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Hematopoietic Stem Cell Transplantation in the Personalized Medicine Era
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Hematopoietic Stem Cell Transplantation in the Personalized Medicine Era

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Clinical Medicine, Cell, and Organism Physiology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 15298

Special Issue Editors

Prof. Dr. Michael Uhlin

E-Mail Website
Guest Editor
1. Department of Clintec, Karolinska Insitutet, SE-141 86 Stockholm, Sweden
2. Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, SE-141 86 Stockholm, Sweden
Interests: hematopoietic stem cell transplantation; immune therapy; graft characteristics; T-cells; gamma-delta T cells; predictive biomarkers
Prof. Dr. Moustapha Hassan

E-Mail Website
Co-Guest Editor
Division of Experimental Cancer Medicine (ECM), Department of Laboratory Medicine, Karolinska Institutet, SE-141 86 Stockholm, Sweden
Interests: hematopoetic stem cell transplantation; chemotherapy; pharmacokinetics; conditioning regiments; animal models

Special Issue Information

Dear Colleagues,

Allogeneic hematopoietic stem cell transplantation (HSCT) can be curative for patients with severe hematological malignancies.  Though the treatment modality has improved drastically over the last decade, e.g. tumor resistance, relapse, infections and Graft-versus-host-disease (GVHD) are still common challenges for these patients. The era of personalized medicine has dramatically changed the game plan for several diseases in the last decade including patients that undergo HSCT. Current advances in technology have provided scientists and physicians with a huge toolbox with possible instruments in order to improve the clinical outcome of these patients. This Special Issue of the Journal of Personalized Medicine aims to highlight the knowledge and illustrate some of the findings in HSCT. It will among other things include studies on the impact of donor characteristics and how pre-transplantation factors impact clinical outcome. It will also give examples of studies on the use of biomarkers to predict and govern clinical practise. Some examples will also illustrate how the use of tailor-made chemotherapy can be beneficial in patient care in a personalized setting.

Prof. Dr. Michael Uhlin
Guest Editor

Prof. Moustapha Hassan
Co-Guest Editor

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

  • Hematopoetic stem cell transplantation
  • Graft characteristics
  • Biomarkers
  • Conditioning regiments
  • Immune therapy
  • Cell therapy
  • Pharmacokinetics
  • Leukapheresis
  • Donor characteristics

Published Papers (5 papers)

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Research

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14 pages, 4682 KiB  
Article
COL-3-Induced Molecular and Ultrastructural Alterations in K562 Cells
by Mona Fares, Sandra Oerther, Kjell Hultenby, Danica Gubrianska, Ying Zhao, Manuchehr Abedi-Valugerdi and Moustapha Hassan
J. Pers. Med. 2022, 12(1), 42; https://doi.org/10.3390/jpm12010042 - 4 Jan 2022
Cited by 4 | Viewed by 1726
Abstract
Tetracycline-3 (4-dedimethylamino sancycline, COL-3) is a non-antibiotic tetracycline derivative. COL-3 exerts potent anti-metalloproteinase activity and its antitumor effects have been reported both in vitro and in vivo. In this study, we investigated the mechanisms of COL-3-induced cytotoxicity in a chronic myeloid leukemia cell [...] Read more.
Tetracycline-3 (4-dedimethylamino sancycline, COL-3) is a non-antibiotic tetracycline derivative. COL-3 exerts potent anti-metalloproteinase activity and its antitumor effects have been reported both in vitro and in vivo. In this study, we investigated the mechanisms of COL-3-induced cytotoxicity in a chronic myeloid leukemia cell line, K562, characterized by the BCR–ABL fusion protein. COL-3 induced K562 cell death in a concentration-dependent manner with an IC50 of 10.8 µg/mL and exhibited features of both apoptosis and necrosis. However, flow cytometry analysis revealed that necrotic cells dominated over the early and late apoptotic cells upon treatment with COL-3. Transmission electron microscopy analysis in combination with Western blotting (WB) analysis revealed early mitochondrial swelling accompanied by the early release of cytochrome c and truncated apoptosis inducing factor (tAIF). In addition, ultrastructural changes were detected in the endoplasmic reticulum (ER). COL-3 affected the levels of glucose-regulated protein-94 (GRP94) and resulted in m-calpain activation. DNA double strand breaks as a signature for DNA damage was also confirmed using an antibody against γH2AX. WB analyses did not demonstrate caspase activation, while Bcl-xL protein remained unaffected. In conclusion, COL-3-induced cell death involves DNA damage as well as mitochondrial and ER perturbation with features of paraptosis and programmed necrosis. Full article
(This article belongs to the Special Issue Hematopoietic Stem Cell Transplantation in the Personalized Medicine Era)
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10 pages, 1396 KiB  
Article
Thrombotic Microangiopathy: Multi-Institutional Review of Pediatric Patients Who Underwent HSCT
by Archana Ramgopal, Shiva Sridar, Jignesh Dalal and Ramasubramanian Kalpatthi
J. Pers. Med. 2021, 11(6), 467; https://doi.org/10.3390/jpm11060467 - 25 May 2021
Cited by 6 | Viewed by 5129
Abstract
Thrombotic microangiopathy (TMA) is a rare but serious complication of hematopoietic stem cell transplantation (HSCT). The purpose of our study is to estimate the incidence, prevalence, and analyze the risk factors and outcome of TMA in children receiving HSCT. Patients under the age [...] Read more.
Thrombotic microangiopathy (TMA) is a rare but serious complication of hematopoietic stem cell transplantation (HSCT). The purpose of our study is to estimate the incidence, prevalence, and analyze the risk factors and outcome of TMA in children receiving HSCT. Patients under the age of 21 who underwent HSCT at one of the 42 Pediatric Health Information System (PHIS) hospitals from 2000–2012 were analyzed, including demographics, hospitalizations, TMA, and other HSCT-related complications. From 2000 to 2012, a total of 12,369 unique pediatric patients who received HSCT were identified. Among these, 93 (0.8%) children were identified to have the diagnosis of TMA. TMA was significantly associated with allogeneic HSCT, peripheral blood stem cell trasnplants (PBSCT), cytomegalovirus (CMV), human herpes virus 6 (HHV6), fungal infection, graft-versus-host disease (GVHD), and veno-occlusive disease (VOD) (p = 0.01). Multivariate logistic regression analysis of mortality showed only HHV6 was an independent risk factor associated with increased mortality in patients with TMA (hazard ratio: 2.86 [1.01, 8.39], p = 0.05). The prevalence of TMA in our study is 0.8% with a mortality in our pediatric TMA cohort of 30%, which is in contrast to the higher mortality reported in previously published, small-case series. HHV6 emerged as not only a risk factor for TMA but also as associated with increased mortality in these patients. Full article
(This article belongs to the Special Issue Hematopoietic Stem Cell Transplantation in the Personalized Medicine Era)
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Review

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15 pages, 468 KiB  
Review
Cardiovascular Complications in Hematopoietic Stem Cell Transplanted Patients
by Ying Zhao, Rui He, Sandra Oerther, Weiying Zhou, Massoud Vosough and Moustapha Hassan
J. Pers. Med. 2022, 12(11), 1797; https://doi.org/10.3390/jpm12111797 - 31 Oct 2022
Cited by 6 | Viewed by 3870
Abstract
Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for many patients suffering from hematologic malignancies, solid tumors, inborn errors of metabolism or genetic disorders. Despite decades of successful HSCT, clinical outcomes are still far from satisfactory due to treatment-related complications, including [...] Read more.
Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for many patients suffering from hematologic malignancies, solid tumors, inborn errors of metabolism or genetic disorders. Despite decades of successful HSCT, clinical outcomes are still far from satisfactory due to treatment-related complications, including graft-versus-host disease (GvHD) and cardiovascular complications (CVC). CVC may affect patients in the acute period post-HSCT; however, the occurrence is far higher among long-term survivors. Induction treatment using cardiotoxic treatments, e.g., anthracyclines and radiotherapy, conditioning regimens containing cyclophosphamide, and post-HSCT comorbidities, including GvHD, are factors contributing to CVC. Cardiac function evaluation prior to and post-transplantation is an important strategy for choosing the proper conditioning regimen, HSCT protocol and post-HSCT supportive care. Cardiac systolic function evaluation by echocardiography, in addition to serum cardiac biomarkers, such as troponins and brain natriuretic peptides, is recommended as a routine follow-up for HSCT patients. Angiotensin-converting enzyme inhibitors, angiotensin-II-receptor blockers, and beta-blockers, which are mostly used for the treatment of chemotherapy-induced cardiotoxicity, might be used as treatments for HSCT-related CVC. In summary, the present review reveals the urgent need for further investigations concerning HSCT-related CVC both at the preclinical and clinical levels due to the lack of knowledge about CVC and its underlying mechanisms. Full article
(This article belongs to the Special Issue Hematopoietic Stem Cell Transplantation in the Personalized Medicine Era)
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11 pages, 279 KiB  
Review
The Use of Allogeneic Hematopoietic Stem Cell Transplantation in Primary Myelofibrosis
by Heather R. Wolfe, Mitchell E. Horwitz and Lindsay A. M. Rein
J. Pers. Med. 2022, 12(4), 571; https://doi.org/10.3390/jpm12040571 - 2 Apr 2022
Viewed by 2055
Abstract
Primary myelofibrosis (PMF) is a BCR-ABL1 negative myeloproliferative neoplasm characterized by clonal proliferation of myeloid cells. This leads to reactive bone marrow fibrosis, ultimately resulting in progressive marrow failure, hepatosplenomegaly, and extramedullary hematopoiesis. PMF is considered the most aggressive of the BCR-ABL1 negative [...] Read more.
Primary myelofibrosis (PMF) is a BCR-ABL1 negative myeloproliferative neoplasm characterized by clonal proliferation of myeloid cells. This leads to reactive bone marrow fibrosis, ultimately resulting in progressive marrow failure, hepatosplenomegaly, and extramedullary hematopoiesis. PMF is considered the most aggressive of the BCR-ABL1 negative myeloproliferative neoplasms with the least favorable prognosis. Constitutional symptoms are common, which can impact an individual’s quality of life and leukemic transformation remains an important cause of death in PMF patients. The development of the Janus kinase 2 (JAK2) inhibitors have provided a good option for management of PMF-related symptoms. Unfortunately, these agents have not been shown to improve overall survival or significantly alter the course of disease. Allogenic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment option in PMF. However, allo-HSCT is associated with significant treatment-related morbidity and mortality and has historically been reserved for younger, high-risk patients. This review examines patient, disease, and transplant-specific factors which may impact transplant-related outcomes in PMF. Through the vast improvements in donor selection, conditioning regimens, and post-transplant care, allo-HSCT may provide a safe and effective curative option for a broader range of PMF patients in the future. Full article
(This article belongs to the Special Issue Hematopoietic Stem Cell Transplantation in the Personalized Medicine Era)
12 pages, 266 KiB  
Review
Hepatitis B Virus Infection in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation
by Yi-Chang Liu, Chi-Mu Hsu, Samuel Yien Hsiao and Hui-Hua Hsiao
J. Pers. Med. 2021, 11(11), 1108; https://doi.org/10.3390/jpm11111108 - 28 Oct 2021
Cited by 4 | Viewed by 1903
Abstract
Considering a steady increase in the number of allogeneic hematopoietic stem cell transplantations (allo-HSCT) worldwide and the significant proportion of the world’s population that has been exposed to hepatitis B virus (HBV) infection, HBV reactivation following allo-HSCT remains an important issue for post-transplant [...] Read more.
Considering a steady increase in the number of allogeneic hematopoietic stem cell transplantations (allo-HSCT) worldwide and the significant proportion of the world’s population that has been exposed to hepatitis B virus (HBV) infection, HBV reactivation following allo-HSCT remains an important issue for post-transplant morbidity and mortality. Antiviral prophylaxis can reduce HBV replication, severity of HBV-related hepatitis, and mortality; therefore, identification of patients at risk is crucial. It is recommended that all recipients and donors should be screened for active or prior HBV infection, including HBsAg, antiHBc, and antiHBs. Adoptive immunity transfer from the donor seems to have protective effects against HBV reactivation. Antiviral prophylaxis should be initiated in all HBsAg-positive patients. HBsAg-negative, antiHBc-positive patients remain at risk; therefore, antiviral prophylaxis should be considered if baseline serum HBV DNA is detectable. In HBsAg-negative, antiHBc-positive patients without detectable HBV DNA, close monitoring of viral load with an on-demand therapy is necessary. Entecavir or tenofovir rather than lamivudine are more appropriate for the emergence of lamivudine resistance. The treatment duration remains unclear, with 6- to 12-month therapy after cessation of immunosuppressive therapy commonly recommended. Here we review the updated evidence and recent recommendations regarding HBV reactivation in patients undergoing allo-HSCT for individualized therapy. Full article
(This article belongs to the Special Issue Hematopoietic Stem Cell Transplantation in the Personalized Medicine Era)
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