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

Abstract

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, cytogenetically 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 Ͻ 0.05 and 84% vs 45%, P Ͻ 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 radiotherapyassociated 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. Leukemia (2002) IntroductionEver since the mid-1970s, when the first case reports describing chromosomal abnormalities in treatment-related acute myeloid leukemias (t-AML) were published, 1,2 the cytogenetic features of t-AML and of therapy-associated myelodysplastic syndromes (t-MDS) have received much attention. 3,4 To date, two distinct karyotypic patterns that correlate with specific types of chemotherapeutic agents have emerged. Previous chemotherapy (CT) with alkylators (alk) has been strongly linked to the development of t-MDS/t-AML harboring unbal- anced changes, mainly whole or partial losses of chromosomes 5 and 7, often in complex, hypodiploid karyotypes, 5-9 whereas prior CT with DNA topoisomerase II inhibitors (topo II) has been associated with t-AML characterized by, in particular, translocations involving chromosome band 11q23 resulting in MLL gene rearrangements. 4,[10][11][12] It has been debated, but remains to be settled, whether prior radiotherapy (RT) alone or exposure to CT other than alk/topo II may correla...

Diffuse blastoid B-cell lymphoma: a histologically aggressive variant of t(14;18)-negative follicular lymphoma

“…Monosomy 7 is common in myelodysplastic syndrome and acute myeloid leukemia, particularly in therapy-related cases, in which it is considered as a poor prognostic factor. 36 Monosomy 7 also may be occasionally seen in acute lymphoblastic lymphoma/leukemia, but is not particularly associated with other subtypes of nonHodgkin's lymphoma. Therefore, the presence of monosomy 7 is a unique finding; however, its significance in our cases, if any, is not clear.…”

Risk stratification using a new prognostic score for patients with secondary acute myeloid leukemia: results of the prospective AML96 trial

“…8 Cytogenetically low-risk sAML patients were excluded, as they accounted for only n ¼ 4. Patients aged p60 years received intravenous double-induction chemotherapy containing cytosine arabinoside (100 mg/m 2 , days 1-8), mitoxantrone (10 mg/m 2 , days [4][5][6][7][8] and etoposide (100 mg/m 2 , days 4-8) ( ¼ MAV) in the first induction and cytosine arabinoside (2 Â 1000 mg/m 2 , days 1-5) and m-AMSA (100 mg/m 2 , days 1-5) ( ¼ MAMAC) during the second induction therapy. Patients with intermediate cytogenetic risk and an HLA-identical sibling donor were referred for allogeneic hematopoietic stem cell transplantation (HSCT).…”

“…3 Following chemo-and/or radiotherapy, tAML represents B10-20% of all the AML patients. 4 The risk associated with alkylating agents or radiation therapy increases with age, whereas the risk of developing tAML remains similar across all age groups after treatment with topoisomerase-II inhibitors. 5 Mutations induced by cytotoxic therapy, genetic predispositions that affect drug metabolism and DNA repair are implicated in the etiology of tAML.…”

Newly emerged isolated Del(7q) in patients with prior cytotoxic therapies may not always be associated with therapy-related myeloid neoplasms

“…7 Del(7q)/ − 7 presents in~50% of patients with therapy-related myeloid neoplasms and are often associated with prior exposure to alkylating agents or ionizing radiation. 1,[8][9][10][11][12][13] Any newly emerged cytogenetic abnormalities in patients with a prior history of cytotoxic therapies often raises the concern of development of therapy-related myeloid neoplasms, especially when the abnormalities include del(7q)/ − 7.…”