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Cells
Special Issues
Clinical and Methodological Aspects of HSC Transplantation in Hematological Malignancies
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Clinical and Methodological Aspects of HSC Transplantation in Hematological Malignancies

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 20844

Special Issue Editor

Prof. Dr. Luca Pierelli

E-Mail Website
Guest Editor
1. Immunohematology and Transfusion Medicine, San Camillo-Forlanini Hospital, 00152 Rome, Italy
2. Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy
Interests: transfusion medicine; hematopoietic stem cell biology and transplantation; mesenchymal stem cell biology; adoptive immunotherapy and innate immunity biology; regenerative medicine

Special Issue Information

Dear Colleagues,

Since the mid-20th century, hematopoietic stem cell transplantation (HSCT) has been used to treat defective or leukemic hematopoiesis in congenital and acquired diseases. Since its first use, HSCT had developed and improved considerably, and today, it represents a unique opportunity to cure several hematological malignancies. Thanks to the current knowledge of immunogenetics, stem cell biology, the antineoplastic and immunosuppressive properties of several drugs, and ex vivo procedures, HSCT can be applied to treat patients within a wide age range, and can overcome HLA- and ABO-group barriers. The ability of HSCT to manage the main adverse immune effects (i.e., graft versus host disease), and to maintain its intended immune effects (i.e., graft versus malignancy), renders it a powerful therapeutic strategy for preventing disease relapse or progression, and an instructive model for the development of future cell therapies.  

Prof. Dr. Luca Pierelli
Guest Editor

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Keywords

  • hematopoietic stem cells
  • hematological malignancies
  • transplantation
  • ABO groups
  • HLA compatibility
  • stem cell mobilization
  • stem cell collection
  • stem cell freezing
  • acute leukemia
  • multiple myeloma
  • graft versus host prophylaxis
  • graft versus host treatment
  • extracorporeal photopheresis
  • haploidentical transplantation

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Published Papers (6 papers)

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Review

35 pages, 4530 KiB  
Review
Current Approaches for the Prevention and Treatment of Acute and Chronic GVHD
by Attilio Olivieri and Giorgia Mancini
Cells 2024, 13(18), 1524; https://doi.org/10.3390/cells13181524 - 11 Sep 2024
Cited by 7 | Viewed by 5280
Abstract
Whereas aGVHD has strong inflammatory components, cGVHD displays autoimmune and fibrotic features; incidence and risk factors are similar but not identical; indeed, the aGVHD is the main risk factor for cGVHD. Calcineurin Inhibitors (CNI) with either Methotrexate (MTX) or Mycophenolate (MMF) still represent [...] Read more.
Whereas aGVHD has strong inflammatory components, cGVHD displays autoimmune and fibrotic features; incidence and risk factors are similar but not identical; indeed, the aGVHD is the main risk factor for cGVHD. Calcineurin Inhibitors (CNI) with either Methotrexate (MTX) or Mycophenolate (MMF) still represent the standard prophylaxis in HLA-matched allogeneic stem cell transplantation (HSCT); other strategies focused on ATG, Post-Transplant Cyclophosphamide (PTCy), Abatacept and graft manipulation. Despite the high rate, first-line treatment for aGVHD is represented by corticosteroids, and Ruxolitinib is the standard second-line therapy; investigational approaches include Microbiota transplant and the infusion of Mesenchymal stem cells. GVHD is a pleiotropic disease involving any anatomical district; also, Ruxolitinib represents the standard for steroid-refractory cGVHD in this setting. It is a pleiotropic disease involving any anatomical district; also, Ruxolitinib represents the standard for steroid-refractory cGVHD in this setting. Extracorporeal Photopheresis (ECP) is still an option used for steroid refractoriness or to achieve a steroid-sparing. For Ruxolitinib-refractory cGVHD, Belumosudil and Axatilimab represent the most promising agents. Bronchiolitis obliterans syndrome (BOS) still represents a challenge; among the compounds targeting non-immune effectors, Alvelestat, a Neutrophil elastase inhibitor, seems promising in BOS. Finally, in both aGVHD and cGVHD, the association of biological markers with specific disease manifestations could help refine risk stratification and the availability of reliable biomarkers for specific treatments. Full article
(This article belongs to the Special Issue Clinical and Methodological Aspects of HSC Transplantation in Hematological Malignancies)
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18 pages, 344 KiB  
Review
Multiple Myeloma: The Role of Autologous Stem Cell Transplantation in the Era of Immunotherapy
by Serena Rocchi, Beatrice Anna Zannetti, Giovanni Marconi and Francesco Lanza
Cells 2024, 13(10), 853; https://doi.org/10.3390/cells13100853 - 16 May 2024
Cited by 5 | Viewed by 2717
Abstract
Upfront high-dose therapy with melphalan (HDM) followed by autologous stem cell transplantation (ASCT) has established itself as a core treatment for newly diagnosed multiple myeloma (NDMM) patients in the past 30 years. Induction therapy, HDM-ASCT, and subsequent consolidation and maintenance therapy comprise the [...] Read more.
Upfront high-dose therapy with melphalan (HDM) followed by autologous stem cell transplantation (ASCT) has established itself as a core treatment for newly diagnosed multiple myeloma (NDMM) patients in the past 30 years. Induction therapy, HDM-ASCT, and subsequent consolidation and maintenance therapy comprise the current fundamental framework for MM treatment. The introduction of anti-CD38 monoclonal antibodies such as daratumumab and isatuximab has changed the treatment paradigm for transplant-eligible NDMM patients in that quadruplets have become the new standard induction therapy. The treatment landscape of MM is undergoing a transformative shift with the introduction of potent new immunotherapies, such as chimeric antigen receptor (CAR)-T cells and bispecific antibodies (BsAbs), which are currently used in the relapsed/refractory setting (RRMM) and are already being tested in the NDMM. This review will focus on the incorporation of immunotherapy in the treatment scenario of NDMM patients eligible for ASCT. Full article
(This article belongs to the Special Issue Clinical and Methodological Aspects of HSC Transplantation in Hematological Malignancies)
10 pages, 235 KiB  
Review
Immuno-Hematologic Complexity of ABO-Incompatible Allogeneic HSC Transplantation
by Antonella Matteocci and Luca Pierelli
Cells 2024, 13(10), 814; https://doi.org/10.3390/cells13100814 - 10 May 2024
Viewed by 2520
Abstract
ABO incompatibility is not considered a contraindication for hematopoietic stem cell transplantation (HSCT). Approximately 30% of transplants from related donors and up to 50% of transplants from unrelated donors are ABO incompatible. Immuno-hematologic investigations allow to estimate donor/recipient ABO mismatch and anti-A/B isohemagglutinin [...] Read more.
ABO incompatibility is not considered a contraindication for hematopoietic stem cell transplantation (HSCT). Approximately 30% of transplants from related donors and up to 50% of transplants from unrelated donors are ABO incompatible. Immuno-hematologic investigations allow to estimate donor/recipient ABO mismatch and anti-A/B isohemagglutinin (IHA) titration in the pre-HSCT phase. Immediate hemolysis or delayed complications (passenger lymphocyte syndrome and pure red cell aplasia) can occur post HSCT. Some preventive measures take into consideration either decision-making algorithms based on the recipient’s IHA titration or clinical protocols for the removal/reduction of IHAs through plasma exchange or immunoadsorption procedures. Product manipulation through red blood cell (RBC) and/or plasma depletion can also be taken into account. Currently, the best approach in the management of ABO-incompatible transplant is not defined in expert consensus documents or with solid evidence. In addition, the methods for IHA titration are not standardized. A transfusion strategy must consider both the donor’s and recipient’s blood group systems until the RBC engraftment catches on and ABO conversion (forward and reverse typing) is confirmed on two consecutive and independent samples. Therefore, ABO incompatibility in HSCT represents a demanding immuno-hematologic challenge and requires all necessary preventive measures, including the appropriate selection of ABO blood components for transfusion. Full article
(This article belongs to the Special Issue Clinical and Methodological Aspects of HSC Transplantation in Hematological Malignancies)
18 pages, 526 KiB  
Review
Allogeneic Stem Cell Transplantation in Refractory Acute Myeloid Leukaemia
by Roberto Bono, Giuseppe Sapienza, Stefania Tringali, Cristina Rotolo, Caterina Patti, Antonino Mulè, Valeria Calafiore, Alessandra Santoro and Luca Castagna
Cells 2024, 13(9), 755; https://doi.org/10.3390/cells13090755 - 26 Apr 2024
Cited by 3 | Viewed by 2460
Abstract
Refractory acute myeloid leukaemia is very difficult to treat and represents an unmet clinical need. In recent years, new drugs and combinations of drugs have been tested in this category, with encouraging results. However, all treated patients relapsed and died from the disease. [...] Read more.
Refractory acute myeloid leukaemia is very difficult to treat and represents an unmet clinical need. In recent years, new drugs and combinations of drugs have been tested in this category, with encouraging results. However, all treated patients relapsed and died from the disease. The only curative option is allogeneic transplantation through a graft from a healthy donor immune system. Using myeloablative conditioning regimens, the median overall survival regimens is 19%. Several so-called sequential induction chemotherapies followed by allogeneic transplantation conditioned by reduced intensity regimens have been developed, improving the overall survival to 25–57%. In the allogeneic transplantation field, continuous improvements in practices, particularly regarding graft versus host disease prevention, infection prevention, and treatment, have allowed us to observe improvements in survival rates. This is true mainly for patients in complete remission before transplantation and less so for refractory patients. However, full myeloablative regimens are toxic and carry a high risk of treatment-related mortality. In this review, we describe the results obtained with the different modalities used in more recent retrospective and prospective studies. Based on these findings, we speculate how allogeneic stem cell transplantation could be modified to maximise its therapeutic effect on refractory acute myeloid leukaemia. Full article
(This article belongs to the Special Issue Clinical and Methodological Aspects of HSC Transplantation in Hematological Malignancies)
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18 pages, 1315 KiB  
Review
Stem Cells Collection and Mobilization in Adult Autologous/Allogeneic Transplantation: Critical Points and Future Challenges
by Michele Prisciandaro, Enrico Santinelli, Valeria Tomarchio, Maria Antonietta Tafuri, Cecilia Bonchi, Gloria Palazzo, Carolina Nobile, Alessandra Marinucci, Marcella Mele, Ombretta Annibali, Luigi Rigacci and Michele Vacca
Cells 2024, 13(7), 586; https://doi.org/10.3390/cells13070586 - 28 Mar 2024
Cited by 6 | Viewed by 4304
Abstract
Achieving successful hematopoietic stem cell transplantation (HSCT) relies on two fundamental pillars: effective mobilization and efficient collection through apheresis to attain the optimal graft dose. These cornerstones pave the way for enhanced patient outcomes. The primary challenges encountered by the clinical unit and [...] Read more.
Achieving successful hematopoietic stem cell transplantation (HSCT) relies on two fundamental pillars: effective mobilization and efficient collection through apheresis to attain the optimal graft dose. These cornerstones pave the way for enhanced patient outcomes. The primary challenges encountered by the clinical unit and collection facility within a transplant program encompass augmenting mobilization efficiency to optimize the harvest of target cell populations, implementing robust monitoring and predictive strategies for mobilization, streamlining the apheresis procedure to minimize collection duration while ensuring adequate yield, prioritizing patient comfort by reducing the overall collection time, guaranteeing the quality and purity of stem cell products to optimize graft function and transplant success, and facilitating seamless coordination between diverse entities involved in the HSCT process. In this review, we aim to address key questions and provide insights into the critical aspects of mobilizing and collecting hematopoietic stem cells for transplantation purposes. Full article
(This article belongs to the Special Issue Clinical and Methodological Aspects of HSC Transplantation in Hematological Malignancies)
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21 pages, 1083 KiB  
Review
Cellular Strategies for Separating GvHD from GvL in Haploidentical Transplantation
by Mauro Di Ianni, Carmine Liberatore, Nicole Santoro, Paola Ranalli, Francesco Guardalupi, Giulia Corradi, Ida Villanova, Barbara Di Francesco, Stefano Lattanzio, Cecilia Passeri, Paola Lanuti and Patrizia Accorsi
Cells 2024, 13(2), 134; https://doi.org/10.3390/cells13020134 - 11 Jan 2024
Cited by 1 | Viewed by 2762
Abstract
GvHD still remains, despite the continuous improvement of transplantation platforms, a fearful complication of transplantation from allogeneic donors. Being able to separate GvHD from GvL represents the greatest challenge in the allogeneic transplant setting. This may be possible through continuous improvement of cell [...] Read more.
GvHD still remains, despite the continuous improvement of transplantation platforms, a fearful complication of transplantation from allogeneic donors. Being able to separate GvHD from GvL represents the greatest challenge in the allogeneic transplant setting. This may be possible through continuous improvement of cell therapy techniques. In this review, current cell therapies are taken into consideration, which are based on the use of TCR alpha/beta depletion, CD45RA depletion, T regulatory cell enrichment, NK-cell-based immunotherapies, and suicide gene therapies in order to prevent GvHD and maximally amplify the GvL effect in the setting of haploidentical transplantation. Full article
(This article belongs to the Special Issue Clinical and Methodological Aspects of HSC Transplantation in Hematological Malignancies)
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