THERAPY-RELATED MYELODYSPLASIA AND ACUTE MYELOID-LEUKEMIA - CYTOGENETIC CHARACTERISTICS OF 115 CONSECUTIVE CASES AND RISK IN 7 COHORTS OF PATIENTS TREATED INTENSIVELY FOR MALIGNANT DISEASES IN THE COPENHAGEN SERIES

Citation
J. Pedersenbjergaard et al., THERAPY-RELATED MYELODYSPLASIA AND ACUTE MYELOID-LEUKEMIA - CYTOGENETIC CHARACTERISTICS OF 115 CONSECUTIVE CASES AND RISK IN 7 COHORTS OF PATIENTS TREATED INTENSIVELY FOR MALIGNANT DISEASES IN THE COPENHAGEN SERIES, Leukemia, 7(12), 1993, pp. 1975-1986
Citations number
67
Categorie Soggetti
Hematology,Oncology
Journal title
ISSN journal
08876924
Volume
7
Issue
12
Year of publication
1993
Pages
1975 - 1986
Database
ISI
SICI code
0887-6924(1993)7:12<1975:TMAAM->2.0.ZU;2-R
Abstract
Therapy-related acute myeloid leukemia (t-AML), often presenting as my elodysplasia (t-MDS), has become the most serious longterm complicatio n of cancer therapy and offers a unique opportunity to study chemical leukemogenesis. Seven cohorts of patients treated for six different ty pes of primary tumor have been followed closely for leukemic complicat ions, and 115 consecutive patients with t-MDS or t-AML, including 45 c ases from the cohorts, have been investigated cytogenetically at our i nstitutions during the past 16 years. In patients primarily treated wi th alkylating agents, the risk of t-MDS and t-AML increased by approxi mately 1% per year from 2 to at least 8 years after start of treatment . In most cases, the disease presented as t-MDS with loss of a whole c hromosome 5 or 7, or various parts of their long arms, and the leukemi as were of FAB-subtypes M1, M2, or M4. In patients treated with drugs targeting at DNA-topoisomerase II, such as etoposide, doxorubicin, 4-e pidoxorubicin, or mitoxantrone combined with drugs reacting directly w ith DNA, such as cisplatin or alkylating agents, the risk of leukemia increased much more steeply from only one year after start of therapy. These early onset cases often presented as overt leukemia of FAB-subt ypes M4 or M5 with balanced translocations to chromosome bands 11q23 a nd 21q22, whereas later onset cases often shared characteristics with cases observed after therapy with alkylating agents alone. Both alkyla tion of DNA and poisoning of DNA-topoisomerase II may result in develo pment of t-AML with different clinical and cytogenetic characteristics . There may be a synergistic leukemogenic effect between the two types of drug, and in patients with germ cell tumors treated with etoposide , cisplatin and bleomycin, reassessment suggested the risk of leukemia to increase exponentially with increasing doses of cisplatin and etop oside.