Personalized Medicine in Blood Disease of Children

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Methodology, Drug and Device Discovery".

Deadline for manuscript submissions: closed (5 September 2022) | Viewed by 22918

Special Issue Editors


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Guest Editor
Fondazione per la Ricerca Farmacologica Gianni Benzi Onlus, Valenzano, Italy
Interests: clinical and laboratory haematology

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Co-Guest Editor
Molecular Genetics Thalassaemia Department, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus
Interests: hemoglobinopathies; genetic modifiers; patient registries; biological databases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue of the Journal of Personalized Medicine aims to highlight the current state of the research and current practice on personalized medicines in children's blood non-malignant disorders, such as haemoglobinopathies and bleeding disorders. It aims to collect, share, and expand knowledge on the genetic and molecular basis of phenotypic variation in these disorders, and on the use of omics and digital science, leading to the identification of possibly successful candidate diagnostic and therapeutic approaches. Moreover, the Special Issue will explore the complexity of conducting personalized medicine clinical studies in children affected by rare haematological diseases, including patient registry standardization, ethics, feasibility, cost, and patient engagement and roles. Papers may also address the use of digital tools and advanced therapy medicinal products (ATMPs) for preliminary results. Original articles and reviews are welcome.

Prof. Dr. Adriana Ceci
Dr. Petros Kountouris
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 Personalized Medicine is an international peer-reviewed open access monthly 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

  • Child blood non-malignant diseases
  • Molecular target and disease models
  • Genetic variation and diagnosis
  • Genotype–phenotype correlation and patient stratification
  • Advanced therapy medicinal products
  • Biomarkers targeting paediatric blood diseases
  • Computational approaches in personalized medicine
  • Patient registries and standardization
  • Ethics issues and patients-oriented perspectives

Published Papers (8 papers)

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Editorial

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4 pages, 175 KiB  
Editorial
Special Issue “Personalized Medicine in Blood Disease of Children”
by Adriana Ceci, Petros Kountouris, Antonella Didio and Fedele Bonifazi
J. Pers. Med. 2024, 14(3), 285; https://doi.org/10.3390/jpm14030285 - 5 Mar 2024
Viewed by 971
Abstract
Personalized medicine is defined as a medical model using the characterization of individuals’ phenotypes and genotypes (e [...] Full article
(This article belongs to the Special Issue Personalized Medicine in Blood Disease of Children)

Research

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9 pages, 240 KiB  
Article
Transition in Sickle Cell Disease (SCD): A German Consensus Recommendation
by Ferras Alashkar, Carmen Aramayo-Singelmann, Janine Böll, Annette Hoferer, Andrea Jarisch, Haytham Kamal, Lena Oevermann, Michaela Schwarz and Holger Cario
J. Pers. Med. 2022, 12(7), 1156; https://doi.org/10.3390/jpm12071156 - 17 Jul 2022
Cited by 4 | Viewed by 2213
Abstract
Sickle cell disease (SCD) is considered a rare disease in Germany. Due to the increasing prevalence, the acute and chronic morbidities associated with the disease and the sharp increase in the mortality rate of young adults, a need-based transition structure for patients with [...] Read more.
Sickle cell disease (SCD) is considered a rare disease in Germany. Due to the increasing prevalence, the acute and chronic morbidities associated with the disease and the sharp increase in the mortality rate of young adults, a need-based transition structure for patients with SCD in Germany is explicitly required. This is the first multicenter German consensus statement addressing the importance of implementing a standardized transition guideline that allows adolescents and young adults to safely transition from pediatric to adult care. Early identification of medical needs and intervention remains important in the context of chronic diseases. Effective measures can improve health care in general, as they lead to a reduction in disease and the consequential economic burden. It is noteworthy that improving structural barriers remains a key challenge even in highly developed countries such as Germany. Inclusion of these transition services for patients with SCD into the regular care of chronically ill adolescents and young adults should be ensured, as well as the coverage of costs associated with a structured transition process. Full article
(This article belongs to the Special Issue Personalized Medicine in Blood Disease of Children)
23 pages, 1069 KiB  
Article
Global Globin Network Consensus Paper: Classification and Stratified Roadmaps for Improved Thalassaemia Care and Prevention in 32 Countries
by Bin Hashim Halim-Fikri, Carsten W. Lederer, Atif Amin Baig, Siti Nor Assyuhada Mat-Ghani, Sharifah-Nany Rahayu-Karmilla Syed-Hassan, Wardah Yusof, Diana Abdul Rashid, Nurul Fatihah Azman, Suthat Fucharoen, Ramdan Panigoro, Catherine Lynn T. Silao, Vip Viprakasit, Norunaluwar Jalil, Norafiza Mohd Yasin, Rosnah Bahar, Veena Selvaratnam, Norsarwany Mohamad, Nik Norliza Nik Hassan, Ezalia Esa, Amanda Krause, Helen Robinson, Julia Hasler, Coralea Stephanou, Raja-Zahratul-Azma Raja-Sabudin, Jacques Elion, Ghada El-Kamah, Domenico Coviello, Narazah Yusoff, Zarina Abdul Latiff, Chris Arnold, John Burn, Petros Kountouris, Marina Kleanthous, Raj Ramesar, Bin Alwi Zilfalil and on behalf of the Global Globin Network (GGN)add Show full author list remove Hide full author list
J. Pers. Med. 2022, 12(4), 552; https://doi.org/10.3390/jpm12040552 - 31 Mar 2022
Cited by 9 | Viewed by 3627
Abstract
The Global Globin Network (GGN) is a project-wide initiative of the Human Variome/Global Variome Project (HVP) focusing on haemoglobinopathies to build the capacity for genomic diagnosis, clinical services, and research in low- and middle-income countries. At present, there is no framework to evaluate [...] Read more.
The Global Globin Network (GGN) is a project-wide initiative of the Human Variome/Global Variome Project (HVP) focusing on haemoglobinopathies to build the capacity for genomic diagnosis, clinical services, and research in low- and middle-income countries. At present, there is no framework to evaluate the improvement of care, treatment, and prevention of thalassaemia and other haemoglobinopathies globally, despite thalassaemia being one of the most common monogenic diseases worldwide. Here, we propose a universally applicable system for evaluating and grouping countries based on qualitative indicators according to the quality of care, treatment, and prevention of haemoglobinopathies. We also apply this system to GGN countries as proof of principle. To this end, qualitative indicators were extracted from the IthaMaps database of the ITHANET portal, which allowed four groups of countries (A, B, C, and D) to be defined based on major qualitative indicators, supported by minor qualitative indicators for countries with limited resource settings and by the overall haemoglobinopathy carrier frequency for the target countries of immigration. The proposed rubrics and accumulative scores will help analyse the performance and improvement of care, treatment, and prevention of haemoglobinopathies in the GGN and beyond. Our proposed criteria complement future data collection from GGN countries to help monitor the quality of services for haemoglobinopathies, provide ongoing estimates for services and epidemiology in GGN countries, and note the contribution of the GGN to a local and global reduction of disease burden. Full article
(This article belongs to the Special Issue Personalized Medicine in Blood Disease of Children)
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14 pages, 620 KiB  
Article
Link between Genotype and Multi-Organ Iron and Complications in Children with Transfusion-Dependent Thalassemia
by Antonella Meloni, Laura Pistoia, Paolo Ricchi, Maria Caterina Putti, Maria Rita Gamberini, Liana Cuccia, Giuseppe Messina, Francesco Massei, Elena Facchini, Riccardo Righi, Stefania Renne, Giuseppe Peritore, Vincenzo Positano and Filippo Cademartiri
J. Pers. Med. 2022, 12(3), 400; https://doi.org/10.3390/jpm12030400 - 4 Mar 2022
Cited by 6 | Viewed by 2443
Abstract
We evaluated the impact of the genotype on hepatic, pancreatic and myocardial iron content, and on hepatic, cardiac and endocrine complications in children with transfusion-dependent β-thalassemia (β-TDT). We considered 68 β-TDT patients (11.98 ± 3.67 years, 51.5% females) consecutively enrolled in the Extension-Myocardial [...] Read more.
We evaluated the impact of the genotype on hepatic, pancreatic and myocardial iron content, and on hepatic, cardiac and endocrine complications in children with transfusion-dependent β-thalassemia (β-TDT). We considered 68 β-TDT patients (11.98 ± 3.67 years, 51.5% females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia network. Iron overload was quantified by T2* technique and biventricular function by cine images. Replacement myocardial fibrosis was evaluated by late gadolinium enhancement technique. Three groups of patients were identified: homozygous β+ (N = 19), compound heterozygous β0β+ (N = 24), and homozygous β0 (N = 25). The homozygous β0 group showed significantly lower global heart and pancreas T2* values than the homozygous β+ group. Compared to patients with homozygous β+ genotype, β0β+ as well as β0β0 patients were more likely to have pancreatic iron overload (odds ratio = 6.53 and 10.08, respectively). No difference was detected in biventricular function parameters and frequency of replacement fibrosis. No patient had cirrhosis/fibrosis, diabetes or heart failure, and the frequency of endocrinopathies was comparable among the groups. In pediatric β-TDT patients, there is an association between genotype and cardiac and pancreatic iron overload. The knowledge of patients’ genotype can be valuable in predicting some patients’ phenotypic features and in helping the clinical management of β-TDT patients. Full article
(This article belongs to the Special Issue Personalized Medicine in Blood Disease of Children)
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13 pages, 1591 KiB  
Article
The Prevalence of β-Thalassemia and Other Hemoglobinopathies in Kuwaiti Premarital Screening Program: An 11-Year Experience
by Najat Rouh AlDeen, Asmaa A Osman, Monira J Alhabashi, Rasha Al Khaldi, Hassan Alawadi, Maha K Alromh, Eiman G Alyafai and Nagihan Akbulut-Jeradi
J. Pers. Med. 2021, 11(10), 980; https://doi.org/10.3390/jpm11100980 - 29 Sep 2021
Cited by 13 | Viewed by 3578
Abstract
This study aims to estimate the prevalence rates of β-thalassemia and Sickle cell disorders in the adult population screened (n = 275,819) as part of the Kuwaiti National Premarital Screening Program. All the individuals who applied for a marriage license during the [...] Read more.
This study aims to estimate the prevalence rates of β-thalassemia and Sickle cell disorders in the adult population screened (n = 275,819) as part of the Kuwaiti National Premarital Screening Program. All the individuals who applied for a marriage license during the years 2009 and 2020 were covered by the program. A network of four reception centers in the Ministry of Health facilities and one Premarital Diagnostic Laboratory (PDL) in Maternity Hospital were involved in performing all investigations for hemoglobinopathies. The total number of individuals identified with β-thal trait was 5861 (2.12%), while 22 individuals (0.008%) were diagnosed with β-thal disease. A total of 5003 subjects (1.81%) were carrying the Sickle cell trait, while 172 subjects (0.062%) had Sickle cell disease including Sickle cell anemia (SCA). Results showed that the program succeeded indeed in preventing the marriage of 50.4% of risky couples by issuing unsafe marriage certificates. Yet more efforts are needed to improve the program’s main objective of decreasing high-risk marriages. In particular, health care systems should be ameliorated in a way to intensify the counselling mechanism for the high-risk couples, strengthen the awareness of the general population and induce earlier age screening policies. Full article
(This article belongs to the Special Issue Personalized Medicine in Blood Disease of Children)
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17 pages, 771 KiB  
Article
Pregnancies and Neonatal Outcomes in Patients with Sickle Cell Disease (SCD): Still a (High-)Risk Constellation?
by Pia Proske, Laura Distelmaier, Carmen Aramayo-Singelmann, Nikolaos Koliastas, Antonella Iannaccone, Maria Papathanasiou, Christian Temme, Hannes Klump, Veronika Lenz, Michael Koldehoff, Alexander Carpinteiro, Hans Christian Reinhardt, Angela Köninger, Alexander Röth, Raina Yamamoto, Ulrich Dührsen and Ferras Alashkar
J. Pers. Med. 2021, 11(9), 870; https://doi.org/10.3390/jpm11090870 - 30 Aug 2021
Cited by 4 | Viewed by 2816
Abstract
Background: This monocentric study conducted at the University Hospital of Essen aims to describe maternal and fetal/neonatal outcomes in sickle cell disease (SCD) documented between 1996 to 2021 (N = 53), reflecting the largest monocentric analysis carried out in Germany. Methods/Results: 46 pregnancies [...] Read more.
Background: This monocentric study conducted at the University Hospital of Essen aims to describe maternal and fetal/neonatal outcomes in sickle cell disease (SCD) documented between 1996 to 2021 (N = 53), reflecting the largest monocentric analysis carried out in Germany. Methods/Results: 46 pregnancies in 22 patients were followed. None of the patients died. In total, 35% (11/31) of pregnancies were preterm. 15 pregnancies in eight patients were conceived on hydroxycarbamide (HC), of which nine had a successful outcome and three were terminated prematurely. There was no difference regarding the rate of spontaneous abortions in patients receiving HC compared to HC-naive patients prior to conception. In patients other than HbS/C disease, pregnancies were complicated by vaso-occlusive crises (VOCs)/acute pain crises (APCs) (96%, 23/24); acute chest syndrome (ACS) (13%, 3/24), transfusion demand (79%, 19/24), urinary tract infections (UTIs) (42%, 10/24) and thromboembolic events (8%, 2/24). In HbS/C patients complications included: VOCs/APCs (43%, 3/7; ACS: 14%, 1/7), transfusion demand (14%, 1/7), and UTIs (14%, 1/7). Independent of preterm deliveries, a significant difference with respect to neonatal growth in favor of neonates from HbS/C mothers was observed. Conclusion: Our data support the results of previous studies, highlighting the high rate of maternal and fetal/neonatal complications in pregnant SCD patients. Full article
(This article belongs to the Special Issue Personalized Medicine in Blood Disease of Children)
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11 pages, 790 KiB  
Article
Unique Polymorphisms at BCL11A, HBS1L-MYB and HBB Loci Associated with HbF in Kuwaiti Patients with Sickle Cell Disease
by Nagihan Akbulut-Jeradi, Maria Jinky Fernandez, Rasha Al Khaldi, Jalaja Sukumaran and Adekunle Adekile
J. Pers. Med. 2021, 11(6), 567; https://doi.org/10.3390/jpm11060567 - 17 Jun 2021
Cited by 4 | Viewed by 2509
Abstract
Patients with sickle cell disease (SCD) in Kuwait have elevated HbF levels ranging from ~10–44%; however, the modulating factors are unclear. We investigated the association of single nucleotide polymorphisms (SNPs) at BCL11A, HBS1L-MYB and HBB with HbF levels in 237 Kuwaiti SCD [...] Read more.
Patients with sickle cell disease (SCD) in Kuwait have elevated HbF levels ranging from ~10–44%; however, the modulating factors are unclear. We investigated the association of single nucleotide polymorphisms (SNPs) at BCL11A, HBS1L-MYB and HBB with HbF levels in 237 Kuwaiti SCD patients, divided into 3 subgroups according to their HbF levels. Illumina Ampliseq custom DNA panel was used for genotyping and confirmed by arrayed primer extension or Sanger sequencing. In the BCL11A locus, the CC genotype of rs7606173 [χ2 = 16.5] and (GG) of rs10195871 [χ2 = 15.0] were associated with Hb-F1 and HbF-2 subgroups, unlike rs1427404-T [χ2 = 17.3], which showed the highest association across the three subgroups. HBS1L-MYB locus revealed 2 previously-described SNPs (rs66650371 [χ2 = 9.5] and rs35795442 [χ2 = 9.2]) and 2 previously-unreported SNPs, (rs13220662 [χ2 = 6.2] and rs1406811 [χ2 = 6.7]) that were associated with the HbF-3 subgroup, making this the key locus elevating HbF to the highest levels. HBB cluster variants were associated with lower levels of HbF (β = −1.1). We report four previously-unpublished variants showing significant association with HbF. Each of the three quantitative trait loci affects HbF levels differently; unique SNPs, especially in HBS1L-MYB, elevate HbF to the highest levels. Full article
(This article belongs to the Special Issue Personalized Medicine in Blood Disease of Children)
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9 pages, 238 KiB  
Article
Diagnosis of Sickle Cell Disease and HBB Haplotyping in the Era of Personalized Medicine: Role of Next Generation Sequencing
by Adekunle Adekile, Nagihan Akbulut-Jeradi, Rasha Al Khaldi, Maria Jinky Fernandez and Jalaja Sukumaran
J. Pers. Med. 2021, 11(6), 454; https://doi.org/10.3390/jpm11060454 - 23 May 2021
Cited by 5 | Viewed by 3249
Abstract
Hemoglobin genotype and HBB haplotype are established genetic factors that modify the clinical phenotype in sickle cell disease (SCD). Current methods of establishing these two factors are cumbersome and/or prone to errors. The throughput capability of next generation sequencing (NGS) makes it ideal [...] Read more.
Hemoglobin genotype and HBB haplotype are established genetic factors that modify the clinical phenotype in sickle cell disease (SCD). Current methods of establishing these two factors are cumbersome and/or prone to errors. The throughput capability of next generation sequencing (NGS) makes it ideal for simultaneous interrogation of the many genes of interest in SCD. This study was designed to confirm the diagnosis in patients with HbSS and Sβ-thalassemia, identify any ß-thal mutations and simultaneously determine the ßS HBB haplotype. Illumina Ampliseq custom DNA panel was used to genotype the DNA samples. Haplotyping was based on the alleles on five haplotype-specific SNPs. The patients studied included 159 HbSS patients and 68 Sβ-thal patients, previously diagnosed using high performance liquid chromatography (HPLC). There was considerable discordance between HPLC and NGS results, giving a false +ve rate of 20.5% with a sensitivity of 79% for the identification of Sβthal. Arab/India haplotype was found in 81.5% of βS chromosomes, while the two most common, of the 13 β-thal mutations detected, were IVS-1 del25 and IVS-II-1 (G>A). NGS is very versatile and can be deployed to simultaneously screen multiple gene loci for modifying polymorphisms, to afford personalized, evidence-based counselling and early intervention. Full article
(This article belongs to the Special Issue Personalized Medicine in Blood Disease of Children)
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