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Advancements and Challenges in Treating Chronic Myeloproliferative Neoplasms
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Advancements and Challenges in Treating Chronic Myeloproliferative Neoplasms

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: closed (25 February 2025) | Viewed by 9770

Special Issue Editors

Dr. Ivan Krečak

E-Mail Website
Guest Editor
1. Department of Internal Medicine, General Hospital of Šibenik-Knin County, Šibenik, Croatia
2. Faculty of Medicine, University of Rijeka, Rijeka, Croatia
Interests: hematology; chronic myeloproliferative neoplasms; cardiovascular risk
Special Issues, Collections and Topics in MDPI journals
Dr. Marko Skelin

E-Mail Website
Co-Guest Editor
1. Pharmacy Department, General Hospital of Šibenik-Knin County, Šibenik, Croatia
2. Faculty of Medicine, University of Rijeka, Rijeka, Croatia
Interests: clinical trials
Special Issues, Collections and Topics in MDPI journals
Dr. Zinaida Perić

E-Mail Website
Co-Guest Editor
1. Division of Hematology, University Hospital Rijeka, Rijeka, Croatia
2. Faculty of Medicine, University of Rijeka, Rijeka, Croatia
Interests: hematology; myeloproliferative neoplasms; stem cell transplantation; cellular therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This is an invitation to be part of a new Special Issue of the Journal of Clinical Medicine (JCM) entitled “Advancements and Challenges in Treating Chronic Myeloproliferative Neoplasms”. BCR::ABL1-negative chronic myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are disorders characterized by strong myeloproliferation, a chronic inflammatory state, the presence of various disease-related debilitating symptoms, high cardiovascular risk, and the intrinsic tendency to transform into secondary MF or acute leukemia. In recent years, significant advances in the MPN field have profoundly affected the diagnostic (i.e., novel molecular risk stratifications) and therapeutic landscapes (i.e., approval of ropeginterferon alfa-2b and the arrival of novel JAK inhibitors) in MPNs.

Therefore, the aim of this Special Issue is to give JCM readers an update on the diagnosis and the contemporary management of MPNs. In addition, manuscripts covering current controversies in the MPN field as well as original research articles providing novel concepts related to the pathophysiology, risk stratification, and management of MPNs are welcomed.

Dr. Ivan Krečak
Dr. Marko Skelin
Dr. Zinaida Perić
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • chronic myeloproliferative neoplasms
  • thrombosis
  • survival
  • cardiovascular risk
  • treatment

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Published Papers (5 papers)

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Research

13 pages, 1470 KiB  
Article
Gene Expression Analysis of Autophagy Markers in Primary and Secondary Myelofibrosis
by Marin Medugorac, Katarina Marija Glick, Ana Livun, Marko Lucijanic, Davor Galusic and Rajko Kusec
J. Clin. Med. 2025, 14(7), 2333; https://doi.org/10.3390/jcm14072333 - 28 Mar 2025
Viewed by 343
Abstract
Background/Objectives: According to previous research, the process of autophagy in myeloid neoplasms has proven to be ambivalent depending on the type and stage of the disease. The aim of our work was to investigate the mechanism of autophagy in patients with primary [...] Read more.
Background/Objectives: According to previous research, the process of autophagy in myeloid neoplasms has proven to be ambivalent depending on the type and stage of the disease. The aim of our work was to investigate the mechanism of autophagy in patients with primary and secondary myelofibrosis. Methods: Based on the RT-PCR method, we retrospectively analyzed the expression of Beclin-1 and LC3B-II in bone marrow cells of patients with primary and secondary myelofibrosis (74 participants) compared to the control group which had patients with lymphoma in a localized stage without bone marrow infiltration (11 participants). Results: There was no statistically significant difference in the expression of Beclin-1 and LC3B-II between patients with primary and secondary myelofibrosis and control participants. Among patients with primary myelofibrosis, higher expression of LC3B-II was statistically significantly associated with lower DIPSS. Higher Beclin-1 expression was statistically significantly associated with better patient survival. Conclusions: Our results suggest that the upregulation of autophagy genes may be associated with favorable prognosis and survival of patients with myelofibrosis. Full article
(This article belongs to the Special Issue Advancements and Challenges in Treating Chronic Myeloproliferative Neoplasms)
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13 pages, 3354 KiB  
Article
Systemic Inflammatory Index in Polycythemia Vera and Its Prognostic Implications
by Ivan Krecak, Danijela Lekovic, Isidora Arsenovic, Andrija Bogdanovic, Hrvoje Holik, Ivan Zekanovic, Martina Moric Peric and Marko Lucijanic
J. Clin. Med. 2024, 13(15), 4459; https://doi.org/10.3390/jcm13154459 - 30 Jul 2024
Cited by 2 | Viewed by 1664
Abstract
Background: This study aimed to evaluate the clinical and prognostic associations of the systemic inflammatory index (SII) in polycythemia vera (PV) patients. SII integrates information on absolute neutrophil (ANC), lymphocyte (ALC), and platelet counts into one index (calculated as ANCxALC/platelet count) and [...] Read more.
Background: This study aimed to evaluate the clinical and prognostic associations of the systemic inflammatory index (SII) in polycythemia vera (PV) patients. SII integrates information on absolute neutrophil (ANC), lymphocyte (ALC), and platelet counts into one index (calculated as ANCxALC/platelet count) and was previously shown to predict thrombotic and mortality risks in the general population. Methods: A total of 279 PV patients treated in several hematologic centers in Croatia and Serbia was retrospectively evaluated. Results: The median SII for the overall cohort was 1960. Higher SII stratified at the specific cut-off points was significantly associated with shorter time to thrombosis (TTT; p = 0.004) driven by arterial thrombotic events, and shorter overall survival (OS; p < 0.001). Higher SII was able to refine the European Leukemia Net-defined high-risk patient subgroup for both thrombotic and survival risks, especially in individuals over 60 years of age. SII and all other evaluated CBC components and indices (leukocytes, ANC, ALC, platelets, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR)) demonstrated low-to-modest prognostic properties, whereas SII outperformed other parameters with respect to TTT and OS prognostications. Discussion: The presented results complement prior studies evaluating the prognostic performance of different CBC components for thrombotic and survival risk predictions and offer more options to personalize PV treatments. Full article
(This article belongs to the Special Issue Advancements and Challenges in Treating Chronic Myeloproliferative Neoplasms)
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10 pages, 1005 KiB  
Article
Initial Low-Dose Hydroxyurea and Anagrelide Combination in Essential Thrombocythemia: Comparable Response with Lower Toxicity
by Young Hoon Park, Yeung-Chul Mun, Sewon Lee and Yongchel Ahn
J. Clin. Med. 2024, 13(10), 2901; https://doi.org/10.3390/jcm13102901 - 14 May 2024
Viewed by 2623
Abstract
Background and Objectives: Essential thrombocythemia (ET) is a myeloproliferative neoplasm that overproduces platelets and is associated with life-threatening thrombosis. Medical cytoreduction either with hydroxyurea (HU) or anagrelide (AG) is widely used, but drug intolerance or resistance are major concerns. Low-dose combination of HU [...] Read more.
Background and Objectives: Essential thrombocythemia (ET) is a myeloproliferative neoplasm that overproduces platelets and is associated with life-threatening thrombosis. Medical cytoreduction either with hydroxyurea (HU) or anagrelide (AG) is widely used, but drug intolerance or resistance are major concerns. Low-dose combination of HU and AG as an alternative strategy has been explored in various studies. It showed comparable response with acceptable toxicity in second-line settings for patients who experienced side effects from prior monotherapy. In this study, we evaluated the efficacy and safety of upfront combination for ET patients. Materials and Methods: From January 2018 to June 2022, a total of 241 ET patients with intermediate to high risk were enrolled. We identified 21 patients with initial drug combinations and compared treatment outcomes and adverse events (AEs) between combination and monotherapy groups. Results: The median age was 62 years old (range, 26–87) and median platelet count was 912 × 109/L (range, 520–1720). Overall treatment response did not exhibit significant differences between the groups, although there was a trend towards a lower response rate in patients treated with AG alone at 3 months post-treatment (AG + HU, 85.7% vs. AG alone, 75.4%, p = 0.068). AEs of any grade occurred in 52.3% of the combination group, 44.3% of the HU monotherapy group, and 43.4% of the AG single group, respectively. Of note was that the HU plus AG combination group suffered a lower incidence of grade 3–4 AEs compared to the other two groups, with statistical significance (p = 0.008 for HU monotherapy vs. combination therapy and p < 0.01 for AG monotherapy vs. combination therapy). Conclusions: Our findings demonstrated that the upfront low-dose combination approach showed feasible clinical outcomes with significantly lower severe AEs compared to conventional monotherapy. These results may offer valuable insights to clinicians for future prospective investigations. Full article
(This article belongs to the Special Issue Advancements and Challenges in Treating Chronic Myeloproliferative Neoplasms)
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11 pages, 4098 KiB  
Article
Does Double Mean Trouble? Coexistence of Myeloproliferative and Lymphoproliferative Neoplasms
by Danijela Lekovic, Jelena Ivanovic, Tatjana Terzic, Maja Perunicic Jovanovic, Marija Dencic Fekete, Jelica Jovanovic, Isidora Arsenovic, Vojin Vukovic, Jelena Bila, Andrija Bogdanovic and Darko Antic
J. Clin. Med. 2024, 13(6), 1816; https://doi.org/10.3390/jcm13061816 - 21 Mar 2024
Viewed by 1739
Abstract
Background: The occurrence of myeloproliferative neoplasms (MPNs) that evolve into each other is well-described, as is this occurrence of lymphoproliferative neoplasms (LPNs). However, less is known about rare MPN/LPN coexistence, and the aim of our study was to analyze charachteristics of these patients [...] Read more.
Background: The occurrence of myeloproliferative neoplasms (MPNs) that evolve into each other is well-described, as is this occurrence of lymphoproliferative neoplasms (LPNs). However, less is known about rare MPN/LPN coexistence, and the aim of our study was to analyze charachteristics of these patients after long term follow-up. Methods: Fourteen patients with MPN/LPN coexistence were diagnosed and treated according to guidelines at a single university center across two decades. Results: The overall median age was 53 years (22–69). MPNs patients with subsequent LPNs had a shorter period of second malignancy development and a more aggressive course of LPN, which can cause fatal outcomes. Polycythemia vera and chronic lymphocytic leukemia were most commonly associated (36%). The JAK2V617F mutation had 2/3 and cytogenetic abnormalities occurred in 1/3 of patients. MPN/LPN coexistence cases had significantly higher thrombotic potential (42.8%) and a higher third malignancy accruement frequency (21.4%) versus those without such malignancies. Conclusions: Considering the younger ages at MPN diagnosis, it is recommended to check regularly for blood lymphocytosis or lymphadenopathy occurrences and organomegaly progression faster than expected for MPN, with the aim of timely LPN diagnoses. The presence of molecular-cytogenetic abnormalities in a majority of patients indicate possible genetic instability and increased risk of development of multiple neoplasms, thus elevating thrombotic risk. Full article
(This article belongs to the Special Issue Advancements and Challenges in Treating Chronic Myeloproliferative Neoplasms)
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12 pages, 2185 KiB  
Article
e14a2 Transcript Favors Treatment-Free Remission in Chronic Myeloid Leukemia When Associated with Longer Treatment with Tyrosine Kinase Inhibitors and Sustained Deep Molecular Response
by Sílvia Marcé, Aleix Méndez, Blanca Xicoy, Natalia Estrada, Marta Cabezón, Antonella Luciana Sturla, Miriam Ratia García, Anna Angona, Paula Amat, Silvia Escribano Serrat, Emilia Scalzulli, Mireia Morgades, Alicia Senín, Juan Carlos Hernández-Boluda, Francisca Ferrer-Marín, Eduardo Anguita, Montserrat Cortés, Esther Plensa, Massimo Breccia, Valentín García-Gutierrez and Lurdes Zamoraadd Show full author list remove Hide full author list
J. Clin. Med. 2024, 13(3), 779; https://doi.org/10.3390/jcm13030779 - 29 Jan 2024
Cited by 3 | Viewed by 2438
Abstract
e13a2 and e14a2 are the most frequent transcript types of the BCR::ABL1 fusion gene in chronic myeloid leukemia (CML). The current goal with tyrosine kinase inhibitors (TKI) is to achieve sustained deep molecular response (DMR) in order to discontinue TKI treatment and remain [...] Read more.
e13a2 and e14a2 are the most frequent transcript types of the BCR::ABL1 fusion gene in chronic myeloid leukemia (CML). The current goal with tyrosine kinase inhibitors (TKI) is to achieve sustained deep molecular response (DMR) in order to discontinue TKI treatment and remain in the so-called treatment-free remission (TFR) phase, but biological factors associated with these goals are not well established. This study aimed to determine the effect of transcript type on TFR in patients receiving frontline treatment with imatinib (IM) or second-generation TKI (2G-TKI). Patients treated at least 119 months with IM presented less post-discontinuation relapse than those that discontinued IM before 119 months (p = 0.005). In addition, cases with the e14a2 transcript type treated at least 119 months with IM presented a better TFR (p = 0.024). On the other hand, the type of transcript did not affect the cytogenetic or molecular response in 2G-TKI treated patients; however, the use of 2G-TKI may be associated with higher and earlier DMR in patients with the e14a2 transcript. Full article
(This article belongs to the Special Issue Advancements and Challenges in Treating Chronic Myeloproliferative Neoplasms)
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