Treatment-related myelodysplasia (t-MDS
IntroductionAlkylating agent therapy does not cure patients with indolent lymphoma and can result in late morbidity such as treatmentrelated myelodysplasia (t-MDS). 1 Alternatives to alkylators include biologic agents and purine nucleoside analogs, which have a low reported frequency of t-MDS. 2 The combination of fludarabine, mitoxantrone, and dexamethasone (FND) is an effective regimen for patients with indolent lymphoma. [3][4][5] Recently, we combined rituximab with FND, either concurrently (R-FND) or sequentially (FND3R), followed by interferon alpha (IFN-␣) maintenance, for patients with stage IV indolent lymphoma. Preliminary reports have described good short-term safety and efficacy of this program, including a 3-year failure-free survival rate of greater than 65% and a 3-year survival rate of 95%. 6,7 The current report describes the occurrence of t-MDS in 8 patients in this trial. The lymphoma protocol included FND for the majority of patients, either concurrently with rituximab or followed by rituximab. Patients also received IFN-␣ maintenance. The doses of FND were as follows: fludarabine 25 mg/m 2 intravenously days 1 to 3, mitoxantrone 10 mg/m 2 intravenously on day 1, and dexamethasone 20 mg orally or intravenously days 1 to 5, every 4 weeks for 8 cycles. In R-FND, rituximab 375 mg/m 2 was given intravenously on days 1 and 8 of course 1; in courses 2 to 5, it was given on day 1 only. Responding patients received maintenance with 3 million units/m 2 interferon alpha 2b subcutaneously daily on days 2 to 14 and dexamethasone 40 mg orally on days 1 to 3, given monthly for 1 year. In FND3R, rituximab 375 mg/m 2 was given intravenously once monthly for 6 doses, starting at month 12.
Patients and methods
PatientsPatients with follicular lymphoma without BCL2 gene rearrangement 8 received alternating triple therapy (ATT) with concurrent rituximab, followed by maintenance IFN-␣. ATT is a rotation of 3 regimens, CHOD-Bleo (cyclophosphamide, doxorubicin, vincristine, dexamethasone, bleomycin), ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin), and NOPP (mitoxantrone, vincristine, prednisone, procarbazine), for 12 courses (3-4 courses of each); doses have previously been reported. 4 Six doses of rituximab (375 mg/m 2 ) were included with ATT: 2 in courses 1 and 3 and 1 dose in courses 4 and 6.
Diagnosis of t-MDS and t-AMLThe diagnosis of t-MDS, using World Health Organization criteria, 9 was considered when the bone marrow contained excess blasts (Ͼ 5%) or was dysplastic or when unexpected cytopenias occurred. Marrow assessment was done pretreatment and every 3 to 6 months if initially positive. However, neither pretreatment nor follow-up cytogenetic monitoring was part of the study design; cytogenetics was performed only when MDS was The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 U.S.C. section 1734.
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