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Preprint CASE REPORT | doi:10.20944/preprints202404.0739.v1

Possible New Histological Prognostic Index for Aggressive Mature T-cell Lymphoma (TCL Urayasu Classification)— a Brief Review of the Literature on the Functional Proteins Involved in Refractory Hematologic Malignancy—

Hideaki Nitta, Haruko Takizawa, Toru Mitsumori, Hiroko Iizuka-Honmal), Tomonori Ochiai, Chiho Furuya, Yoshihiko Araki, Maki Fujishiro, Shigeki Tomita, Akane Hashizume, Tomohiro Sawada, Kazunori Miyake, Mitsuo Okubo, Yasunobu Sekiguchi, Miki Ando, Masaaki Noguchi

Subject: Medicine And Pharmacology, Hematology Keywords: TCL, prognostic classification, GRP94, PD-L1, PD-L2, PD-1, AKR1C3, P53, GRP78, thymidine phosphorylase

Online: 10 April 2024 (12:17:56 CEST)

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Aggressive mature T-cell lymphoma (TCL) is a disease that carries a poor prognosis. The mechanism, at the functional protein level, of the resistance to therapy of TCL has not yet been well clarified. To comprehensively clarify the mechanism, we first reviewed the literature, as mentioned in the Introduction section, on 22 types of representative functional proteins reported as being potentially associated with treatment resistance, mainly in hematologic tumors. Next, we retrospectively analyzed the tumor cell expressions of these 22 functional proteins in 16 randomly selected patients with TCL who had received CHOP (cyclophosphamide, hydroxyl doxorubicin, oncovin, and prednisolone) therapy as first-line treatment. As a result, we propose a new three-group prognostic classification of TCL (the TCL Urayasu Classification) based on the mechanism of resistance to treatment of these tumors. The study subjects included 7 patients (44%) with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), 6 patients (38%) with angioimmunoblastic T-cell lymphoma (AITL), and 3 patients (19%) with anaplastic large T-cell lymphoma (ALCL). Immunohistochemistry was performed in paraffin-embedded tumor tissue sections prepared from these patients as antigens using antibodies against the 22 previously reported treatment-resistance-related proteins to determine the tumor cell expression statuses of these proteins. Log-rank test was performed to compare the overall survival (OS) after CHOP therapy of the patients showing positive and negative immunostaining for these proteins, as well as among patients grouped based on other factors. Overall, the median OS of the TCL patients was about 33.5 months. When compared by the disease type, the prognosis was found to be worse in the order of ALCL, AITL, and PTCL. A multivariate analysis showed that expression of glucose-regulated protein 94 (GRP94), a protein that serves as a pro-survival component under endoplasmic reticulum (ER) stress in the tumor microenvironment, was significantly associated with shortened survival. No significant difference was observed for the conventional poor prognostic factors: high-risk International Prognostic Index (IPI) and high-risk Prognostic Index for peripheral T-cell lymphoma, unspecified (PTCL-U) (PIT). However, when GRP94 was combined with six other factors, listed below, as survival-shortening factors, significant differences were observed. The 6 factors were 1) programmed cell death-ligand 1 (PD-L1) and 2) programmed cell death 1 (PD-1), which are involved in immune surveillance; 3) aldo-keto reductase family 1 member C3 (AKR1C3), which is an enzyme that inactivates HO (hydroxyl doxorubicin [H] and oncovin [O]) of CHOP; 4) P53, a tumor suppressor; 5) Glucose-regulated protein 78 (GRP78), an ER stress protein; 6) thymidine phosphorylase (TP), which is an enzyme involved in thymidine catabolism. Based on the combination of GRP94 and the six other factors expressed in the tumors, we propose a new prognostic classification system for TCL (TCL Urayasu classification). Group 1 (group with a relatively good prognosis): GRP94-negative (n = 6; median OS, 88 months; p < 0.01); Group 2 (group with a poor prognosis): GRP94-positive, plus expression of 2 of the 6 aforementioned factors (n = 5; median OS, 25 months; p > 0.05); and Group 3 (group with a very poor prognosis): GRP94-positive, plus expression of at least 3 of the 6 aforementioned factors (n = 5; median OS, 10 months; p < 0.01). Thus, the TCL Urayasu prognostic classification is a simple, useful, and innovative classification that also explains the mechanism of resistance to treatment for each functional protein. Accumulation of more cases and further analyses are expected in the future to enable clinical application, such as use of a stratified treatment approach and treatment using inhibitors.

Preprint BRIEF REPORT | doi:10.20944/preprints202404.0686.v1

Support Vector Machine-Based Formula for Detecting Suspected α Thalassemia Carriers: A Path Toward Universal Screening

Idit Lachover-Roth, Sari Peretz, Hiba Zoabi, Harel Eitam, Leonid Livshits, Dvora Filon, Carina Levin, Ariel Koren

Subject: Medicine And Pharmacology, Hematology Keywords: Alpha Thalassemia, Screening, Support Vector Machine, Mathematical Formulas

Online: 10 April 2024 (09:45:35 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202404.0717.v1

A Simple Frailty Score Predicts Survival and Early Mortality in Systemic AL Amyloidosis

Rafael Ríos-Tamayo, Ramón Lecumberri, Maria Teresa Cibeira, Veronica Gonzalez-Calle, Rafael Alonso, Amalia Domingo, Elena Landete, Cristina Encinas, Belén Iñigo, Maria Jesus Blanchard, Elena Alejo, Isabel Krsnik, Manuel Gómez-Bueno, Pablo Garcia-Pavia, Javier Segovia-Cubero, Laura Rosiñol, Juan-José Lahuerta, Joaquín Martínez-López, Joan Bladé

Subject: Medicine And Pharmacology, Hematology Keywords: AL amyloidosis; survival; early mortality; frailty

Online: 10 April 2024 (09:14:36 CEST)

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Preprint REVIEW | doi:10.20944/preprints202404.0091.v1

Menin Inhibitors: New Players in KMT2A-Rearranged and NPM1-Mutated Acute Myeloid Leukemia

Gabriele Coppola, Anna Candoni

Subject: Medicine And Pharmacology, Hematology Keywords: menin; menin inhibitors; leukemia; KMT2A; NPM1

Online: 2 April 2024 (02:51:43 CEST)

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Preprint REVIEW | doi:10.20944/preprints202404.0049.v1

Pulmonary Hypertension in Sickle Cell Disease: Novel Findings of Gene Polymorphisms Related to Pathophysiology

Sevastianos Chatzidavid, Pagona Flevari, Ioanna Tombrou, Georgios Anastasiadis, Maria Dimopoulou

Subject: Medicine And Pharmacology, Hematology Keywords: Sickle cell disease; Pulmonary hypertension; Gene polymorphisms; Gene sequencing

Online: 1 April 2024 (12:44:57 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202403.1619.v1

A Rare Onset of T Lymphoid Blast Crisis in Chronic Myeloid Leukemia with Two Distinct Blast Populations

Alessandra Mongia, Francesca Romano, Sara Ciullini Mannurita, Benedetta Peruzzi, Sara Bencini, Daniela Parrini, Laura Fasano, Alessandra Fanelli

Subject: Medicine And Pharmacology, Hematology Keywords: chronic myeloid leukemia; T lymphoid blastic crisis

Online: 27 March 2024 (06:21:04 CET)

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Preprint REVIEW | doi:10.20944/preprints202403.1155.v1

Hematological and Hemorheological Parameters of Blood Platelets as Biomarkers in Diabetes Mellitus Type 2. A Comprehensive Review

Elissaveta Zvetkova, Ivan Ivanov, Eugeni Koytchev, Nadia Antonova, Yordanka Gluhcheva, Anika Alexandrova, Georgi Kostov

Subject: Medicine And Pharmacology, Hematology Keywords: Diabetes mellitus type 2 (DM-2); blood platelets (PLTs); PLT-hematological / hemorheological / hemostatic parameters (indices); PLT "activaion" / "hyperactivation", computational modeling of PLTs, macro- and microvascular deseas (complications) in DM2

Online: 20 March 2024 (12:21:42 CET)

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Diabetes mellitus – type 2 (DM2) is a hypercoaguable state with enhanced platelets (PLTs) activation and increased clotting factor production. Simultaneously, the fibrinolytic cell system is inhibited due to formation of clots with high resistance to fibrinolysis. The stages of PLTs "activation" have been well-characterized microscopically, morphometrically and nanomechanically (by light microscope, transmisiion electron microscope - TEM, scanning electron microscope - SEM and atomic force microscope - AFM). Thrombocytes in "acivated" (pro-coagulant) state play central role in two main biological processes: hemostasis and repair of vascular vessels. Pro-coagulant PLTs participate in generation of thrombin and in development of fibrin fibers in the clot matrix. Enhanced PLTs reactivity in dibetic- (diabetes mellitus - DM2) patients is considered as a "pro-thrombotic" state. In the retrospective- and prospective- studies on the topic, the higher are the PLTs' hematometrical indices: PLTs (count), MPV (mean platelet volume), PDW (platelet distribution width), PCR (plateletcrit), as well as PLTs/Ly ratio. The PLТs parameters/indices are usefull biomarkers in early diagnosis and prognosis of DM2. The precise studies of PLTs' state of activation during DM2 might be useful for creation of new diabetes (DM2) treatment strategies and effective medicines. Using the amount of blood glucose, attached to hemoglobin (HbA1c values) as markers of glycemic control in diabetic patients, researchers have observed association between MPV and medications as Insulin, Metformin, sulphonyl ureas. Computational modellng of PLTs' activation in DM2 is also a controlling factor for thrombocyte distribution and margination in bood vessels, associated with micro- and macrovascular disease in DM2. PLTs-derived miRNAs are novel molecular biomarkers for diagnosis and prognosis of DM2, insulin resistance and diabetes complications. We have proposed (2010) oleic acid (OA) as a substance suppressing "PLT hyperactivation" and inhibiting “thrombocyte aggregation”. Antiplatelet agents, natural plant products including, could be effective in the prevention and the secondary treatment of micro- and macrovascular complications in the type 2 Diabetes mellitus. Our proposal on following up of a combination of hematological-, hemorheological- and hemostatic parameters (indices) as a new way in diagnosis, treatment, predicting and management of DM2 and its related vascular complications, probably could be more explored in future studies.

Preprint REVIEW | doi:10.20944/preprints202403.0836.v1

Precision Medicine Approaches in Acute Myeloid Leukemia with Adverse Genetics

Nicole Santoro, Prassede Salutari, Mauro Di Ianni, Andrea Marra

Subject: Medicine And Pharmacology, Hematology Keywords: acute myeloid leukemi; adverse genetics; leukemogenesis; targeted therapy; immunotherapy

Online: 14 March 2024 (10:08:08 CET)

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Preprint REVIEW | doi:10.20944/preprints202403.0755.v1

Autoimmune Hemolytic Anemias

Melika Loriamini, Christine Cserti-Gazdewich, Donald R. Branch

Subject: Medicine And Pharmacology, Hematology Keywords: autoimmune hemolytic anemia; AIHA; categories; diagnosis; CAD; PCH

Online: 13 March 2024 (07:20:53 CET)

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Preprint ARTICLE | doi:10.20944/preprints202403.0645.v1

Best Administration Schedule for Optimal Efficacy and Safety of Arsenic Trioxide Treatment in Chronic Graft versus Host Disease

Dominique Rongvaux-Gaïda, Lieven Huysse, François Rieger, Carole Nicco

Subject: Medicine And Pharmacology, Hematology Keywords: Arsenic trioxide; Chronic Graft-versus-Host Disease; cGvHD; Corticosteroid; autoimmunity

Online: 11 March 2024 (15:18:01 CET)

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Chronic graft-versus-host disease (cGvHD) occurs in 20-50% of recipients following allogeneic haematopoietic stem cell transplantation (allo-HSCT). Corticosteroids (CS) remain the first line treatment but have suboptimal efficacy and carry the risk of long-term side effects. New agents with a better safety profile and higher efficacy, ideally combining immunomodulatory and antifibrotic properties, are urgently needed. From 2016 to 2020, we conducted a phase 2 clinical trial with ATO in chronic GvHD (ClinicalTrials.gov ID NCT02966301 - GMED16-001). This study aimed to evaluate the efficacy and safety of a first-line combination of arsenic trioxide (ATO) and CS in adult patients with cGvHD who require systemic therapy after a first allo-HSCT for a haematological disease. In this prospective, national, multicenter, single-arm, open-label phase II study, conducted in 5 university hospital centers in France, ATO was initiated within 10 days of starting CS at 1 mg/kg/day. Patients received 11 infusions of ATO per 4-week cycle, at a dose of 0.15 mg/kg per infusion. Patients received 1 or 2 cycles of treatment depending on the clinical response and the assessment of the treating physician. The results were published in July 2022 in a paper entitled "High Response Rate and Corticosteroid Sparing with ATO-Based First-Line Therapy in Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation". The GMED16-001 study demonstrated convincing efficacy and safety characteristics of the intravenous drug (Trisenox^®/Arscimed^®): the first-line use of ATO in addition to corticosteroids was associated with a high clinical response rate and correlated with rapid corticosteroid (CS) sparing in moderate to severe cGvHD after allo-HSCT. We performed a post-hoc analysis of the data to determine the best schedule for treating cGvHD patients with ATO. Our post-hoc analysis leads us to the conclusion that two cycles of ATO, at 0.15 mg/kg/day, 5 days per week for 4 weeks each, separated by a 4-week therapy-free interval, appears to be the most promising treatment schedule.

Preprint REVIEW | doi:10.20944/preprints202403.0439.v1

Comparative Review of the Current and Future Strategies to Evaluate Bone Marrow Infiltration at Diffuse Large B-Cell Lymphoma Diagnosis

Fernando Martin-Moro, Javier Lopez-Jimenez, Jose Antonio Garcia-Marco, Jose Antonio Garcia-Vela

Subject: Medicine And Pharmacology, Hematology Keywords: Bone marrow; Large B cell lymphoma; Lymphoma; Histology; Flow cytometry; PET

Online: 7 March 2024 (13:08:22 CET)

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Preprint ARTICLE | doi:10.20944/preprints202403.0449.v1

Systemic Inflammation Index: A New Candidate Minor Criterion in the Diagnosis of Polycythemia vera

Emine Gulturk, Korhan Kapucu

Subject: Medicine And Pharmacology, Hematology Keywords: polycythemia vera; secondary polycythemia; systemic inflammation index; erythropoietin; neutrophil-to-lymphocyte ratio; platelet-to-lymphocyte ratio

Online: 7 March 2024 (12:04:07 CET)

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Preprint BRIEF REPORT | doi:10.20944/preprints202403.0380.v1

Systemic Hypertension in Patients with Transfusion Dependent Thalassaemia: More than Co-incidence?

Melani Shobia Emmanuel, Janitha Bandara Gunasena, Dulani Kottachchi, Sanjeewa Rajapaksa, Anuja Premawardhena

Subject: Medicine And Pharmacology, Hematology Keywords: thalassemia, systemic hypertension

Online: 7 March 2024 (10:14:49 CET)

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Preprint ARTICLE | doi:10.20944/preprints202403.0347.v1

The Role of Thromboelastography as a Predictor of Acute Kidney Injury in COVID-19 Patients in ICU

Usi Sukorini, Ira Puspitawati, Yulia Wardhani, Muhammad Roihan Munajih

Subject: Medicine And Pharmacology, Hematology Keywords: thromboelastography; acute kidney injury; COVID-19; hypercoagulable

Online: 6 March 2024 (13:07:01 CET)

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Preprint ARTICLE | doi:10.20944/preprints202403.0042.v1

Characterization of CD34+ Cells from Patients with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) Using a t-distributed Stochastic Neighbor Embedding (T-SNE) Protocol

Cathrin Nollmann, Wiebke Moskorz, Christian Wimmenauer, Paul S. Jäger, Ron P. Cadeddu, Jörg Timm, Thomas Heinzel, Rainer Haas

Subject: Medicine And Pharmacology, Hematology Keywords: Hematopoietic stem and progenitor cell (HSPC); acute myeloid leukemia (AML); Myelodysplastic syndromes (MDS); leukemic stem cell (LSC) CD34; CD38; CD45RA; CD123; PD-L1; flow cytometry; t-SNE; high-dimensional space analyses; classification; dimensionality reduction; immunophenotyping

Online: 4 March 2024 (01:30:54 CET)

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Preprint REVIEW | doi:10.20944/preprints202402.1767.v1

Identification and Diagnosis of Complete Haptoglobin Gene Deletion, the Gene Responsible for Adverse Posttransfusion Reactions

Mikiko Soejima, Yoshiro Koda

Subject: Medicine And Pharmacology, Hematology Keywords: adverse reactions, haptoglobin deficiency, haptoglobin gene deletion, serum protein, transfusion,.

Online: 29 February 2024 (21:07:24 CET)

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Preprint ARTICLE | doi:10.20944/preprints202402.1399.v1

Biological Monitoring of Extracorporeal Photopheresis for Steroid Resistant Acute Graft versus Host Disease by a Short Culture Method and Flow Cytometry

Luca Pierelli, Anna Capalbo, Eleonora Ponte, Paola Iudicone, Stefano Spurio, Sara Morara, Roberta Battistini, Anna Proia

Subject: Medicine And Pharmacology, Hematology Keywords: graft versus host disease; extracorporeal photopheresis; T cell death; biological quality control

Online: 26 February 2024 (09:40:12 CET)

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Preprint ARTICLE | doi:10.20944/preprints202402.1332.v1

Application of Optical Genome Mapping to the Risk Stratification and Treatment Optimization of Hematologic Diseases

Meena Naik, Nishit Ojha, Trilochan Sahoo, Amey Panchal, Yesheswini Naik, Rahul Arora, Vishvdeep Khushoo, Vasu Babu, Nishad Dhakate, Poonam Jain, Punit Jain, Govind Babu, Jen Hauenstein, Anusha Myelavarapu, Beth Matthews, Stephen J Wicks, Alex Hastie, Alka Chaubey, Sandeep Rao, Sachin Jadhav

Subject: Medicine And Pharmacology, Hematology Keywords: structural variation; optical genome mapping; cytogenetic; hematological disorders

Online: 23 February 2024 (11:04:40 CET)

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Preprint ARTICLE | doi:10.20944/preprints202402.1079.v2

Integrated Multi-Cohort Analysis of Whole-Genome and Transcriptome Data Reveals Interplay between Metabolism and Methylation in Myelodysplastic Syndrome (MDS)

Waseem Alzamzami, Sael Alatawi

Subject: Medicine And Pharmacology, Hematology Keywords: Myelodysplastic syndrome (MDS); Metabolism; DNA Methylation; DNMT3A; TET2

Online: 22 February 2024 (11:39:16 CET)

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Preprint ARTICLE | doi:10.20944/preprints202402.0620.v1

Prognostic Significance of Heart Failure in Acute Pulmonary Embolism: A Comprehensive Assessment of 30-Day Outcomes

Mariam Farid-Zahran Osuna, Manuel Méndez-Bailón, José María Pedrajas, Rubén Alonso-Beato, Francisco Galeano-Valle, Vanesa Sendín Martín, Javier Marco-Martínez, Pablo Demelo-Rodríguez

Subject: Medicine And Pharmacology, Hematology Keywords: heart failure; venous thromboembolism; pulmonary embolism; mortality; bleeding; comorbidity; left ventricular ejection fraction (LVEF)

Online: 12 February 2024 (08:51:07 CET)

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Preprint ARTICLE | doi:10.20944/preprints202402.0593.v1

Towards the Gene Profile of Acute Myeloid Leukaemia Using Machine Learning and Blood Transcriptomics

Athanasios Angelakis, Romar Nathoe, Michael Filippakis

Subject: Medicine And Pharmacology, Hematology Keywords: acute myeloid leukemia; blood transcriptomics; machine learning; explainable artificial intelligence; Catboost

Online: 12 February 2024 (04:56:38 CET)

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Preprint REVIEW | doi:10.20944/preprints202402.0477.v1

Immuno-Hematologic Complexity of ABO-Incompatible Allogeneic HSC Transplantation

Luca Pierelli, Antonella Matteocci

Subject: Medicine And Pharmacology, Hematology Keywords: HSCT; ABO-incompatibility; immuno-hematologic monitoring; anti-A/B titration

Online: 8 February 2024 (09:46:51 CET)

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Preprint COMMUNICATION | doi:10.20944/preprints202312.0651.v2

Lactoferricin B Combined with Antibiotics Exhibits Leukemic Selectivity and Antimicrobial Activity

Jan Jakub Lica, Katarzyna Gucwa, Mateusz Heldt, Anna Stupak, Natalia Maciejewska, Natalia Ptaszyńska, Anna Łęgowska, Bhaskar Pradhan, Agata Gitling-Domagalska, Dawid Dębowski, Joanna Jakóbkiewicz-Banecka, Krzysztof Rolka

Subject: Medicine And Pharmacology, Hematology Keywords: alternative leukemia treatment; antileukemic agents; antimicrobial peptide; dual-activity compounds; bioconjugates; cell penetration peptide; ciprofloxacin; hematopoietic stem cell transplantation; levofloxacin; lactoferricin B; fluconazole; fluoroquinolones.

Online: 29 January 2024 (08:40:14 CET)

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Preprint ARTICLE | doi:10.20944/preprints202401.1937.v1

Real-World Data Analysis of Patients Affected by Acquired Thrombotic Thrombocytopenic Purpura in Italy

Emanuele Angelucci, Andrea Artoni, Luana Fianchi, Melania Dovizio, Biagio Iacolare, Stefania Saragoni, Luca Degli Esposti

Subject: Medicine And Pharmacology, Hematology Keywords: acquired thrombotic thrombocytopenic purpura; caplacizumab; epidemiology; mortality; real-world evidence

Online: 27 January 2024 (10:54:56 CET)

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Preprint REVIEW | doi:10.20944/preprints202401.1747.v1

Chronic Lymphocytic Leukemia: Prognostic/Predictive Factors in the Era of Novel Drugs

Antonio Urso, Enrica Antonia Martino, Antonio Cuneo, Massimo Gentile, Gian Matteo Rigolin

Subject: Medicine And Pharmacology, Hematology Keywords: chronic lymphocytic leukemia; BTK inhibitors; BCL-2 inhibitors; prognostic scores; predictive factors; TP53 abnormalities; IGHV; complex karyotype

Online: 24 January 2024 (13:39:51 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202401.1359.v1

Primary Bone Lymphoma of the Scapula with an Unexpected Complication

Josip Lovaković, Inga Mandac Smoljanović, Andro Matković, Tomislav Smoljanović

Subject: Medicine And Pharmacology, Hematology Keywords: Primary bone lymphoma; scapula; diffuse large B cell lymphoma; immunochemotherapy; radiotherapy

Online: 18 January 2024 (10:29:02 CET)

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Preprint ARTICLE | doi:10.20944/preprints202401.1109.v1

Impact of Patient Blood Management on Red Blood Cell Utilization in an Urban Community Teaching Hospital: A Seven-Year Retrospective Study

Ding Wen Wu, Mark T Friedman, Daniel Lombardi, Richard Hwang, Joel Sender, Valdet Cobaj, Masooma Niazi, Yanhua Li, Robert Karpinos

Subject: Medicine And Pharmacology, Hematology Keywords: Patient blood management; red blood cell; transfusion

Online: 15 January 2024 (08:02:43 CET)

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Preprint REVIEW | doi:10.20944/preprints202401.0994.v1

Approach to Acute Myeloid Leukemia with Increased Eosinophils and Basophils

Stavros Papadakis, Ioannis Liapis, Stefanos I. Papadhimitriou, Emmanouil Spanoudakis, Ioannis Kotsianidis, Konstantinos Liapis

Subject: Medicine And Pharmacology, Hematology Keywords: acute myeloid leukemia; AML; eosinophil; eosinophilia; basophil; basophilia; morphology; CBF; PDGFRA; PDGFRB

Online: 12 January 2024 (07:13:16 CET)

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Preprint COMMUNICATION | doi:10.20944/preprints202401.0604.v1

Next Generation Sequencing Study of clonal Evolution in AML Shows Mutations in RAS-MAPK Signaling Pathway as an Emergent Mechanism of Progression in Low-Intensity Treatments

Carlos Jiménez-Vicente, Monica Lopez-Guerra, Amanda Isabel Pérez-Valencia, Daniel Munarriz, Francesca Guijarro, Sandra Castaño-Diez, Alexandra Martinez-Roca, Albert Cortes-Bullich, Aina Cardus, Daniel Esteban, Ana Triguero, Natalia Tovar, Isabel Hernandez, Dolors Colomer, Marina Diaz-Beya, Jordi Esteve

Subject: Medicine And Pharmacology, Hematology Keywords: clonal evolution; NGS; escape mechanisms; low-intensity treatment; AML

Online: 8 January 2024 (14:04:24 CET)

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Preprint REVIEW | doi:10.20944/preprints202401.0466.v1

Platelets and Thrombotic Antiphospholipid Syndrome

Ibrahim Tohidi, Prabal Mittal, David Isenberg, Hannah Cohen, Maria Efthymiou

Subject: Medicine And Pharmacology, Hematology Keywords: ; Antiphospholipid syndrome; antiphospholipid antibodies; thrombosis; platelets; antiplatelets ;

Online: 5 January 2024 (07:11:24 CET)

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Preprint REVIEW | doi:10.20944/preprints202401.0262.v1

p38 MAPK Molecular Targeting for Next-Generation Multiple Myeloma Therapy

Mario Morales-Martinez, Mario I Vega

Subject: Medicine And Pharmacology, Hematology Keywords: multiple myeloma; p38 mapk; transcriptional factor; cancer progression; clinical implication; gene expression

Online: 4 January 2024 (05:44:50 CET)

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Preprint REVIEW | doi:10.20944/preprints202401.0323.v1

Haemophilia and Cancer: A Systematic Review

Ezio Zanon, Annamaria Porreca, Paolo Simioni

Subject: Medicine And Pharmacology, Hematology Keywords: haematology; haemophilia; cancer; malignancy; congenital bleeding disorders

Online: 4 January 2024 (03:47:09 CET)

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Preprint ARTICLE | doi:10.20944/preprints202401.0265.v1

Type II JAK2 Inhibitor CHZ‐868 and HSP90 Inhibitors Are Potent towards the Ruxolitinib Resistant JAK2 Variants in JAK2 Driven Myeloproliferative Neoplasms

Sivahari Prasad Gorantla, Gerin Prince, Jasmin Osius, Dhurvas Dinesh, Vijay Kumar Boddu, Justus Duyster, Nikolas Von Bubnoff

Subject: Medicine And Pharmacology, Hematology Keywords: Myeloproliferative neoplasms; JAK2-V617F mediated resistance; ruxolitinib; JAK2-STAT5 signaling; HSP90 inhibition

Online: 3 January 2024 (14:39:52 CET)

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Preprint ARTICLE | doi:10.20944/preprints202401.0239.v1

Clinical Validation Of ANKRD36 Mutations As A Novel Biomarker For Monitoring Early Progression and Timely Clinical Interventions In Blast Crisis CML

Nawaf Al-anazi, Muhammad Absar, Abdulaziz Siyal, Salman Basit, Masood Shammas, Amer Mahmood, Sarah Almukhaylid, Zafar Iqbal

Subject: Medicine And Pharmacology, Hematology Keywords: Chronic Myeloid Leukemia; CML progression; Poor survival; Genomic instability; Blast crisis; ANKRD36; Clinical validation

Online: 3 January 2024 (10:25:49 CET)

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Background: Chronic Myeloid Leukemia (CML) is initiated in the bone marrow due to the chromosomal translocation t(9;22), resulting in the fusion oncogene BCR-ABL. Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have transformed fatal CML into an almost curable disease. However, TKIs lose efficacy during disease progression, and the mechanism of CML progression remains to be fully understood. Additionally, common molecular biomarkers for CML progression are lacking. Our studies previously detected ANKRD36 (c.1183_1184 delGC and c.1187_1188 dupTT) associated exclusively with advanced phase CML. However, clinical validation of this finding was pending. Therefore, this study aimed to clinically validate mutated ANKRD36 as a novel biomarker of CML progression. Materials and Methods: The study enrolled 124 patients in all phases of CML, recruited from Mayo Hospital and Hameed Latif Hospital in Lahore, Punjab, between January 2020 and September 2023. All response criteria were adopted from the European LeukemiaNet guideline 2020. Informed consent was obtained from all study subjects. The study was approved byscientific and ethical review committees of all participating centers. Sanger sequencing was employed to detect ANKRD36mutations in CML patients in accelerated phase (AP) (n=11) and blast crisis (BC) (n=10), with chronic-phase CML (CP-CML) patients as controls (n=103). Samples were processed using Big Dye Terminator Cycle Sequencing Ready Reaction kits and sequenced using ABI Prism 3730 Genetic Analyzer, and sequencing using forward and reverse primers for ANKRD36.Results: During our study, 17% of CML patients progressed to advanced phases AP-CML n= 11 (8.9%) and BC-CML n=10(8.1%). The chronic- and advanced-phase patients showed significant difference with respect to male-to-female ratio, hemoglobin level, WBC count, and platelet count. Sanger sequencing detected ANKRD36 mutations c.1183_1184 delGC and c.1187_1185 dupTT exclusively in all AP- and BC-CML patients but in none of the CP-CML patients. Nevertheless, mutations status was not associated with male-to-female ratio, hemoglobin level, WBC count, and platelet count, which makes ANKRD32 as an independent predictor of early and terminal disease progression in CML. Conclusions: The study confirms ANKRD36 as a novelgenomic biomarker for early and late CML progression. Further prospective studies should be carried out in this regard. ANKRD36, although fully uncharacterized in humans, shows the highest expression in bone marrow, particularly myeloid cells. Functional integrated genomic studies are recommended to further explore the role of ANKRD36 in the biology and pathogenesis of CML.

Preprint ARTICLE | doi:10.20944/preprints202311.0952.v2

Flow-cytometry Assessment of DNA content Analysis and Immunophenotyping of Immune-cells in Lymph-node-specimens as Potential Diagnostic Signature of Aggressiveness in B-Non-Hodgkin Lymphomas

David Azoulay, Tal Tapuchi, Ohad Ronen, Luiza Akria, Hector I Cohen, Celia Surio, Svetlana Rodin Chepa, Moran Zarfati, Galia Stemmer, Elizabeth Eshel, Netanel A Horowitz

Subject: Medicine And Pharmacology, Hematology Keywords: Lymph-node (LN); Aggrressive-lymphoma; ; Indolent-lymphoma; DNA-cell-cycle-indexing; immune-cells; tumor-microenvironment ;

Online: 3 January 2024 (05:31:53 CET)

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Preprint REVIEW | doi:10.20944/preprints202312.2256.v1

Unmet Horizons: Assessing the Challenges in the Treatment of TP53-Mutated Acute Myeloid Leukemia

Christos Stafylidis, Dimitra Vlachopoulou, Christina-Nefeli Kontandreopoulou, Panagiotis Diamantopoulos

Subject: Medicine And Pharmacology, Hematology Keywords: acute myeloid leukemia; TP53 mutations; TP53-mutated acute myeloid leukemia; novel targeted AML therapies; AML immunotherapies

Online: 29 December 2023 (05:27:17 CET)

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Preprint REVIEW | doi:10.20944/preprints202312.1578.v1

Vaccine-Induced Immune Thrombotic Thrombocytopenia—Clinicopathologic Features and New Perspectives on Anti-PF4 Antibody-Mediated Disorders

Yi Zhang, Anna-Lise Bissola, Jared Treverton, Michael Hack, Mark Lychacz, Sarah Kwok, Addi Arnold, Ishac Nazy

Subject: Medicine And Pharmacology, Hematology Keywords: vaccine-induced immune thrombotic thrombocytopenia; adenoviral-vector based COVID-19 vaccines; platelet-factor 4; anti-PF4 antibody-mediated disorders; platelet; SARS-CoV-2

Online: 20 December 2023 (16:45:08 CET)

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Preprint ARTICLE | doi:10.20944/preprints202312.0728.v1

Cell‐Free DNA as a Biomarker at Diagnosis and Follow up in 256 B and T Cell Lymphomas

Ramón Diez-Feijoo, Marcio Andrade-Campos, Joan Gibert, Blanca Sánchez-González, Lierni Fernández-Ibarrondo, Concepción Fernández-Rodríguez, Nieves Garcia-Gisbert, Laura Camacho, Marta Lafuente, Ivonne Vázquez, Lluís Colomo, Antonio Salar, Beatriz Bellosillo

Subject: Medicine And Pharmacology, Hematology Keywords: cfDNA; Liquid biopsy; Lymphoma; monitoring

Online: 11 December 2023 (15:59:03 CET)

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Preprint COMMUNICATION | doi:10.20944/preprints202312.0651.v1

Lactoferrin B Combined with Antibiotics Exhibits Leukemic Selectivity and Antimicrobial Activity

Jan Jakub Lica, Katarzyna Gucwa, Mateusz Heldt, Anna Stupak, Natalia Maciejewska, Natalia Ptaszyńska, Anna Łęgowska, Bhaskar Pradhan, Agata Gitling-Domagalska, Dawid Dębowski, Joanna Jakóbkiewicz-Banecka, Krzysztof Rolka

Subject: Medicine And Pharmacology, Hematology Keywords: Alternative Leukemia Treatment; Antileukemic Agents; Dual-Activity Compounds; Bioconjugates; Cell Penetration Peptide; Ciprofloxacin; Hematopoietic Stem Cells Transplantation; Levofloxacin; Fluconalozle; Fluoroquinolones; LfcinB

Online: 11 December 2023 (06:06:21 CET)

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Preprint ARTICLE | doi:10.20944/preprints202312.0595.v1

Safety and Efficacy of TKIs in Very Elderly Patients (≥75 Years) with Chronic Myeloid Leukemia

Alessandro Costa, Elisabetta Abruzzese, Roberto Latagliata, Olga Mulas, Ida Carmosino, Emilia Scalzulli, Maria Laura Bisegna, Claudia Ielo, Maurizio Martelli, Giovanni Caocci, Massimo Breccia

Subject: Medicine And Pharmacology, Hematology Keywords: chronic myeloid leukemia; tyrosine kinase inhibitor; very elderly; safety; efficacy; outcome; dose optimization

Online: 8 December 2023 (10:26:16 CET)

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Background: While outcomes of chronic phase chronic myeloid leukemia (CP-CML) patients aged over 65 years have been extensively evaluated in real-life experiences, limited data exist for the very elderly population (i.e., aged ≥ 75 years), especially for next-generation tyrosine kinase inhibitors (TKIs). In this retrospective study, we sought to evaluate the safety and efficacy of TKIs in this particular setting of patients. Methods: We conducted a retrospective analysis of a multicenter cohort of 123 newly diagnosed CP-CML very elderly patients. Results: The median age at diagnosis was 80 years (range: 75-96). In the first-line, 86.1% of patients received imatinib, 7.1% dasatinib, 5.6% nilotinib, and 0.81% received bosutinib. A total of 31 patients (25.2%) switched to second-line therapy, nine patients to a third-line and one patient to a fourth line of therapy. Resistance to treatment was the primary reason for switching therapy in both the first (64.5%) and second lines (77.7%). At diagnosis, reduced doses were administered in 36.5% of patients, in 61.2% in the second line, and in all patients in subsequent lines of therapy. In first-line setting, 71.9% of patients achieved an early molecular response (EMR, i.e. 3-month BCR::ABL1 IS <10%); at 6, 12, and 24 months, MR3 was reached by 35.7%, 55.7%, and 75.0% of patients, with 16.6%, 35.7%, and 51.7% achieving DMR at the same timepoints. Treatment-free remission (TFR) was successfully attempted in 11 patients. During the follow-up period, adverse events (AEs) were observed in 78.8% of patients, including 22 cases of cardiovascular AEs. Toxicity grade ≥ 3 was more commonly observed in patients treated with standard doses of TKIs compared to reduced doses (p=0.033). Overall, median follow-up was 46.62 months (range: 1.8-206.2), and 43 patients died due to non CML related causes. Three patients died due to disease progression to advanced (n=1) and blastic (n=2) phases. The 5-year overall survival (OS) for the entire cohort was 71.9% (95% CI: 0.63-0.81), with no significant difference between patients treated with standard doses of TKI compared to those treated with reduced doses (p=0.35). Conclusions: TKIs appear to be safe and effective even in very elderly CML patients, and dose optimization strategies yield satisfactory molecular responses for adequate disease control with an improved safety profile.

Preprint REVIEW | doi:10.20944/preprints202312.0095.v1

Hematological Neoplasm with Eosinophilia

Rosario M Morales-Camacho, Teresa Caballero-Velázquez, Juan José Borrero, Ricardo Bernal, Concepción Prats-Martín

Subject: Medicine And Pharmacology, Hematology Keywords: Eosinophilia,; hematological neoplasm; myeloid/lymphoid neoplasm with eosinophilia; tyrosine kinase fusion genes; acute leukemia

Online: 1 December 2023 (16:34:12 CET)

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Preprint ARTICLE | doi:10.20944/preprints202311.1973.v1

Smart Conditioning with Venetoclax Enhanced Sequential FLAMSA + RIC in Patients with High-Risk Myeloid Malignancies

Felicitas Schulz, Paul Sebastian Jäger, Johanna Tischer, Alessia Fraccaroli, Gesine Bug, Andreas Hausmann, Ben Niklas Baermann, Patrick Tressin, Alexander Sebastian Hoelscher, Annika Kasprzak, Kathrin Nachtkamp, Johannes Schetelig, Inken Hilgendorf, Ulrich Germing, Sascha Dietrich, Guido Kobbe

Subject: Medicine And Pharmacology, Hematology Keywords: FLAMSA; allogeneic transplant (aHSCT); sequential conditioning; AML; MDS; myeloid malignancies; reduced-intensity conditioning; RIC; Venetoclax

Online: 30 November 2023 (10:24:31 CET)

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Preprint REVIEW | doi:10.20944/preprints202311.1158.v1

Parenteral Iron Therapy for Pediatric Patients

Elpis Mantadakis, Sonia Alexiadou, Panagiota Zikidou

Subject: Medicine And Pharmacology, Hematology Keywords: iron deficiency; iron deficiency anemia; intravenous iron; iron sucrose; ferric carboxymaltose; iron isomaltoside; inflammatory bowel diseases

Online: 20 November 2023 (02:41:19 CET)

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Preprint ARTICLE | doi:10.20944/preprints202311.0952.v1

Flow-cytometry Assessment of DNA content Analysis and Immunophenotyping of Immune-cells in Lymph-node-specimens as Potential Diagnostic Signature of Aggressiveness in B-Non-Hodgkin Lymphomas

Tal Tapuchi, Ohad Ronen, Luiza Akria, Hector I Cohen, Celia Surio, Svetlana Rodin Chepa, Moran Zarfati, Galia Stemmer, Netanel A Horowitz, David Azoulay

Subject: Medicine And Pharmacology, Hematology Keywords: Lymph-node (LN); Aggrressive-lymphoma; Indolent-lymphoma; DNA-cell-cycle-indexing; immune-cells; tumor-microenvironment

Online: 15 November 2023 (01:56:10 CET)

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Preprint REVIEW | doi:10.20944/preprints202311.0714.v1

Primary Cutaneous CD30 positive Lymphoproliferative Disorders—Current Therapeutic Approach with Focus on Brentuximab Vedotin

Tomas Stein, Tadeusz Robak, Wojciech Biernat, Ewa Robak

Subject: Medicine And Pharmacology, Hematology Keywords: Anaplastic large cell lymphoma; Brentuximab vedotin; CD30 positive lymphomas; Diagnosis; Lymphomatoid papulosis; Primary cutaneous T-cell lymphoma; Treatment

Online: 13 November 2023 (08:27:17 CET)

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Preprint CASE REPORT | doi:10.20944/preprints202311.0678.v1

Chromosomal Translocations t(1; 22)(q21; q11.2) and t(6; 18)(p25; q21) in a Patient with Diffuse Large B-cell Lymphoma: FISH Analysis

Hiroaki Kitamura, Yasushi Kubota, Ichiro Hanamura, Sivasundaram Karnan, Rika Tomimasu, Michiaki Akashi, Shiho Tsuruda, Akiyoshi Takami, Shinya Kimura, Masaharu Miyahara

Subject: Medicine And Pharmacology, Hematology Keywords: diffuse large B-cell lymphoma; fluorescence in situ hybridization; 1q21; immunoglobulin lambda; BCL2

Online: 10 November 2023 (07:25:54 CET)

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Preprint ARTICLE | doi:10.20944/preprints202311.0145.v1

Predictive Model for Occurrence of Febrile Neutropenia after Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma: A Multicenter, Retrospective, Observational Study

Masaya Morimoto, Yuma Yokoya, Kikuaki Yoshida, Hideki Kosako, Yoshikazu Hori, Toshiki Mushino, Shinobu Tamura, Reiko Ito, Ryosuke Koyamada, Takuya Yamashita, Shinichiro Mori, Nobuyoshi Mori, Sachiko Ohde

Subject: Medicine And Pharmacology, Hematology Keywords: febrile neutropenia; chemotherapy; diffuse large B-cell lymphoma; outcomes; multivariate logistic regression model

Online: 2 November 2023 (10:24:29 CET)

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Preprint REVIEW | doi:10.20944/preprints202311.0006.v1

Engagement of Mesenchymal Stromal Cells in the Remodeling of Bone Marrow Microenvironment in Hematological Cancers

Sebastiano Giallongo, Andrea Duminuco, Ilaria Dulcamare, Tatiana Zuppelli, Enrico La Spina, Grazia Scandura, Annalisa Santisi, Alessandra Romano, Francesco Di Raimondo, Daniele Tibullo, Giuseppe Alberto Palumbo, Cesarina Giallongo

Subject: Medicine And Pharmacology, Hematology Keywords: MSCs; tumor transformation; hematological cancers; senescence; inflammation

Online: 1 November 2023 (04:05:53 CET)

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Preprint REVIEW | doi:10.20944/preprints202310.1750.v1

The Journey to Clonal Hematopoiesis and Applications Incardiovascular Disease and Cancer

Santiago Redondo, Jaime Perez de Oteyza

Subject: Medicine And Pharmacology, Hematology Keywords: Atherosclerotic; Inflammation; Bone marrow; Clonal Hematopoiesis; Myeloproliferative Neoplasm; Autoimmunity; Cardiovascular Risk; Cardio-Oncology

Online: 30 October 2023 (06:54:10 CET)

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Preprint ARTICLE | doi:10.20944/preprints202310.1611.v1

Hematopoietic Cell Transplantation Trends and Outcomes in Canada: A Registry-based Cohort Study

Matthew D. Seftel, Ivan Pasic, Gaganvir Parmar, Oliver Bucher, David S. Allan, Sita Bhella, Kevin Anthony Hay, Olaweseun Ikuomola, Grace Musto, Anca Prica, Erin Richardson, Tony H Truong, Kristjan Paulson

Subject: Medicine And Pharmacology, Hematology Keywords: hematopoietic cell transplant; cellular therapy; health outcomes

Online: 25 October 2023 (11:50:41 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202310.1317.v1

Steroid-Induced Hyperglycemia and Its Effect on Outcomes of R-CHOP Chemotherapy for Non-Hodgkin Lymphoma

Mark Kristjanson, Pascal Lambert, Kathleen Decker, Sonja Bruin, Elizabeth Tingey, Pamela Skrabek

Subject: Medicine And Pharmacology, Hematology Keywords: lymphoma; steroid; hyperglycemia; toxicities

Online: 20 October 2023 (08:13:04 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202310.1017.v1

Comparative Effect of Human Recombinant Erythropoietin and Roxadustat on Blood Pressure and Micro-Inflammatory Response in Hemodialysis Anemia

Wenwen Li, Fei Zha, Chunhua Shi

Subject: Medicine And Pharmacology, Hematology Keywords: roxadustat; rhEPO; blood pressure; micro-inflammatory state; lipid metabolism

Online: 17 October 2023 (08:29:21 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202310.0918.v1

Understanding the Role of Activation Loop Mutants in Drug Efficacy for FLT3-ITD

Julhash U. Kazi, Lina Al Ashiri, Rituraj Purohit, Lars Rönnstrand

Subject: Medicine And Pharmacology, Hematology Keywords: drug sensitivity scores; molecular modeling; molecular docking; four-parameter logistic curve

Online: 16 October 2023 (11:38:46 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202310.0833.v1

Red Blood Cell Exchange as a Valid Therapeutic Approach for Pregnancy Management in Sickle Cell Disease. Three Explicative Cases and Systematic Review of Literature

Caterina Giovanna Valentini, Claudio Pellegrino, Sara Ceglie, Vincenzo Arena, Francesca Di Landro, Patrizia Chiusolo, Luciana Teofili

Subject: Medicine And Pharmacology, Hematology Keywords: sickle cell disease; pregnancy; erytrocytapheresis; transfusion; HbS

Online: 12 October 2023 (13:09:36 CEST)

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Preprint REVIEW | doi:10.20944/preprints202310.0556.v1

Leukemia Cutis—the Current View on Pathogenesis, Diagnosis and Treatment

Ewa Robak, Marcin Braun, Tadeusz Robak

Subject: Medicine And Pharmacology, Hematology Keywords: acute leukemia; chronic leukemia; cutis; diagnosis; pathogenesis; prolympchocytic leukemia; Richter transformation; skin lesions; treatment

Online: 10 October 2023 (05:36:42 CEST)

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Preprint REVIEW | doi:10.20944/preprints202309.2129.v1

Refractory Immune Thrombocytopenia or Myelodysplastic Syndrome Presenting with Isolated Thrombocytopenia? A Review of Literature and a Case Report

Riccardo Tomasello, Claudia Cammarata, Marta Mattana, Manuela Giuseppa Ingrascì, Giulio Giordano, Alessandro Lucchesi, Waleed Ghanima, Sergio Mario Siragusa, Mariasanta Napolitano

Subject: Medicine And Pharmacology, Hematology Keywords: Immune thrombocytopenia; chronic ITP; myelodysplastic syndrome; chronic myelomonocytic leukemia; refractory thrombocytopenia

Online: 30 September 2023 (07:14:13 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202309.1391.v1

Prophylactic Therapy with Emicizumab in Patients with Hemophilia A: Benefits and Challenges

Melen Brinza, Valentina Uscatescu, Mihai Himcinschi, Elisabeta Chiriac, Georgiana Gherghe, Daniel Coriu

Subject: Medicine And Pharmacology, Hematology Keywords: hemophilia A; inhibitors; Emicizumab

Online: 21 September 2023 (03:32:12 CEST)

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This study presents a transversal investigation, that we performed at Fundeni hospital, into the therapeutic benefits and efficacy of Emicizumab, a non-factor therapy, in the context of hemophilia A. Ten patients diagnosed with hemophilia A were closely monitored, using clinical and laboratory resources, during the course of Emicizumab treatment, with an average of 12.8 months. Among these patients, six exhibited anti-factor VIII inhibitors, changing the medical approach and adding complexity to their clinical profiles. A comprehensive approach was adopted to assess the coagulation status of patients under Emicizumab therapy. The study employed several key coagulation monitoring tools, of which including thrombin generation time (TGT) and thrombelastography (TEG). These methodologies proved highly valuable results in evaluating the patients' coagulation profiles during the treatment regimen. Additionally, traditionally coagulation assays were utilized to gain a comprehensive understanding of the overall coagulation dynamics. Noteworthy, impressive outcomes emerged from the study. During prophylaxis with Emicizumab all patients had experienced a reduced number of bleeding events. Moreover, a subset of these patients underwent major surgical procedures (orthopedic joint replacements) with successful outcomes. These findings underscore the potential of Emicizumab therapy as an effective option for hemophilia A patients, including those that presented a prompt production of anti-factor VIII inhibitors. As for the outcomes, this transversal study sheds some light on the positive impact of Emicizumab therapy in addressing the coagulation challenges posed by hemophilia A. The utilization of global coagulation assays, such as thrombin generation time, thrombelastography and combined with traditional coagulation assays, used as monitoring tools highlights their significance once more in evaluating the therapeutic response. This research contributes by providing physicians with valuable insights to the field, offering a potential avenue for improved patients’ care and treatment strategies that translate in enhanced quality of life for hemophilia A patients undergoing Emicizumab therapy.

Preprint ARTICLE | doi:10.20944/preprints202309.1338.v1

Iron Chelation in Patients with Myelodysplastic Syndromes and Myeloproliferative Neoplasms—Real-World Data from the German Non- Interventional Study EXCALIBUR

Felicitas Schulz, Ulrich Hauch, Sandra Ketzler-Henkel, Eyck Von der Heyde, Michael Koenigsmann, Michael Lauseker, Nora Schulte, Ulrich Germing

Subject: Medicine And Pharmacology, Hematology Keywords: iron chelation; iron overload; myelodysplastic syndromes; MDS; myeloproliferative neoplasms; MPN; ferritin; hematologic improvement

Online: 20 September 2023 (05:39:06 CEST)

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Preprint REVIEW | doi:10.20944/preprints202309.1180.v1

Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future

Hanley N. Abramson

Subject: Medicine And Pharmacology, Hematology Keywords: myeloma; daratumumab; bispecific antibodies; chimeric antigen receptor T-cells; immunotherapy

Online: 19 September 2023 (05:28:58 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202309.1120.v1

C-Type Lectin-like Receptor 2 Expression Is Decreased upon Platelet Activation and Is Lower in Most Tumor Entities Compared to Healthy Controls

Mani Etemad, Foteini Christodoulou, Stefanie Uhlig, Jessica C. Hassel, Petra Schrotz-King, Hermann Brenner, Cornelia M. Ulrich, Karen Bieback, Harald Klüter, Peter Bugert

Subject: Medicine And Pharmacology, Hematology Keywords: platelet function; podoplanin; soluble CLEC-2; cancer thrombosis

Online: 18 September 2023 (10:50:11 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202309.0959.v1

T Lymphoblastic Lymphoma Hiding in Mature Plasmacytoid Dendritic Cell Proliferation: A Case Report and Literature Review

Cong Deng, Bei-bei Gao, Tian-li Wang, Xiao-Na Chang, Gui-xiang Xiao, Qin Xia, Hua-xiong Pan, Xiu Nie

Subject: Medicine And Pharmacology, Hematology Keywords: mature plasmacytoid dendritic cell proliferation, T lymphoblastic lymphoma, myeloid neoplasms, case report

Online: 14 September 2023 (07:22:23 CEST)

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Preprint REVIEW | doi:10.20944/preprints202309.0848.v1

p53 Biology and Reactivation for Improved Therapy in MDS and AML–Are We Building Castles in the Air?

Joanna Zawacka

Subject: Medicine And Pharmacology, Hematology Keywords: MDS; AML; p53; MDM2; MDM4; p73; improved therapy

Online: 13 September 2023 (10:09:18 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202309.0619.v1

Low-Intensity and Chemo-Free Treatments in Ph+ ALL: Progression-Free Survival Based on Indirect Comparisons

Melania Rivano, Daniele Mengato, Marco Chiumente, Andrea Messori

Subject: Medicine And Pharmacology, Hematology Keywords: acute lymphoblastic leukemia; imatinib; dasatinib: nilotinib; ponatinib; blinatumomab; reducedintensity chemotherapy; chemotherapy-free; progression-free

Online: 11 September 2023 (04:05:57 CEST)

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Preprint REVIEW | doi:10.20944/preprints202309.0229.v1

Immunotherapy of Acute Myeloid Leukemia: A Work in Progress

Matteo Molica, Salvatore Perrone, Marco Rossi

Subject: Medicine And Pharmacology, Hematology Keywords: acute myeloid leukemia; immunotherapy; checkpoint inhibitors; new therapeutic landscapes

Online: 6 September 2023 (14:36:13 CEST)

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Preprint REVIEW | doi:10.20944/preprints202309.0378.v1

Recommendations for the Clinical Approach to Primary Immune Thrombocytopenia

Maria Eva Mingot-Castellano, Mariana Canaro Hirnyk, Blanca Sánchez-González, Maria Teresa Alvarez-Roman, Abelardo Bárez-García, Ángel Bernardo-Gutiérrez, Silvia Bernat-Pablo, Estefanía Bolaños-Calderón, Nora Butta-Coll, Gonzalo Caballero-Navarro, Isabel Socorro Caparrós-Miranda, Laura Entrena Ureña, Luis Fernando Fernández-Fuertes, Luis Javier García-Frade, María del Carmen Gómez del Castillo Solano, Tomás José González-López, Carlos Grande-García, José María Guinea de Castro, Isidro Jarque-Ramos, Reyes Jiménez-Bárcenas, Elsa López-Ansoar, Daniel Martínez-Carballeira, Violeta Martínez-Robles, Emilio Monteagudo-Montesinos, José Antonio Páramo-Fernández, María del Mar Perera-Álvarez, Inmaculada Soto-Ortega, David Valcárcel-Ferreiras, Cristina Pascual-Izquierdo

Subject: Medicine And Pharmacology, Hematology Keywords: Primary immune thrombocytopenia; Glucocorticoids; Intravenous immunoglobulins; Fostamatinib; Rituximab; Recommendations

Online: 6 September 2023 (09:38:18 CEST)

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Preprint REVIEW | doi:10.20944/preprints202309.0016.v1

Neutropenia in Childhood. A Narrative Review and Practical Diagnostic Approach

Georgios Katsaras, Silouani Koutsi, Evdokia Psaroulaki, Dimitra Gouni, Pelagia Tsitsani

Subject: Medicine And Pharmacology, Hematology Keywords: neutropenia; neutrophils; childhood

Online: 1 September 2023 (11:49:11 CEST)

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Preprint REVIEW | doi:10.20944/preprints202308.1982.v1

The Role of Non-Coding RNAs in Myelodysplastic Neoplasms

Vasileios Georgoulis, Epameinondas Koumpis, Eleftheria Hatzimichael

Subject: Medicine And Pharmacology, Hematology Keywords: myelodysplastic syndromes; non-coding RNA; microRNA; lnc-RNA; circ-RNA; piwi-RNA; t-RNA; sno-RNA

Online: 29 August 2023 (13:42:14 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202308.1585.v1

Manifestation of Pancytopenia Associated with COVID-19 as Paroxysmal Nocturnal Hemoglobinuria (PNH) and Aplastic Anemia (AA)

Jeff Justin Aguilar, Vikram Dhillon, Suresh Balasubramanian

Subject: Medicine And Pharmacology, Hematology Keywords: Paroxysmal nocturnal hemoglobinuria; aplastic anemia; SARS-CoV-2

Online: 22 August 2023 (13:19:19 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202308.1526.v1

Prospective Comparative Study of Etoposide plus G-CSF versus G-CSF Alone, Followed by Risk-Adapted Plerixafor for Peripheral Blood Stem Cell Mobilization in Patients with Newly Diagnosed Multiple Myeloma: Catholic Research Network for Multiple Myeloma Study (CARE-MM 2001)

Sung-Soo Park, Chang-Ki Min, Young-Woo Jeon, Seung-Ah Yhang, Seung-Hwan Shin

Subject: Medicine And Pharmacology, Hematology Keywords: Etoposide; plerixafor; mobilization; multiple myeloma

Online: 22 August 2023 (09:34:00 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202308.1373.v1

Possible New Histological Prognostic Index for Large B-Cell Lymphoma

Hideaki Nitta, Haruko Takizawa, Toru Mitsumori, Hiroko Iizuka-Honma, Yoshihiko Araki, Maki Fujishiro, Shigeki Tomita, Satsuki Kishikawa, Akane Hashizume, Tomohiro Sawada, Mitsuo Okubo, Yasunobu Sekiguchi, Miki Ando, Masaaki Noguchi

Subject: Medicine And Pharmacology, Hematology Keywords: Large B-cell lymphoma (LBCL); Immunohistochemical (IHC) staining; Glucoseregulated protein 94 (GRP94); CYP3A4; Multidrug resistance protein 1 (MDR1); Aldo-keto reductase family 1 member C3 (AKR1C3); Multi-drug resistance-associated protein 1 (MRP1); P53

Online: 18 August 2023 (11:42:22 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202308.1141.v1

Prevalence and Significance of Elevated Cardiac Enzymes among Sickle Cell Disease Patients at King Abdulaziz University Hospital

Roaa Shaban, Osman O. Radhwi, Nadin Alharbi, Sondos Jar, Weam Bajunaid, Abdulaziz Alzahrani, Majed Alhuzali, Adel F. Almarzouki

Subject: Medicine And Pharmacology, Hematology Keywords: sickle cell; cardiac markers; vaso-occlusive; troponin; lactate dehydrogenase

Online: 16 August 2023 (03:18:46 CEST)

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Preprint REVIEW | doi:10.20944/preprints202308.0936.v1

Early Complications in the Era of ATRA Plus ATO Therapy Outside of Clinical Trials‐One Center Experience during Three Years and Literature Review‐

Ghiaur Alexandra, Cristina Doran, Bogdan Ionescu, Maria Camelia Stancioaica, Roxana Hirjan, Aurelia Tatic, Mihaela Cirstea, Mihaela Dragomir, Onda Calugaru, Codruta Popa, Cerasela Jardan, Didona Vasilache, Daniel Coriu

Subject: Medicine And Pharmacology, Hematology Keywords: acute promyelocytic leukemia; arsenic trioxide; all‐trans retinoic acid; non‐hematologic toxicities

Online: 14 August 2023 (09:52:50 CEST)

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Abstract The hallmark of acute promyelocytic leukemia (APL) is the presence of the characteristic fusion transcript of the promyelocytic leukemia gene with the retinoic acid receptor α gene (PML::RARA), which is a molecular target for all-transretinoic acid (ATRA) and arsenic trioxide (ATO). Therapies with ATRA plus ATO have excellent outcomes in terms of complete remission rate, overall survival, and achievement of a deep and durable molecular response with a very low incidence of relapse. However, although the combination of ATRA and ATO has lower hematologic toxicity than standard chemotherapy, its use is associated with a spectrum of unique toxicities, such as hepatic toxicity, QTc (QT interval corrected) prolongation, neurotoxicity, and differentiation syndrome. Hematologists treating patients with acute promyelocytic leukemia should be aware of possible early-complications of the ATRA plus ATO regimen and aim to balance treatment-related adverse events and efficacy. Careful follow-up of the patient’s clinical course is essential to identify and treat each complication. This study focused on treatment-related complications during induction and consolidations in patients with APL who received ATRA plus ATO. We retrospectively analyzed 26 adult patients diagnosed with APL between 2019 and 2022 at our center to identify the incidence rate, severity and time of onset of short-term non-hematologic adverse events relative to the initiation of the ATRA and ATO regimen. Additionally, we review the existing literature regarding the toxic side effects of ATO in APL and discuss how its most frequent toxicities should be managed. The median follow-up of our patients was 21.5 months (range, 1-48 months) and the most common adverse events were hepatic toxicity (69.2%), infections (46.1%), differentiation syndrome(23%) and QT prolongation (11.5%). All patients experienced at least one adverse event and grade 3 and 4 toxicities occurred in 57.6 % patients; these generally consisted of liver enzyme elevations, QTc prolongation, but also some rare manifestations such as musculoskeletal pain syndrome (1 patient) and ATO-related pancreatitis (1 patient). Most patients developed side-effects during induction. This is the first study about Romanian patients diagnosed with APL. Our results suggest that all treatment-related adverse events, except for differentiation syndrome are manageable, self-limiting and reversible. All patients, except for two (one died during induction and one died during consolidation), were able to complete the treatment consolidation with ATO and ATRA.

Preprint ARTICLE | doi:10.20944/preprints202308.0100.v1

Evidence for distinct mechanisms of immune suppression in EBV-positive and EBV-negative Hodgkin lymphoma

Makka Adam, Yonas Bekueretsion, Amha Gebremedhin, Anna Kwiecinska, Rawleigh Howe, Beyene Petros, Mats Jerkeman

Subject: Medicine And Pharmacology, Hematology Keywords: Epstein Barr Virus, HL microenvironment, Immune suppression

Online: 2 August 2023 (05:14:23 CEST)

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Preprint BRIEF REPORT | doi:10.20944/preprints202307.2162.v1

Long-Term L-Glutamine Treatment Reduces Hemolysis Without Ameliorating Hepatic Vasoocclusion and Liver Fibrosis in a Mouse Model of Sickle Cell Disease

Omika Katoch, Ramakrishna UV, Tomasz Kaminski, Ziming Li, Rikesh K Dubey, Isabella Burholt, Shweta Gudapati, Tirthadipa Pradhan-Sundd

Subject: Medicine And Pharmacology, Hematology Keywords: Sickle cell disease; hemolysis; vasoocclusion; l-glutamine; Liver injury; Kupffer cells

Online: 1 August 2023 (14:24:19 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202307.1984.v1

Pretreatment Cancer-Related Cognitive Impairment in Hodgkin Lymphoma Patients

Veronika Juríčková, Dan Fayette, Juraj Jonáš, Iveta Fajnerová, Jiří Horáček

Subject: Medicine And Pharmacology, Hematology Keywords: Cancer-related cognitive impairment; Hodgkin lymphoma; neuropsychology; affective distress; quality of life

Online: 28 July 2023 (09:23:56 CEST)

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Preprint REVIEW | doi:10.20944/preprints202307.1943.v1

Developing New Strategies for Relapsed/Refractory Diffuse Large B-Cell Lymphoma

EVA GONZALEZ-BARCA

Subject: Medicine And Pharmacology, Hematology Keywords: diffuse large B-cell lymphoma. relapsed/refractory; therapy; efficacy; toxicity

Online: 28 July 2023 (03:55:02 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202307.1450.v1

Thrombin Generation is Associated with Venous Thrombo-embolism Recurrence, but not with Major Bleeding and Death in the Elderly: A Prospective Multicenter Cohort Study

Kristina Vrotniakaite-Bajerciene, Sereina Rütsche, Sara Calzavarini, Claudia Quarroz, Odile Stalder, Marie Méan, Marc Righini, Daniel Staub, Juerg H. Beer, Beat Frauchiger, Joseph Österwalder, Nils Kucher, Christian M. Matter, Marc Husmann, Martin Banyai, Markus Aschwanden, Lucia Mazzolai, Olivier Hugli, Nicolas Rodondi, Drahomir Aujesky, Anne Angelillo-Scherrer

Subject: Medicine And Pharmacology, Hematology Keywords: Thrombin generation; venous thromboembolism; elderly; bleeding; mortality

Online: 21 July 2023 (12:46:36 CEST)

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Preprint REVIEW | doi:10.20944/preprints202307.1468.v1

Atypical Chronic Lymphocytic Leukemia—The Current Status

Tadeusz Robak, Anna Krawczyńska, Barbara Cebula-Obrzut, Marta Urbaniak, Elżbieta Iskierka-Jażdżewska, Paweł Robak

Subject: Medicine And Pharmacology, Hematology Keywords: CLL; atypical CLL; CD5; CD23; CLL differential diagnosis.

Online: 21 July 2023 (09:07:06 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202307.1234.v1

Comparison of Efficiency and Side Effects of Daily and Alternate Day Oral Iron

Ibrahim Nahit Sendur, Umit Yavuz Malkan

Subject: Medicine And Pharmacology, Hematology Keywords: Iron deficiency anemia; oral iron; side effects

Online: 18 July 2023 (14:17:18 CEST)

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Introduction: In the recent years alternate day dosing has been recommended in iron deficieny treatment. The aim of this study is to compare the efficacy and side effects of oral iron treatments given daily 1x1, alternate day 1x1 and 2x1 alternate day dosing in iron deficieny anemia patients. Methods: A total of 52 patients with a diagnosis of iron deficiency anemia with serum ferritin level of 25 µg/L or less were included in this retrospective study. Statistical analyzes were done with SPSS V.25. Results: The patients included in our study were between the ages of 18-51. All of the patients included in the study were female. A statistically significant increase was found between 0-14 days(p<0.001), 14-28 days(p<0.001) and 0-28 days(p<0.001) hemoglobin values in all patients. There was no statistically significant difference between 0-14 days (p=0.397) and 0-28 days(p=0.310) ferritin values in all patients. A statistically significant difference was found between 14-28 days(p<0.001) ferritin values. When the rate of change of hemoglobin and ferritin values between the groups was compared and no statistically significant difference was observed between the groups. The rate of change of ferritin values for 14-28 days was significant (p=0.012). There was no significant difference in the frequency of symptoms in the 14th day and 28th day controls for each group (p>0.05). The incidence of metallic taste and bloating symptoms was found to be statistically significant in the third control in the group with 2x1 drug use alternate day (p=0.094). Discussion: The only difference in efficacy was observed in ferritin values between 14th and 28th days. The increase in ferritin values was higher in the group that used 1x1 oral iron every day. However, since no difference was observed between the groups in terms of ferritin and hemoglobin values on days 0 and 28, all three groups were considered equally efficient. Side effects were mainly gastrointestinal side effects. Since the group that received 2x1 oral treatment alternate day had a statistically significantly higher rate of side effects, the patients’ treatment tolerance will be lower compared to the other groups. In conlusion, there is no difference in efficacy and side effects between the patient groups receiving 1x1 daily and 1x1 alternate day oral iron therapy, so 1x1 use alternate day is the most appropriate treatment method for oral iron therapy in terms of patient tolerance, adherence to treatment and pharmacoeconomics.

Preprint REVIEW | doi:10.20944/preprints202307.1091.v1

Hematopoietic Stem Cell Transplantation in Acute Promyelocytic Leukemia in the ATRA/ATO Era

Andrei Colita, Alina Daniela Tanase, Ciprian Tomuleasa, Anca Colita

Subject: Medicine And Pharmacology, Hematology Keywords: acute promyelocytic leukemia; relapse; hematopoietic stem cell transplantation

Online: 17 July 2023 (10:10:56 CEST)

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Preprint REVIEW | doi:10.20944/preprints202307.1039.v1

A Review of the Relationship between the Immune Response, Inflammation, Oxidative Stress, and the Pathogenesis of Sickle cell Anaemia

Florence Ifechukwude Aboderin, Taofeeq Oduola, Glenda Mary Davison, Oluwafemi Omoniyi Oguntibeju

Subject: Medicine And Pharmacology, Hematology Keywords: Keywords: sickle cell anaemia, chronic inflammation, immune system, oxidative stress, hemolysis, blood transfusion

Online: 17 July 2023 (09:25:33 CEST)

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Preprint REVIEW | doi:10.20944/preprints202307.0430.v1

Optimizing Treatment for Relapsed/Refractory Classic Hodgkin lymphoma in the Era of Immunotherapy

Michael P. Randall, Michael A. Spinner

Subject: Medicine And Pharmacology, Hematology Keywords: Hodgkin lymphoma; relapsed/refractory; brentuximab vedotin; checkpoint inhibitor; PD-1 inhibitor; nivolumab; pembrolizumab; autologous hematopoietic cell transplantation

Online: 6 July 2023 (11:44:13 CEST)

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Preprint REVIEW | doi:10.20944/preprints202306.1996.v1

Comparison of Different Rabbit Anti-thymocyte Globulin Formulations in the Prophylaxis of Graft-versus-Host Disease: A Systematic Review

Jarosław Dybko, Ugo Giordano, Justyna Pilch, Jakub Mizera, Artur Borkowski, Monika Mordak-Domagała

Subject: Medicine And Pharmacology, Hematology Keywords: anti-thymocyte globulin; acute graft-versus-host disease; chronic graft-versus-host disease; allogeneic stem cell transplantation; thymoglobuline; grafalon

Online: 28 June 2023 (10:20:03 CEST)

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Preprint REVIEW | doi:10.20944/preprints202306.1942.v1

Insights into Hepatocellular Carcinoma in Patients with Thalassemia: From Pathophysiology to Novel Therapies

Pei-Chin Lin, Wan-Yi Hsu, Po-Yi Lee, Shih-Hsien Hsu, Shyh-Shin Chiou

Subject: Medicine And Pharmacology, Hematology Keywords: Hepatocellular carcinoma (HCC); Thalassemia; Iron; Transfusion-Dependent Thalassemia (TDT); Non-Transfusion-Dependent Thalassemia (NTDT); Reactive Oxygen Species (ROS)

Online: 28 June 2023 (03:55:10 CEST)

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Preprint REVIEW | doi:10.20944/preprints202306.1898.v1

First-line Treatment of the Older Patients with CLL: A New Approach in the Chemo-free Era

Antonio Urso, Francesco Cavazzini, Maria Pia Ballardini, Silvia Gambara, Sara Consolo, Gian Matteo Rigolin, Antonio Cuneo

Subject: Medicine And Pharmacology, Hematology Keywords: chronic lymphocytic leukemia; older patient; ibrutinib; acalabrutinib; zanubrutinib; venetoclax; sustainabiity

Online: 27 June 2023 (12:04:57 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202306.1128.v1

Myeloid Sarcoma as an Unusual Presentation of Acute and Chronic Myeloid Leukemia: A Case Series

Ugo Giordano, Mateusz Sawicki, Justyna Pilch, Jakub Mizera, Artur Borkowski, Krzysztof Zduniak, Jarosław Dybko

Subject: Medicine And Pharmacology, Hematology Keywords: myeloid sarcoma; acute myeloid leukemia; chronic myeloid leukemia; chloroma; granulocytic sarcoma; case report

Online: 16 June 2023 (07:15:03 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202306.1076.v1

Enhancing the Anti-Leukemic Potential of Thymoquinone- SBE-β-CD Inclusion Complex

ELTAYEB E.M. EID, Salah Abdalrazak Alshehade, Amer A. Almiman, Sareh Kamran, Vannajan Sanghiran Lee, Mohammed Abdullah Alshawsh

Subject: Medicine And Pharmacology, Hematology Keywords: Thymoquinone; SBE-β-CD; Leukemia; Drug delivery system; Telomerase inhibition; Apoptosis

Online: 15 June 2023 (05:37:50 CEST)

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Preprint CASE REPORT | doi:10.20944/preprints202306.0943.v1

Hemophagocytic Lymphohistiocytosis Secondary to Hodgkin Lymphoma with Isolated Bone Marrow Involvement in a Newly Diagnosed HIV Patient

Alberto Lopez-Garcia, Laura Solan, Beatriz Alvarez, Juan Carlos Caballero, Javier Cornago, Laura Pardo, Francisco Javier Diaz de la Pinta, Raul Cordoba, Maria Rodriguez-Pinilla

Subject: Medicine And Pharmacology, Hematology Keywords: Lymphoma; HL; HIV; EBV; HLH

Online: 13 June 2023 (14:33:46 CEST)

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Preprint REVIEW | doi:10.20944/preprints202306.0849.v1

Epigenetic Alterations That Are the Backbone of Immune Evasion in T-Cell Malignancies

Mihaela Andreescu

Subject: Medicine And Pharmacology, Hematology Keywords: Molecular biology; infectious diseases; clinical diagnostic; early detection; prognosis

Online: 12 June 2023 (14:31:24 CEST)

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Preprint REVIEW | doi:10.20944/preprints202306.0742.v1

IgM Associated Cryoglobulinaemia

Jahanzaib Khwaja, Simon J Salter, Shirley D’Sa

Subject: Medicine And Pharmacology, Hematology Keywords: Cryoglobulinaemia; IgM; Waldenström macroglobulinemia; monoclonal gammopathy of clinical significance

Online: 12 June 2023 (03:16:55 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202306.0579.v1

Haematological Profile of Hb Adana Among High School Students in Northeast of Peninsular, Malaysia

Lee Miin Phoon, Mat Jusoh Siti Asmaa, Nur Atikah Zakaria, Suryati Hussin, Rosnah Bahar, Mohd Nazri Hassan, Zefarina Zulkafli, Salfarina Iberahim, Marne Abdullah, Noor Haslina Mohd Noor, Shafini Mohd Yusoff, Marini Ramli

Subject: Medicine And Pharmacology, Hematology Keywords: Hb Adana; non-deletional α-thalassaemia; Hb Constant Spring; HbE

Online: 8 June 2023 (03:58:49 CEST)

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Hb Adana is a non-deletional α-thalassaemia variant, due to mutations in α1- or α2-globin codon 59 (αCD59) that produce unstable α-globin. Clinical appearance can range from silent carrier to blood transfusion reliance, hepatosplenomegaly, skeletal deformities, and spinal cord compression. Despite the importance of Hb Adana inheritance, this Hb variant is challenging to study since molecular tests are scarce and routine diagnosis can be missed. This study explored the distribution of Hb Adana among local high school students and evaluate the hematological parameters and haemoglobin analysis of Hb Adana in this region of Malaysia. This retrospective study included 13,721 blood samples from high school students enrolled in Malaysia's National Thalassaemia Screening Program at Hospital Raja Perempuan Zainab II (HRPZ II). Multiplex Gap PCR was used to detect deletional α-thalassaemia. Common non-deletional α-thalassaemia was detected using multiplex ARMS PCR. Evaluable data were retrieved from the HRPZ II database. Results: A total of 2327 subjects exhibited common deletional (n=1037, 44.6%) and non-deletional (n=1290, 55.4%) α-thalassaemia. Hb Constant Spring was the most frequent non-deletional α-thalassaemia. Thirty-one participants (1.33%) had αCD59α/αα and one (0.04%) had αCD59α/-α3.7. The 32 Hb Adana subjects were 87.5% Malay, and 12.5% Orang Asli. Additionally, seven cases of HbE/Hb Adana were discovered. The haemoglobin level in heterozygous Hb Adana ranged from mild anaemia to normal, 95.0 g/L to 153.0 g/L. The MCV and MCH were approximately 73 fL and 23 pg, respectively. Conclusions: We have denoted the distribution of alpha thalassaemia mutation patterns among high school students in Kelantan, Northeast Peninsular of Malaysia. Our observation showed Hb Adana was rarely uncommon in our region and the co-inheritance with an α-gene deletion generates α+-thalassaemia; with HbE, α0-thalassaemia. All heterozygous Hb Adana exhibited low MCVs and MCHs.

Preprint REVIEW | doi:10.20944/preprints202306.0213.v1

Understanding the Intricacies of Iron Overload Associated With β-Thalassemia: A Comprehensive Review

Subhangi Basu, Motiur Rahaman, Tuphan Kanti Dolai, Praphulla Chandra Shukla, Nishant Chakravorty

Subject: Medicine And Pharmacology, Hematology Keywords: β-thalassemia; iron overload; iron chelators; TDT; NTDT

Online: 2 June 2023 (14:27:31 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.2148.v1

Real-World Clinical Characterization of Polycythemia Vera Patients From a Prospective Registry in Portugal: Is Resistance to Hydroxyurea a Reality?

Maria Sarmento, Marta Duarte, Sandra Ponte, Juan Sanchez, Diana Roriz, Laura Fernandes, Maria José Monteiro Silva, Judite Pacheco, Gisela Ferreira, Jorge Freitas, Inês Costa, Daniel Brás

Subject: Medicine And Pharmacology, Hematology Keywords: disease management; hemorragic events; hydroxyurea; resistance; symptomatic evaluation; patient-reported outcomes; thrombotic events; polycythemia vera

Online: 30 May 2023 (13:11:32 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.2138.v1

The Real-World Evidence on the Fragility and Its Impact on the Choice of Treatment Regimen in Newly Diagnosed Patients With Multiple Myeloma Over 75 Years of Age

Agata Tyczyńska, Marcela Krzysława Krzemek, Alexander Jorge Cortez, Artur Jurczyszyn, Katarzyna Godlewska, Hanna Ciepłuch, Edyta Subocz, Janusz Hałka, Anna Kulikowska de Nałęcz, Anna Wiśniewska, Alina Swiderska, Anna Waszczuk-Gajda, Joanna Drozd-Sokołowska, Renata Guzicka-Kazimierczak, Agnieszka Porowska, Kamil Wiśniewski, Wanda Knopińska-Posłuszny, Janusz Kłoczko, Piotr Rzepecki, Dariusz Woszczyk, Hanna Symonowicz, Grzegorz Władysław Basak, Barbara Zdziarska, Krzysztof Jamroziak, Jan M. Zaucha

Subject: Medicine And Pharmacology, Hematology Keywords: frailty; elderly; multiple myeloma; choice of treatment; over 75 years old; early mortality

Online: 30 May 2023 (12:26:24 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.1725.v1

Molecular Insights into the Role of Gut Microbiota in Antibiotic Therapy Selection and Resistance Mitigation

Mihaela Andreescu

Subject: Medicine And Pharmacology, Hematology Keywords: Molecular biology; infectious diseases; clinical diagnostic; early detection; prognosis

Online: 25 May 2023 (03:34:18 CEST)

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Preprint REVIEW | doi:10.20944/preprints202304.0843.v2

Zanubrutinib: Coming of Age for BTK Inhibitors in the Treatment of Chronic Lymphocytic Leukemia?

Stefano Molica, Constantine Tam, David Allsup, Aaron Polliack

Subject: Medicine And Pharmacology, Hematology Keywords: CLL, Zanubrutinib, BTK inhibitors, efficacy, safety, chronic lymphocytic leukemia

Online: 22 May 2023 (16:15:16 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1500.v1

Autologous Transplantation May Still Effectively Treat Relapsed Diffuse Large B-cell Lymphoma in Selected Patients

Reka Rahel Bicsko, Lili Antal, Ferenc Magyari, Róbert Szász, Miklós Udvardy, Arpad Illes, Lajos Gergely

Subject: Medicine And Pharmacology, Hematology Keywords: diffuse large B-cell lymphoma; relapsed; refractory; autologous stem cell transplantation

Online: 22 May 2023 (10:29:20 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1477.v1

Study of the Symptoms’ Severity and Adherence to Therapy of Myelofibrosis Patients Treated With Ruxolitinib

Vera Stoeva, Guenka Petrova, Konstantin Mitov, Konstantin Tihomirov Tachkov

Subject: Medicine And Pharmacology, Hematology Keywords: myelofibrosis; ruxolitinib; severity of symptoms; adherence to therapy

Online: 22 May 2023 (08:52:13 CEST)

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Preprint ARTICLE | doi:10.20944/preprints202305.1382.v1

Prospective Evaluation of Fetal Hemoglobin Expression in Maternal Erythrocytes: an Analysis of a Cohort of 345 Parturients

Laurence Blain, Christian Watier, Xiaoduan Weng, Andre Masse, Marie-Josée Bédard, Nazila Bettache, Florence Weber, Michele Mahone, Stéphanie Forte, Vincent-Philippe Lavallée, Pierre-Olivier Gaudreau, Michael J. Newmarch, Denis Soulières

Subject: Medicine And Pharmacology, Hematology Keywords: Fetal hemoglobin; pregnancy; glycosylated hemoglobin; HbA1C; β-HCG

Online: 19 May 2023 (05:17:09 CEST)

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Preprint REVIEW | doi:10.20944/preprints202305.1213.v1

Unravelling the Immune Microenvironment in Classic Hodgkin Lymphoma: Prognostic and Therapeutic Implications

Vasileios Georgoulis, Alexandra Papoudou-Bai, Alexandros Makis, Panagiotis Kanavaros, Eleftheria Hatzimichael

Subject: Medicine And Pharmacology, Hematology Keywords: Hodgkin lymphoma; tumor microenvironment; tumor associated macrophages; CD169+ macrophages; immune evasion; immunosuppression

Online: 17 May 2023 (09:37:22 CEST)

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Medicine and Pharmacology