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Blood, Vol. 94 No. 5 (September 1), 1999:
pp. 1814-1819
Detection of Abnormal Pretransplant Clones in Progenitor Cells of
Patients Who Developed Myelodysplasia After Autologous Transplantation
Elisabetta Abruzzese,
James E. Radford,
Jeffrey S. Miller,
James
J. Vredenburgh,
P. Nagesh Rao,
Mark J. Pettenati,
Julia M. Cruz,
James J. Perry,
Sergio Amadori, and
David D. Hurd
From the Section on Hematology and Oncology, the Department of
Medicine, and the Section on Medical Genetics, the Department of
Pediatrics, Wake Forest University School of Medicine, Winston-Salem,
NC; the Blood and Marrow Transplant Program, the Division of
Hematology, Oncology and Transplantation, University of Minnesota
Cancer Center, Minneapolis, MN; the Adult Bone Marrow and Stem Cell
Transplant Program, the Division of Hematology-Oncology, the Department
of Medicine, Duke University, Durham, NC; and Universita' degli Studi
di Roma Tor Vergata, Rome, Italy.
Secondary myelodysplastic syndromes (MDS) have been reported after
autologous transplantation. It is not known whether the MDS results
from the pretransplant conventional-dose chemotherapy or from the
high-dose chemotherapy (HDC) used for the transplant procedure. We
performed a multicenter, retrospective 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 fluorescence in situ
hybridization (FISH) to detect the cytogenetic markers observed at the
onset of posttransplant MDS. Cryopreserved, pretransplant bone marrow,
peripheral blood stem cell specimens, obtained at the time of harvest,
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 support the hypothesis that, in many cases of posttransplant
MDS, the stem cell damage results from prior conventional-dose
chemotherapy and may be unrelated to HDC or the transplantation process itself.
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