Clinical characteristics and prognosis of therapy-related hematological neoplasms: A single-center retrospective study

Abstract Objective: With expanding treatment modalities for solid and hematologic malignancies leading to improved patient survival, the incidence of therapy-related hematological neoplasms (t-HN) has risen significantly. However, the characteristics of t-HN remain poorly understood. This study aims to investigate the clinical features and prognosis of patients with t-HN through a retrospective analysis. Methods: Clinical data from 48 t-HN patients treated at the Department of Hematology, Hebei Medical University Second Hospital between January 2013 and December 2022 were retrospectively analyzed. Results: Among the 48 patients (30 female, 18 male), the median age at t-HN diagnosis was 58 years. Breast cancer was the most common primary malignancy (14/48), followed by lung cancer（4/48） and non-Hodgkin lymphoma（4/48）. Alkylating agent exposure was documented in 53.8% (14/26) of patients, and topoisomerase II inhibitor exposure in 61.5% (16/26). Primary malignancies were treated with combined chemotherapy and radiotherapy (n=20), chemotherapy alone (n=26), or radiotherapy alone (n=2). The median latency period from primary malignancy diagnosis to t-HN development was 38 months. t-HN subtypes included therapy-related acute myeloid leukemia (t-AML, n=31), therapy-related myelodysplastic syndromes (t-MDS, n=10), therapy-related acute lymphoblastic leukemia (t-ALL, n=5), therapy-related chronic myelomonocytic leukemia (t-CMML, n=1), and therapy-related mixed-phenotype acute leukemia (t-MPAL, n=1). Cytogenetic abnormalities were present in 70.4% (19/27) of t-AML and 60.0% (6/10) of t-MDS patients. MLLgene rearrangements were most frequent in t-AML, while deletions or partial deletions of chromosomes 5 and/or 7 predominated in t-MDS. BCR-ABL1 fusion was positive in 40.0% (2/5) of t-ALL patients.The complete response (CR) rate after first induction therapy was 68.2% (15/22) for t-AML patients, with a minimal residual disease (MRD) negativity rate of 26.7% (4/15). One patient with therapy-related acute promyelocytic leukemia (t-APL) achieved CR with ATO+ATRA targeted therapy. Both BCR-ABL1-positive t-ALL patients treated with VCD regimen plus tyrosine kinase inhibitor (TKI) achieved CR. Among 6 treated t-MDS patients, 3 (50.0%) rapidly progressed to AML. Collectively, t-MDS patients demonstrated poor therapeutic outcomes. The median overall survival (OS) for t-HN patients was 12 months, with a 3-year cumulative survival rate of 18.3%. Survival rates did not differ significantly between t-AML and t-MDS patients (P=0.999). Conclusion: t-HN is a rare group of hematologic malignancies secondary to prior solid or hematologic cancers, closely associated with the type and cumulative dose of cytotoxic agents, as well as the intensity and dose of radiotherapy. t-HN frequently harbors cytogenetic abnormalities, exhibits poor treatment response, and is associated with short median survival. Clinicians must carefully select cytotoxic regimens for cancer patients, weighing treatment benefits against the risk of developing t-HN.