## 1 Introduction  
Chronic lymphocytic leukemia (CLL) is the most common hematologic malignancy worldwide [1, 2], which is characterized by the accumulation of monoclonal CD5\({}^{+}\) mature B cells in the bone marrow, peripheral blood, and lymphoid organs, such as lymph nodes, and spleen [2, 3]. Increasing the number of mature B cells in the blood reduces the ability of the bone marrow to produce red blood cells (RBCs) and platelets (PT) in CLL patients [4]. According to reported evidence, there is a relationship between induction of oxidative stress and antileukemia chemotherapeutic agents [5, 6, 7]. Leukemic cells have increasedbasal oxidative stress, making them vulnerable to chemotherapeutic drugs that further elevate ROS levels [8; 9; 10]. There is no doubt that chemotherapy drugs cause inevitable damage to normal human cells. Therefore, the development of new avenues, such as gas plasma technology, may be promising for CLL treatment.  
In recent decades, scientists have proposed the ROS-generating action as the primary treatment modality of gas plasma technology, as this partially ionized gas generates a plethora of reactive oxygen and nitrogen species (ROS/RNS) simultaneously [11]. Besides the treatment of chronic wounds, which has entered clinical practice [12], the opportunity of cancer treatment came into researchers' focus in the past years [13]. It has been demonstrated that ROS/RNS produced by cold plasma can stimulate cellular signaling pathways, including JNK, p38 [14], and p53 [15], and can promote mitochondrial dysfunction and caspase activation, ultimately leading to apoptosis or non-apoptotic cell death [16; 17]. Another mode of action increasingly investigated is the generation of plasma-treated solutions (PTS) [18]. These plasma-oxidized liquids are dominated by the long-lived oxidation products of the initially short-lived reactive species. Among the long-lived oxidants are hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)), and nitrite (NO\({}_{2}\)\({}^{-}\)) and nitrate (NO\({}_{3}\)\({}^{-}\)), which have been attributed synergistic effects in anticancer activity [19].  
Perclinical reports are promising that cold plasma or PTS can effectively induce cell death in various types of solid tumors, including melanoma [20; 21; 22], glioblastoma [23], breast [24], lung [25], gastric [26], prostate [27], and colon cancers [28], partially in a selective manner. However, successful clinical application of cold-plasma-treated tumors showing an evident decline of tumor mass is still limited to case reports of head and neck cancer palliation [29], and an immunological dimension of this treatment has been suggested [30]. Apart from in vitro reports, the role of plasma medicine in hematological malignancies has not been reported.  
To this end, we exposed the whole blood of healthy donors and of CLL patients to cold plasma or to PTS ex vivo. While we did not investigate leukemia cells directly, we identified cold plasma and PTS components to reach the blood without disturbing main hematological parameters, being the first proof-of-concept studies on the adverse effects of cold plasma and PTS in this matrix, demonstrating the general feasibility of this approach.