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Simple Summary: Autologous hematopoietic cell transplantation (auto-HCT) can be used to salvage at least a proportion of plasma cell myeloma patients who relapse after a previous auto-HCT. It may, however, occur that there is either no or an insufficient stem cell dose in storage to proceed to transplantation. Remobilization to procure new cells is then required. There are very limited data in the literature concerning the efficacy of stem cell remobilization after previous auto-HCT. In our previous report, we showed that remobilization with cytarabine was associated with a lower risk of remobilization failure in comparison to etoposide or cyclophosphamide. In the current study, we analyze the efficacy and safety of different doses of cytarabine (800, 1600, and 2400 mg/m2), showing that all doses are efficacious but that the dose of 2400 mg/m2 is associated with the most toxicity. Therefore, lower doses of cytarabine seem to be preferable, with plerixafor rescue when needed. Salvage autologous hematopoietic cell transplantation (auto-HCT) may be used to treat relapse of plasma cell myeloma occurring after previous auto-HCT. When an insufficient number of hematopoietic stem cells have been stored from the initial harvest, remobilization is necessary. Here, we aimed to analyze the efficacy and safety of different doses of cytarabine (total 800 vs. 1600 vs. 2400 mg/m2) for remobilization. Sixty-five patients, 55% male, with a median age at remobilization 63 years, were included. Remobilization was performed with cytarabine_800 in 7, cytarabine_1600 in 36, and cytarabine_2400 in 22 patients. Plerixafor rescue was used in 25% of patients receiving cytarabine_1600 and 27% of those receiving cytarabine_2400. Patients administered cytarabine_800 were not rescued with plerixafor. Remobilization was successful in 80% of patients (57% cytarabine_800; 86% cytarabine_1600; 77% cytarabine_2400; p = 0.199). The yield of collected CD34+ cells did not differ between the different cytarabine doses (p = 0.495). Patients receiving cytarabine_2400 were at the highest risk of developing severe cytopenias, requiring blood product support, or having blood-stream infections. One patient died of septic shock after cytarabine_2400. In summary, remobilization with cytarabine is feasible in most patients. All doses of cytarabine allow for successful remobilization. Cytarabine_2400 is associated with higher toxicity; therefore, lower doses (800 or 1600 mg/m2) seem to be preferable. [ABSTRACT FROM AUTHOR]

Introduction: Buerger's Disease (BD), or thromboangiitis obliterans (TAO), is a vasculoocclusive disorder of unknown etiology. Cigarette smoking is considered to be the main risk factor for the development of TAO. This study aimed to assess the activation of platelets in patients with BD compared to a control group. Materials and methods: Thirty patients (24 men and six women, median age 51.4 years) with TAO were included in the study. In the control group there were 20 healthy adults (16 men and four women, median age 44.0 years). Platelet activation was measured by light aggregometry and flow cytometry methods with and without platelet activators, such as thrombin receptor agonist peptide (TRAP-6) and adenosine diphosphate (ADP). Results: The velocity and intensity of aggregation increased in patients with TAO (p <0.05). MFI (mean fluorescence intensity) of P-selectin, CD63 (GP53-component of lysosomal membrane), and PAC-1 (platelet activation complex-1) on platelets increased in patients (p <0.05). Significantly higher aggregation velocities were noted in smoking patients in response to collagen (Coll) and to arachidonic acid (AA) compared to non-smoking ones. Aggregation velocity in response to AA was higher in heavy smokers compared to all smokers. A significantly higher intensity of aggregation was found in moderate smokers in response to epinephrine (EPI) and AA compared to non-smoking ones. A positive correlation between cholesterol concentrations and its fractions (LGL, TG), and platelet aggregation and the MFI of platelets, was found in patients with an increased cholesterol level. The aggregation velocity with EPI and AA was negatively correlated with HDL level. [ABSTRACT FROM AUTHOR]

Bruton's tyrosine kinase inhibitors (BTKis) have become one of the most vital drugs in the treatment of patients with chronic lymphocytic leukemia (CLL). BTKis are currently a well-established therapy for treatment-naïve, as well as relapsed or refractory, cases. BTKis have been shown to be crucial in the treatment of high-risk CLL patients bearing TP53 aberrations or characterized by the unmutated status of the immunoglobulin heavy-chain variable region (IGHV) gene. Ibrutinib was the first-in-class BTK inhibitor; however, despite its therapeutic potential, it is also characterized by specific adverse events, including hypertension, increased bleeding risk, cardiac toxicity, and skin changes. Although the next generation of BTKis was shown to be more specific, this adverse event profile is regarded currently as class--specific. In this review, we discuss the current status of acalabrutinib, a second-generation BTKi. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Richter transformation (RT) is defined as developing an aggressive lymphoma in 2–10% of patients suffering from chronic lymphocytic leukemia (CLL). So far, no complex analysis of RT demographics and treatment outcomes has been performed in Poland. Thus, the retrospective analysis of 124 patients with RT from Polish hematology centers was designed. Ninety-nine patients with diffuse large B-cell lymphoma (DLBCL-RT) were identified. The median overall survival (OS) for DLBCL-RT was 17.3 months, while for Hodgkin lymphoma (HL-RT)-21.3 months. In multivariate analysis, the independent factors of worse OS for DLBCL-RT were: prior CLL therapy, ECOG stage ≥2, and elevated serum LDH activity. Patients who proceeded to hematopoietic stem cell transplantation (HSCT) achieved better results. The median OS in allogeneic HSCT recipients was not reached, while in autologous HSCT median OS was 51.3 months. In conclusion, our study represents the largest dataset of patients diagnosed with RT in Poland and confirms its dismal prognosis. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver disease. About 70% of infections lead to chronic hepatitis, which is associated with a risk of cirrhosis within 20 years in 15-30% of patients. A vaccine against hepatitis C is still not available, but directly-acting antiviral drugs allow eradication of the virus in more than 95% of those infected. HCV infection is particularly dangerous in patients with cancer, including proliferative hematological diseases. This is because patients chronically infected with HCV can develop exacerbations of hepatitis during oncological treatment, making therapy much more difficult to manage and thus adversely affecting prognosis. In addition, HCV infection plays an important role in the development of certain subtypes of B-cell non-Hodgkin lymphoma (NHL), such as marginal zone lymphoma, diffuse large cell lymphoma, and Waldenström macroglobulinemia. Antiviral treatment leads to a hematological response in 60-75% of patients with HCV-associated indolent NHL. This article presents epidemiological data on HCV infection in hematooncological patients, as well as recommendations on methods of diagnosis and principles of treatment of the infection in hematooncological patients, including patients with lymphomas associated with HCV infection. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, with a median age at diagnosis of c.70 years. The natural course of the disease varies greatly, and patients with non-progressive and asymptomatic leukemia do not require treatment. But advanced and progressive CLL do require treatment. The results of CLL treatment have improved significantly in recent years, mainly due to the introduction of new and more effective drugs, including B-cell receptor inhibitors and B-cell lymphoma 2 (BCL2) inhibitors. These new drugs are used continuously as monotherapy, or in combination schemes for specified periods. Venetoclax in combination with anti-CD20 antibodies is used for 24 (rituximab) or 12 (obinutuzumab) months, while treatment with ibrutinib and venetoclax lasts 15 months. The choice of treatment protocol should largely depend on the assessment of 17p deletion/TP53 mutation, and in second treatment line immunoglobulin variable heavy chain (IGVH) mutation status, which correlate with a response to immunochemotherapy. The role played by immunochemotherapy has recently significantly decreased. It is still an option for first line treatment in patients without 17p deletion/TP53 mutation, with mutated gene encoding IGVH and in good performance status. However, the results of recent studies have shown that these patients may also obtain major benefit from chemotherapy- free regimens. The remaining patients, both in the first and subsequent treatment lines, should receive new targeted therapies, which are currently available in Poland under the drug program. In this article, we present an update of the guidelines for the diagnosis and treatment of CLL, including the treatment of autoimmune complications, as well as the prophylaxis and treatment of infections, developed by the Polish Society of Haematologists and Transfusiologists and the Polish Adult Leukemia Group-CLL working group. [ABSTRACT FROM AUTHOR]

Patients with hematologic malignancies are particularly vulnerable to severe infectious complications. SARS‐CoV‐2 infection is associated with a high risk of severe course and death in this patient population. In addition, immune deficits associated with both the blood cancer and the treatment used make vaccination against SARS‐CoV‐2 less effective than in immunocompetent individuals. Molnupiravir is one of the first oral antiviral drugs to demonstrate a significant benefit in reducing hospitalisation and death in COVID‐19 in the general population. In this context, 175 haematology patients with diagnosed COVID‐19, and treated with MOL between January and April 2022, came under our scrutiny with a view to defining their clinical characteristics and outcomes. The most common underlying conditions were lymphomas (45%), multiple myelomas (21%) and acute leukaemias or myelodysplastic syndrome (35%). Of all, 77% of the patients were vaccinated, and half of them received a booster. At 28 days after the breakthrough COVID‐19 diagnosis, 35 (20%) subjects required hospital admission. Out of those patients, seven (4%) died during the follow‐up due to the progression of COVID. Our results corroborate what has been established to date with regard to the positive clinical and safety outcomes of MOL in haematology patients with mild or moderate COVID‐19. What's new? SARS‐CoV‐2 infection is associated with a high risk of severe disease and death in patients with haematological malignancies, who are also less responsive to vaccination. Molnupiravir has been one of the first oral antiviral drugs to demonstrate a significant benefit in reducing hospitalisation and death due to COVID‐19 in the general population. However, the efficacy and drug tolerability of molnupiravir in patients with haematological cancer during the Omicron wave remain understudied. The results of our study corroborate the positive clinical and safety outcomes of molnupiravir in patients with haematological malignancies with mild or moderate COVID‐19 in daily clinical practice. [ABSTRACT FROM AUTHOR]