Characteristics and Outcomes of Patients with Lymphoma Who Developed Therapy-Related Acute Myeloid Leukemia or Myelodysplastic Syndrome - a Retrospective Analysis of the Polish Adult Leukemia Group

Background: Since several decades, the outcome of patients with lymphoma has improved. Unfortunately, because of that, the risk of therapy-related secondary neoplasms like acute myeloid leukemia (t-AML), and myelodysplastic syndrome (t-MDS) has increased. Still, little is known about the characteristics and outcome of these patients.

Materials and Methods: A retrospective study reviewed patients who developed t-AML or t-MDS between 2011-2018 during or after lymphoma treatment in 7 hematology departments of the Polish Adult Leukemia Group (PALG). Aim: The aim of the study was to assess the clinical characteristics of the patients, the latency to the diagnosis of t-AML/t-MDS, and overall survival (OS) defined as the time from diagnosis of t-AML/t-MDS to death of any cause or loss of follow up (FU), whichever occurred first.

Results: The analysis included 50 patients (22 women, 28 men). Primary diagnosis were multiple myeloma (MM) in 16 (32%), diffuse large B-cell lymphoma (DLBCL) in 12 (24%), Hodgkin lymphoma (HL) in 9 (18%), chronic lymphocytic leukemia in 7 (14%), mantle cell lymphoma in 3 (6%), and other lymphomas in 3 (6%) of patients. Median FU since secondary neoplasm diagnosis was 10 months (range: 0-70). The median number of treatment regimens was 3 (range: 1-6). Autologous hematopoietic cell transplantation (autoHCT) as a treatment for lymphoma/MM was performed in 11 (24%) patients. The median time from diagnosis of primary neoplasm to the development of t-AML/t-MDS was 58 months (range: 6-327). Patients who had autoHCT had longer latency period to development of secondary malignancy than those who did not (107 vs 46 months, p=.002). However, the OS did not differ between the groups. Thirty four patients (68%) was diagnosed with t-MDS, and 16 (32%) with t-AML. The median age at the time of diagnosis of t-MDS/t-AML was 65 (range: 30-92). Thirty two patients (64%) had performance status of ≥2 according to Eastern Cooperative Oncology Group (ECOG).- The most common subtypes of MDS according to World Health Organization (WHO) 2016 classification were: MDS with ring sideroblasts (8 pts), MDS, unclassifiable (7 pts), subtype with multilineage dysplasia (6 pts) and subtypes with excess of blasts 1 and 2 (each 5 pts). The majority of MDS patients were classified as intermediate risk according to international prognostic scoring system (IPSS) - 15 patients in intermediate-2 risk group and 10 in intermediate -1. Twelve patients (35%) had poor cytogenetic risk. After the diagnosis of t-MDS 17 patients (50%) received hypomethylating agents (HMA) and the other 17 only palliative treatment. The cytogenetics was available for 14 AML patients. Of these, 4 (28%) had poor cytogenetic risk (2 had complex, and 2 monosomal karyotype), 2 (14%) - favourable risk, 3 (21%) - intermediate-1 risk, and 5 (35%) - intermediate-2 risk according to European LeukemiaNet classification (ELN). Eight patients (50%) underwent induction therapy according to 3+7 regimen, 6 of them achieved CR, but they relapsed within 6 months. Allogeneic hematopoietic cell transplantation (alloHCT) was possible for 3 patients whereas 4 patients received HMA and 4 only palliative treatment. The median OS did not differ between the t-MDS and t-AML patients (12 vs 6 months, respectively, p=0.6). The main reasons for death were infections in 14 patients (47%) and disease progression in 10 (30%). In the univariate Cox proportional hazards analysis for the interval to the development of t-MDS/t-AML, we did not find significant relationship of the following factors: age of diagnosis (>65 vs ≤65, p=.1), type of lymphoma/MM (p=.2), the number of treatment lines for lymphoma/MM (p=.7), achievement of CR (p=.4), or use of purine analogs (p=.9). The analysis performed for OS did not reveal significant impact of the history of autoHCT for the lymphoma/MM, kind of treatment for t-MDS/t-AML, or alloHCT performed for secondary neoplasm.

Conclusions: t-MDS/t-AML after lymphoma treatment is associated with dismal prognosis mainly due to poor performance status at diagnosis which prevents from alloHCT setting, and high percentage of poor cytogenetics risk.