimens are highly myelosuppressive, with high rates of neutropenia and infectious complications, and require support with hematopoietic growth factors. Common aspects of these regimens include intensive induction therapy with multiple chemotherapy agents, relatively short treatment duration, absence of any proven benefit from prolonged or maintenance therapy, and the use of CNS prophylaxis and therapy. In view of the high proliferation rate of these tumors, the importance of rapid initiation of cycles of chemotherapy as early as possible after hematopoietic recovery has been realized, and the use of nonmyelosuppressive drugs at the time of neu-trophil nadir to maintain dose intensity is also a principle of several regimens.

The use of radiation therapy, even as a method of CNS treatment or prophylaxis, has been largely abandoned in the absence of data from randomized trials demonstrating its benefit compared with high-dose systemic methotrexate of cytarabine, coupled with

Table 56.5 Pregnostic risk factors for adult Burkitt's lymphoma

Berlin-Frankfurt-Munich (BFM) group56

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