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Next Article 
Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3273-3279
REVIEW ARTICLE
Therapy-related acute myeloid leukemia and myelodysplasia after
high-dose chemotherapy and autologous stem cell transplantation
Jens Pedersen-Bjergaard,
Mette Klarskov Andersen, and
Debes H. Christiansen
From the Section for Hematology/Oncology, Cytogenetic Laboratory;
Department of Clinical Genetics, Juliane Marie Center, Rigshospitalet,
Copenhagen, Denmark.
Therapy-related myelodysplasia (t-MDS) and acute myeloid leukemia
(t-AML) after high-dose chemotherapy (HD-CT) and autologous stem cell
transplantation (ASCT) for malignant diseases have become an important
problem. The actuarial risk has varied, but has often been high if
compared to the risk after conventional therapy. Prior chemotherapy
with large cumulative doses of alkylating agents is the most important
risk factor. In addition, patient age and previous radiotherapy,
particularly the use of total body irradiation (TBI) in the preparative
regimen for ASCT, have been identified as risk factors. In 3 studies,
patients transplanted with CD34+ cells from peripheral
blood after chemotherapy priming showed a higher risk of t-MDS or t-AML
than patients transplanted with cells isolated from the bone marrow
without priming. To what extent this higher risk relates to the prior
therapy with a different contamination with preleukemic, hematopoietic
precursors of the CD34+ cells obtained by the 2 methods,
or is a direct result of chemotherapy priming, or of an increasing
awareness of these complications, remains to be determined. The latent
period from ASCT to t-MDS and t-AML has often been short, 12 months or
less in 27% of the patients. Bone marrow pathology of early cases of
t-MDS after ASCT has often been neither diagnostic nor prognostic, but
most patients presented chromosome aberrations, primarily deletions or
loss of the long arms of chromosomes 5 and 7. The prognosis was in
general poor, although 17% with indolent t-MDS survived more than 18 months from diagnosis, and most of these presented a normal karyotype
or a single chromosome aberration.
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