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Infections are still a major reason of morbidity and one of the most common causes of death after hematopoietic cell transplantation (HCT). Antimicrobial prophylaxis plays a crucial role in decreasing non-relapse mortality after HCT. The objective of this guideline paper is presentation of current recommendations of antimicrobial prophylaxis for children and adults after hematopoietic cell transplantation, prepared in cooperation of Polish scientific hematological societies. Recommendations were prepared by the working group and finally approved by all 23 Polish transplant centers for children and adults. Existing ECIL (European Conference on Infections in Leukemia) and EBMT (European Society of Blood and Marrow Transplantation) guidelines, as well as results of survey performed among all Polish transplant centers, were the background material for working group. Recommendations are presented in sections dedicated to antibacterial prophylaxis, antifungal prophylaxis, antiviral prophylaxis, as well as prophylaxis of toxoplasmosis and infections with Pneumocystis jiroveci. Recommendations on principles of vaccination against COVID-19 are provided based on the state of knowledge in September 2021. A section on guidelines of environmental prophylaxis is also presented.

High-dose chemotherapy with autologous stem-cell transplantation (ASCT) remains the standard of care in multiple myeloma (MM) patients. This retrospective study aimed to assess the impact of neutrophil-to-lymphocyte ratio (NLR) and other complete blood count (CBC)-based predictors on PFS and OS of transplant-eligible MM patients. The CBC-based biomarkers were evaluated in a single-center cohort of 176 MM patients at three time points: at the diagnosis, the time of ASCT, and +100 d after ASCT. Univariable and multivariable Cox's regression analyses and Kaplan-Meier estimate were used in statistical analysis. NLR at ASCT (HR 1.15, 95% CI: 1.05-1.26) and hemoglobin at ASCT (HR 0.80, 95% CI: 0.68-0.94) were independent factors influencing PFS. In the model for OS, the only statistically significant factors were NLR at ASCT (HR 1.15, 95% CI: 1.04-1.27), bortezomib administration prior to ASCT (HR 0.52, 95% CI: 0.33-0.83) and age at diagnosis (HR 1.03, 95% CI: 1.00-1.06). NLR at ASCT is an independent predictive factor in MM patients undergoing ASCT.

The classification of myeloid neoplasms and acute leukemias was last updated in 2016 within a collaboration between the World Health Organization (WHO), the Society for Hematopathology, and the European Association for Haematopathology. This collaboration was primarily based on input from a clinical advisory committees (CACs) composed of pathologists, hematologists, oncologists, geneticists, and bioinformaticians from around the world. The recent advances in our understanding of the biology of hematologic malignancies, the experience with the use of the 2016 WHO classification in clinical practice, and the results of clinical trials have indicated the need for further revising and updating the classification. As a continuation of this CAC-based process, the authors, a group with expertise in the clinical, pathologic, and genetic aspects of these disorders, developed the International Consensus Classification (ICC) of myeloid neoplasms and acute leukemias. Using a multiparameter approach, the main objective of the consensus process was the definition of real disease entities, including the introduction of new entities and refined criteria for existing diagnostic categories, based on accumulated data. The ICC is aimed at facilitating diagnosis and prognostication of these neoplasms, improving treatment of affected patients, and allowing the design of innovative clinical trials.

Several methodologies that rely on the detection of immunophenotypic or molecular abnormalities of the neoplastic cells are now available to quantify measurable (“minimal”) residual disease (MRD) in acute myeloid leukemia (AML). Although the perfect MRD test does not (yet) exist, the strong association between MRD and adverse patient outcomes has provided the impetus to use measures of MRD as biomarker in the routine care of AML patients and during clinical trials. MRD test results may inform the selection of postremission therapy in some patients but evidence supporting the use of MRD as predictive biomarker is still limited. Several retrospective studies have shown that conversion from undetectable to detectable MRD or increasing MRD over time is associated with overt disease recurrence, and MRD testing may therefore be valuable as a monitoring biomarker for early detection of relapse. Interpreting serial MRD data is complex, with open questions regarding the optimal timing and frequency of testing, as well as the identification of test-specific thresholds to define relapse. Importantly, it is unknown whether intervening at the time of MRD detection, rather than at overt disease recurrence, improves outcomes. Finally, using MRD as a surrogate efficacy-response biomarker to accelerate drug development/approval has already been accepted by regulatory authorities in other diseases and is of great interest as a potential strategy in AML. While the prognostic value of MRD in AML is well established, data from prospective clinical trials confirming that treatment effects on MRD directly relate to clinical outcomes are needed to further establish the role of MRD as a surrogate endpoint in AML.

Introduction: Calculating accurate blood volume to process is a critical practice in apheresis planning; therefore, researchers try to develop dedicated prediction models. In this analysis, we have attempted to compare three algorithms for two different apheresis collection protocols. Methods: In a retrospective study, we have analyzed 137 apheresis procedures performed on 100 autologous patients. Apheresis procedures were performed with the Spectra Optia apheresis device with two protocols: mononuclear cell collection (MNC) and continuous mononuclear cell collection (cMNC). Three algorithms: a model based on mean collection efficiency (CE2), a linear regression model, and a power regression model were validated by plotting collected CD34 + cell dose versus predicted CD34 + cell dose. Results: All models showed high predictability for MNC procedure, a high correlation of predicted CD34 + yield and actual CD34 + yield ( R 2 = 0.9547; 0.9487; 0.9474 for CE2-based model, linear and power regression model, respectively). In contrast, alteration between models for the cMNC procedure was greater ( R 2 = 0.8049, 0.7970, and 0.8169) with a higher number of overpredictions. Further analysis revealed that for low CD34 + precounts blood volume to process, calculated with the three models, differ significantly up to fivefold times. Conclusions: Utilizing regression models may lead to calculation errors, which can affect undercollection, repetition of apheresis, or even mobilization failure. Contrary to regression models, the model based on mean CE2 gave the most accurate prediction both for MNC and cMNC procedures. Although new prediction algorithms are created, this simple formula remains a reliable tool that promotes careful planning of apheresis, thus improving patient safety.

The number of newly diagnosed haematological malignancies in Polish adults and children is about 9,000 a year, which constitutes about 5.5% of all malignancies in the country. Adult patients with haematological malignancies are diagnosed and treated in 42 institutions in Poland. The scientific and educational support for this activity is provided under the umbrella of the Polish Society of Haematologists and Transfusiologists (PTHiT, Polskie Towarzystwo Hematologow i Transfuzjologow ), the Polish Adult Leukemia Group (PALG), the Polish Lymphoma Research Group (PLRG), the Polish Myeloma Study Group (PMSG), the Polish Myeloma Consortium (PMC), and consultants in haematology. The aim of this position paper is to present the current status and progress in therapy of haematological malignancies in Polish haematology adult centres, focusing on the activity of PALG, PLRG, and PMSG. The achievements of Polish haemato-oncology at the beginning of the third decade of the 21 st century are set out in this paper. Polish haemato-oncology today has an important international position based on contributions to the development of knowledge, international cooperation, and a high quality of patient care. In many instances, clinical trials run by Polish collaborative groups have influenced international standards. Polish haematologists have been the authors of treatment recommendations, and their research has indicated areas for further research.

The 2010 and 2017 editions of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults are widely recognized among physicians and investigators. There have been major advances in our understanding of AML, including new knowledge about the molecular pathogenesis of AML, leading to an update of the disease classification, technological progress in genomic diagnostics and assessment of measurable residual disease, and the successful development of new therapeutic agents, such as FLT3, IDH1, IDH2, and BCL2 inhibitors. These advances have prompted this update that includes a revised ELN genetic risk classification, revised response criteria, and treatment recommendations.

Background Multiple myeloma (MM) has become a chronic disease in majority of patients, and remission consolidation with autologous hematopoietic stem cell transplant (ASCT) remains the backbone of treatment in transplant-eligible patients. Objective The aim of this multicenter cross-sectional nationwide retrospective study was to evaluate the epidemiology, etiology, and outcome of infections in patients with MM undergoing ASCT in 13 Polish transplant centers, carried out on behalf of the Infectious Complications Study Group of the Polish Adult Leukemia Group. Methods A total number of consecutive 1374 patients with MM treated in Polish adult transplant centers from 2012 to 2014 were followed for infectious complications up to day +100 after ASCT in nationwide study. Results Altogether 490 infection episodes in 336 patients (49% male, aged 21-72 years) were reported, including 145 episodes of neutropenic fever (103 patients) and 34 episodes of clinically documented infections (CDIs) (27 patients). Among microbiologically confirmed infections there were 251 episodes of bacterial infections (180 patients), 42 episodes of fungal infections (38 patients), and 18 episodes of viral infections (17 patients). The overall incidence of infections reached 13.1% for bacterial, 3.6% for fungal, and 1.3% for viral infections. There were 16 cases of infection-related deaths after ASCT (1.2%). The mortality risk factors included multidrug-resistant bacteria etiology (odds ratio [OR], 3.5; P = .033), coexistence of bacterial and fungal infection (OR, 6.3; P = .002), and CDI (OR, 5.5; P = .007). Conclusion ASCT in patients with MM was connected with low risk of life-threatening infections. However, multidrug-resistant bacteria bacterial etiology, mixed etiology, and CDI increased the risk of fatal outcome.

Invasive fungal disease (IFD) is one of the most serious complications of therapy in patients with immune suppression. It particularly concerns patients treated for malignant hematological diseases, immune deficiencies, or undergoing hematopoietic cell transplantation (HCT). Development of IFD can abrogate the effect of previous therapy and contributes to dismal outcome of the underlying disease. The Working Group consisting of members of the Polish Society of Hematology and Blood Transfusion, the Polish Society of Pediatric Oncology and Hematology, and the Polish Adult Leukemia Study Group has prepared recommendations for the diagnostic and therapeutic management of IFD in adults and children. This paper presents the current recommendations for patients in immune suppression treated in Polish pediatric and adult hematology and HCT centers, based on the guidelines of the European Conference on Infections in Leukaemia (ECIL) 2015–2019. Levels of diagnosis of IFD (possible, probable, and proven) and antifungal management (prophylaxis, as well as empirical and targeted therapies) are declared according to updated international criteria of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) 2019. Patients with primary diagnosis of acute lymphoblastic leukemia, acute myeloblastic leukemia, severe aplastic anemia, chronic granulomatous disease, and severe combined immunodeficiency, as well as patients after allogeneic HCT, are included in the high-risk groups for development of IFD. For these patients, antifungal prophylaxis based on azoles or micafungin is recommended. In empirical therapy, caspofungin or liposomal/lipid formulas of amphotericin B are recommended. The Working Group has discouraged the use of itraconazole in capsules and amphotericin deoxycholate. Detailed guidelines for first- and second-line targeted therapies for invasive candidiasis, aspergillosis, mucormycosis, fusariosis, and scedosporiosis, as well as the principles of the recommended dosing of antifungals, are presented in this paper.

We investigated clinical associations of ficolins and mannose-binding lectin (MBL) in 157 patients suffering from acute myeloid leukaemia (AML). Concentrations of ficolin-1, ficolin-2, ficolin-3 and MBL (before chemotherapy) in serum were determined as were selected polymorphisms of the corresponding genes (FCN1, FCN2, FCN3 and MBL2). The control group (C) consisted of 267 healthy unrelated individuals. Median level of ficolin-1 in patients was lower (p p p p = 0.0016, respectively) compared with controls. These findings were generally associated with AML itself, however the highest MBL levels predicted higher risk of severe hospital infections (accompanied with bacteremia and/or fungaemia) (p = 0.012) while the lowest ficolin-1 concentrations tended to be associated with prolonged (> 7 days) fever (p = 0.026). Genotyping indicated an association of G/G homozygosity (corresponding to FCN1 gene − 542 G > A polymorphism) with malignancy [p = 0.004, OR = 2.95, 95% CI (1.41–6.16)]. Based on ROC analysis, ficolin-1, -2 and -3 may be considered candidate supplementary biomarkers of AML. Their high potential to differentiate between patients from non-malignant controls but also from persons suffering from other haematological cancers (multiple myeloma and lymphoma) was demonstrated.

Acute myeloid leukemia (AML) is a highly heterogeneous disease. Mutation with internal tandem duplication of fms-like tyrosine kinase-3 (FLT3-ITD) is one of the two most common driver mu­tations in AML, the presence of which is associated with a poor outcome. Midostaurin (Mido) is a multi-targeted tyrosine kinase inhibitor that potently inhibits kinase FLT3, other kinases including platelet-derived growth factor receptors α (PDGFR- α ) and b (PDGFR- β ), tyrosine-protein kinase Src, KIT receptor tyrosine kinase, and vascular endothelial growth factor receptor (VEGFR). Mido is the first targeted therapy to demonstrate improved outcome, and as such it represents a game-changer. The RATIFY study demonstrated significant improvements in overall survival, and in event-free survival, when Mido was added to standard chemotherapy in patients with newly diagnosed FLT3-mutated AML. This paper reviews the current clinical evidence regarding Mido and its use in the induction and treatment of relapsed or refractory disease, and maintenance setting.

Measurable residual disease (MRD) quantified by multiparameter flow cytometry (MFC) is a strong and independent prognostic factor in acute myeloid leukemia (AML). However, several technical factors may affect the final read-out of the assay. Experts from the MRD Working Party of the European LeukemiaNet evaluated which aspects are crucial for accurate MFC-MRD measurement. Here, we report on the agreement, obtained via a combination of a cross-sectional questionnaire, live discussions, and a Delphi poll. The recommendations consist of several key issues from bone marrow sampling to final laboratory reporting to ensure quality and reproducibility of results. Furthermore, the experiences were tested by comparing two 8-color MRD panels in multiple laboratories. The results presented here underscore the feasibility and the utility of a harmonized theoretical and practical MFC-MRD assessment and are a next step toward further harmonization.

Context: Mutations in the FLT3 tyrosine kinase and in IDH1/IDH2 (collectively IDHm) co-occur in up to 30% of adults with acute myeloid leukemia (AML). SEL24/MEN1703 is an orally available, first-in-class, dual PIM/FLT3 kinase inhibitor. Preliminary results from the phase 1/2 first-in-human DIAMOND-01 trial (NCT03008187) demonstrated antitumor activity of single-agent SEL24/MEN1703 in adult patients with relapsed/refractory (R/R) IDHm AML, where 3 of 8 IDHm patients responded. Objective: To report the first safety and efficacy results from an additional expansion cohort of the DIAMOND-01 trial in 20 patients with R/R IDHm AML. Design: DIAMOND-01 is a phase 1/2, open-label, multicenter study consisting of 2 parts: dose escalation and cohort expansion, including an additional expansion cohort (IDHm) that is ongoing. Patients: Patients with R/R IDHm AML and no standard therapeutic options were eligible. Intervention(s): Patients received the recommended dose of 125 mg SEL24/MEN1703 orally, once daily for 14 days over a 21-day cycle until disease progression or unacceptable toxicity. Main Outcome Measure(s): The number and frequency of adverse events (AEs; primary) and overall response rate (ORR; secondary). Results: As of 10 January 2022, 14 patients were enrolled in the IDHm cohort. Seven patients had IDH2, 1 had IDH1/2, and 4 had IDH1 mutations. Two patients had a concomitant FLT3-ITD mutation. Safety data (N=12) showed that grade ≥3 TEAEs (≥10% of patients) were pneumonia (33%) and asthenia (17%), both unrelated to the study drug. Of the 7 patients who completed ≥1 treatment cycle and had ≥1 post-baseline assessment or clear disease progression, ORR was 28.6%; 1 patient achieved a complete response with incomplete blood count recovery at cycle 3 and underwent hematopoietic stem cell transplant, and 1 patient had a partial response at cycle 4 (confirmed at cycle 7 and still on treatment). Among the 7 remaining patients, 3 discontinued before completion of cycle 1 without progression or response, and 4 patients are ongoing and have not yet undergone post-baseline assessments. Conclusions: SEL24/MEN1703 had a manageable safety profile and single-agent activity in adult patients with R/R IDHm AML and may be a feasible therapeutic option in this difficult-to-treat population.

More than 97% of patients with acute myeloid leukemia (AML) demonstrate genetic mutations leading to excessive proliferation combined with the evasion of regulated cell death (RCD). The most prominent and well-defined form of RCD is apoptosis, which serves as a defense mechanism against the emergence of cancer cells. Apoptosis is regulated in part by the BCL-2 family of pro- and anti-apoptotic proteins, whose balance can significantly determine cell survival. Apoptosis evasion plays a key role in tumorigenesis and drug resistance, and thus in the development and progression of AML. Research on the structural and biochemical aspects of apoptosis proteins and their regulators offers promise for new classes of targeted therapies and strategies for therapeutic intervention. This review provides a comprehensive overview of current AML treatment options related to the mechanism of apoptosis, particularly its mitochondrial pathway, and other promising concepts such as neddylation. It pays particular attention to clinically-relevant aspects of current and future AML treatment approaches, highlighting the molecular basis of individual therapies.

In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research1 aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by 1-2 section editors who were leading international experts in the field. In the 5 years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including 11 sections, each of which will be published separately. The updated EHA Research Roadmap identifies the most urgent priorities in hematology research and clinical science, therefore supporting a more informed, focused, and ideally a more funded future for European hematology research. The 11 EHA Research Roadmap sections include Normal Hematopoiesis; Malignant Lymphoid Diseases; Malignant Myeloid Diseases; Anemias and Related Diseases; Platelet Disorders; Blood Coagulation and Hemostatic Disorders; Transfusion Medicine; Infections in Hematology; Hematopoietic Stem Cell Transplantation; CAR-T and Other Cell-based Immune Therapies; and Gene Therapy.

Simple Summary Lymphoproliferative disorders comprise a heterogeneous group of hematological malignancies characterized by abnormal lymphocyte proliferation. Autologous hematopoietic stem cell transplantation plays a very important role in the treatment of lymphoproliferative diseases. The key element in this process is the effective mobilization of hematopoietic cells from the marrow niche to the peripheral blood. Mobilization of HSC is regulated by many factors, out of which miRNAs present in the hematopoietic niche via targeting cytokines, and signaling pathways may play an important regulatory role. This study investigated the expression of selected miRNAs in patients with multiple myeloma, Hodgkin’s lymphomas, and non-Hodgkin’s lymphomas undergoing mobilization procedures. The aim of the study was to evaluate the expression of hsa-miR-15a-5p, hsa-miR-16-5p, hsa-miR-34a-5p, hsa-miR-126-3p, hsa-miR-146a-5p, hsa-miR-155-5p, and hsa-miR-223-3p during the mobilization procedure, and to assess their role in mobilization efficacy. The level of miRNAs was tested at two time points before the initiation of mobilization and on the day of the first apheresis. Our results suggest that the investigated miRNAs, especially hsa-miR-146a-5p, may influence the efficacy of HSC mobilization. Abstract microRNAs play an important role in the regulation of gene expression, cell fate, hematopoiesis, and may influence the efficacy of CD34+ cell mobilization. The present study examines the role of hsa-miR-15a-5p, hsa-miR-16-5p, hsa-miR-34a-5p, hsa-miR-126-3p, hsa-miR-146a-5p, hsa-miR-155-5p, and hsa-miR-223-3p in the course of hematopoietic stem cell mobilization. The numbers of CD34+ cells collected in patients with hematological malignancies (39 multiple myelomas, 11 lymphomas) were determined during mobilization for an autologous hematopoietic stem cell transplantation. The miRNA level was evaluated by RT-PCR. Compared to baseline, a significant decline in hsa-miR-15a-5p, hsa-miR-16-5p, hsa-miR-126-3p, hsa-miR-146a-5p, and hsa-miR-155-5p was observed on the day of the first apheresis (day A). An increase was observed only in the expression of hsa-miR-34a-5p. On day A, a negative correlation was found between hsa-miR-15a-5p and hsa-miR-146a-5p levels and the number of CD34+ cells in peripheral blood. A negative correlation was observed between hsa-miR-146a-5p and the number of collected CD34+ cells after the first apheresis. Good mobilizers, defined according to GITMO criteria, demonstrated a lower hsa-miR-146a-5p level on day A than poor mobilizers. Patients from the hsa-miR-146a-5p “low expressors” collected more CD34+ cells than “high expressors”. Our results suggest that the investigated miRNAs, especially hsa-miR-146a-5p, may influence the efficacy of HSC mobilization.

Acute myeloid leukemia (AML) is a heterogeneous, highly malignant neoplasm. Apoptosis is a complex process executed by caspases and suppressed by the inhibitor of apoptosis (IAP) family. Neuronal apoptosis inhibitory protein (NAIP), IAP’s member, may play an exceptional role in the mechanisms of tumors’ resistance to chemotherapy. The aims of the study were to assess the expression of NAIP in leukemic blasts of AML patients using flow cytometry and to evaluate its influence on disease outcome. NAIP expression was found in 106 out of 108 patients. A higher complete response rate was associated with a low expression of NAIP, age < 60 yo, and white blood cell count < 20 G/L (p= 0.009,p= 0.033, andp= 0.076, respectively) in univariate analyses and a low NAIP expression and age < 60 yo (p= 0.025 andp= 0.013, respectively) in multivariate analyses. Longer overall survival (OS) in the univariate analysis was influenced by a low NAIP expression, age < 60 yo, and intensive chemotherapy (p= 0.033,p< 0.001, andp< 0.001, respectively). In the intensively treated group, better OS was observed in patients with age < 60 yo,de novoAML, and a low NAIP expression (p= 0.03,p= 0.024, andp= 0.07, respectively). In multivariate analysis, longer OS was associated with age < 60 yo (p= 0.009) andde novoAML (p= 0.007). In conclusion, we suggest that NAIP might play an adverse role in response to chemotherapy.

Introduction SLIT–ROBO is a ligand–receptor family of neuronal guidance cues that has been involved in pathological and physiological angiogenesis. SLIT–ROBO expression is altered in many tumours. However, no data exist about the role of the whole family in acute myelogenous myeloid leukemia (AML). Purpose Herein, we assessed the expression of all SLIT–ROBO family in bone marrow (BM) biopsy of AML patients and control group on both protein and RNA levels. Methods The paraffin-embedded tissue blocks were subjected to immunohistochemistry for SLIT1, SLIT2, SLIT3, ROBO1, ROBO2, ROBO3, and ROBO4. Microvessel density (MVD) was evaluated by CD34 immunohistochemistry. An in silico analysis using The Cancer Genome Atlas data repository was conducted for assessment of RNA level. Results Acute myeloid leukemia patients were generally high expressers of ROBO1 and ROBO2 compared to the controls (p