Therapy-related acute myeloid leukemia and myelodysplasia after high-dose chemotherapy and autologous stem cell transplantation

Therapy-related myelodysplasia (t-MDS) and acute myeloid leukemia (t-AML) a fter high-dose chemotherapy (HD-CT) and autologous stem cell transplantatio n (ASCI) for malignant diseases have become an important problem, The actua rial risk has varied, but has often been high if compared to the risk after conventional therapy. Prior chemotherapy with large cumulative doses of al kylating agents is the most important risk factor. In addition, patient age end previous radiotherapy, particularly the use of total body irradiation (TBI) in the preparative regimen for ASCT, have been identified as risk fac tors, In 3 studies, patients transplanted with CD34(+) cells from periphera l blood after chemotherapy priming showed a higher risk of t-MDS or t-AML t han 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 chemothe rapy 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 patholog y of early cases of t-MDS after ASCT has often been neither diagnostic nor prognostic, but most patients presented chromosome aberrations, primarily d eletions 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 mo nths from diagnosis, and most of these presented a normal karyotype or a si ngle chromosome aberration. (Blood, 2000;95:3273-3279) (C) 2000 by The Amer ican Society of Hematology.