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Despite recent progress in treatment methods, acute myeloid leukemia (AML) continues to pose significant clinical challenges and is associated with generally unfavorable prognoses. Patients considered fit for intensive therapy are usually treated with cytarabine-anthracycline-based induction chemotherapy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended for patients with adverse-risk AML and most patients with intermediaterisk AML. The standard therapy for patients who are deemed too poorly for intensive treatment is the combination of azacitidine and venetoclax. AML cells can escape the immune system through various mechanisms, including reduced expression of MHC complex molecules, ligand shedding, manipulation of chemical signaling, and enhanced inhibitory ligand expression. Increased expression of ligands for T-cell-regulation checkpoints is present in AML cells and correlates with worse outcomes. Therefore, this article reviews the current research progress in immune checkpoint inhibitors in AML. [ABSTRACT FROM AUTHOR]

Introduction: Therapeutic adherence (TA) is one of the most important factors influencing the effectiveness of treatment. Oral anti-cancer drugs are increasingly used to treat malignancy including multiple myeloma (MM). Our study aimed to determine TA of patients with MM treated with IMiDs, to identify TA risk factors, and to determine satisfaction with medical care during the treatment with IMiDs. Methods: A cross-sectional survey-based study involving adult patients with MM treated with IMiDs. Results: Between January 2021 and May 2021, 267 patients with MM were enrolled in the study. The dosing schedule was declared as easy by 71.8% of patients, as standard for 24.0%, and difficult for 4.2% of patients. During MM treatment, 85.0% of patients did not skip any IMiDs dose, and 87.6% did not skip the IMiDs dose in the last cycle of chemotherapy. Identified factors affecting TA included the treatment duration and education level. In addition, depending on the patient's well-being, gender, and household companionship influenced TA. Satisfaction with medical care during the treatment with IMiDs was declared by 95.5% of patients with MM. In our cohort, 95.5% of patients were satisfied with the information they received from the hematologist during treatment with IMiDs. Conclusions: Patients with MM treated with IMiDs are highly adherent to treatment. With time from the beginning of treatment, patients need more attention and motivation to adhere to the therapy rules. [ABSTRACT FROM AUTHOR]

This study presents a retrospective analysis of patients with acute myeloid leukemia <60 years of age, who had ≥10% blasts in early bone marrow evaluation on day 14 of their first DAC (daunorubicin + AraC + cladribine) induc- tion cycle. Patients included in this analysis were treated according to the PALG-AML-1/2012 and PALG AML-1/2016 studies. As the second early induction, 22 patients received DAC and 35 patients received CLAM (cladribine + AraC + mitoxantrone). There was no significant difference between patients treated with CLAM and those treated with DAC chemotherapy in terms of overall survival (OS after 2 years 52% vs. 76% for DAC, HR 0.68, 95% CI: 0.26--1.77, p = 0.4). Furthermore, there was no significant difference in composite complete remission (cCR) rates between the two treatment regimens: 60% (21/35) for CLAM and 54.6% (12/22) for DAC (p >0.05). Both treatment regimens had a similar toxicity profile and early death rate. [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]

Introduction: Richter syndrome (RS) is defined as development of an aggressive lymphoma with dismal prognosis in 2-10% of patients suffering from chronic lymphocytic leukemia (CLL). The most often diagnosed variant of RS is diffuse large B-cell lymphoma (DLBCL-RS). The treatment options and risk factors of worse outcome for RS still need to be expanded. Aims: To study the characteristic and treatment outcomes of DLBCL-RS patients. Methods: The retrospective analysis of patients with DLBCL-RS treated in hematology centers between 2011 and 2021. Results: Ninety-nine patients with DLBCL-RS were identified. Median time since CLL diagnosis to Richter transformation was 43.0 months (range 0-252.0). Thirty-seven patients transformed during CLL treatment, 56.7% of them were receiving novel agents (Bruton's tyrosine kinase inhibitor or BCL2 inhibitor). Seventy-six patients had RS treated with intensive chemotherapy protocols, mainly R-CHOP-like regimens. Only 42.3% had response to the treatment (25/76 complete responses and 11/76 partial responses). In forty patients RS was primarily resistant to administered treatment, in 47.5% of these patients p53 pathway aberration was noted. Median overall survival (OS) after transformation was 17.3 months (95% CI 11.9-46.8). Significantly lower OS (3.4 months, 95% CI 14.13 -- not reached) was observed in heavily pretreated CLL patients (>3 lines of therapy preceding transformation). Other factors identified as poor OS predictors in univariate analysis were: ECOG ≥2 (p = 0.0014), hemoglobin level <10 g/dL (p = 0.017) and platelet count <100 × 109/L (p = 0.0065). Median progression-free survival (PFS) was 13.5 months (95% CI 9.6-22.7). Better results were achieved for patients who proceeded to autologous hematopoietic stem cell transplantation (auto-HSCT; n = 8) or allogeneic HSCT (allo-HSCT; n = 10). The median OS in auto-HSCT recipients was 46.1 months, in allo-HSCT -- 18.3 months. Conclusions: Our study represents the largest dataset of DLBCL-RS patients in Polish hematology centers and confirms its poor prognosis. Only proceeding to hematopoietic stem cell transplantation may improve the outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Data concerning the safety and efficacy of SARS-CoV-2 vaccines in patients with paroxysmal nocturnal hemoglobinuria (PNH) are very scarce. It may be anticipated that vaccine can be associated with pharmacodynamic crisis of PNH, as well with other non-PNH-oriented complications. Methods: Retrospective analysis of PNH patients treated with eculizumb, who received any SARS-CoV-2 vaccine, while on eculizumab. Results: Twenty-five patients, 52% males, median age at the first vaccination 37 years (1-76) were included. Patients received median 3 (1-3) doses of SARS-CoV-2 vaccine. Most patients received BNT162b2 (96%) either alone or in combination with other vaccines; 16% patients received at least one dose of mRNA-1273 vaccine, and 4% ChAdOx1-S. Fifty-six percent patients experienced any complication after the first vaccine, 52% after the second, and 50% after the third. The complications were mostly mild and comprised arm pain and fatigue. No cases of patient-reported breakthrough hemolysis were diagnosed, exacerbation of hemolysis in biochemical tests was noted in 24%, 42% and 7% after the first, second and third dose respectively. Three serious adverse events were diagnosed in two patients: one case of possible vaccine-induced immune thrombotic thrombocytopenia (VITT) according to ASH criteria, requiring hospitalization and anti-coagulation after the first dose of BNT162b2; one splenic infarction after the second dose of BNT162b2 with thrombocytopenia complicating heparin treatment and one case of atrial fibrillation after the third dose of BNT162b2. No patient succumbed to complications of SARS-CoV-2 vaccines. Conclusions: SARS-CoV-2 vaccine in patients diagnosed with paroxysmal nocturnal hemoglobinuria may be associated with serious adverse events. Careful monitoring and appropriate treatment of emergent complications are mandatory. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis (TB) is an infrequent infectious complication of hematopoietic cell transplantation, either autologous (auto-HCT) or allogeneic (allo-HCT). There is a paucity of data on the frequency and outcome of TB in patients after HCT. Material and methods: Retrospective analysis of patients who developed TB after HCT. The analysis covered the years 1996-2021. Results: Seventeen patients from 11 centers were identified, 9 (53%) females, the median age at TB was 44 years (19-69). Five patients (29.4%) developed TB after auto-HCT, 12 (70.6%) after allo-HCT. The underlying hematological diagnoses were mostly acute leukemias (52.9%). The median time from the most recent HCT to TB diagnosis was 431 days (5-973). Microbiologically proven TB was confirmed in 13 (76.5%) patients. All patients were diagnosed with pulmonary TB; the extrapulmonary sited accompanying the lung involvement were the bones or the joints (18%). The most frequent symptoms were cough (64.7%) and fever (52.9%). 3-drug anti-TB regimen was used in 5 (31.3%), 4-drug regimen (in all patients INH-RIF/Rifabutin-PZA-EMB) in 10 (62.5%) out of 16 patients. Treatment success was obtained in 13 (81.3%) patients. With median follow-up of 48 months (95% CI 19-95 months), the median overall survival (OS) calculated from the time of TB diagnosis was not reached, the 6-month OS was 93.9% (64-99%), the 12-month OS 87.9% (59-96%). One patient (5.9%) succumbed to TB, translating into 1-year cumulative incidence of TB-associated death of 6.25% (95% CI 3.3-9.2%). Conclusions: Tuberculosis is a rare complication of HCT. It can develop anytime, although most frequently it develops after more than a year from the most recent HCT. Treatment success rate is similar to the rate obtained in the general population as reported by the World Health Organization. TB may be associated with death of the affected patients. [ABSTRACT FROM AUTHOR]

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.

Background: Non-secretory multiple myeloma (NSMM) accounts for approx. 2-3% of multiple myeloma (MM) cases. Due to the rare occurrence and ineligibility of patients with NSMM to participate in clinical trials, we have limited data on treatment efficacy and the clinical course in these patients. Most of the literature consists of case reports and small retrospective studies., Objectives: The study aimed to analyze patient characteristics, prognostic factors and treatment outcomes in newly diagnosed (ND) NSMM., Material and Methods: This is a multicenter, retrospective analysis of 43 patients with NSMM diagnosed between June 2010 and September 2021, conducted in 8 Polish hematology centers., Results: The median overall survival (OS) was 103 months (95% confidence interval (95% CI): 20-72). The most common cause of death was MM disease progression. The overall response rate (ORR) was 84.6%; complete response (CR), very good partial response (VGPR), partial response (PR), and no response (NR) rates were 20.5%, 46.2%, 17.9%, and 15.4%, respectively. In multivariable analysis, factors contributing to worse OS included International Staging System stage 3 (ISS-3) (p = 0.0277), anemia (Hb <10 g/dL or >2 below upper limit of normal value (ULN), p = 0.0270), renal insufficiency (RI, serum creatinine >2 mg/dL, p = 0.0476), and serum albumin <5.5 mg/L (0.0408)., Conclusions: Non-secretory multiple myeloma is a rare subtype of MM. This small study demonstrates that outcomes are comparable to secretory MM. However, the inclusion of this subset of patients in clinical trials is essential to assess prognosis, treatment efficacy and clinical outcomes.

Introduction: Recent studies in a mouse model of chronic lymphocytic leukemia (CLL) demonstrated that inhibition of the programmed death receptor 1 (PD‑1)-PD‑L1 axis resulted in correction of leukemia‑induced CD8+ T cell‑related immune dysfunction and protected mice against CLL development. However, it remains unclear whether CLL development and progression can be also associated with CD4+ T cells expressing PD‑1., Objectives: We aimed to analyze whether a quantitative assessment of CD4+PD‑1+ T cells performed at the time of diagnosis can have prognostic significance in patients with CLL., Patients and Methods: We examined 56 patients with newly diagnosed CLL at different stages of the disease. The quantitative assessment of PD‑1‑expressing CD4+ T cells was performed in all patients, using multicolor flow cytometry., Results: We demonstrated that CLL patients with an advanced (high and intermediate risk) stage had a significantly higher number of CD4+PD‑1+ T cells compared with subjects with low‑grade disease. Importantly, we showed that the number of PD‑1‑expressing CD4+ T cells in the peripheral blood of patients referred for immediate treatment due to the advanced stage of the disease was significantly higher compared with subjects on watchful waiting. Finally, we found that treatment‑naive patients with higher numbers of CD4+PD‑1+ T cells at baseline showed a significantly shortened time to the first treatment compared with patients with a low number of CD4+PD‑1+ T cells., Conclusions: Our study showed that the quantative assessment of CD4+PD‑1+ T cells in peripheral blood using flow cytometry can facilitate prognostication of patients with newly diagnosed CLL.