Characteristics and outcome of therapy‐related myeloid neoplasms: Report from the Italian network on secondary leukemias

Abstract

Therapy-related myeloid neoplasms (t-MN) are a complication of cytotoxic treatment for primary tumors and autoimmune diseases. We report data on 277 t-MN patients, recruited between 1999 and 2013 by the Italian Network on Secondary Leukemias (104 retrospectively and 173 prospectively registered). Median age at t-MN diagnosis was 64 years (range, 21-87). Most frequent primary malignancies (PMs) were lymphoproliferative diseases and breast cancer. One hundred and thirty-three patients had received chemotherapy (CHT), 43 patients radiotherapy (RT), and 101 patients combined CHT/RT for PM. Median time between cytotoxic treatment and t-MN was 5.7 years, with t-MN following RT alone associated with significantly longer latency, compared to CHT or combined CHT/RT (mean, 11.2 vs. 7.1 years, P 5 0.0005). The addition of topoisomerase-II inhibitors to alkylating agents was associated with shorter latency compared to alkylating agents alone (median, 6 vs. 8.4 years, P 5 0.02). Median survival was 14.6 months from t-MN diagnosis, and was significantly longer in patients treated with allogeneic stem cell transplantation. Significant factors for survival at the multivariable analysis included age, adverse karyotype, and degree of anemia. Our data underline the prognostic importance of karyotype and age in t-MN, similar to de novo acute myeloid leukemia. Treatment approaches should not preclude the use of conventional treatments for younger t-MN patients, including allogeneic stem cell transplantation as potentially curative approach.Am. J. Hematol. 90:E80-E85,

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel

“…[257][258][259][260][261] Therapy may be compromised by a higher treatment-related morbidity and mortality. 259 There is still little prospective treatment data because these patients have often been excluded from frontline clinical trials.…”

Therapy-related myelodysplastic syndromes, or are they?

“…Also, in this study, neither age nor donor type was associated with worse outcomes [104]. Retrospective data from Fianchi et al showed that patients with t-MN who received HCT have better OS than those who did not (58.8 months for allogeneic SCT vs. 12.1 months, P b0.0001) [75]. Given the retrospective nature of the study, this advantage could be secondary to selection bias.…”

“…As expected, the IPSS-R risk distribution is in t-MDS/oligoblastic AML is skewed toward higher risk groups (high and very high groups) compared to their de novo counterparts (59.3% vs 23.1%) [16]. Fianchi et al identified age, degree of anemia, and karyotype as important predictors of survival and a simplified prognostic score can be formulated based on these 3 variables [75].…”

“…2) [74,75]. Genome-wide association studies have revealed genomic regions associated with increased risk of developing t-MN [76,77].…”

“…Patients with t-MDS have a higher frequency of abnormal karyotypes, with an increased prevalence of high-risk cytogenetics compared to de novo MDS [16,75,93]. Karyotypic abnormalities were reported in up to 77% of patients with t-MN (MDS and oligoblastic AML) with 50% of the patients having a complex karyotype.…”