Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976-1993 and on 5098 unselected cases reported in the literature 1974-2001.
To ascertain the frequency of treatment-related acute myeloid leukemias and myelodysplastic syndromes (t-AML/t-MDS) in an unselected series, we have identified all adult cases analyzed in our department from 1976 to 1993. Further aims were to compare karyotypic features of t-AML/t-MDS with de novo AML/MDS, in our material as well as in 5098 unselected, cyto- genetically abnormal, published cases, and to analyze associations between type of prior therapy and karyotype. Among our 372 AML and 389 MDS, 47 (13%) were t-AML and 62 (16%) were t-MDS. Clonal abnormalities were significantly more common in t-AML and t-MDS than in de novo disease (68% vs 50%, P < 0.05 and 84% vs 45%, P < 0.001, respectively). Among the available 4230 AML and 1629 MDS (the present series and published cases), 14% were t-AML and 15% were t-MDS. In t-AML/t-MDS, the number of anomalies and the ploidy levels differed significantly from de novo cases, with complex and hypodiploid karyotypes being more common in t-AML/t-MDS. In t-AML, unbalanced changes in general, t(1;3), der(1;7), 3p-, -5, 5q-, -7, 7q-, t(9;11), t(11;19), t(11q23), der(12p), -17, der(17p), -18, and -21 were significantly more frequent than in de novo AML. In t-MDS, -5, -7, 7q-, 13q-, der(17p), and -18 were significantly more common. Type of prior treatment correlated significantly with number of anomalies in t-AML and with ploidy levels in t-AML/t-MDS. The frequencies of several aberrations varied with type of therapy, eg, 5q- was more frequent in radiotherapy-associated t-MDS, monosomy 7 was more common in t-AML and t-MDS after treatment with alkylators, and t(11q23) in t-AML was associated with topoisomerase II inhibitors. Abnormalities significantly more common in de novo disease were +8 as a sole anomaly, balanced changes in general, t(8;21), t(9;22), t(15;17), inv(16), and t(21q22) in AML, and -Y, 5q-, and 20q- as sole anomalies and +8 in MDS. The results emphasize the strong association between previous genotoxic exposure and karyotypic features.
Mauritzson
N
N
Department of Hematology, Lund University Hospital, Sweden.
Albin
M
M
Rylander
L
L
Billström
R
R
Ahlgren
T
T
Mikoczy
Z
Z
Björk
J
J
Strömberg
U
U
Nilsson
P G
PG
Mitelman
F
F
Hagmar
L
L
Johansson
B
B
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D002869:Chromosome Aberrations; D004791:Enzyme Inhibitors / Q000009:adverse effects; D005260:Female; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D011878:Radiotherapy / Q000009:adverse effects; D012189:Retrospective Studies; D015996:Survival Rate; D059005:Topoisomerase II Inhibitors
D018906:Antineoplastic Agents, Alkylating; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors