Failure to comply with treatment recommendations is very common in patients, but still poorly recognised by doctors. The current practice of using oral therapy on a large scale has been increasingly adopted for cancer patients. Chronic myeloid leukaemia (CML) is just such an example, where the introduction of taking new oral medications, the tyrosine kinase BCR-ABL inhibitors (TKI), has now revolutionised the treatment. The aim of our study was to assess treatment adherence in a group of Polish CML patients (a survey was conducted on 140 patient aged ≥18 years) treated with oral TKI (imatinib, dasatinib and nilotinib) taking into account the following variables: gender, age, education, place of residence, family circumstances and duration of therapy. In addition, we evaluated whether there is a relationship between how patients perceive their level of adherence to treatment recommendations with how subjectively the required dosage regimen was followed. Half the patients admitted to skipping at least one drug dose during the entire course of treatment and 39% did so within their last treatment month. Patients were also found to overestimate their own adherence assessment; around 60% of those missing at least 1 drug dose within the last treatment month believed they ‘always’ followed recommendations. The study demonstrated that adherence deteriorates over time. Furthermore, patients aged >65 years and patients suffering at least one comorbid disease had better adherence (p < 0.011). There were no differences in adherence among patients treated with imatinib, dasatinib and nilotinib (p = 0.249).

We retrospectively analyzed the rates of significant non-hematological adverse events (AEs) in 105 patients with chronic myeloid leukemia (CML) treated with second-generation tyrosine kinase inhibitor (TKIs) dasatinib or nilotinib used as second-line therapy in Polish tertiary care centers. Our analysis revealed that in a "real life setting," nearly half of patients with CML on second-generation TKIs suffer from therapy complications. Grade 2-5 non-hematological AEs were observed in 40% of patients treated with nilotinib and in 42% treated with dasatinib (p=0.83). Severe vascular events including peripheral artery occlusive disease (PAOD) occurred in 11% of patients on nilotinib and 4% on dasatinib (p=0.16). Pleural effusion occurred more often in the dasatinib group (26%) than in the nilotinib group (2%) (p=0.003). Importantly, most AEs occurred late, after more than 1 year of treatment. Since AEs are most often the reason for poor therapy compliance, careful monitoring of tolerability is crucial for an optimal treatment response in CML.

Background The standard first‐line treatment for primary mediastinal B‐cell lymphoma (PMBCL) patients is rituximab‐based immunochemotherapy; however, this is not due to the result of randomized clinical trials. Aims We retrospectively investigated 53 PMBCL patient outcomes treated either with R‐CHOP‐21 or DA‐EPOCH‐R‐28. The primary endpoint was overall survival (OS). Secondary endpoints were complete remission (CR), overall response rate (ORR), progression‐free survival (PFS), and treatment‐related complications. Results Treatment with R‐CHOP‐21 resulted in a 92.0% ORR (60% CR), while DA‐EPOCH‐R yielded a 92.6% ORR (70.4% CR). There were no differences in the occurrence of grade 3‐4 hematological adverse events, but grade 1‐2 cardiologic complications (P = .003) were observed more frequently in the DA‐EPOCH‐R arm. Median PFS and OS were not achieved. The differences in estimated 12‐month PFS in R‐CHOP and DA‐EPOCH‐R group (87% vs 73.9%) and OS (100% vs 92%) were insignificant. Patients treated with R‐CHOP‐21 and autologous hematopoietic stem cell transplantation (auto‐HSCT) had an improved OS (P = .03) but not PFS (P = .43) compared to those treated solely with R‐CHOP‐21. No differences in PFS or OS were observed between patients treated with R‐CHOP‐21/auto‐HSCT and DA‐EPOCH‐R. Conclusion The results of this study suggest that R‐CHOP‐21 may be an alternative to DA‐EPOCH‐R treatment for PMBCL patients.

Epidemiological studies on myelodysplastic syndromes (MDS) in Middle-Eastern Europe are scarce. No data about the demographic, clinical, and laboratory features of Polish MDS patients have been published. The aim of this study was to assess the epidemiological data and toxic exposure of Polish MDS patients and their association with hematological parameters and clinical outcomes. For 15 months, 966 living MDS patients were enrolled at 24 centers (12 university and 12 community hospitals). Follow-up was conducted for the next 55 months. The percentage of patients older than 80 years (16%) was between the values for Eastern and Western countries. In patients younger than 55 years, a female predominance was observed (male/female ratio 0.70:1 vs. 1.29:1; p < 0.001). Female patients had higher platelet counts (160 × 10⁹/l vs. 111 × 10⁹/l; p < 0.001). Patients exposed to chemicals were younger than patients without such exposure; their median age at MDS diagnosis was 66 vs. 70 years (p = 0.037). Smokers had significantly lower hemoglobin concentrations (8.6 vs. 9.1 g/dl; p = 0.032) and lower platelet counts (99 × 10⁹/l vs. 137 × 10⁹/l; p < 0.001) than nonsmokers. We provide the first description of the characteristics of Polish MDS patients. Females predominated in the group aged <60 years and they had higher platelet counts. The course of the disease is affected by toxic exposure and smoking.

Spleen tyrosine kinase (SYK) is an important oncogene and signaling mediator activated by cell surface receptors crucial for acute myeloid leukemia (AML) maintenance and progression. Genetic or pharmacologic inhibition of SYK in AML cells leads to increased differentiation, reduced proliferation, and cellular apoptosis. Herein, we addressed the consequences of SYK inhibition to leukemia stem-cell (LSC) function and assessed SYK-associated pathways in AML cell biology. Using gain-of-function MEK kinase mutant and constitutively active STAT5A, we demonstrate that R406, the active metabolite of a small-molecule SYK inhibitor fostamatinib, induces differentiation and blocks clonogenic potential of AML cells through the MEK/ERK1/2 pathway and STAT5A transcription factor, respectively. Pharmacological inhibition of SYK with R406 reduced LSC compartment defined as CD34+CD38−CD123+ and CD34+CD38−CD25+ in vitro, and decreased viability of LSCs identified by a low abundance of reactive oxygen species. Primary leukemic blasts treated ex vivo with R406 exhibited lower engraftment potential when xenotransplanted to immunodeficient NSG/J mice. Mechanistically, these effects are mediated by disturbed mitochondrial biogenesis and suppression of oxidative metabolism (OXPHOS) in LSCs. These mechanisms appear to be partially dependent on inhibition of STAT5 and its target gene MYC, a well-defined inducer of mitochondrial biogenesis. In addition, inhibition of SYK increases the sensitivity of LSCs to cytarabine (AraC), a standard of AML induction therapy. Taken together, our findings indicate that SYK fosters OXPHOS and participates in metabolic reprogramming of AML LSCs in a mechanism that at least partially involves STAT5, and that SYK inhibition targets LSCs in AML. Since active SYK is expressed in a majority of AML patients and confers inferior prognosis, the combination of SYK inhibitors with standard chemotherapeutics such as AraC constitutes a new therapeutic modality that should be evaluated in future clinical trials.