Cytogenetic abnormalities and therapy-related myelodysplastic syndromes in rheumatic disease.
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.


CONCLUSIONS
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.
University of Michigan Medical Center, Ann Arbor, USA.
C J
CJ
McCarthy
S
S
Sheldon
C W
CW
Ross
W J
WJ
McCune
D000328:Adult; D000368:Aged; D000477:Alkylating Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002699:Chlorambucil / Q000009:adverse effects / Q000627:therapeutic use; D002869:Chromosome Aberrations / Q000139:chemically induced; D025063:Chromosome Disorders; D002895:Chromosomes, Human, Pair 5; D002897:Chromosomes, Human, Pair 7; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced*; D012216:Rheumatic Diseases / Q000188:drug therapy* / Q000235:genetics
D000477:Alkylating Agents; D007166:Immunosuppressive Agents; D002699:Chlorambucil; D003520:Cyclophosphamide