Although considered an indolent disease, marginal zone lymphoma (MZL) often requires treatment. No standard therapy has been clearly established. Mitoxantrone has been effective in combination for indolent lymphomas, and is associated with considerably less cardiotoxicity and alopecia than doxorubicin. Thiotepa likewise does not induce alopecia, and does not display the immunosuppressive properties of fludarabine, which is also frequently employed as therapy for indolent lymphoma. The combination of thiotepa, vincristine, prednisone and mitoxantrone chemotherapy, with a scope similar to CHOP, has been demonstrated to be useful in elderly patients with diffuse large cell lymphoma (

Lichtman, et al, Am J Clin Oncol, 24(4):360–2, 2001
). The TOP-M regimen consists of thiotepa 7.5 mg/m2, mitoxantrone 7.5 mg/m2, vincristine and prednisone as per the CHOP regimen, with rituximab 375 mg/m2 all given on day 1 with a 21–28 day cycle (in accordance with resolution of cytopenias). Thiotepa and mitoxantrone doses were escalated by a total of 2.5 mg/m2 to a maximum of 20 mg/m2, respectively, based on nadir blood counts. We have retrospectively reviewed data on 12 patients with disseminated MZL treated with TOP-M either alone (n=4) or with rituximab (n=8). All subjects had advanced stage disease (4 with stage III, 8 with stage IV), 4 had B symptoms, and all patients clinically required treatment. Median age was 69, and 4 (33%) had an elevated LDH. Myeloid growth factor support was routinely applied, and anti-emetics were generally unnecessary. Central venous access was not required since neither thiotepa nor mitoxantrone are associated with tissue injury in the event of extravasation. Treatment was well tolerated, with only two episodes of hospitalization for fever. There was no cardiac toxicity. Eleven of 12 patients (92%) demonstrated clinical responses, with 9 CR/CRu (75%) and 3 PR (17%). Median duration of response has not been reached at with a range of 11 to 40 months of followup. TOP-M with rituximab is an easily administered, well tolerated and active regimen for disseminated marginal zone lymphoma, and may have utility for other indolent lymphomas.

Topics:
chemotherapy regimen, marginal zone b-cell lymphoma, mitoxantrone, prednisone, rituximab, thiotepa, vincristine, non-hodgkin's lymphoma, indolent, alopecia, cardiotoxicity

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2005, The American Society of Hematology
2004
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