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Marta Masternak,1 Bartosz Puła,2 Joanna Knap,1 Anna Waszczuk-Gajda,3 Joanna Drozd-Sokołowska,3 Kamil Wdowiak,4 Sebastian Grosicki,5 Izabela Kozłowska,6 Marta Kaźmierczak,6 Anna Łabędź,7 Łukasz Szukalski,8 Kamil Wiśniewski,2 Edyta Subocz,9 Janusz Hałka,10 Agnieszka Szymczyk,11 Marek Hus,12 Krzysztof Jamroziak,2 Krzysztof Giannopoulos13 1Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland; 2Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland; 3Department of Hematology, Oncology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland; 4Department of Internal Medicine and Oncological Chemotherapy, Silesian Medical University, Katowice, Poland; 5Department of Hematology and Cancer Prevention in Chorzow, Faculty of Health Sciences in Bytom, Silesian Medical University, Katowice, Poland; 6Department of Hematology and Cancer Prevention, Municipal Hospital in Chorzów, Chorzów, Poland; 7Department of Hematology, Rydrygier’s Hospital in Cracow, Cracow, Poland; 8Department of Hematology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Toruń, Poland; 9Department of Hematology, Military Institute of Medicine, Warsaw, Poland; Clinical Department of Hematology, Independent Public Healthcare Centre of the Ministry of Internal Affairs and Administration with Warmia-Mazury Region’s Oncology Centre in Olsztyn, Olsztyn, Poland; 10Clinical Department of Hematology, Independent Public Healthcare Centre of the Ministry of Internal Affairs and Administration with Warmia-Mazury Region’s Oncology Centre in Olsztyn, Olsztyn, Poland; 11Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland; Hematology Department, St John’s Cancer Center, Lublin, Poland; 12Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland; 13Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland; Hematology Department, St John’s Cancer Center, Lublin, PolandCorrespondence: Krzysztof Giannopoulos Tel +48 81448 6632Fax +48 81448 6634Email krzysztof.giannopoulos@gmail.comPurpose: Mean platelet volume (MPV) is a readily accessible and commonly tested hematological indicator. Recent studies revealed a significant impact of MPV on the course and prognosis of many diseases, including some types of cancer, as well as on the incidence of atrial fibrillation and bleeding. The study aimed to perform a retrospective analysis of MPV in terms of time to first treatment (TTFT) and to determine its prognostic value in the group of patients with chronic lymphocytic leukemia (CLL). Moreover, the study includes a retrospective analysis of platelet parameters in patients treated with ibrutinib concerning bleeding and atrial fibrillation.Patients and Methods: The study included 523 patients with CLL, for 344 the most important cytogenetic aberrations were reported. The Mann–Whitney, Kruskal–Wallis, Kaplan–Meier, chi-squared, log‑rank tests and multivariate Cox proportional hazard regression model were used to analyze collected data.Results: The receiver operating characteristic curve analysis was performed to identify optimal cut-off value for MPV. The analysis of survival curves showed that in the group of patients with higher values of MPV TTFT was significantly longer than in the group with lower MPV (17.9 vs 36 months, p=0.0015, cut-off value for MPV= 10.4 fl). In multivariate Cox proportional hazard regression model low MPV, the presence of del11q and del13q provided independent prognostic value for TTFT (HR=0.69, 95%-CI, 0.5293 to 0.9081; p=0.0078; HR=1.76, 95%-CI, 1.3000 to 2.3882, p=0.0003, HR=0.74, 95%-Cl, 0.5674 to 0.9588, p=0.0229, respectively). In the group treated with ibrutinib, 59 patients had no significant correlation between MPV level and the incidence of therapy complications, although in the group of patients with low MPV there was a tendency for more frequent occurrence of atrial fibrillation (p=0.259).Conclusion: Low MPV values are associated with unfavorable prognosis and might represent a novel, independent prognostic factor in CLL.Keywords: MPV, chronic lymphocytic leukemia, TTFT

Abstract: Mass spectrometry (MS) can detect multiple myeloma-derived monoclonal proteins in the peripheral blood (PB) with high sensitivity, potentially serving as a PB assay for measurable residual disease (MRD). This study evaluated the significance of PB MS MRD negativity during posttransplant therapy in patients with newly diagnosed multiple myeloma. Serum samples from 138 patients treated in the phase 3 ATLAS trial of posttransplant maintenance with either carfilzomib, lenalidomide, and dexamethasone, or with lenalidomide alone were analyzed using EXENT MS methodology. We established feasibility of measuring MRD by MS in the PB in the posttransplant setting, despite unavailability of pretreatment calibration samples. There was high agreement between MRD by MS in the PB and paired bone marrow (BM) MRD results at the 10-5 threshold, assessed by either next-generation sequencing (NGS) or multiparameter flow cytometry (MFC) (70% and 67%, respectively). Agreement between PB MS and both BM MRD methods was lowest early after transplant and increased with time. MS negativity was associated with improved progression-free survival (PFS), which, in landmark analysis, reached statistical significance after 18 cycles after transplant. Combined PB/BM MRD negativity by MFC or NGS was associated with superior PFS compared with MRD negativity by only 1 modality. Sustained MS negativity carried similar prognostic performance to sustained BM MRD negativity at the 10-5 threshold. Overall, posttransplant MS assessment was feasible and provided additional prognostic information to BM MRD negativity. Further studies are needed to confirm the role and optimal timing of MS in disease evaluation algorithms. The ATLAS trial is registered at www.clinicaltrials.gov as #NCT02659293., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Previous studies suggest that postautologous stem cell transplant (ASCT) recovery of polyclonal immunoglobulin from immunoparesis in patients with multiple myeloma is a positive prognostic marker. We performed a longitudinal analysis of polyclonal immunoglobulin concentrations and unique B-cell sequences in patients enrolled in the phase 3 ATLAS trial that randomized 180 subjects to either carfilzomib, lenalidomide, dexamethasone (KRd) or lenalidomide (R) maintenance. In the KRd arm, standard-risk patients with minimal residual disease negativity after six cycles de-escalated to R alone after cycle 8. One year from the initiation of maintenance at least partial recovery of polyclonal immunoglobulin was observed in more patients on the R arm (58/66, p < 0.001) and in those who de-escalated from KRd to R (27/38, p < 0.001) compared to the KRd arm (9/36). In patients who switched from KRd to R, the concentrations of uninvolved immunoglobulin and the number of B-cell unique sequences increased over time, approaching values observed in the R arm. There were no differences in progression-free survival between the patients with at least partial immunoglobulin recovery and the remaining population. Our analysis indicates that patients receiving continuous therapy after ASCT experience prolonged immunoparesis, limiting prognostic significance of polyclonal immunoglobulin recovery in this setting., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

The goal of therapy in essential thrombocythemia (ET) is reducing thrombotic risk. No algorithm to predict hemorrhage risk exists. The impact ofanti-platelet, cytoreductive and anticoagulation therapies on risk of major bleeding (MB) was evaluated. MB events were retrospectively analyzed in 1381 ET from 10 European centers. There were 0.286 MB events/person-year. Neither the International Thrombosis Prognostic Score for thrombosis in essential thrombocythemia (IPSET-t) nor the revised IPSET-t (r-IPSET-t) was predictive for hemorrhage-free survival at 10 years (p = 0.092 vs p = 0.1). Ageand leukocyte count were MB risk factors, while low hemoglobin was protective. For ET with extreme thrombocytosis (ExtT) and leukocytosis cytoreduction was not protective. MB were more frequent in ET with ExtT who received anticoagulation. Antiplatelet therapy was not, while anticoagulation was a risk factor for MB (HR 3.05, p = 0.016, CI 1.23-7.56), in particular vitamin K antagonists (22.6% of those treated had a MB event, HR 2.96, p = 0.004, CI 1.41-6.22). Survival at 10 years was associated with hemorrhage (OR 2.54, p < 0.001) but not thrombosis (HR 0.95, p = 0.829). Hemorrhage has a higher risk of mortality than thrombosis. Improved risk stratification for MB is necessary. The choice of anticoagulation, cytoreduction and antiplatelet therapies is an important area of research in ET., (© 2023. The Author(s).)

Background: Lenalidomide is a cornerstone of maintenance therapy in patients with newly diagnosed multiple myeloma after autologous stem-cell transplantation. We aimed to compare the efficacy and safety of maintenance therapy with carfilzomib, lenalidomide, and dexamethasone versus lenalidomide alone in this patient population., Methods: This study is an interim analysis of ATLAS, which is an investigator-initiated, multicentre, open-label, randomised, phase 3 trial in 12 academic and clinical centres in the USA and Poland. Participants were aged 18 years or older with newly diagnosed multiple myeloma, completed any type of induction and had stable disease or better, autologous stem-cell transplantation within 100 days, initiated induction 12 months before enrolment, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) using permuted blocks of sizes 4 and 6 and a web-based system to receive up to 36 cycles of carfilzomib, lenalidomide, and dexamethasone (28-day cycles of carfilzomib 20 mg/m 2 administered intravenously in cycle one on days 1 and 2 then 36 mg/m 2 on days 1, 2, 8, 9, 15, and 16 in cycles one to four and 36 mg/m 2 on days 1, 2, 15, and 16 from cycle five up to 36 [per protocol]; lenalidomide 25 mg administered orally on days 1-21; and dexamethasone 20 mg administered orally on days 1, 8, 15, and 22) or lenalidomide alone (10 mg administered orally for the first three cycles and then at the best tolerated dose [≤15 mg for 28 days in 28-day cycles]) until disease progression or unacceptable toxicity as maintenance therapy. After 36 cycles, patients in both treatment groups received lenalidomide maintenance. Randomisation was stratified by response to previous treatment, cytogenetic risk factors, and country. Investigators and patients were not masked to treatment allocation. Patients in the carfilzomib, lenalidomide, and dexamethasone group with no detectable minimal residual disease after cycle six (as per International Myeloma Working Group criteria) and standard-risk cytogenetics were switched to lenalidomide maintenance as of cycle nine. The primary endpoint was progression-free survival in the intention-to-treat population (defined as all randomly assigned patients). Safety was analysed in all randomly assigned patients who received at least one dose of study treatment. This unplanned interim analysis was triggered by the occurrence of 59 (61%) of the expected 96 events for the primary analysis and the results are considered preliminary. This trial is registered with ClinicalTrials.gov, NCT02659293 (active, not recruiting) and EudraCT, 2015-002380-42., Findings: Between June 10, 2016, and Oct 21, 2020, 180 patients were randomly assigned to receive either carfilzomib, lenalidomide, and dexamethasone (n=93) or lenalidomide alone (n=87; intention-to-treat population). The median age of patients was 59·0 years (IQR 49·0-63·0); 84 (47%) patients were female and 96 (53%) were male. With a median follow-up of 33·8 months (IQR 20·9-42·9), median progression-free survival was 59·1 months (95% CI 54·8-not estimable) in the carfilzomib, lenalidomide, and dexamethasone group versus 41·4 months (33·2-65·4) in the lenalidomide group (hazard ratio 0·51 [95% CI 0·31-0·86]; p=0·012). The most common grade 3 and 4 adverse events were neutropenia (44 [48%] in the carfilzomib, lenalidomide, and dexamethasone group vs 52 [60%] in the lenalidomide group), thrombocytopenia (12 [13%] vs six [7%]), and lower respiratory tract infections (seven [8%] vs one [1%]). Serious adverse events were reported in 28 (30%) patients in the carfilzomib, lenalidomide, and dexamethasone group and 19 (22%) in the lenalidomide group. One treatment-related adverse event led to death (respiratory failure due to severe pneumonia) in the carfilzomib, lenalidomide, and dexamethasone group., Interpretation: This interim analysis provides support for considering carfilzomib, lenalidomide, and dexamethasone therapy in patients with newly diagnosed multiple myeloma who completed any induction regimen followed by autologous stem-cell transplantation, which requires confirmation after longer follow-up of this ongoing phase 3 trial., Funding: Amgen and Celgene (Bristol Myers Squibb)., Competing Interests: Declaration of interests DD reports speaker honoraria and participation in advisory boards for Amgen and Celgene (Bristol Myers Squibb) and had conference fees paid by Amgen. TW reports honoraria from AbbVie, Amgen, BeiGene, Celgene (Bristol Myers Squibb), Gilead, GlaxoSmithKline, Janssen-Cilag, Novartis, Pfizer, Roche, and Takeda; conference fees or travel support (or both) from AbbVie, Amgen, Celgene (Bristol Myers Squibb), Gilead, GlaxoSmithKline, Janssen-Cilag, Pfizer, Roche, and Takeda; and advisory board participation for AbbVie, Amgen, BeiGene, Celgene (Bristol Myers Squibb), Gilead, GlaxoSmithKline, Janssen-Cilag, Pfizer, Roche, Novartis, and Takeda. KJ reports grants paid to his institution and payment for expert testimony from Janssen; honoraria from Amgen, Celgene (Bristol Myers Squibb), GlaxoSmithKline, Janssen, Sandoz, and Takeda; financial support for attending meetings or travel support (or both) from Amgen, Celgene, and Janssen; and consulting and advisory board participation for Amgen, Celgene (Bristol Myers Squibb), Janssen, Sandoz, and Takeda. TK reports honoraria from AbbVie and Celgene (Bristol Myers Squibb) and financial support for attending meetings or travel support (or both) from Sanofi. AD-S reports honoraria for presentations and lectures from Amgen and Celgene (Bristol Myers Squibb); and financial support for attending meetings or travel support (or both) and advisory board participation from Celgene (Bristol Myers Squibb). KrG reports honoraria from Amgen and Celgene (Bristol Myers Squibb). AN reports fees for lectures and presentations from Amgen, Celgene (Bristol Myers Squibb), and Janssen; and financial support for attending meetings or travel support (or both) from Amgen, Celgene (Bristol Myers Squibb), Janssen, and Teva. BP reports grants or contracts from AbbVie, Amgen, Celgene (Bristol Myers Squibb), and Janssen; consultation fees from AbbVie, Roche, and Sandoz; honoraria for lectures and presentations from AbbVie, Amgen, Celgene (Bristol Myers Squibb), and Janssen; and financial support for attending meetings or travel support (or both) from AbbVie and Celgene (Bristol Myers Squibb). JR reports speaker honoraria and advisory board participation from Amgen, Celgene (Bristol Myers Squibb), and Janssen. LU-Z reports financial support for attending meetings or travel support (or both) from Janssen. AK reports payment for clinical trial participation from Janssen. JMZ reports grants from Celgene (Bristol Myers Squibb); financial support for attending meetings or travel support (or both) from AbbVie and Takeda; and participation on a data safety monitoring board or advisory board for Amgen, Celgene (Bristol Myers Squibb), Roche, and Takeda. JW reports personal and institutional grants from GlaxoSmithKline, Novartis, and Roche; and personal consulting, lecture and presentation fees, speaker bureaus, and educational events fees from AbbVie, Gilead, Novartis, Roche, and Takeda. DM reports lecture and presentation fees from Amgen and Janssen. TR reports research grants from Amgen and Celgene (Bristol Myers Squibb). OBL reports participation on an advisory board for MorphoSys. JAZ reports an institutional grant from Celgene (Bristol Myers Squibb); personal consulting fees from Alnylam, Celgene (Bristol Myers Squibb), Janssen, Prothena, and Regeneron; and participation on an advisory board for Takeda. KeG reports personal payment for the statistical design of this study and consulting fees related to other studies from the University of Chicago. BAD reports consulting fees from COTA Healthcare, Janssen, and Sanofi; payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from MJH Life Sciences and Plexus Communications. AJJ reports consulting fees and honoraria for lectures and presentations from AbbVie, Amgen, Celgene (Bristol Myers Squibb), Gracell, GlaxoSmithKline, Janssen, and Sanofi-Aventis. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Thrombosis and haemorrhage are frequent in patients with essential thrombocythaemia (ET). The 2016 revised International Prognostic Score for Thrombosis in Essential Thrombocythaemia-thrombosis (r-IPSET-t) score stratifies patients into very-low- (VLR), low- (LR), intermediate- (IR) and high-risk (HR) groups. We validated the r-IPSET-t in the biggest population of patients with ET (n = 1381) to date and found it to be a better fit than the earlier IPSET-t score. With an average follow-up of 87.7 months, there were 0.578 thrombotic events/person-year and 0.286 bleeding events/person-year after diagnosis. The 10-year thrombosis-free survival was 88% and 99% for the r-IPSET-t LR and VLR groups (p < 0.001). Cytoreduction was a thrombotic risk factor in younger patients (aged <60 years, hazard ratio 9.49, p = 0.026; aged ≥60 years, hazard ratio 1.04, p = 0.93). In multivariable Cox regression analysis, anti-aggregation after diagnosis was protective for thrombosis (hazard ratio 0.31, p = 0.005) but a risk factor for major bleeding (hazard ratio 10.56, p = 0.021). Of the IPSET-t HR and LR groups, 132/780 and 249/301 were re-classified as LR and VLR respectively (p < 0.001). The European LeukemiaNET (ELN) does not recommend aspirin for VLR patients but in this real-life analysis 83.1% of VLR patients received it. Our results validate the r-IPSET-t score as more predictive for thrombosis than the ELN-recommended IPSET-t and raise concerns about unnecessary cytoreductive and anti-aggregative therapy., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

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.

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are characterized by genomic instability, which may arise from the global hypomethylation of the DNA. The active DNA demethylation process may be linked with aberrant methylation and can be involved in leukemogenesis. The levels of 5-methylcytosine oxidation products were analyzed in minimally invasive material: the cellular DNA from peripheral blood cells and urine of patients with AML and MDS along with the control group, using isotope-dilution two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry. The receiver operating characteristic curve analysis was used for the assessment of the ability to discriminate patients' groups from the control group, and AML from MDS. The most diagnostically useful for discriminating AML patients from the control group was the urinary excretion of 5-hydroxymethylcytosine (AUC = 0.918, sensitivity: 85%, and specificity: 97%), and 5-(hydroxymethyl)-2'-deoxyuridine (0.873, 74%, and 92%), while for MDS patients 5-(hydroxymethyl)-2'-deoxycytidine in DNA (0.905, 82%, and 98%) and urinary 5-hydroxymethylcytosine (0.746, 66%, and 92%). Multi-factor models of classification trees allowed the correct classification of patients with AML and MDS in 95.7% and 94.7% of cases. The highest prognostic value of the analyzed parameters in predicting the transformation of MDS into AML was observed for 5-carboxy-2'-deoxycytidine (0.823, 80%, and 97%) and 5-(hydroxymethyl)-2'-deoxyuridine (0.872, 100%, and 75%) in DNA. The presented research proves that the intermediates of the active DNA demethylation pathway determined in the completely non-invasive (urine) or minimally invasive (blood) material can be useful in supporting the diagnostic process of patients with MDS and AML. The possibility of an early identification of a group of MDS patients with an increased risk of transformation into AML is of particular importance.

Background: The severe acute respiratory syndrome coronavirus (SARS-CoV-2) has become the cause of a worldwide pandemic, and its clinical infection course in patients with hematological malignancies may be severe., Methods: We performed a retrospective study on 188 chronic lymphocytic leukemia patients (CLL) with COVID-19 infection., Results: At the time of infection 51 patients (27.1%) were treated with Bruton tyrosine kinase inhibitor (BTKi), 46 (24.5%) with anti-CD20 antibodies while 37 patients (19.7%) received venetoclax. In total, 111 patients (59.0%) required hospitalization and 50 patients (26.5%) died due to COVID-19. Patients with poor performance status (ECOG >1; p = 0.02), advanced age (>65 years; p = 0.04), low hemoglobin concentration (≤10 g/dl; p = 0.0001), low platelets (<100 × 109/L; p = 0.003), and elevated lactate dehydrogenase level (LDH; p = 0.014) had an increased risk of death due to COVID-19. Neither CLL treatment status (treatment naïve vs. treated) nor the type of CLL-directed treatment had impact on the SARS-CoV-2 related risk of death. The multivariate survival analysis showed that advanced age ( p = 0.009) and low platelet count ( p = 0.0001) were associated with significantly shorter patients' overall survival., Conclusions: SARS-CoV-2 infection in CLL patients is associated with poor outcome regardless of administered CLL-directed treatment.

COVID-19, as a disease involving the endothelium of multiple organs, is characterized by high mortality rates among hospitalized patients. Patients with hematological malignancies are particularly at risk of an unfavorable course of COVID-19. The endothelial activation and stress index (EASIX) score has been used as a simple predictor of overall survival (OS) in specific groups of hematological cancer patients. EASIX, as a biomarker of endothelial dysfunction, might play a prognostic role in patients with COVID-19. Here, we performed a comprehensive retrospective analysis of the EASIX score in 523 hospitalized COVID-19 patients with or without coexisting hematological cancer. Hematological cancer COVID-19 patients had higher EASIX scores compared to the overall population with COVID-19. In hematological patients, EASIX was a strong predictor of the occurrence of sepsis during COVID-19. Our findings demonstrated EASIX as a strong predictor of intensive care unit admission, in-hospital mortality, the occurrence of acute renal failure and the need for hemodialysis, both in hematological and non-hematological COVID-19 patients. Patients with a high EASIX score on COVID-19 diagnosis had significantly inferior OS compared to patients with low EASIX. We showed for the first time that EASIX might serve as a simple, universal prognostic tool of OS in both hematological and non-hematological COVID-19 patients.

Introduction: Patients with hematological malignancies (HM) require intensive chemotherapy with curative intent, especially in case of AML that results in more frequent admissions to Intensive Care Units (ICU). Due to our knowledge, this study is the first multicenter retrospective analysis in Polish population., Methods: A total of 200 patients with HM hospitalized in 4 Polish hematological centers. Data concerning clinical indices and outcomes during admission and ICU stay were collected retrospectively., Results: The most common hematological malignancy was acute leukemia (55%). The main cause of ICU admission was respiratory failure (88.5%), often accompanied by sepsis (58.5%) and acute renal failure (51.5%). In patients with hematological malignancies, the following factors were associated with ICU mortality: prolonged ICU stay (odd ratio [OR] = 6.98, 95% confidence interval [CI]: 1.38-35.33, χ 2  = 5.61, p = 0.02), the presence of acute respiratory failure (odd ratio [OR] = 5.35, 95% confidence interval [CI]: 1.01-28.46, χ 2  = 3.93, p = 0.04), and the need for renal replacement therapy (odd ratio [OR] = 8.75, 95% confidence interval [CI]: 1.23-62.11, χ 2  = 4.78, p = 0.03). There were following associations with in-hospital mortality in patients with hematological malignancies: prolonged ICU stay (odd ratio [OR] = 10.12, 95% confidence interval [CI]: 1.85-55.37, χ 2  = 7.21, p = 0.008), the presence of acute respiratory failure (odd ratio [OR] =5.24, 95% confidence interval [CI]: 1.36-20.16, χ 2  = 5.87, p = 0.02), the need for catecholamine support (odd ratio [OR] =3.43, 95% confidence interval [CI]: 1.06-11.05, χ 2  = 4.32, p = 0.04), and renal replacement therapy (odd ratio [OR] =5.55, 95% confidence interval [CI]: 1.14-26.92, χ 2  = 4.59, p = 0.03)., Conclusions: We have demonstrated that ICU and in-hospital mortalities among patients with hematological malignancies are still poor, but easier access to the intensive care unit and close cooperation between hematologists and intensivists may improve outcomes. We have found that acute failure of key organs (acute respiratory failure, end-stage renal failure requires renal replacement therapy) and length of ICU stay (but probably no comorbidities and illness severity) may have impact on mortality (both ICU and in-hospital).

Purpose: High-dose methylprednisolone (HDMP) with or without anti-CD20 antibody treatment in the pre B-cell receptor inhibitor (BCRi) era was used as potential salvage therapy for relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (r/r CLL/SLL) patients bearing the 17p deletion., Patients and Methods: Outcomes were compared in retrospect between r/r patients treated with HDMP (n = 20), ibrutinib (n = 39) and idelalisib with rituximab (n = 14)., Results: Higher overall response rates were found in those patients undergoing BCRi therapy compared to HDMP (79.2% vs. 0%; p < 0.0001), along with longer median progression-free survival (not reached vs. 24.1 months; p < 0.01). Nevertheless, there were no differences in the overall survival (HDMP 35.87 months vs. not reached; p = 0.58)., Conclusion: HDMP treatment was significantly inferior in terms of response rate and progression-free survival in r/r CLL/SLL patients with the 17p deletion, and may only be used whenever novel compounds are unavailable., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

The MAF translocations, t(14;16) and t(14;20), are considered as adverse prognostic factors based on few studies with small sample sizes. We report on their prognostic impact in a large group of 254 patients - 223 (87.8%) with t(14;16) and 31 (12.2%) with t(14;20). There were no intergroup differences in survival estimates. Median progression-free survival was 16.6 months for t(14;16) and 24.9 months for t(14;20) ( p  = 0.28). Median overall survival (OS) was 54.0 months and 49.0 months, respectively ( p  = 0.62). Median OS in patients who underwent double autologous stem cell transplantation (ASCT) was 107.0 months versus 60.0 months in patients who received single ASCT ( p  < 0.001). ISS 3 was associated with shorter OS (HR = 1.89; 95% CI 1.24-3.19; p  = 0.005) in Cox analysis. Our study suggests that t(14;20) should be considered as an adverse factor of equal prognostic implication to t(14;16).

The t(14;16) translocation, found in 3%-5% of newly diagnosed (ND) multiple myeloma (MM), has been associated with adverse outcomes. However, the studies establishing the characteristics of t(14;16) included solely small cohorts. The goal of the current international, multicenter (n = 25 centers), retrospective study was to describe the characteristics and outcomes of t(14;16) patients in a large, real-world cohort (n = 223). A substantial fraction of patients had renal impairment (24%) and hemoglobin <10 g/dL (56%) on initial presentation. Combined therapy of both immunomodulatory drug and proteasome inhibitor (PI) in the first line was used in 35% of patients. Autologous stem cell transplantation was performed in 42% of patients. With a median follow up of 4.1 years (95% CI 3.7-18.7), the median progression-free survival (PFS) and overall survival (OS) from first line therapy were 2.1 years (95% CI 1.5-2.4) and 4.1 years (95% CI 3.3-5.5), respectively. Worse OS was predicted by age > 60 years (HR = 1.65, 95% CI [1.05-2.58]), as well as revised International Scoring System (R-ISS) 3 (vs R-ISS 2; HR = 2.59, 95% CI [1.59-4.24]). In conclusion, based on the largest reported cohort of t(14;16) patients, quarter of this subset of MM patients initially presents with renal failure, while older age and the R-ISS 3 predict poor survival., (© 2020 Wiley Periodicals, Inc.)

Competing Interests: The authors declare no conflict of interest.