Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series

Abstract

Therapy-related myelodysplasia and myeloid leukemia (t-MDS/t-AML) is a distinctive clinical syndrome occurring after exposure to chemotherapy (CT) or radiotherapy (RT).We report findings on 306 consecutive patients referred to our institution with morphologic review and cytogenetic analyses. Since 1972, 141 males and 165 females with a median age of 51 years (range, 3-83 years) at primary diagnosis and 58 years (range, 6-86 years) at secondary diagnosis were analyzed. Patients had been administered various cytotoxic agents, including alkylating agents (240 patients, 78%) and topoisomerase 2 inhibitors (115 patients, 39%).One hundred twenty-one (40%) had undergone CT alone, 43 (14%) had undergone RT alone, and 139 (45%) had undergone both modalities. At diagnosis of t-MDS/t-AML, 282 (92%) had clonal abnormalities involving chromosome 5 (n ‫؍‬ 63), chromosome 7 (n ‫؍‬ 85), chromosomes 5 and 7 (n ‫؍‬ 66), recurring balanced rearrangements (n ‫؍‬ 31), other clonal abnormalities (n ‫؍‬ 39), or normal karyotype (n ‫؍‬ 24). Abnormalities of chromosome 5, 7, or both accounted for 76% of all cases with an abnormal karyotype. Seventeen patients acquired t-MDS/t-AML after autologous stem cell transplantation, but no unique pattern of cytogenetic abnormalities was observed. Shorter latency was observed for patients with balanced rearrangements (median, 28 vs 67 months; P < .0001). Patients with acute leukemia were more likely to have balanced rearrangement than those with myelodysplasia (28% vs 4%; P < .0001). Median survival time after diagnosis of t-MDS/t-AML was 8 months; survival at 5 years was less than 10%. These data confirm and extend previous associations between clinical, morphologic, and cytogenetic findings in t-MDS/t-AML. (Blood. 2003;102:43-52)

Characterization and prognostic features of secondary acute myeloid leukemia in a population‐based setting: A report from the Swedish Acute Leukemia Registry

“…Median latency times between MPN and AML were between 7 and 8 years, whereas the median latency between the malignancy and t-AML was slightly longer compared to most previous studies with 5.8 years [8,18,24,25]. Median latency between a nonmalignant disease and t-AML is seldom reported, but was shown to be 14.3 years in our cohort.…”

Recurrent genetic defects on chromosome 7q in myeloid neoplasms

“…Interstitial deletion of the long arm of chromosome 5 (del(5q)), is the most common karyotypic abnormality in myeloid neoplasms, observed in 10-15% of patients with myelodysplastic syndromes (MDS) [1][2][3][4][5] or primary acute myeloid leukemia (pAML) [6,7], and in up to 40% of secondary myeloid leukemias (sAML) [8]. While a smaller fraction of more homogenous patients with the isolated del(5q) and classical 5q-syndrome show more favorable prognosis [9,10], the majority of myeloid neoplasms with del(5q) are morphologically heterogeneous, and have additional cytogenetic abnormalities [7,11,12].…”

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.…”