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Advance in Hematopoietic Stem Cell Transplantation
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Advance in Hematopoietic Stem Cell Transplantation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 16592

Special Issue Editor

Dr. Chi-Cheng Li

E-Mail Website
Guest Editor
1. Department of Hematology and Oncology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97002, Taiwan
2. Center of Stem Cell & Precision Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97002, Taiwan
Interests: hematopoietic stem cell transplantation

Special Issue Information

Dear Colleagues,

Since the introduction of hematopoietic stem cell transplantation (HSCT) in the 1960s by Dr. E. Donnall Thomas, winner of the Nobel Prize in Physiology or Medicine in 1990, increasingly advanced knowledge has been discovered in the field, including unrelated donor transplantation, cord blood stem cell transplantation, and even if partially HLA-matched family donor transplantation of haploidentical transplants in recent years. At this time, IJMS aims to publish a Special Issue on “Advance in Hematopoietic Stem Cell Transplantation” and everyone is welcome to submit an article focusing on modern development or investigational studies in HSCT. It is especially welcome for unmet clinical needs, such as HSCT for the elderly or relapsed and refractory leukemia, congenital metabolic disorders, and the extension from traditional HSCT to different kinds of cell therapy. The other important issues include monitoring of disease burdens, such as minimal residual disease, before and after HSCT, a combination of targeted or immunotherapy to HSCT and maintenance therapy. Newly development in the management of HSCT complications such as graft-versus-host disease, and special infection considerations are welcome as well.

Dr. Chi-Cheng Li
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • 1. Hematopoietic stem cell transplantation 2. Unrelated donor transplantation 3. Haploidentical transplant 4. HSCT for the elderly 5. Relapsed/refractory leukemia 6. Congenital metabolic disorder 7. Cell therapy 8. Graft-versus-host-disease

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Published Papers (6 papers)

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Research

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15 pages, 1424 KiB  
Article
The Benefits of the Post-Transplant Cyclophosphamide in Both Haploidentical and Mismatched Unrelated Donor Setting in Allogeneic Stem Cells Transplantation
by Jarosław Dybko, Małgorzata Sobczyk-Kruszelnicka, Sebastian Makuch, Siddarth Agrawal, Krzysztof Dudek, Sebatian Giebel and Lidia Gil
Int. J. Mol. Sci. 2023, 24(6), 5764; https://doi.org/10.3390/ijms24065764 - 17 Mar 2023
Cited by 5 | Viewed by 2408
Abstract
Allogeneic hematopoietic cell transplantation (alloHSCT) is a standard therapeutic approach for acute leukemias and many other hematologic malignancies. The proper choice of immunosuppressants applicable to different types of transplantations still requires strict and careful consideration, and data in this regard are divergent. For [...] Read more.
Allogeneic hematopoietic cell transplantation (alloHSCT) is a standard therapeutic approach for acute leukemias and many other hematologic malignancies. The proper choice of immunosuppressants applicable to different types of transplantations still requires strict and careful consideration, and data in this regard are divergent. For this reason, in this single-centered, retrospective study, we aimed to compare the outcome of 145 patients who received post-transplant cyclophosphamide (PTCy) for MMUD and haplo-HSCT or GvHD prophylaxis for MMUD-HSCT alone. We attempted to verify if PTCy is an optimal strategy in MMUD setting. Ninety-three recipients (93/145; 64.1%) underwent haplo-HSCT while 52 (52/145; 35.9%) underwent MMUD-HSCT. There were 110 patients who received PTCy (93 in haplo and 17 in MMUD group) and 35 patients received conventional GvHD prophylaxis based on antithymocyte globulin (ATG), cyclosporine (CsA), and methotrexate (Mtx) in the MMUD group only. Our study revealed that patients receiving post-transplant cyclophosphamide (PTCy) show decreased acute GvHD rates and CMV reactivation as well as a statistically lower number of CMV copies before and after antiviral treatment compared to the CsA + Mtx + ATG group. Taking into account chronic GvHD, the main predictors are donor age, ≥40 years, and haplo-HSCT administration. Furthermore, the survival rate of patients following MMUD-HSCT and receiving PTCy with tacrolimus and mycophenolate mofetil was more than eight times greater in comparison to patients receiving CsA + Mtx + ATG (OR = 8.31, p = 0.003). These data taken together suggest that the use of PTCy displays more benefits in terms of survival rate compared to ATG regardless of the type of transplantation performed. Nevertheless, more studies with a larger sample size are required to confirm the conflicting results in the literature studies. Full article
(This article belongs to the Special Issue Advance in Hematopoietic Stem Cell Transplantation)
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9 pages, 1690 KiB  
Article
Immune Ablation and Stem Cell Rescue in Two Pediatric Patients with Progressive Severe Chronic Graft-Versus-Host Disease
by Jaspar Kloehn, Anne Kruchen, Kerstin Schütze, Katharina Wustrau, Johanna Schrum and Ingo Müller
Int. J. Mol. Sci. 2022, 23(23), 15403; https://doi.org/10.3390/ijms232315403 - 6 Dec 2022
Cited by 2 | Viewed by 1739
Abstract
Transplantation of allogeneic hematopoietic stem cells represents an established treatment for children with high-risk leukemia. However, steroid-refractory chronic graft-versus-host disease (SR-cGvHD) represents a severe life-threatening complication, for which there is no standard therapy. After failing several lines of immunosuppressive and biological treatment, we [...] Read more.
Transplantation of allogeneic hematopoietic stem cells represents an established treatment for children with high-risk leukemia. However, steroid-refractory chronic graft-versus-host disease (SR-cGvHD) represents a severe life-threatening complication, for which there is no standard therapy. After failing several lines of immunosuppressive and biological treatment, we applied an immunoablative therapy with re-transplantation of purified CD34+ donor stem cells to reset the aberrant immune system. Two pediatric patients, who had been transplanted for high-risk acute lymphoblastic leukemia, underwent the procedure. Interestingly, enough stem cells could be mobilized, harvested, and purified to be used as grafts more than one year after allogeneic transplantation under intensive immunosuppressive therapy and ongoing SR-cGvHD. With a follow-up of 8 and 22 months, respectively, both patients are without immunosuppressive therapy and do not show signs of active disease. Regeneration of skin manifestations started promptly, other damaged organs did not progress and continue to show recovery from severe fibrotic transformation. Bone marrow function is robust and T cell receptor repertoires showed polyclonal immune reconstitution. In conclusion, stem cell harvest and re-transplantation of human CD34+-selected allogeneic stem cells is possible and represents a new therapeutic option in SR-cGvHD by resetting a profoundly disturbed immune network. Full article
(This article belongs to the Special Issue Advance in Hematopoietic Stem Cell Transplantation)
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8 pages, 1308 KiB  
Article
IL3 Has a Detrimental Effect on Hematopoietic Stem Cell Self-Renewal in Transplantation Settings
by Parisa Tajer, Kirsten Canté-Barrett, Brigitta A. E. Naber, Sandra A. Vloemans, Marja C. J. A. van Eggermond, Marie-Louise van der Hoorn, Karin Pike-Overzet and Frank J. T. Staal
Int. J. Mol. Sci. 2022, 23(21), 12736; https://doi.org/10.3390/ijms232112736 - 22 Oct 2022
Cited by 6 | Viewed by 2788
Abstract
The ex vivo expansion and maintenance of long-term hematopoietic stem cells (LT-HSC) is crucial for stem cell-based gene therapy. A combination of stem cell factor (SCF), thrombopoietin (TPO), FLT3 ligand (FLT3) and interleukin 3 (IL3) cytokines has been commonly used in clinical settings [...] Read more.
The ex vivo expansion and maintenance of long-term hematopoietic stem cells (LT-HSC) is crucial for stem cell-based gene therapy. A combination of stem cell factor (SCF), thrombopoietin (TPO), FLT3 ligand (FLT3) and interleukin 3 (IL3) cytokines has been commonly used in clinical settings for the expansion of CD34+ from different sources, prior to transplantation. To assess the effect of IL3 on repopulating capacity of cultured CD34+ cells, we employed the commonly used combination of STF, TPO and FILT3 with or without IL3. Expanded cells were transplanted into NSG mice, followed by secondary transplantation. Overall, this study shows that IL3 leads to lower human cell engraftment and repopulating capacity in NSG mice, suggesting a negative effect of IL3 on HSC self-renewal. We, therefore, recommend omitting IL3 from HSC-based gene therapy protocols. Full article
(This article belongs to the Special Issue Advance in Hematopoietic Stem Cell Transplantation)
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11 pages, 1093 KiB  
Communication
Post-Transplant Cyclophosphamide after Matched Sibling and Unrelated Donor Hematopoietic Stem Cell Transplantation in Pediatric Patients with Acute Myeloid Leukemia
by Irtiza N. Sheikh, Shaikha Alqahtani, Dristhi Ragoonanan, Priti Tewari, Demetrios Petropoulos, Kris M. Mahadeo, Uday Popat, Elizabeth J. Shpall and Sajad Khazal
Int. J. Mol. Sci. 2022, 23(15), 8748; https://doi.org/10.3390/ijms23158748 - 6 Aug 2022
Cited by 3 | Viewed by 1991
Abstract
Non-relapse mortality due to GVHD and infections represents a major source of morbidity and mortality in pediatric HSCT recipients. Post-transplant cyclophosphamide (PTCy) has emerged as an effective and safe GVHD prophylaxis strategy, with improved GVHD and relapse-free survival in matched (related and unrelated) [...] Read more.
Non-relapse mortality due to GVHD and infections represents a major source of morbidity and mortality in pediatric HSCT recipients. Post-transplant cyclophosphamide (PTCy) has emerged as an effective and safe GVHD prophylaxis strategy, with improved GVHD and relapse-free survival in matched (related and unrelated) and mismatched haploidentical HSCT adult recipients. However, there are no published data in pediatric patients with acute myeloid leukemia who received matched-donor HSCT with PTCy. We demonstrate, in this case series, that the use of PTCy in this population is potentially safe, effective in preventing acute GVHD, does not impair engraftment, is associated with reduced non-relapse mortality, and does not hinder immune reconstitution post HSCT. Full article
(This article belongs to the Special Issue Advance in Hematopoietic Stem Cell Transplantation)
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Review

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14 pages, 1504 KiB  
Review
Do CAR-T and Allogeneic Stem Cell Transplant Both Have a Place in Lymphoid Neoplasms?
by Massimo Martino, Filippo Antonio Canale, Virginia Naso, Gaetana Porto, Demetrio Gerace and Alessandro Allegra
Int. J. Mol. Sci. 2023, 24(2), 1045; https://doi.org/10.3390/ijms24021045 - 5 Jan 2023
Cited by 4 | Viewed by 3234
Abstract
Allogeneic stem cell transplantation (allo-SCT) represented the first immunotherapy to treat hematologic malignancies: it has been considered as a cure for the disease and never as an approach to extend the life of patients. The success of allo-SCT derives both from the ability [...] Read more.
Allogeneic stem cell transplantation (allo-SCT) represented the first immunotherapy to treat hematologic malignancies: it has been considered as a cure for the disease and never as an approach to extend the life of patients. The success of allo-SCT derives both from the ability to treat patients with intensive chemoradiotherapy and from the potent graft-versus-leukemia effects mediated by donor immunity. Although considerable progress has been made in the last years, significant barriers still remain in the form of disease relapse, graft-versus-host disease, infectious complications, and regimen-related toxicities. Moreover, the treatment of hematologic malignancies, particularly acute lymphoblastic leukemia and certain forms of lymphomas, has been revolutionized by the commercial introduction of genetically modified autologous T-lymphocyte therapy (CAR-T). Our review discusses current standards and the shifting paradigms in the indications for allo-SCT and the role of CAR-T cell therapy for lymphoid neoplasms. Full article
(This article belongs to the Special Issue Advance in Hematopoietic Stem Cell Transplantation)
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24 pages, 1229 KiB  
Review
Leveraging Natural Killer Cell Innate Immunity against Hematologic Malignancies: From Stem Cell Transplant to Adoptive Transfer and Beyond
by Chenyu Lin, Mitchell E. Horwitz and Lindsay A. M. Rein
Int. J. Mol. Sci. 2023, 24(1), 204; https://doi.org/10.3390/ijms24010204 - 22 Dec 2022
Cited by 2 | Viewed by 3451
Abstract
Numerous recent advancements in T-cell based immunotherapies have revolutionized the treatment of hematologic malignancies. In the race towards the first approved allogeneic cellular therapy product, there is growing interest in utilizing natural killer (NK) cells as a platform for off-the-shelf cellular therapies due [...] Read more.
Numerous recent advancements in T-cell based immunotherapies have revolutionized the treatment of hematologic malignancies. In the race towards the first approved allogeneic cellular therapy product, there is growing interest in utilizing natural killer (NK) cells as a platform for off-the-shelf cellular therapies due to their scalable manufacturing potential, potent anti-tumor efficacy, and superior safety profile. Allogeneic NK cell therapies are now being actively explored in the setting of hematopoietic stem cell transplantation and adoptive transfer. Increasingly sophisticated gene editing techniques have permitted the engineering of chimeric antigen receptors, ectopic cytokine expression, and tumor recognition signals to improve the overall cytotoxicity of NK cell therapies. Furthermore, the enhancement of antibody-dependent cellular cytotoxicity has been achieved through the use of NK cell engagers and combination regimens with monoclonal antibodies that act synergistically with CD16-expressing NK cells. Finally, a greater understanding of NK cell biology and the mechanisms of resistance have allowed the preclinical development of NK checkpoint blockade and methods to modulate the tumor microenvironment, which have been evaluated in early phase trials. This review will discuss the recent clinical advancements in NK cell therapies in hematologic malignancies as well as promising avenues of future research. Full article
(This article belongs to the Special Issue Advance in Hematopoietic Stem Cell Transplantation)
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