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Cells
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State of the Art and Future Prospects in Stem Cell...
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State of the Art and Future Prospects in Stem Cell Transplantation

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: closed (30 April 2025) | Viewed by 9883

Special Issue Editor

Prof. Dr. Shin Mineishi

E-Mail Website
Guest Editor
Bone Marrow Transplant Program, Penn State Hershey Medical Center, 500 University Drive, P.O. Box 850, Hershey, PA 17033, USA
Interests: bone marrow transplantation; graft versus host disease; complications after stem cell transplantation; reduced intensity stem cell transplantation; HLA-mismatch stem cell transplantation; graft engineering; cell therapy; and gene therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hematopoietic Stem Cell Transplantation (HSCT) has emerged as a pivotal tool against hematological malignancies. This Special Issue of "Cells" illuminates state-of-the-art advancements in HSCT, focusing on transformative strides in treating leukemia, lymphoma, and myeloma. Since the inception of allogeneic stem cell transplantation in the mid-20th century, the field has seen remarkable progress. The shift from conventional myeloablative regimens to prevalent reduced-intensity regimens signifies this evolution. The donor landscape has also broadened with cord blood transplantation and the innovative haploidentical HSCT using PTCy. A significant milestone is the recent incorporation of the Minimal Residual Disease (MRD) strategy, making HSCT decisions more scientific and precise. While we celebrate these advancements, challenges like post-transplant relapse, GVHD, and optimal donor selection remain. This Special Issue provides a comprehensive snapshot of the current landscape, emphasizing groundbreaking research and the evolving paradigms in stem cell transplantation for hematological malignancies. As readers explore these articles, from seasoned experts to newcomers, they are invited to discover the innovations shaping the future of hematologic oncology.

Prof. Dr. Shin Mineishi
Guest Editor

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Keywords

  • hematopoietic stem cell transplantation
  • conditioning
  • graft-versus-host disease
  • minimal residual disease
  • HSCT

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Published Papers (7 papers)

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Research

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12 pages, 993 KiB  
Article
Mixed T-Cell Chimerism Following Hematopoietic Cell Transplantation for Non-Malignant Disorders Is Common, Facilitates Anti-Viral Immunity, and Is Not Associated with Graft Failure in Pediatric Patients
by Rubiya Nadaf, Helena Lee, Denise Bonney, Ramya Hanasoge-Nataraj, Srividhya Senthil, Claire Horgan, Malcolm Guiver, Kay Poulton and Robert Wynn
Cells 2024, 13(24), 2119; https://doi.org/10.3390/cells13242119 - 20 Dec 2024
Viewed by 848
Abstract
Myeloid chimerism better reflects donor stem cell engraftment than whole-blood chimerism in assessing graft function following allogeneic hematopoietic stem cell transplant (HCT). We describe our experience with 130 patients aged younger than 18 years, treated with allogeneic HCT using bone marrow or PBSC [...] Read more.
Myeloid chimerism better reflects donor stem cell engraftment than whole-blood chimerism in assessing graft function following allogeneic hematopoietic stem cell transplant (HCT). We describe our experience with 130 patients aged younger than 18 years, treated with allogeneic HCT using bone marrow or PBSC from HLA-matched donors for non-malignant diseases, whose pre-transplant conditioning therapy included alemtuzumab and who were monitored with lineage-specific chimerism after transplant. At 6 years post-transplant, overall survival (OS) was 91.1% and event-free survival (EFS) was 81.5%, with no grade III-IV acute GvHD or chronic GVHD observed. Recipient T-cells did not contribute to graft loss. Mixed T-cell chimerism (MC) did not affect EFS, and there was no connection between T-cell chimerism and myeloid chimerism in patients with MC or graft loss. MC significantly correlated with virus infection; more children with MC were CMV seropositive than those with complete chimerism (CC). Additionally, MC was more common in patients with CMV viramia post-transplant. CD8 T-cell reconstitution was affected by viral reactivation, including CMV, with CD8 T-cell counts higher in the MC group than in the CC group. Mixed T-cell chimerism is due to autologous, virus-specific, predominantly CD8, T-cell expansion, and is protective and not deleterious to the recipient. Full article
(This article belongs to the Special Issue State of the Art and Future Prospects in Stem Cell Transplantation)
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Review

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22 pages, 1453 KiB  
Review
Evolution of Allogeneic Stem Cell Transplantation: Main Focus on AML
by Yoshitaka Inoue, Joseph Cioccio, Shin Mineishi and Kentaro Minagawa
Cells 2025, 14(8), 572; https://doi.org/10.3390/cells14080572 - 10 Apr 2025
Viewed by 375
Abstract
In recent years, treatments in the field of hematologic malignancies have undergone significant evolution; allogeneic hematopoietic stem cell transplantation (allo-HSCT) has shifted from an “ultimate” therapy to becoming a component of a comprehensive therapeutic strategy for acute myeloid leukemia (AML). Advances in risk [...] Read more.
In recent years, treatments in the field of hematologic malignancies have undergone significant evolution; allogeneic hematopoietic stem cell transplantation (allo-HSCT) has shifted from an “ultimate” therapy to becoming a component of a comprehensive therapeutic strategy for acute myeloid leukemia (AML). Advances in risk stratification (including molecular profiling and measurable residual disease assessment), conditioning regimens, and graft-versus-host disease (GVHD) prophylaxis—such as post-transplant cyclophosphamide—have improved outcomes and expanded donor selection and transplant eligibility. We should not only focus on the transplantation procedure but also consider various therapeutic components, including chemotherapy, targeted therapy (possibly including chimeric antigen receptor T-cell therapy), and post-transplant maintenance therapy, which need to be orchestrated within the broader context of leukemia treatment. In this review, we summarized key developments in allo-HSCT for AML and aim to “decipher” each component of transplantation. Full article
(This article belongs to the Special Issue State of the Art and Future Prospects in Stem Cell Transplantation)
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20 pages, 344 KiB  
Review
Significance of Measurable Residual Disease in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia
by Margery Gang, Megan Othus and Roland B. Walter
Cells 2025, 14(4), 290; https://doi.org/10.3390/cells14040290 - 15 Feb 2025
Viewed by 866
Abstract
Allogeneic hematopoietic cell transplantation (HCT) remains an important curative-intent treatment for many patients with acute myeloid leukemia (AML), but AML recurrence after allografting is common. Many factors associated with relapse after allogeneic HCT have been identified over the years. Central among these is [...] Read more.
Allogeneic hematopoietic cell transplantation (HCT) remains an important curative-intent treatment for many patients with acute myeloid leukemia (AML), but AML recurrence after allografting is common. Many factors associated with relapse after allogeneic HCT have been identified over the years. Central among these is measurable (“minimal”) residual disease (MRD) as detected by multiparameter flow cytometry, quantitative polymerase chain reaction, and/or next-generation sequencing. Demonstration of a strong, independent prognostic role of pre- and early post-HCT MRD has raised hopes MRD could also serve as a predictive biomarker to inform treatment decision-making, with emerging data indicating the potential value to guide candidacy assessment for allografting as a post-remission treatment strategy, the selection of conditioning intensity, use of small molecule inhibitors as post-HCT maintenance therapy, and preemptive infusion of donor lymphocytes. Monitoring for leukemia recurrence after HCT and surrogacy for treatment response are other considerations for the clinical use of MRD data. In this review, we will outline the current landscape of MRD as a biomarker for patients with AML undergoing HCT and discuss areas of uncertainty and ongoing research. Full article
(This article belongs to the Special Issue State of the Art and Future Prospects in Stem Cell Transplantation)
13 pages, 1615 KiB  
Review
Treatment Response in Individual Organs Affected by Chronic Graft-Versus-Host Disease
by Takanobu Morishita, Paul J. Martin and Yoshihiro Inamoto
Cells 2025, 14(4), 238; https://doi.org/10.3390/cells14040238 - 7 Feb 2025
Cited by 1 | Viewed by 983
Abstract
Chronic graft-versus-host disease (GVHD) occurs in 30–70% of patients after allogeneic hematopoietic cell transplantation (HCT) and increases the risks of morbidity and mortality. Systemic corticosteroids are the standard initial treatment, but one-third of patients require subsequent treatment with other systemic agents. Treatment decisions [...] Read more.
Chronic graft-versus-host disease (GVHD) occurs in 30–70% of patients after allogeneic hematopoietic cell transplantation (HCT) and increases the risks of morbidity and mortality. Systemic corticosteroids are the standard initial treatment, but one-third of patients require subsequent treatment with other systemic agents. Treatment decisions are often based on physicians’ experience. The expected treatment response rates in specific organs affected by chronic GVHD may inform such decisions. In this review, we identify 20 studies reporting treatment response rates in individual organs according to objective criteria, summarize the results, discuss the caveats in data interpretation, identify the unmet needs, and suggest future directions in the field. For cutaneous sclerosis, we observed large discrepancies in organ response rates according to the current NIH criteria and patient-reported improvement, highlighting the need for better measurement tools. High response rates for lung involvement with certain novel drugs deserve further investigation. Full article
(This article belongs to the Special Issue State of the Art and Future Prospects in Stem Cell Transplantation)
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16 pages, 1246 KiB  
Review
High-Dose Chemotherapy and Autologous or Allogeneic Transplantation in Aggressive B-Cell Lymphoma—Is There Still a Role?
by Michael Daunov and Koen van Besien
Cells 2024, 13(21), 1780; https://doi.org/10.3390/cells13211780 - 27 Oct 2024
Viewed by 2026
Abstract
Novel therapies such as CAR-T, BTK inhibitors and PD-1 inhibitors have changed the management of aggressive B-cell lymphomas. Nonetheless, these novel therapies have their own risk of late toxicities including second malignancies. They also create a subgroup of patients with relapse, treatment failure, [...] Read more.
Novel therapies such as CAR-T, BTK inhibitors and PD-1 inhibitors have changed the management of aggressive B-cell lymphomas. Nonetheless, these novel therapies have their own risk of late toxicities including second malignancies. They also create a subgroup of patients with relapse, treatment failure, or indefinite maintenance. We discuss the current role of autologous and allogeneic stem cell transplantation in this context. In patients with recurrent diffuse large B-cell lymphoma, CAR-T cell treatment has largely replaced autologous transplant. Autologous transplant should be considered in patients with late relapses and in selected patients with T-cell-rich B-cell lymphoma, where CAR-T cell therapy may be less effective. It also remains the treatment of choice for consolidation of patients with primary CNS lymphoma. In mantle cell lymphoma, intensive chemotherapy combined with BTK inhibitors and rituximab results in excellent outcomes, and the role of autologous transplantation is declining. In Hodgkin’s lymphoma, autologous transplant consolidation remains the standard of care for patients who failed initial chemotherapy. Allogeneic transplantation has lower relapse rates but more complications and higher non-relapse mortality than autologous transplantation. It is usually reserved for patients who fail autologous transplantation or in whom autologous stem cells cannot be collected. It may also have an important role in patients who fail CAR-T therapies. The increasing complexity of care and evolving sequencing of therapies for patients with aggressive B-cell lymphomas only emphasizes the importance of appropriate patient selection and optimal timing of stem cell transplantation. Full article
(This article belongs to the Special Issue State of the Art and Future Prospects in Stem Cell Transplantation)
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Other

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11 pages, 302 KiB  
Perspective
HLA and Non-HLA Factors for Donor Selection in Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide GvHD Prophylaxis
by Hiroko Shike and Aiwen Zhang
Cells 2024, 13(24), 2067; https://doi.org/10.3390/cells13242067 - 14 Dec 2024
Viewed by 1447
Abstract
Human leukocyte antigen (HLA) mismatches in stem cell transplantation can be well-tolerated with the use of post-transplant cyclophosphamide (PTCy) for graft-versus-host-disease (GvHD) prophylaxis. Haploidentical (Haplo) and HLA-mismatched unrelated donors become acceptable donors. This review focuses on Haplo and unrelated donor selection in the [...] Read more.
Human leukocyte antigen (HLA) mismatches in stem cell transplantation can be well-tolerated with the use of post-transplant cyclophosphamide (PTCy) for graft-versus-host-disease (GvHD) prophylaxis. Haploidentical (Haplo) and HLA-mismatched unrelated donors become acceptable donors. This review focuses on Haplo and unrelated donor selection in the context of PTCy-transplant for hematological malignancy, in comparison with conventional GvHD prophylaxis. Evaluating patient’s donor-specific antibody (DSA) is critical in donor selection regardless of donor type or the use of PTCy. High DSA levels and positive C1q increase the risk of engraftment failure and unsuccessful desensitization. On the other hand, the degree of donor HLA matching is less critical under PTCy compared to conventional GvHD prophylaxis. Donor age was found to be important, as younger donors improve survival outcomes. HLA-B leader match appears to be preferable. The impacts of donor gender, donor cytomegalovirus serostatus, and ABO mismatch are unclear or non-significant. Additionally, available studies suggest that, in PTCy-transplant, preferred Haplo-donors are HLA class II mismatched (DRB1 mismatch and DPB1 non-permissive), siblings or offspring over parents, and if parent, father over mother, while preferred unrelated donors are HLA class I matched. Further study is warranted. Full article
(This article belongs to the Special Issue State of the Art and Future Prospects in Stem Cell Transplantation)
8 pages, 551 KiB  
Commentary
The Evolution of Hematopoietic Stem Cell Transplantation to Overcome Access Disparities: The Role of NMDP
by Steven M. Devine
Cells 2024, 13(11), 933; https://doi.org/10.3390/cells13110933 - 29 May 2024
Viewed by 2371
Abstract
NMDP recognizes that despite advances in hematopoietic stem cell transplantation (HSCT) and other cell therapies, not all patients have equitable access to treatment, and disparities in outcomes remain. This paper explores the recent work of NMDP to accelerate progress and expand access to [...] Read more.
NMDP recognizes that despite advances in hematopoietic stem cell transplantation (HSCT) and other cell therapies, not all patients have equitable access to treatment, and disparities in outcomes remain. This paper explores the recent work of NMDP to accelerate progress and expand access to more patients through transformative clinical research, particularly in the use of mismatched unrelated donors for HSCT. Full article
(This article belongs to the Special Issue State of the Art and Future Prospects in Stem Cell Transplantation)
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