Cytogenetic abnormalities and therapy-related myelodysplastic syndromes in rheumatic disease

Abstract

Objective: To describe the myelodysplastic syndromes (MDS) and cytogenetic abnormalities that occur in patients who have been treated with alkylating drugs for their rheumatic disease.

Methods: Patients with rheumatic disease who developed MDS after current or previous treatment with alkylating drugs were selected for evaluation by chart review and cytogenetic studies.

Results: Eight patients with rheumatic disease (mean age 56.9 years) developed MDS over the study period. Seven had received oral cyclophosphamide and 1 chlorambucil as their main immunosuppressive drug. The mean total cumulative dose of cyclophosphamide or chlorambucil was 118 gm and 6.5 gm, respectively, over a period of 2-10 years. The cytogenetic abnormalities included a deletion of all or part of chromosome 7 in 5 patients, while 4 had a deletion of part of the long arm of chromosome 5. Six of the patients have since died.

Conclusion: Large cumulative doses of cyclophosphamide and chlorambucil were associated with the development of MDS, the occurrence of abnormalities of chromosome 5 and/or chromosome 7 deletions, and a poor prognosis.