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
Authors: Golos Aleksandra , Mądry Krzysztof , Lis Karol , Sobas Marta , Ożańska Agnieszka , Czemerska Magdalena , Hawrylecka Dorota , Stelmach-Gołdyś Agnieszka , Chromik Karolina , Pula Bartosz , Lech-Maranda Ewa , Gora Tybor Joanna 
Published: November 2019

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.

Disclosures
Golos: Novartis: Honoraria. Gora Tybor:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.