High Level of CD8+PD-1+ Cells in Patients with Chronic Myeloid Leukemia Who Experienced Loss of MMR after Imatinib Discontinuation.

Treatment-free remission (TFR) is achieved in approximately half of chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors. The mechanisms responsible for TFR maintenance remain elusive. This study aimed to identify immune markers responsible for the control of residual CML cells early in the TFR (at 3 months), which may be the key to achieving long-term TFR and relapse-free survival (RFS) after discontinuation of imatinib. Our study included 63 CML patients after imatinib discontinuation, in whom comprehensive analysis of changes in the immune system was performed by flow cytometry, and changes in the BCR::ABL1 transcript levels were assessed by RQ-PCR and ddPCR. We demonstrated a significant increase in the percentage of CD8+PD-1+ cells in patients losing TFR. The level of CD8+PD-1+ cells is inversely related to the duration of treatment and incidence of deep molecular response (DMR) before discontinuation. Analysis of the ROC curve showed that the percentage of CD8+PD-1+ cells may be a significant factor in early molecular recurrence. Interestingly, at 3 months of TFR, patients with the e13a2 transcript had a significantly higher proportion of the PD-1-expressing immune cells compared to patients with the e14a2. Our results suggest the important involvement of CD8+PD-1+ cells in the success of TFR and may help in identifying a group of patients who could successfully discontinue imatinib.

Polycythemia vera and essential thrombocythemia of intermediate-age: A real-life, multicenter analysis of first-line treatment approach.

BACKGROUND: The treatment of patients with polycythemia vera (PV) and essential thrombocythemia (ET) is conducted according to well-defined risk stratification systems. We hypothesized that adherence to the guidelines, namely the decision to refrain from introducing cytoreduction in non-high-risk patients, is particularly difficult in patients diagnosed when they are between 40 and 59 years of age (intermediate-age group). OBJECTIVES: To evaluate the group of intermediate-age PV and ET patients, focusing on a first-line treatment approach adapted at diagnosis. MATERIAL AND METHODS: The study group consisted of 308 PV and ET patients recruited from 6 Polish Adult Leukemia Group (PALG) Centers. Patients were analyzed with respect to disease phenotype, risk group, treatment approach, cardiovascular (CV) risk factors, and occurrence of bleeding or thrombosis. RESULTS: Overall, 74% of patients in the study group were started on cytoreduction at diagnosis, including 70% of the low-risk PV patients and 85-89% of the non-high-risk ET patients. Factors influencing the decision to start the treatment included higher hemoglobin (Hb) concentration (in PV) as well as higher platelet (PLT) count, and the presence of CV risk factors (in ET). Introducing cytoreduction at diagnosis had no impact on thrombotic events. Patients harboring CV risk factors experienced a higher incidence of complications both at diagnosis and follow-up, independently of the treatment strategy. CONCLUSIONS: We underline the low adherence to recommendations in the treatment of intermediate-age PV and ET patients. Moreover, we emphasize the importance of CV risk factors and stress their impact on disease phenotype in this patient population.

Endothelial function in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors is not related to cardiovascular risk assessed by the Systematic Coronary Risk Estimation 2 algorithm.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) revolutionized treatment of chronic myeloid leukemia (CML), but are endowed with negative effects on endothelial function. OBJECTIVES: We aimed to characterize endothelial function in patients with CML treated with various TKIs. PATIENTS AND METHODS: A total of 48 patients diagnosed with chronic­phase CML treated with TKIs, such as imatinib, bosutinib, nilotinib, ponatinib, and asciminib were included. Endothelial function was assessed in the brachial artery and microcirculation based on flow­mediated dilation (FMD), reactive hyperemia peripheral arterial tonometry (RH­PAT) and flow­mediated skin fluorescence (FMSF). RESULTS: Reactive hyperemia index, FMD, reactive hyperemia response (RHR), normoxia oscillatory index, and hyperemic response index did not differentiate between the group of patients with low / moderate risk in the Systematic Coronary Risk Estimation 2 (SCORE2), SCORE2­Older Persons (SCORE2­OP), and those with high / very high risk scores. Among the patients with low / intermediate risk based on the SCORE2 algorithm, some had lower (below the first quartile) values of the endothelial parameters, reflecting impaired endothelial function, as compared with the high / very high risk patient population. Lower values of the endothelial function parameters were associated with overall long­term treatment with TKIs or ponatinib. Importantly, endothelial function assessed by FMSF (RHR) negatively correlated with total duration of TKI treatment, also after adjustment for age. CONCLUSIONS: Endothelial function in CML patients treated with TKIs was not related to cardiovascular risk based on SCORE2/SCORE2­OP algorithms but correlated with CML­specific factors, including duration of TKI treatment. FMSF­based assessment of skin microcirculation was a sensitive method for detecting the vascular effects of TKIs.

Management and outcome of patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era - analysis of the European LeukemiaNet Blast Phase Registry.

Blast phase (BP) of chronic myeloid leukemia (CML) still represents an unmet clinical need with a dismal prognosis. Due to the rarity of the condition and the heterogeneity of the biology and clinical presentation, prospective trials and concise treatment recommendations are lacking. Here we present the analysis of the European LeukemiaNet Blast Phase Registry, an international collection of the clinical presentation, treatment and outcome of blast phases which had been diagnosed in CML patients after 2015. Data reveal the expected heterogeneity of the entity, lacking a clear treatment standard. Outcomes remain dismal, with a median overall survival of 23.8 months (median follow up 27.8 months). Allogeneic stem cell transplantation (alloSCT) increases the rate of deep molecular responses. De novo BP and BP evolving from a previous CML do show slightly different features, suggesting a different biology between the two entities. Data show that outside clinical trials and in a real-world setting treatment of blast phase is individualized according to disease- and patient-related characteristics, with the aim of blast clearance prior to allogeneic stem cell transplantation. AlloSCT should be offered to all patients eligible for this procedure.

ROP-ET: a prospective phase III trial investigating the efficacy and safety of ropeginterferon alfa-2b in essential thrombocythemia patients with limited treatment options.

Interferon-based therapies, such as ropeginterferon alfa-2b have emerged as promising disease-modifying agents for myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET). Current ET treatments aim to normalize hematological parameters and reduce the thrombotic risk, but they do not modify the natural history of the disease and hence, have no impact on disease progression. Ropeginterferon alfa-2b (trade name BESREMi®), a novel, monopegylated interferon alfa-2b with an extended administration interval, has demonstrated a robust and sustained efficacy in polycythemia vera (PV) patients. Given the similarities in disease pathophysiology and treatment goals, ropeginterferon alfa-2b holds promise as a treatment option for ET. The ROP-ET trial is a prospective, multicenter, single-arm phase III study that includes patients with ET who are intolerant or resistant to, and/or are ineligible for current therapies, such as hydroxyurea (HU), anagrelide (ANA), busulfan (BUS) and pipobroman, leaving these patients with limited treatment options. The primary endpoint is a composite response of hematologic parameters and disease-related symptoms, according to modified European LeukemiaNet (ELN) criteria. Secondary endpoints include improvements in symptoms and quality of life, molecular response and the safety profile of ropeginterferon alfa-2b. Over a 3-year period the trial assesses longer term outcomes, particularly the effects on allele burden and clinical outcomes, such as disease-related symptoms, vascular events and disease progression. No prospective clinical trial data exist for ropeginterferon alfa-2b in the planned ET study population and this study will provide new findings that may contribute to advancing the treatment landscape for ET patients with limited alternatives. TRIAL REGISTRATION: EU Clinical Trials Register; EudraCT, 2023-505160-12-00; Registered on October 30, 2023.

Momelotinib vs. ruxolitinib in myelofibrosis patient subgroups by baseline hemoglobin levels in the SIMPLIFY-1 trial.

A key hallmark of myelofibrosis is anemia, which ranges from mild to severe based on hemoglobin levels. To more clearly define outcomes with the Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor momelotinib by anemia severity, we performed a descriptive post hoc exploratory analysis of the double-blind, randomized, phase 3 SIMPLIFY-1 study (NCT01969838; N = 432, JAK inhibitor naive, momelotinib vs. ruxolitinib); subgroups were defined by baseline hemoglobin: <10 (moderate/severe), ≥10 to <12 (mild), or ≥12 g/dL (nonanemic). Spleen and symptom results were generally consistent with those previously reported for the intent-to-treat population. In anemic subgroups, momelotinib was associated with higher rates of transfusion independence and reduced/stable transfusion intensity vs. ruxolitinib. No new or unexpected safety signals were identified. Overall, momelotinib provides spleen, symptom, and anemia benefits to JAK inhibitor-naive patients with myelofibrosis regardless of baseline hemoglobin level, and greater anemia-related benefits vs. ruxolitinib in patients with hemoglobin <12 g/dL.

Changes in bone marrow fibrosis during momelotinib or ruxolitinib therapy do not correlate with efficacy outcomes in patients with myelofibrosis.

Bone marrow fibrosis (BMF) is a pathological feature of myelofibrosis, with higher grades associated with poor prognosis. Limited data exist on the association between outcomes and BMF changes. We present BMF data from Janus kinase (JAK) inhibitor-naive patients from SIMPLIFY-1 (NCT01969838), a double-blind, randomized, phase 3 study of momelotinib vs ruxolitinib. Baseline and week 24 bone marrow biopsies were graded from 0 to 3 as per World Health Organization criteria. Other assessments included Total Symptom Score, spleen volume, transfusion independence status, and hemoglobin levels. Paired samples were available from 144 and 160 patients randomized to momelotinib and ruxolitinib. With momelotinib and ruxolitinib, transfusion independence was achieved by 87% and 44% of patients with BMF improvement of ≥1 grade and 76% and 56% of those with stable/worsening BMF; there was no association between BMF changes and transfusion independence for either arm (momelotinib, p = .350; ruxolitinib, p = .096). Regardless of BMF changes, hemoglobin levels also generally increased on momelotinib but decreased on ruxolitinib. In addition, no associations between BMF changes and spleen (momelotinib, p = .126; ruxolitinib, p = .407)/symptom (momelotinib, p = .617; ruxolitinib, p = .833) outcomes were noted, and no improvement in overall survival was observed with ≥1-grade BMF improvement (momelotinib, p = .395; ruxolitinib, p = .407). These data suggest that the anemia benefit of momelotinib is not linked to BMF changes, and question the use of BMF assessment as a surrogate marker for clinical benefit with JAK inhibitors.

The SNP rs460089 in the gene promoter of the drug transporter OCTN1 has prognostic value for treatment-free remission in chronic myeloid leukemia patients treated with imatinib.

Membrane transporters are important determinants of drug bioavailability. Their expression and activity affect the intracellular drug concentration in leukemic cells impacting response to therapy. Pharmacogenomics represents genetic markers that reflect allele arrangement of genes encoding drug transporters associated with treatment response. In previous work, we identified SNP rs460089 located in the promotor of SLC22A4 gene encoding imatinib transporter OCTN1 as influential on response of patients with chronic myeloid leukemia treated with imatinib. Patients with rs460089-GC pharmacogenotype had significantly superior response to first-line imatinib treatment compared to patients with rs460089-GG. This study investigated whether pharmacogenotypes of rs460089 are associated with sustainability of treatment-free remission (TFR) in patients from the EUROpean Stop Kinase Inhibitor (EURO-SKI) trial. In the learning sample, 176 patients showed a significantly higher 6-month probability of molecular relapse free survival (MRFS) in patients with GC genotype (73%, 95% CI: 60-82%) compared to patients with GG (51%, 95% CI: 41-61%). Also over time, patients with GC genotype had significantly higher MRFS probabilities compared with patients with GG (HR: 0.474, 95% CI: 0.280-0.802, p = 0.0054). Both results were validated with data on 93 patients from the Polish STOP imatinib study. In multiple regression models, in addition to the investigated genotype, duration of TKI therapy (EURO-SKI trial) and duration of deep molecular response (Polish study) were identified as independent prognostic factors. The SNP rs460089 was found as an independent predictor of TFR.

The Complexities of Diagnosis with Co-Existing Gaucher Disease and Hemato-Oncology-A Case Report and Review of the Literature.

Hematological abnormalities are the most common early symptoms of Gaucher disease (GD), with an increased risk of hematopoietic system malignancies reported in patients with GD. GD may be associated with monoclonal and polyclonal gammopathies; however, the mechanism of association of GD with multiple myeloma (MM) remains uncertain. Enzyme replacement therapy (ERT) has been shown to improve patients' cytopenia and it seems to facilitate anti-myeloma therapy in patients with co-occurring GD and MM. Although it is necessary to demonstrate the deficiency of enzymatic activity, as well as using genetic tests to finally diagnose GD, due to changes in the blood count image, bone marrow biopsy is still a frequent element of the GD diagnosis procedure. The diagnosis of GD is often delayed, mainly due to the heterogeneity of the histopathological picture of bone marrow biopsy or overlapping hematological abnormalities. Unrecognized and untreated GD worsens the response of a patient with an oncological disease to targeted treatment. We present a literature review, inspired by the case of a Caucasian patient initially diagnosed with MM and later confirmed with comorbid GD type 1 (GD1). We would like to point out the problem of underdiagnosis and delay in patients with GD.

Immediate Response to Brentuximab Vedotin in a Patient with Localized MF-LCT.

The large cell transformation of mycosis fungoides (MF-LCT) is a phenomenon observed in the advanced stages of mycosis fungoides (MF), which is the most common primary cutaneous lymphoma. The diagnostic criteria of MF-LCT are a minimum of 25% of large cells or a formation of microscopic nodules of them in the histological examination of skin samples. The clinical outcomes for MF-LCT are poor, as less than 20% of patients survive 5 years after diagnosis, but the expression of the CD30 antigen is generally considered to be associated with a better prognosis. We present a case of a patient with the diagnosis of MF with LCT, with an ulcerated tumor lesion approximately 30 × 20 cm in size on the right lateral abdominal wall. Brentuximab vedotin (BV) treatment was started due to the presence of the CD30 antigen, with a quick and impressive regression of the cutaneous lesion and tumor mass and good treatment tolerance. After follow-up of 20 months, patient remains in complete remission. A schedule of treatment for MF-LCT is directed mainly by the clinical stage of the disease and the comorbidities; the more severe clinical course of the disease requires systemic treatment. If at least 5% of the cells found in the skin lesions biopsy sample express the CD30 antigen, a beneficial effect of BV treatment could be expected. It may seem that the use of BV is one of the optimal therapeutic options in patients with advanced MF-LCT showing expression of CD30.

Avatrombopag increased platelet count in a patient with chronic immune thrombocytopenia refractory to multiple lines of treatment.

We present a case of a 30-year-old man suffering from chronic refractory immune thrombocytopenia (ITP) from early childhood. The patient was treated with all the therapeutic methods available in Poland, without platelet response: corticosteroids, intravenous immunoglobulins, splenectomy, cyclophosphamide, vinblastine, azathioprine, mycophenolate mofetil, rituximab, ciclosporin A, romiplostim, and eltrombopag. He continued to function persistently with deep thrombocytopenia, symptoms of hemorrhagic diathesis, and one episode of spontaneous subarachnoid bleeding. In April 2022, at the age of 29, the patient received avatrombopag. Within 4 weeks of starting avatrombopag 20 mg daily for 2 weeks and then 40 mg daily, he reached a platelet (PLT) count of 67 x 10 9 /l. In the next month, platelets fell below 30 x 10 9 /l, but subsequently the count increased to 47 x 10 9 /l, then to 52 x 10 9 /l, and remained stable. The symptoms of cutaneous hemorrhage diathesis have resolved completely since avatrombopag was introduced and did not reappear despite the decrease in PLT count.

Momelotinib long-term safety and survival in myelofibrosis: integrated analysis of phase 3 randomized controlled trials.

Momelotinib is the first inhibitor of Janus kinase 1 (JAK1) and JAK2 shown to also inhibit activin A receptor type 1 (ACVR1), a key regulator of iron homeostasis, and has demonstrated improvements in splenomegaly, constitutional symptoms, and anemia in myelofibrosis (MF). This long-term analysis pooled data from 3 randomized phase 3 studies of momelotinib (MOMENTUM, SIMPLIFY-1, and SIMPLIFY-2), representing MF disease from early (JAK inhibitor-naive) to late (JAK inhibitor-experienced) stages. Patients in the control arms (danazol in MOMENTUM, ruxolitinib in SIMPLIFY-1, and best available therapy in SIMPLIFY-2) could cross over to receive momelotinib at the end of the 24-week randomized period, and all patients could continue momelotinib treatment after the completion of these studies via an extended access protocol (XAP). Across these studies, 725 patients with MF received momelotinib; 12% remained on therapy for ≥5 years, with a median treatment exposure of 11.3 months (range, 0.1-90.4 months). The most common nonhematologic treatment-emergent adverse event (AE) occurring in ≥20% of patients was diarrhea (any grade, 27% and grade ≥3, 3%). Any-grade thrombocytopenia, anemia, and neutropenia occurred in 25%, 23%, and 7% of patients, respectively. The most common reason for momelotinib discontinuation was thrombocytopenia (4% discontinuation rate). The incidence of AEs of clinical importance (eg, infections, malignant transformation, peripheral neuropathy, and hemorrhage) did not increase over time. This analysis of one of the largest randomized trial databases for a JAK inhibitor to date in MF demonstrated a consistent safety profile of momelotinib without long-term or cumulative toxicity. These trials were registered at www.clinicaltrials.gov as: MOMENTUM (#NCT04173494), SIMPLIFY-1 (#NCT01969838), SIMPLIFY-2 (#NCT02101268), and XAP (#NCT03441113).

Immune Thrombocytopenia: Characteristics of the Population and Treatment Methods-One-Center Experience.

BACKGROUND: Immune thrombocytopenia (ITP) is a disease with variable clinical presentation, requiring different treatment lines. AIM: The study aimed to characterize a group of ITP patients in terms of clinical picture and disease treatment, as well as to present the current standard of care of ITP in Poland, in the context of local and international guidelines. MATERIALS AND METHODS: The study included adult patients diagnosed with ITP, treated at the Department of Haematology of the Jagiellonian University Hospital in Krakow from January 2006 to January 2021. Patient characteristics, clinical manifestation of ITP, and treatment methods were analyzed. RESULTS: A total of 245 ITP patients were included. 57.1% of them were asymptomatic at diagnosis. Most common symptoms were thrombocytopenic purpura (68.2%), followed by epistaxis (34.7%) and gum bleeds (19.2%). Life-threatening bleedings were noted in three cases (1.2%). 23.2% of patients did not require treatment. Prednisone was the most commonly used first-line therapy (75.5% of patients). Treatment with eltrombopag and romiplostim was used in 40.4 and 8.5% of patients requiring second-line therapy, respectively. 14.3% of all patients ultimately underwent splenectomy, including 51.5% of those who needed second-line treatment. The initial response rate was 74.3%; however, post-splenectomy relapses occurred in 22.9% of patients. CONCLUSIONS: ITP is a disease of mild clinical course, often asymptomatic. Chronic disease often requires multiple treatment lines and balancing between bleeding risk and treatment toxicity, based on individual risk-benefit assessment. Local access restrictions to thrombopoietin receptor agonists determined the treatment strategy.

Analysis of Predictive Factors for Early Response to Ruxolitinib in 320 Patients with Myelofibrosis From the Polish Adult Leukemia Group (PALG) Registry.

INTRODUCTION: Ruxolitinib is widely used in myelofibrosis (MF). However, some patients do not optimally respond and require more efficacious treatment. Our analysis aimed to establish predictors of ruxolitinib response. PATIENTS AND METHODS: We designed a multicenter, retrospective analysis of the efficacy of ruxolitinib treatment in patients with MF in 15 Polish hematology centers. As responses to ruxolitinib occur within the first 6 months, we used this point to evaluate the efficacy of treatment. Symptoms response was defined as ≥50% reduction of the MF constitutional symptoms assessed by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). Spleen response was defined as ≥50% reduction of the difference between the spleen's baseline length and the upper limit norm measured by ultrasonography. RESULTS: 320 MF patients were enrolled. At 6 months of therapy, the spleen response was detected in 140 (50%) patients, and symptoms response in 241 patients (76%). Multivariable analysis identified leukocytosis <25 G/L (OR 2.06, 95%CI: 1.12-3.88, P = .0200), and reticulin fibrosis MF 1 (OR 2.22, 95%CI: 1.11-4.46, P = .0249) contributed to better spleen response. The time interval between MF diagnosis and ruxolitinib administration shorter than 3 months, and platelets ≥150 G/L (OR 1.69, 95% CI 1.01-2.83, P = .0466) influenced symptoms response. CONCLUSION: Establishing predictive factors for ruxolitinib response is particularly important given the potential for new therapies in MF. In patients with a low likelihood of responding to ruxolitinib, using other JAK inhibitors or adding a drug with a different mechanism of action to ruxolitinib may be of clinical benefit.

Side effects of treatment with tyrosine kinase inhibitors in patients with chronic myeloid leukemia and the occurrence of anxiety symptoms. / Skutki uboczne leczenia inhibitorami kinaz tyrozynowych u pacjentów chorych na przewlekla bialaczke szpikowa a wystepowanie objawów lekowych.

OBJECTIVES: The study aims to check whether individual side effects of treatment with TKIs in patients suffering from CML may contribute to the occurrence of anxiety symptoms. In addition, it was decided to check whether there were any relationships between age, gender, duration of treatment, and the intensity of anxiety, divided by the occurrence of individual side effects. METHODS: The study involved 91 patients and was conducted at the Hematology Clinic of the University Hospital in Krakow. The following questionnaires were used: created by the author, David Goldberg Questionnaire GHQ-28, and the four-dimensional 4DSQ Questionnaire. RESULTS: The most frequently mentioned side effects of treatment were bone and joint pain, muscle cramps and pain, water retention, and fatigue. The mean duration of the disease was ten years. Our research showed that fatigue, nausea/indigestion, frequent infections, bone and joint pain, abdominal pain, and loss of appetite were the most common side effects of TKI treatment, which resulted in increased anxiety symptoms. CONCLUSIONS: The work of doctors, psychologists, and pharmaceutical companies on reducing/alleviating side effects may in the future affect a better quality of life for these patients. Early detection of severe anxiety and taking appropriate steps can prevent the emergence of more significant disorders. In addition, several years of attempts to discontinue treatment with some TKIs (imatinib and nilotinib) in patients who achieve a profound molecular response may improve their mental condition.

Label-free testing strategy to evaluate packed red blood cell quality before transfusion to leukemia patients.

Patients worldwide require therapeutic transfusions of packed red blood cells (pRBCs), which is applied to the high-risk patients who need periodic transfusions due to leukemia, lymphoma, myeloma and other blood diseases or disorders. Contrary to the general hospital population where the transfusions are carried out mainly for healthy trauma patients, in case of high-risk patients the proper quality of pRBCs is crucial. This leads to an increased demand for efficient technology providing information on the pRBCs alterations deteriorating their quality. Here we present the design of an innovative, label-free, noninvasive, rapid Raman spectroscopy-based method for pRBCs quality evaluation, starting with the description of sample measurement and data analysis, through correlation of spectroscopic results with reference techniques' outcomes, and finishing with methodology verification and its application in clinical conditions. We have shown that Raman spectra collected from the pRBCs supernatant mixture with a proper chemometric analysis conducted for a minimum one ratio of integral intensities of the chosen Raman marker bands within the spectrum allow evaluation of the pRBC quality in a rapid, noninvasive, and free-label manner, without unsealing the pRBCs bag. Subsequently, spectroscopic data were compared with predefined reference values, either from pRBCs expiration or those defining the pRBCs quality, allowing to assess their utility for transfusion to patients with acute myeloid leukemia (AML) and lymphoblastic leukemia (ALL).

Assessment of factors affecting the mental condition of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. / Ocena czynników wplywajacych na stan psychiczny chorych na przewlekla bialaczke szpikowa leczonych inhibitorami kinaz tyrozynowych.

OBJECTIVES: The aim of the study was to make a general assessment of mental health, including signs of somatization, depression, anxiety, and functional disorders, in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) and to assess the impact of factors such as the duration of the disease, side effects of therapy, age, and gender on the occurrence of the above-mentioned disorders. Another goal was to identify patients at risk of developing mental disorders. METHODS: The study involved 91 patients and was conducted at the Hematology Clinic of the University Hospital in Krakow. The following questionnaires were used to assess mental health: survey created by the author, David Goldberg's questionnaire GHQ-28, and the fourdimensional 4DSQ, measuring four dimensions of the mental condition. RESULTS: The average level of the mental condition of the studied group was demonstrated. 29 people with mental disorders were identified. Women and people living alone obtained worse results in almost all dimensions of the questionnaires. The analysis revealed that factors such as age, number of side effects and gender significantly affect mental disorders in the studied group. A significant and positive correlation has been found between the number of side effects and the presence of somatization signs. Mediocre correlations occurred between age and mental disorders and all dimensions of the GHQ-28. CONCLUSIONS: The obtained results indicate that attempts should be made to reduce side effects among CML patients. Visiting the psychologist to work on the acceptance of the disease, psychoeducation, behavioral therapy, and contact with a psychiatrist to consider the introduction of pharmacotherapy is recommended. All of these methods may improve a patient's quality of life.

Impact of genetic polymorphisms of drug transporters ABCB1 and ABCG2 and regulators of xenobiotic transport and metabolism PXR and CAR on clinical efficacy of dasatinib in chronic myeloid leukemia.

Introduction: Functional single-nucleotide polymorphisms (SNPs) in genes regulating cellular uptake, elimination, and metabolism of xenobiotics may potentially influence the outcome of chronic myeloid leukemia (CML) patients treated with BCR-ABL1 tyrosine kinase inhibitors (TKI). Dasatinib, a second-generation TKI, is a substrate of the ABC-superfamily xenobiotic transporters ABCB1 (MDR1, Pg-P) and ABCG2 (BCRP). Pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3) are involved in the control of expression of ABCB1 and ABCG2. Aim of the study: In this study, we assessed the impact of inherited variants in ABCB1, ABCG2, PXR, and CAR genes on dasatinib efficacy and toxicity in CML. Materials and methods: Sixty-one tagging SNPs in ABCB1, ABCG2, PXR, and CAR genes were analyzed by real-time quantitative PCR with specific probes in 86 CML patients who failed imatinib therapy. Results: We found the associations between SNPs rs7787082 (ABCB1, OR = 0.2; 95% CI = 0.06-0.66, p = 0.008), rs12505410 (ABCG2, OR = 3.82; 95% CI = 1.38-10.55; p = 0.010), and rs3114018 (ABCG2, OR = 0.24; 95% CI = 0.08-0.71; p = 0.010) and the probability of achieving CCyR. Furthermore, progression-free survival (PFS) was significantly influenced by SNPs rs3732357 (HR = 0.2, 95% CI = 0.26-0.70; p = 0.001), rs3732360 (HR = 0.59; 95% CI = 0.38-0.93; p = 0.020), rs11917714 (HR = 0.58; 95% CI = 0.36-0.92; p = 0.020), and rs3732359 (HR = 0.57; 95% CI = 0.36-0.91; p = 0.024) in PXR; rs2307418 (HR = 2.02; 95% CI = 1.19-3.43; p = 0.048) in CAR; and rs2235023 (HR = 2.49; 95% CI = 1.13-5.50; p = 0.011) and rs22114102 (HR = 1.90; 95% CI = 1.00-3.63; p = 0.028) in ABCB1. Moreover, overall survival (OS) was impacted by rs3842 (HR = 1.84; 95% CI = 1.01-3.33; p = 0.012) and rs2235023 (HR = 2.28; 95% CI = 1.03 = 5.02; p = 0.027) in ABCB1, rs11265571 (HR = 1.59; 95% CI = 0.82-3.08; p = 0.037) and rs2307418 (HR = 73.68; 95% CI = 4.47-1215.31; p = 0.003) in CAR, and rs3732360 (HR = 0.64; 95% CI = 0.40 = 1.04; p = 0.049) in PXR. Taking into account the influence of the tested SNPs on treatment toxicity, we found a significant relationship between allele G of polymorphism in the ABCB1 rs7787082 (OR = 4.46; 95% CI = 1.38-14.39 p = 0.012) and hematological complications assuming the codominant gene inheritance model as well as a significant correlation between the presence of minor allele (G) of SNP rs2725256 in the ABCG2 gene (OR = 4.71; 95% CI = 1.20-18.47; p = 0.026) and the occurrence of non-hematological complications assuming a recessive gene inheritance model. Conclusion: Our data suggest that inherited variants in the genes encoding for proteins involved in the transport of xenobiotics may modify the toxicity and efficacy of dasatinib therapy in CML patients.

Eculizumab treatment in pregnant women with paroxysmal nocturnal hemoglobinuria: A Polish experience.

BACKGROUND: Eculizumab is an antibody targeting the C5 complement protein. Clinical trials suggest that eculizumab significantly reduces transfusion requirements and prevents disease complications in patients with paroxysmal nocturnal hemoglobinuria (PNH). OBJECTIVES: To analyze the outcome of pregnancies among Polish women with PNH treated with eculizumab as a part of the Polish National Health Fund program. MATERIAL AND METHODS: We report the outcomes of 3 pregnancies among women treated with eculizumab between 2017 and 2020. For 1 of these woman, it was the 1st pregnancy, while the remaining 2 patients had previously had 1 previous successful pregnancy each. RESULTS: All 3 mothers survived pregnancy, and all children were born alive. One of the patients had a vaginal delivery. Another required cesarean delivery at the 34th week due to a decreasing platelet count. In 1 case, premature rupture of the fetal membranes occurred at week 36, followed by artificial labor induction. All children were born without any inborn defects. The 2 prematurely born babies required a prolonged hospital stay. CONCLUSION: Treatment with eculizumab seems to reduce the risk to a mother and a child associated with PNH. However, more data are necessary to confirm this notion.