Modified Magrath Regimens for Adults with Burkitt and Burkitt-Like Lymphomas: Preserved Efficacy with Decreased Toxicity

Abstract

Burkitt and Burkitt-like lymphomas are rapidly growing tumors which require specialized therapy. Although intensive, multi-agent regimens have been effective in children, results are more variable in adults. Magrath et al. previously described a regimen that was highly effective in children and young adults. This phase II study of a modified Magrath regimen was designed to assess its efficacy in older adults and reduce treatment-related toxicity. Fourteen patients with Burkitt/Burkitt-like lymphoma and median age of 47 years were stratified into two categories: low-risk (normal LDH and a single focus of disease measuring less than 10 cm, 3 patients) and high risk (all other, 11 patients). Low-risk patients received three cycles of modified CODOX-M (cyclophosphamide, doxorubicin, adriamycin, vincristine with intrathecal methotrexate and cytarabine followed by high-dose systemic methotrexate, regimen A). High-risk patients received four alternating cycles of regimens A and B (A-B-A-B). Regimen B consisted of ifosfamide, cytarabine, etoposide and intrathecal methotrexate (IVAC). The modified treatment regimen was associated with no grade 3/4 neuropathy and only one episode of grade 3/4 mucositis. All patients completed protocol therapy and there were no treatment-related deaths. Twelve patients (86%, 90% CI: 61 97%) achieved a complete response; 1 patient achieved a PR and 1 patient died of progressive disease. Nine patients (64%) are alive and disease free at a median follow-up of 29 months. This modified Magrath regimen is effective and well-tolerated in a representative group of older adult patients.

Burkitt Lymphoma in Adults

“…Two subsequent small Phase II trials have utilized this regimen with minor modifications of drug dosing and intrathecal schedules, and have successfully enrolled greater numbers of older patients, demonstrating cure rates of approximately 64%. 19,20 These cure rates are substantially less than the initial Magrath publication, but still better than historical data with standard-dose regimens, endorsing this approach as a reasonable one for the majority of adult patients.…”

Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma

“…For reasons of comparison with other recently published treatment regimens of adult patients with BL/BLL, we have also reclassified our patients according to the UKLG risk score. 23 This score, which is equivalent to that used by investigators at NCI in trials 77-04 and 89-C-41 for both childhood and adult BL 9 and in Boston for adult BL/BLL, 24 showed that 89% of our patients could be classified as high-risk BL/BLL.…”

“…9 Remarkable improvements in the outcome of patients with high-risk disease, even in those with overt leukemic BL or CNS involvement, have been attributed to the addition of high-dose intravenous MTX and Ara-C to the treatment in children 3,4,6 as well as in adults. [8][9][10][11][12]23,24,37 At high dosages both drugs penetrate well the CNS, which may be one of the reasons of their apparent efficacy. The HOVON-27BL does not contain high-dose MTX and only low-dose Ara-C in the BEAM regimen.…”

“…In the present analysis, patients were retrospectively classified to the age-adjusted International Prognostic Index (aa-IPI), as well as a low-or high-risk group according to the risk grading based on Magrath et al 9 and used by the United Kingdom Lymphoma Group (UKLG) for BL 23 and others. 24 According to this grading system, patients with all of the following features present: (i) Ann Arbor stage I-II(E), (ii) tumor mass o10 cm, (iii) normal serum LDH, and (iv) WHO performance 0 or 1 were graded as low risk, all other patients as high risk. All patients gave informed consent for study participation according to the regulations of the Dutch health authorities.…”

Burkitt lymphoma in adults

“…The authors therefore suggested that this lower dose of methotrexate, which is associated with less toxicity, should be used in future regimens. The Boston group similarly reduced the intravenous methotrexate dose to 3 g/m 2 (Lacasce et al, 2004).…”