Detection of abnormal pretransplant clones in progenitor cells of patientswho developed myelodysplasia after autologous transplantation

Secondary myelodysplastic syndromes (MDS) have been reported after autologo us transplantation. It is not known whether the MDS results from the pretra nsplant conventional-dose chemotherapy or from the high-dose chemotherapy ( HDC) used for the transplant procedure. We performed a multicenter, retrosp ective analysis of morphologically normal pretransplant marrow or stem cell specimens from 12 patients who subsequently developed myelodysplasia after HDC. To determine if the abnormal clone was present before HDC, we used fl uorescence in situ hybridization (FISH) to detect the cytogenetic markers o bserved at the onset of posttransplant MDS. Cryopreserved, pretransplant bo ne marrow, peripheral blood stem cell specimens, obtained at the time of ha rvest, or archival smears were used. Standard cytogenetic analysis had been performed pretransplant in four patients, showing a normal karyotype. In 9 of 12 cases, the same cytogenetic abnormality observed at the time of MDS diagnosis was detected by FISH in the pre-HDC specimens. Our findings suppo rt the hypothesis that, in many cases of posttransplant MDS, the stem cell damage results from prior conventional-dose chemotherapy and may be unrelat ed to HDC or the transplantation process itself. (C) 1999 by The American S ociety of Hematology.