Analysis of Clonal Cytogenetic Abnormalities in 143 Patients with Secondary AML/MDS

Abstract 1473

The incidence of the secondary neoplasms has increased because of the rising numbers of long-term survivors of tumours. Secondary leukemias (sL) and secondary MDS (sMDS) are among the most common types of secondary tumours. Until recently prognosis in cases of sL and sMDS was considered less favorable than in leukemias de novo. Age at presentation and identified clonal cytogenetic abnormalities are among the most important independent prognostic factors in adult patients with leukemias.

It is obvious today that the presence of t(15;17)(q22;q12), t(8;21)(q22;q22), inv(16)(p13;q22)/t(16,16)(p13;q22) predicts a relatively favorable outcome, and in contrast the presence of inv(3)(q21q26)/t(3,3)(q21;q26), del(5q), −5, −7 or a complex karyotype (CK) with 3 or more abnormalities generally suggests a very poor prognosis. The monosomal karyotype (MK) defined as two or more distinct autosomal chromosome monosomies or one single autosomal monosomy in combination with at least one structural chromosomal abnormality is also considered as an adverse prognostic factor according to Breems D.A. et al., 2008; Medeiros B.C. et al., 2010 4-year overall survival in AML patients with MK is very low – 3–4%.

Therefore, the purpose of our analysis was to determine the frequency of “unfavorable” and “highly unfavorable” (according to Breems D.A. et al.) clonal cytogenetic abnormalities, identified in our laboratory in bone marrow samples of 143 patients with sL/sMDS and to compare it with the frequency of MK in leukemias and MDS de novo according to a published multicenter study (Haase D. et al., 2007; Medeiros B.C. et al., 2010; Grimwade D. et al., 2010).

All examined patients with sL/sMDS had solid tumors or lymphomas in anamnesis, for which they received chemotherapy and/or radiotherapy. sMDS was identified in 81 patients (54 patients – ≤5% blasts in bone marrow; in 27 patients – >5%). sAML was identified in 56 patients, sALL – in 1 patient, sCML – in 5 patients.

Abnormal karyotypes were observed in 42 (52%) sMDS patients, in 37 (66%) sAML patients, in all 5 sCML patients, in the only sALL patient.

The most frequent abnormality in sMDS was isolated monosomy 7: it was observed in 24.4% of the tested abnormal karyotypes. CK and MK are considerably more frequent in sMDS than in de novo MDS. CK occurred in 12 (30.9%) sMDS patients with abnormal karyotypes. Monosomies or deletions of the long arm of chromosome 7 were detected in 8 of 12 identified CK. Balanced translocations in sMDS were detected in only 9 (21%) of 42 karyotypes; no rearrangements involving 3q26, rather frequently occurred in de novo MDS, were registered. Very rare for de novo MDS t(1;7)(q10;q10) was found in 5 of these 9 cases. In general, chromosome 7 abnormalities (translocations, monosomies and/or deletions) were observed in 58.5% of sMDS cases with abnormal karyotypes. In de novo MDS chromosome 7 abnormalities were detected only in 21% of cases. On the contrary, del(5q) occurred more frequently in de novo MDS than in sMDS (30% versus 12.2%). Monosomic karyotypes occurred in 23.8% of sMDS patients with abnormal karyotypes. “Favorable” anomalies were presented in 5 of 37 sAML cases (13,5%) abnormal karyotypes. t(15;17), as a single anomaly, was detected in 3 patients; t(8;21) was detected in 2 cases. “Unfavorable” abnormalities, such as inv(3)(q21;q26)/t(3;3)(q21;q26) in complex karyotypes were observed in 4 cases. Chromosome 5 deletions in complex karyotypes were found in 5 cases, and only in 1 case - as a single anomaly. Other deletions, del(11)(q23), del(12)(p11), del(13)(q12), were found only as isolated anomalies. Complex karyotypes in sAML were observed in 40% (15 of 37) of cases with abnormal karyotypes, whereas in de novo AML CK occurred only in 18% of patients with abnormal karyotypes. Monosomic karyotypes occurred more often in patients with sAML - 27% compared to 13% of cases in de novo AML.

In conclusion, prognostically “unfavorable” and “highly unfavorable” cytogenetic abnormalities account for 60% and 25% of all cases with karyotype abnormalities in sAML/sMDS. Thus, our study shows that “unfavorable” and “highly unfavorable” cytogenetic abnormalities in leukemic clone occur more often in sAML/sMDS than in de novo AML/MDS.