Myelodysplastic Syndrome: Recent Advances and Future Directions

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

Deadline for manuscript submissions: closed (20 July 2022) | Viewed by 11384

Special Issue Editor


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Guest Editor
U.O.C. Ematologia, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, 89124 Reggio di Calabria, Italy
Interests: Myelodysplastic syndromes; acute myeloid leukemia; immune thrombocytopenia; anemia; patient-reported outcomes; quality of life
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Special Issue Information

Dear Colleagues,

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem-cell disorders that prevail in elderly patients. They manifest with the development of cytopenias and have a variable tendency for leukemic transformation. With the availability of next-generation sequencing, recurrent somatic mutations in genes involved in epigenetic regulation, RNA splicing, TP53, transcriptional regulation and signal transduction have been identified and have paved the way for the development of individualized treatment. Currently approved drugs for the treatment of MDS include those aimed at reducing the transfusion burden and improving anemia (recombinant erythropoietin, lenalidomide and luspatercept) for lower-risk disease and hypomethylating agents (HMA) to prolong survival in higher-risk MDS. However, these are not curative treatments, so the only possible cure remains allogeneic stem-cell transplantation. Patients eligible for clinical trials may benefit from investigational drugs. Treatments must aim at maintaining or improving health-related quality of life. This Special Edition has been designed to review MDS patients’ unmet needs and will provide the reader with a broadened understanding of novel biological findings integrated with present and future treatment options and their outcomes.

Dr. Esther Natalie Oliva
Guest Editor

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Keywords

  • myelodysplastic syndromes
  • quality of life
  • next-generation sequencing
  • IPSS-R
  • hypomethylating agents
  • anemia
  • transfusions
  • cytopenia
  • hypomethylating agents
  • immunotherapy
  • biological modifiers

Published Papers (5 papers)

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Research

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9 pages, 463 KiB  
Article
Ferric Carboxymaltose and Erythropoiesis-Stimulating Agent Treatment Reduces the Rate of Blood Transfusion in Refractory Anemia
by Antonio Gidaro, Alessandro Palmerio Delitala, Alessandra Berzuini, Mark J. Soloski, Pietro Manca, Dante Castro, Emanuele Salvi, Roberto Manetti, Giorgio Lambertenghi Deliliers and Roberto Castelli
J. Clin. Med. 2022, 11(16), 4744; https://doi.org/10.3390/jcm11164744 - 14 Aug 2022
Cited by 3 | Viewed by 1840
Abstract
Background: Erythropoiesis-stimulating agents (ESAs) are used to treat refractory anemia (RA). Guidelines suggest iron supplementation for unresponsive patients, regardless of iron deficiency. The primary aim of this study was to evaluate the effect of iron supplementation with ferric carboxymaltose (FCM) on the [...] Read more.
Background: Erythropoiesis-stimulating agents (ESAs) are used to treat refractory anemia (RA). Guidelines suggest iron supplementation for unresponsive patients, regardless of iron deficiency. The primary aim of this study was to evaluate the effect of iron supplementation with ferric carboxymaltose (FCM) on the reduction of red blood cell transfusion (RBCT) rate in transfusion-dependent RA patients. Methods: This was a prospective quasi-randomized study, wherein patients were randomly assigned into three groups: (A) ESAs alone, (B) ferric gluconate (FG) and ESAs, and (C) FCM and ESAs. Hemoglobin and ferritin levels, as well as the number of RBCTs at 4 and 28 weeks were compared. Economic evaluation was also performed. Results: A total of 113 RA patients were enrolled. In total, 43 were treated with intravenous FG and ESAs, 38 with FCM and ESAs, and 32 with ESAs alone. At both follow-ups, erythropoietic response was increased in those receiving iron as compared with those with ESAs alone (p = 0.001), regardless of the type of iron. At one month, ferritin levels were higher in the FCM and ESA groups (p = 0.001). RBCTs were lower in both iron groups. The less costly treatment strategy was FCM, followed by FG, and lastly ESAs. Conclusions: Addition of iron to ESAs in RA reduced RBCT requirement and improved hemoglobin values. Full article
(This article belongs to the Special Issue Myelodysplastic Syndrome: Recent Advances and Future Directions)
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9 pages, 805 KiB  
Article
Myelodysplastic Syndromes with Isolated 20q Deletion: A New Clinical–Biological Entity?
by Alessia Campagna, Daniela De Benedittis, Luana Fianchi, Emilia Scalzulli, Lorenzo Rizzo, Pasquale Niscola, Anna Lina Piccioni, Ambra Di Veroli, Stefano Mancini, Nicoletta Villivà, Tiziano Martini, Sara Mohamed, Ida Carmosino, Marianna Criscuolo, Susanna Fenu, Maria Antonietta Aloe Spiriti, Francesco Buccisano, Marco Mancini, Agostino Tafuri, Massimo Breccia, Antonella Poloni and Roberto Latagliataadd Show full author list remove Hide full author list
J. Clin. Med. 2022, 11(9), 2596; https://doi.org/10.3390/jcm11092596 - 5 May 2022
Cited by 1 | Viewed by 1876
Abstract
Aims: To define the peculiar features of patients with the deletion of the chromosome 20 long arm (del20q), data from 69 patients with myelodysplastic syndromes (MDSs) and isolated del20q, followed by the Gruppo Romano-Laziale Sindromi Mielodisplastiche (GROM-L) and Ospedale Torrette of Ancona, were [...] Read more.
Aims: To define the peculiar features of patients with the deletion of the chromosome 20 long arm (del20q), data from 69 patients with myelodysplastic syndromes (MDSs) and isolated del20q, followed by the Gruppo Romano-Laziale Sindromi Mielodisplastiche (GROM-L) and Ospedale Torrette of Ancona, were collected and compared with those of 502 MDS patients with normal karyotype (NK-MDS). Results: Compared to the NK-MDS group, patients with del20q at diagnosis were older (p = 0.020) and mainly male (p = 0.006). They also had a higher rate of bone marrow blast < 5% (p = 0.004), a higher proportion of low and int-1 risk according to IPSS score (p = 0.023), and lower median platelet (PLT) count (p < 0.001). To date, in the del20q cohort, 21 patients (30.4%) received no treatment, 42 (61.0%) were treated with erythropoiesis-stimulating agents (ESA), 3 (4.3%) with hypomethylating agents, and 3 (4.3%) with other treatments. Among 34 patients evaluable for response to ESA, 21 (61.7%) achieved stable erythroid response according to IWG 2006 criteria and 13 (38.2%) were resistant. Nine patients (13.0%) progressed to acute myeloid leukaemia (AML) after a median time from diagnosis of 28 months (IR 4.1–51.7). The median overall survival (OS) of the entire cohort was 60.6 months (95% CI 54.7–66.4). the 5-year cumulative OS was 55.9% (95% CI 40.6–71.2). Conclusion: According to our results, we hypothesize that MDSs with isolated del 20q may represent a distinct biological entity, with peculiar clinical and prognostic features. The physio-pathological mechanisms underlying the deletion of the chromosome 20 long arm are still unclear and warrant future molecular analysis. Full article
(This article belongs to the Special Issue Myelodysplastic Syndrome: Recent Advances and Future Directions)
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14 pages, 7427 KiB  
Article
Health-Related Quality of Life Outcomes in Patients with Myelodysplastic Syndromes with Ring Sideroblasts Treated with Luspatercept in the MEDALIST Phase 3 Trial
by Esther Natalie Oliva, Uwe Platzbecker, Guillermo Garcia-Manero, Ghulam J. Mufti, Valeria Santini, Mikkael A. Sekeres, Rami S. Komrokji, Jeevan K. Shetty, Derek Tang, Shien Guo, Weiqin Liao, George Zhang, Xianwei Ha, Rodrigo Ito, Jennifer Lord-Bessen, Jay T. Backstrom and Pierre Fenaux
J. Clin. Med. 2022, 11(1), 27; https://doi.org/10.3390/jcm11010027 - 22 Dec 2021
Cited by 14 | Viewed by 3814
Abstract
Patients with myelodysplastic syndromes (MDS) often experience chronic anemia and long-term red blood cell transfusion dependence associated with significant burden on clinical and health-related quality of life (HRQoL) outcomes. In the MEDALIST trial (NCT02631070), luspatercept significantly reduced transfusion burden in patients with lower-risk [...] Read more.
Patients with myelodysplastic syndromes (MDS) often experience chronic anemia and long-term red blood cell transfusion dependence associated with significant burden on clinical and health-related quality of life (HRQoL) outcomes. In the MEDALIST trial (NCT02631070), luspatercept significantly reduced transfusion burden in patients with lower-risk MDS who had ring sideroblasts and were refractory to, intolerant to, or ineligible for prior treatment with erythropoiesis-stimulating agents. We evaluated the effect of luspatercept on HRQoL in patients enrolled in MEDALIST using the EORTC QLQ-C30 and the QOL-E questionnaire. Change in HRQoL was assessed every 6 weeks in patients receiving luspatercept with best supportive care (+ BSC) and placebo + BSC from baseline through week 25. No clinically meaningful within-group changes and between-group differences across all domains of the EORTC QLQ-C30 and QOL-E were observed. On one item of the QOL-E MDS-specific disturbances domain, patients treated with luspatercept reported marked improvements in their daily life owing to the reduced transfusion burden, relative to placebo. Taken together with previous reports of luspatercept + BSC reducing transfusion burden in patients from baseline through week 25 in MEDALIST, these results suggest luspatercept may offer a treatment option for patients that reduces transfusion burden while providing stability in HRQoL. Full article
(This article belongs to the Special Issue Myelodysplastic Syndrome: Recent Advances and Future Directions)
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13 pages, 585 KiB  
Article
Lymphocytic Infiltrate and p53 Protein Expression as Predictive Markers of Response and Outcome in Myelodysplastic Syndromes Treated with Azacitidine
by Carlo Pescia, Francesca Boggio, Giorgio Alberto Croci, Ramona Cassin, Marco Barella, Loredana Pettine, Gianluigi Reda, Elena Sabattini, Carlo Finelli and Umberto Gianelli
J. Clin. Med. 2021, 10(21), 4809; https://doi.org/10.3390/jcm10214809 - 20 Oct 2021
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Abstract
High-risk Myelodysplastic syndromes (MDS) represent therapeutical challenges and are usually managed with hypomethylating agents such as azacitidine. Given the lack of data in the literature concerning azacitidine effects on bone marrow, we retrospectively analyzed 57 high-risk MDS cases in order to identify any [...] Read more.
High-risk Myelodysplastic syndromes (MDS) represent therapeutical challenges and are usually managed with hypomethylating agents such as azacitidine. Given the lack of data in the literature concerning azacitidine effects on bone marrow, we retrospectively analyzed 57 high-risk MDS cases in order to identify any changes induced by azacitidine therapy or relevant correlations between therapy response and pre- or post-treatment features. Azacitidine treatment had no significant impact on bone marrow cellularity or morphological dysplastic features. On the contrary, although not statistically significant, we observed a slight decrease in CD34+ and CD117+ blasts and p53+ precursors after treatment. Moreover, pre-treatment IPSS-R cytogenetic score (p = 0.004), lymphocytic infiltrate (p = 0.017) and p53+ elements (p = 0.001) correlated with AML progression; pre-treatment lymphocytic infiltrate was also linked to better response to therapy (p = 0.004), suggesting an anti-tumoral role of bone marrow microenvironment. Post-treatment blast count impacted negatively on overall survival (p = 0.035) and risk of leukemic progression (p = 0.04), while both post-treatment lymphocytic infiltrate and p53+ elements showed significant correlation with treatment response (p = 0.004 and p = 0.003 respectively). Higher post-treatment p53+ elements correlated also with risk of leukemic progression (p = 0.013). Our results suggest the possible role of lymphocytic infiltrate and p53+ elements as predictive markers in MDS treated with azacitidine, disclosing new chapters in the understanding of MDS evolution and treatment. Full article
(This article belongs to the Special Issue Myelodysplastic Syndrome: Recent Advances and Future Directions)
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4 pages, 200 KiB  
Opinion
Quality of Life in Low-Risk MDS: An Undervalued Endpoint
by Bert Heyrman
J. Clin. Med. 2022, 11(19), 5699; https://doi.org/10.3390/jcm11195699 - 27 Sep 2022
Cited by 2 | Viewed by 1139
Abstract
The opinion I put forward in this paper is that attention must be paid to health-related quality of life as a study endpoint in lower-risk MDS patients. At the moment therapeutic options are limited in this population. New treatments are predominantly available in [...] Read more.
The opinion I put forward in this paper is that attention must be paid to health-related quality of life as a study endpoint in lower-risk MDS patients. At the moment therapeutic options are limited in this population. New treatments are predominantly available in clinical studies. In announcing trial publications and during manuscript introductions, quality of life is widely valued as a treatment goal. However, data on health-related quality of life during phase III studies are not published in the original publications, thereby undermining the importance of quality of life as a study endpoint. What seems to be forgotten is that quality of life comprises more than a study endpoint. It is the highest good of lower-risk MDS patients and should also be acknowledged as a safety aspect. Current phase II trials with new medications do not collect data on health-related quality of life, a practice that I consider unethical. In this opinion I demonstrate the current attitude towards health-related quality of life in lower risk MDS patients among leading journals and trial sponsors with several recent examples. I also argue that health-related quality of life should be the main treatment goal in this population. In the event that we shift our focus towards health-related quality of life as the main treatment goal, new treatments could come to a field where gains in overall survival have been marginal over the years. Full article
(This article belongs to the Special Issue Myelodysplastic Syndrome: Recent Advances and Future Directions)
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