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Keywords = haploidentical donor

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21 pages, 2365 KiB  
Review
Natural Killer (NK) Cell Alloreactivity in Haploidentical Stem Cell Transplantation
by Mar Luis-Hidalgo, José Luis Piñana, Carlos Solano and Dolores Planelles
Cells 2025, 14(14), 1091; https://doi.org/10.3390/cells14141091 - 16 Jul 2025
Viewed by 283
Abstract
This paper conducts a literature review on the role of natural killer cells in haploidentical hematopoietic stem cell transplantation. Theoretical concepts related to KIR genes are introduced regarding their structure, nomenclature, genetic organization, polymorphism, and inheritance pattern, types of KIR proteins and receptors, [...] Read more.
This paper conducts a literature review on the role of natural killer cells in haploidentical hematopoietic stem cell transplantation. Theoretical concepts related to KIR genes are introduced regarding their structure, nomenclature, genetic organization, polymorphism, and inheritance pattern, types of KIR proteins and receptors, HLA ligands for KIR receptors, and the definition of different NK alloreactivity prediction models for the donor of haploidentical hematopoietic stem cell transplantation and the recipient. These models include the following and consider incompatibility: ligand–ligand, receptor–ligand, gene–gene, and KIR haplotype models or the KIR-B donor group. These models consider the presence or absence of specific ligands or receptors and/or KIR genes in the donor and recipient to predict alloreactivity. Determining the best model for predicting KIR alloreactivity and its significance in donor selection algorithms for haploidentical transplantation is still under investigation. Full article
(This article belongs to the Section Cellular Immunology)
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16 pages, 1513 KiB  
Article
Post-Transplant Cyclophosphamide-Based Prophylaxis and Its Impact on Infectious Complications and Immune Reconstitution According to Donor Type
by Beatriz Merchán-Muñoz, María Suárez-Lledó, Luis Gerardo Rodríguez-Lobato, Tommaso Francesco Aiello, Antonio Gallardo-Pizarro, Paola Charry, Joan Cid, Miquel Lozano, Alexandra Pedraza, Alexandra Martínez-Roca, Ares Guardia, Laia Guardia, Cristina Moreno, Enric Carreras, Laura Rosiñol, Carolina García-Vidal, Francesc Fernández-Avilés, Carmen Martínez, Montserrat Rovira and María Queralt Salas
Cancers 2025, 17(7), 1109; https://doi.org/10.3390/cancers17071109 - 26 Mar 2025
Viewed by 693
Abstract
Background/Objectives: This study evaluated infectious complications and immune reconstitution in 253 adults undergoing peripheral blood allogeneic hematopoietic cell transplantation (allo-HCT) with post-transplant cyclophosphamide (PTCY)-based GVHD prophylaxis. Methods: Patients received grafts from HLA-matched donors (47.4%), mismatched unrelated donors (MMUD, 33.2%), or haploidentical donors (19.4%). [...] Read more.
Background/Objectives: This study evaluated infectious complications and immune reconstitution in 253 adults undergoing peripheral blood allogeneic hematopoietic cell transplantation (allo-HCT) with post-transplant cyclophosphamide (PTCY)-based GVHD prophylaxis. Methods: Patients received grafts from HLA-matched donors (47.4%), mismatched unrelated donors (MMUD, 33.2%), or haploidentical donors (19.4%). Results: The estimated 2-year non-relapse mortality (NRM) was 11.8%, 26.4%, and 22.4%, respectively (p = 0.0528). The cumulative incidence (Cum.Inc) of acute and chronic GVHD, immunosuppression duration, and post-transplant outcomes were similar across donor types. The day +30 Cum.Inc of bacterial bloodstream infections (BSI) tended to be higher in HLA-matched transplants (49.2%, p = 0.073), while HHV-6 reactivation showed a trend toward higher frequency in haploidentical transplants (22.4%, p = 0.068). Cytomegalovirus (CMV) reactivation occurred between days +30 and +100, with the highest Cum.Inc in MMUD (59.5%, p = 0.033). BK virus-associated hemorrhagic cystitis showed a trend toward higher incidence in MMUD (22.3%, p = 0.056). Respiratory and fungal infections were most frequent in the first 100 days, with comparable rates across donor types. By day +180, most patients achieved immune reconstitution, with normalization of CD4+ T cells, CD8+ T cells, and IgG levels, independent of donor type. Conclusions: Patients undergoing allo-HCT with PTCY-based prophylaxis experience a high infectious density rate early post-transplant, which decreases after 6 months as immune reconstitution progresses, regardless of donor type. Full article
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16 pages, 2646 KiB  
Article
Comparison of Regulatory T-Cell Subpopulations in Antithymocytic Globulin Versus Post-Transplant Cyclophosphamide for Preventing Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation—A Retrospective Study
by Bu-Yeon Heo, Jeong Suk Koh, Su-Young Choi, Thi Thuy Duong Pham, Sang-Woo Lee, Jung-Hyun Park, Yunseon Jang, Myung-Won Lee, Seul-Bi Lee, Wonhyoung Seo, Deog-Yeon Jo, Jaeyul Kwon and Ik-Chan Song
Int. J. Mol. Sci. 2025, 26(6), 2521; https://doi.org/10.3390/ijms26062521 - 11 Mar 2025
Viewed by 934
Abstract
Antithymocytic globulin (ATG) and post-transplant cyclophosphamide (PTCy) are frequently used regimens for graft-versus-host disease (GVHD) prophylaxis. However, there is a lack of data about the difference in regulatory T-cell (Treg) subpopulations between these two regimens. Peripheral blood samples were collected on day +21 [...] Read more.
Antithymocytic globulin (ATG) and post-transplant cyclophosphamide (PTCy) are frequently used regimens for graft-versus-host disease (GVHD) prophylaxis. However, there is a lack of data about the difference in regulatory T-cell (Treg) subpopulations between these two regimens. Peripheral blood samples were collected on day +21 following allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and the Treg subpopulations were analyzed using flow cytometry. The Treg populations were categorized into three distinct subgroups: naïve, effector, and non-suppressive. And we compared overall survival (OS), the cumulative incidence of acute and chronic GVHD, and the relapse rate between the ATG and PTCy groups. We enrolled 45 patients (28 in ATG, 17 in PTCy) in total. In the ATG group, 16 and 12 patients underwent human leukocyte antigen (HLA) matched-sibling donor and unrelated donor HSCT, respectively. In the PTCy group, 12 patients underwent haplo-identical HSCT, and 5 patients underwent HLA-matched unrelated donor HSCT. The cumulative incidence of Grade 2–4 acute GVHD was 18.3% in the ATG group compared to 38.1% in the PTCy group (p = 0.13), while severe chronic GVHD occurred in 19.4% of ATG patients and 41.7% of PTCy patients (p = 0.343). And OS and the relapse rate were not statistically different between the two groups. The conventional CD25+FOXP3+Treg count of CD4 + T cells was higher in the PTCy group than in the ATG group (p = 0.0020). The effector Treg subset was significantly higher in the PTCy group than in the ATG group (p = 0.0412). And the effector Treg cell count had an inverse correlation with the severity of acute GVHD (p = 0.0007). Effector Tregs may be used as a biomarker to predict the severity of acute GVHD after allo-HSCT. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Organ Transplantation)
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12 pages, 920 KiB  
Article
Outcomes of Allogeneic Stem Cell Transplant in Patients with Relapsed/Refractory Hodgkin Lymphoma
by Shiliang Ge, Kylie Lepic, Ravi Bhindi, Tobias Berg, Dina Khalaf, Brian Leber, Michael Radford, Irwin Walker, Gwynivere Davies and Alejandro Garcia-Horton
Curr. Oncol. 2025, 32(2), 118; https://doi.org/10.3390/curroncol32020118 - 18 Feb 2025
Viewed by 1466
Abstract
Background: The aim of this study was to evaluate real-world clinical outcomes and transplant-related complications of allogeneic stem cell transplantation (alloSCT) for Hodgkin lymphoma (HL). Methods: This was a single-centre, retrospective analysis of relapsed and refractory (R/R) HL patients who received an alloSCT [...] Read more.
Background: The aim of this study was to evaluate real-world clinical outcomes and transplant-related complications of allogeneic stem cell transplantation (alloSCT) for Hodgkin lymphoma (HL). Methods: This was a single-centre, retrospective analysis of relapsed and refractory (R/R) HL patients who received an alloSCT between 1 January 2016 and 29 February 2024 in Hamilton, Ontario. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), non-relapse mortality (NRM), and graft-versus-host disease/relapse-free survival (GRFS). Results: Twenty-one patients were identified, with thirteen (62%) pre-treated with programmed death 1 (PD-1) blockade with either nivolumab or pembrolizumab. Seventeen (81%) patients underwent related haploidentical donor transplants, while four (19%) patients received a matched unrelated donor transplant. The 2-year OS and PFS rates were 79% (95% CI: 53–92%) and 63% (95% CI: 37–81%), respectively. Trends towards improved OS, PFS, NRM, and GRFS in PD-1-inhibitor-exposed patients were observed. All PD-1-inhibitor-exposed patients who were in complete remission proceeding to alloSCT remained alive at the last follow-up visit. Among the nine patients in partial remission at the time of alloSCT, three deaths were reported, with a 2-year OS of 61%. Conclusions: Our outcome data of a single-centre, heavily pre-treated cohort of Canadian patients confirm that alloSCT with post-transplant cyclophosphamide-based immunosuppression, which has been associated with improvements in PFS, remains a safe and feasible treatment option for patients with R/R HL in the era of checkpoint inhibitor use. Full article
(This article belongs to the Section Cell Therapy)
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15 pages, 934 KiB  
Article
Exploring Outcomes by Ethnicity in Allogeneic Hematopoietic Cell Transplantation
by Elizabeth Herrity, Sanjay Singhabahu, Mats Remberger, Tommy Alfaro Moya, Igor Novitzky Basso, Ivan Pasic, Wilson Lam, Arjun D. Law, Auro Viswabandya, Armin Gerbitz, Rajat Kumar, Dennis D. Kim, Jeffrey H. Lipton, Jonas Mattsson and Fotios V. Michelis
Cancers 2025, 17(4), 651; https://doi.org/10.3390/cancers17040651 - 14 Feb 2025
Viewed by 862
Abstract
Background: Clinical outcome disparities among racial and ethnic groups have been described following allogeneic hematopoietic cell transplantation (HCT). This study investigated the impact of race and ethnicity on HCT outcomes in a multi-ethnic single-center population. Methods: We analyzed outcomes of 709 allogeneic HCT [...] Read more.
Background: Clinical outcome disparities among racial and ethnic groups have been described following allogeneic hematopoietic cell transplantation (HCT). This study investigated the impact of race and ethnicity on HCT outcomes in a multi-ethnic single-center population. Methods: We analyzed outcomes of 709 allogeneic HCT patients, stratified by racial and ethnic groups, who underwent allogeneic HCT between January 2018 and April 2022. Outcomes examined included overall survival (OS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and graft-versus-host disease/relapse-free survival (GRFS). Results: No significant differences in OS, CIR, NRM, GRFS, acute GVHD (aGVHD), or chronic GVHD (cGVHD) were observed. Significant differences in age, use of human leukocyte antigen-mismatched donors (HLA-MM), and HCT-CI comorbidity scores ≥ 3 across racial and ethnic groups were observed. Overall mean age was 58 years, with Black patients having the youngest mean age of 43 (range 22–73) and White patients the highest mean age of 59 (range 18–76) (p < 0.001). HCT-CI score ≥ 3 was seen in 35.9% of the entire cohort, varying by race and ethnicity: 60.5% in Black, 41.4% in South Asian, 31.5% in White, and 29.0% in East Asian patients (p < 0.001). Utilization of HLA-MM donors (including haploidentical) was 29.2% overall, with highest frequencies in Black (65.1%) and East Asian (45%) patients, and lowest in White patients (20.4%) (p < 0.001). Conclusions: Statistically significant differences were observed across self-identified racial and ethnic groups regarding age, HCT-CI ≥ 3, and the use of HLA-MM donors. However, post-allogeneic HCT outcomes did not differ significantly by race or ethnicity. Larger prospective trials are warranted to validate our findings. Full article
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11 pages, 554 KiB  
Article
Comparison of Outcomes of Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplant Cyclophosphamide in Older Versus Younger Patients
by Giacomo Adoncecchi, Ambuj Kumar, Krishnakar Mogili, Rawan Faramand, Hien Liu, Farhad Khimani, Asmita Mishra, Michael Nieder, Taiga Nishihori, Doris Hansen, Michael Jain, Aleksandr Lazaryan, Lia Perez, Joseph Pidala, Frederick Locke, Claudio Anasetti, Nelli Bejanyan and Hany Elmariah
Cancers 2025, 17(2), 310; https://doi.org/10.3390/cancers17020310 - 19 Jan 2025
Viewed by 1297
Abstract
Background: Previous studies have shown that allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA haploidentical (haplo) donor followed by graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) results in lower relapse rates and improved DFS when compared to haplo bone marrow [...] Read more.
Background: Previous studies have shown that allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA haploidentical (haplo) donor followed by graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) results in lower relapse rates and improved DFS when compared to haplo bone marrow transplant (BMT) with PTCy. However, PBSCT leads to higher rates of GVHD. It is unknown whether the benefits of haplo PBSCT may be nullified in older patients (>60 years) by a higher susceptibility to GVHD and transplant related toxicity. Thus, we sought to determine if older patients receiving haplo PBSCT with PTCy experience significantly worse outcomes than younger patients. Methods: We evaluated 121 adult patients with hematologic malignancies treated at the Moffitt Cancer Center with allogeneic haplo PBSCT followed by PTCy and compared outcomes of patients ≥60 years (n = 55) versus patients <60 years (n = 66). Results: The cumulative incidence of non-relapse mortality (NRM) from the competing risk regression analysis was worse for the older patient group (SHR = 4.05, 95% CI: 1.43–11.47, p = 0.008). However, there was no significant difference between groups in graft-versus-host disease (GVHD), relapse, disease-free survival (DFS), or overall survival (OS). Instead, hematopoietic comorbidity index (HCT-CI) ≥ 3 was associated with worse DFS (HR = 1.87, 95% CI: 1.04–3.34, p = 0.035) and OS (HR = 1.98, 95% CI: 1.03–3.84, p-value = 0.042). Subgroup analysis of patients ≥60 years showed a trend toward improved 2-year OS with fludarabine/cyclophosphamide/total body irradiation (Flu/Cy/TBI) versus fludarabine/busulfan: 71% versus 53% (HR = 0.47, p = 0.121). In patients over 70 years (n = 14), NRM was 8% and OS was 76% at 1 year. Conclusion: Given similar OS and DFS between patients aged >60 years and those <60, haplo PBSCT with PTCy appears to be an appropriate transplant platform for older patients. Full article
(This article belongs to the Section Transplant Oncology)
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14 pages, 1640 KiB  
Article
Impact of First- and Second-Generation Tyrosine Kinase Inhibitors on the Development of Graft-Versus-Host Disease in Individuals with Chronic Myeloid Leukemia: A Retrospective Analysis on Behalf of the Polish Adult Leukemia Group
by Ugo Giordano, Agnieszka Piekarska, Witold Prejzner, Lidia Gil, Jan Maciej Zaucha, Joanna Kujawska, Zuzanna Dybko, Krzysztof Dudek, Sebastian Giebel and Jarosław Dybko
Biomedicines 2025, 13(1), 163; https://doi.org/10.3390/biomedicines13010163 - 11 Jan 2025
Viewed by 1301
Abstract
Background: The implementation of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) has brought a significant improvement in the prognosis for CML patients and a decrease in the number of patients requiring allogeneic hematopoietic stem cell transplantation (allo-HCT). [...] Read more.
Background: The implementation of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) has brought a significant improvement in the prognosis for CML patients and a decrease in the number of patients requiring allogeneic hematopoietic stem cell transplantation (allo-HCT). Nevertheless, the impact of TKIs on allo-HCT outcomes has not been thoroughly explored. Objectives: The main endpoint of our research was to assess the impact of prior TKI treatment on acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD). Methods: In our retrospective analysis, we included 240 patients treated between 1993 and 2013 and divided them into three groups according to the therapy administered prior to haploidentical, matched-related, or matched-unrelated donor allo-HCT (imatinib group n = 41, dasatinib/nilotinib group n = 28, TKI-naïve group n = 171). Results: Both the cumulative incidence of aGvHD (p = 0.044) and cGvHD (p < 0.001) in individuals receiving second-generation TKIs (2G-TKIs) prior to allo-HCT were decreased compared to patients receiving no TKIs or imatinib (IMA) (40.7% vs. 61.4% vs. 70.7%, p = 0.044; 25.0% vs. 76.4% vs. 51.2%, p < 0.001, respectively). In the case of the 2G-TKI cohort, the number of low-grade aGvHD and cGvHD was significantly lower compared to the IMA and TKI-naïve groups (p = 0.018, p = 0.004; p < 0.001 versus TKI-naïve, respectively). In terms of 3-year overall survival (OS), there were no important variations between TKI-naïve, IMA, and 2G-TKI (55% vs. 49.9% vs. 69.6%, p = 0.740). Conclusions: The results of our study suggest that TKI treatment prior to allo-HCT may have a protective impact on immune-mediated outcomes. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Hematologic Malignancies)
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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
Cited by 1 | Viewed by 1813
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)
11 pages, 1091 KiB  
Article
A New Tool Supporting the Selection of the Best Hematopoietic Stem Cell Donor by Modelling Local Own Real-World Data
by Roberto Crocchiolo, Stefania Cacace, Giuseppe Milone, Barbara Sarina, Alessandra Cupri, Salvatore Leotta, Giulia Giuffrida, Andrea Spadaro, Jacopo Mariotti, Stefania Bramanti, Alice Fumagalli, Maria Pia Azzaro, Sebastiana Toscano and Quirico Semeraro
J. Clin. Med. 2024, 13(22), 6869; https://doi.org/10.3390/jcm13226869 - 15 Nov 2024
Viewed by 1113
Abstract
Background: The selection of the best donor for each specific patient is crucial for the success of allogeneic hematopoietic stem cell transplantation (HSCT). However, there is debate on the choice of the best donor when multiple suitable donors exist. Methods: By using own [...] Read more.
Background: The selection of the best donor for each specific patient is crucial for the success of allogeneic hematopoietic stem cell transplantation (HSCT). However, there is debate on the choice of the best donor when multiple suitable donors exist. Methods: By using own data from two transplant centers, we have developed a calculator able to provide the patients’ 2-year overall survival (OS) associated with each of the potential donor options during the selection process, in order to support the transplant physician during the choice. Data on 737 HSCTs with HLA-identical siblings, and unrelated or related haploidentical donors from January 2010 to July 2022 have been retrospectively obtained. Results: Patients’ age, disease, comorbidity index, and donor type were found to be significant variables able to predict the outcome with robustness (concordance index: 0.677). Estimates are provided within an example in the text showing outcomes with four donor options for a specific patient. Conclusions: We present the prototype of a tool supporting the selection of the best donor, guiding transplant physicians during the delicate process of donor selection before HSCT. This approach relies on real data from the centers, reflecting their local clinical experience. Improvements are underway with a larger, ongoing multicenter study. Full article
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11 pages, 710 KiB  
Article
Monitoring and Management of Cytomegalovirus Reactivations After Allogeneic Hematopoietic Stem Cell Transplantation in Children: Experience from a Single Pediatric Center
by Giulia Ferrando, Francesca Bagnasco, Stefano Giardino, Filomena Pierri, Sara Pestarino, Eddi Di Marco, Maria Santaniello, Elio Castagnola and Maura Faraci
Diagnostics 2024, 14(21), 2461; https://doi.org/10.3390/diagnostics14212461 - 3 Nov 2024
Viewed by 1708
Abstract
Background: CMV reactivation represents a frequent complication after HSCT. The aim of this study was to describe the incidence of CMV reactivation in a pediatric HSCT cohort and analyze the potential impact of recipient/donor-related or transplant-related factors on this complication. Furthermore, we analyzed [...] Read more.
Background: CMV reactivation represents a frequent complication after HSCT. The aim of this study was to describe the incidence of CMV reactivation in a pediatric HSCT cohort and analyze the potential impact of recipient/donor-related or transplant-related factors on this complication. Furthermore, we analyzed the management of CMV reactivation in order to purpose criteria for pre-emptive therapy. Methods: Allogeneic HSCTs, performed at IRCCS Istituto Gaslini between 2012 and 2022, were included in this analysis. CMV–DNAemia was regularly monitored. Risk stratification was based on donor/recipient serological status and additional potential risk factors were considered: haploidentical transplant; any HSCT subsequent to the first; acute and chronic GvHD; steroids; and other immunosuppressive therapies. We described also the approach for pre-emptive therapy during the period 2012–2019. Results: A total of 214 allogeneic HSCTs were performed in 189 patients. In total, 100 (46.7%) HSCTs were complicated by at least one reactivation. CMV reactivation was significantly associated with high serological risk and steroid treatment. Pre-emptive therapy was administered in 59/69 (85.5%) HSCTs during 2012–2019. In the presence of predefined risk conditions, therapy was started at a median viremia of 2050 copies/mL. No difference was observed in OS between patients with CMV reactivation versus patients who did not present this complication. Conclusions: These results suggest the potential effectiveness of the approach used in providing pre-emptive therapy based on viral load monitoring and individualized risk factors. Full article
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16 pages, 721 KiB  
Article
Improved Outcomes in Myelofibrosis after Allogeneic Stem-Cell Transplantation in the Era of Ruxolitinib Pretreatment and Intensified Conditioning Regimen—Single-Center Analysis
by Sigrid Machherndl-Spandl, Sarah Hannouf, Alexander Nikoloudis, Otto Zach, Irene Strassl, Emine Kaynak, Gerald Webersinke, Christine Gruber-Rossipal, Holger Rumpold, Wolfgang Schimetta, Johannes Clausen and Veronika Buxhofer-Ausch
Cancers 2024, 16(19), 3257; https://doi.org/10.3390/cancers16193257 - 25 Sep 2024
Cited by 1 | Viewed by 2566
Abstract
(1) Background: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is the only treatment with the potential for cure in patients with myelofibrosis (MF). However, the risk of graft rejection, which is particularly high in MF, and the risk of significant non-relapse mortality must be considered. [...] Read more.
(1) Background: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is the only treatment with the potential for cure in patients with myelofibrosis (MF). However, the risk of graft rejection, which is particularly high in MF, and the risk of significant non-relapse mortality must be considered. (2) Methods: In this retrospective, single-center study, we compared allo-HSCT outcomes in 36 adult patients with MF transplanted at two-time intervals (2001–2015 versus 2016–2021). (3) Results: The estimated median overall survival was 48.9 months (95%CI 0.00–98.2) in the cohort transplanted before 2016 and not reached in the more recent years (p = 0.04) due to markedly lower non-relapse mortality (p = 0.02). The 3-year relapse incidence was low in both cohorts (11.1% and 12.5%, p > 0.99). When comparing only subgroups within the more recent cohort based on the presence or absence of total body irradiation (TBI) or the use of sequential regimens, OS and PFS were comparable. (4) Conclusion: Pretreatment with ruxolitinib, intensified conditioning, and the preferential use of haploidentical related instead of mismatched unrelated donors for patients lacking an HLA-identical donor are most likely responsible for the improved outcome after allo-HCT in MF in recent years. Full article
(This article belongs to the Special Issue Blood Stem Cell and Hematological Malignancies)
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14 pages, 1026 KiB  
Article
Preliminary Data on SNP of Transplantation-Related Genes after Haploidentical Stem Cell Transplantation
by Ching-Ping Tseng, Tung-Liang Lin, Shu-Hui Tsai, Wei-Tzu Lin, Fang-Ping Hsu, Wei-Ting Wang and Ding-Ping Chen
J. Clin. Med. 2024, 13(16), 4681; https://doi.org/10.3390/jcm13164681 - 9 Aug 2024
Viewed by 1462
Abstract
Background: Hematopoietic stem cell transplantation (HSCT) is one of the mainstream treatments for patients with hematologic malignancies. The matching status of human leukocyte antigen (HLA) between the donor and recipient is highly related to the outcomes of HSCT. Haploidentical HSCT (haplo-HSCT) has [...] Read more.
Background: Hematopoietic stem cell transplantation (HSCT) is one of the mainstream treatments for patients with hematologic malignancies. The matching status of human leukocyte antigen (HLA) between the donor and recipient is highly related to the outcomes of HSCT. Haploidentical HSCT (haplo-HSCT) has emerged as a type of HSCT for patients who cannot find a fully HLA-matched donor. In this study, we investigated whether the single nucleotide polymorphisms (SNPs) of the HLA-related genes and the genes encoding co-stimulatory molecules located on the non-HLA region are related to the outcomes of haplo-HSCT. Methods: The genomic DNAs of 24 patients and their respective donors were isolated from the peripheral blood obtained before performing haplo-HSCT. A total of 75 SNPs of the HLA-related genes (HCP5, NOTCH4, HLA-DOA, LTA, HSPA1L, BAG6, RING1, TRIM27, and HLA-DOB) and the genes located in the non-HLA genes involved in co-stimulatory signaling (CTLA4, TNFSF4, CD28, and PDCD1) were selected to explore their relationship with the outcomes after haplo-HSCT, including graft-versus-host disease, survival status, and relapse. Results: Our data revealed that specific donor or patient SNPs, including rs79327197 of the HLA-DOA gene, rs107822 and rs213210 of the RING1 gene, rs2523676 of the HCP5 gene, rs5742909 of the CTLA4 gene, rs5839828 and rs36084323 of the PDCD1 gene, and rs1234314 of the TNFSF4 gene, were significantly related to the development of adverse outcomes post-haplo-HSCT. Conclusions: These SNPs may play important roles in post-transplant immune response that can be considered during the selection of suitable donors. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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11 pages, 903 KiB  
Article
Optimizing Outcomes in Mismatched Unrelated Donor Allogeneic Transplantation: Post-Transplant Cyclophosphamide’s Dual Impact on Graft versus Host Disease Incidence and Overall Survival: Retrospective Analysis on Behalf of Polish Adult Leukemia Group
by Jarosław Dybko, Małgorzata Sobczyk-Kruszelnicka, Alicja Sadowska-Klasa, Agnieszka Piekarska, Sebastian Makuch, Siddarth Agrawal, Krzysztof Dudek, Ugo Giordano, Sebastian Giebel and Lidia Gil
J. Clin. Med. 2024, 13(12), 3569; https://doi.org/10.3390/jcm13123569 - 18 Jun 2024
Viewed by 1428
Abstract
Allogeneic hematopoietic cell transplantation (allo-HSCT) stands as an effective treatment method for various hematologic malignancies. However, graft-versus-host disease (GvHD), an intricate immunological phenomenon where donor immune cells target recipient tissues, remains a significant challenge, particularly in mismatched unrelated donors (MMUD). Post-transplant cyclophosphamide (PTCy) [...] Read more.
Allogeneic hematopoietic cell transplantation (allo-HSCT) stands as an effective treatment method for various hematologic malignancies. However, graft-versus-host disease (GvHD), an intricate immunological phenomenon where donor immune cells target recipient tissues, remains a significant challenge, particularly in mismatched unrelated donors (MMUD). Post-transplant cyclophosphamide (PTCy) has emerged as a promising immunosuppressive strategy, revolutionizing haploidentical transplantation and demonstrating promise in MMUD settings. Background/Objectives: This study aimed to evaluate the impact of PTCy on MMUD allo-HSCT outcomes, specifically its effects on GvHD incidence and overall survival, compared to anthitymocyte globulin (ATG). Methods: One hundred seventy-four patients were classified into three groups based on the type of transplantation: PTCy-haplo (114/174; 65.5%), PTCy-MMUD (23/174; 13.2%), and ATG-MMUD (37/174; 21.2%). Results: Our findings showed that PTCy-MMUD significantly reduced acute GvHD occurrence compared to PTCy-haplo and ATG-MMUD approaches (p = 0.006). The delayed onset of acute GvHD in the PTCy-MMUD group suggests a more controlled immune reconstitution, contributing to the lower incidence. Importantly, PTCy-MMUD exhibited enhanced five-year overall survival rates, aligning with the notion that reduced GvHD correlates with improved patient outcomes (p = 0.032). Conclusions: We believe that this study contributes valuable insights into PTCy-MMUD’s management, underscoring its potential to significantly reduce GvHD incidence and enhance survival outcomes. Although further investigations and clinical trials are warranted, this research underscores the promising role of PTCy-based GvHD prophylaxis in improving MMUD allo-HCT success. Full article
(This article belongs to the Section Hematology)
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27 pages, 1356 KiB  
Review
Haploidentical HSCT in the Treatment of Pediatric Hematological Disorders
by Anna Marszołek, Maria Leśniak, Anna Sekunda, Aleksander Siwek, Zuzanna Skiba, Monika Lejman and Joanna Zawitkowska
Int. J. Mol. Sci. 2024, 25(12), 6380; https://doi.org/10.3390/ijms25126380 - 9 Jun 2024
Cited by 2 | Viewed by 3406
Abstract
Allogeneic hematopoietic stem cell transplantation has become a treatment option for otherwise non-curative conditions, both malignant and benign, affecting children and adults. Nevertheless, the latest research has been focusing extensively on transplantation from related and unrelated haploidentical donors, suitable for patients requiring emergent [...] Read more.
Allogeneic hematopoietic stem cell transplantation has become a treatment option for otherwise non-curative conditions, both malignant and benign, affecting children and adults. Nevertheless, the latest research has been focusing extensively on transplantation from related and unrelated haploidentical donors, suitable for patients requiring emergent hematopoietic stem cell transplantation (HSCT) in the absence of an HLA-matched donor. Haploidentical HSCT (haplo-HSCT) can be an effective treatment for non-malignant pediatric disorders, such as primary immunodeficiencies or hemoglobinopathies, by enabling a much quicker selection of the appropriate donor for virtually all patients, low incidence of graft-versus-host disease (GVHD), and transplant-related mortality (TRM). Moreover, the outcomes of haplo-HSCT among children with hematological malignancies have improved radically. The most demanding tasks for clinicians are minimizing T-cell-mediated alloreactivity as well as early GVHD prevention. As a result, several T-cell depletion approaches, such as ex vivo T-cell depletion (TCD), and T-cell replete approaches, such as a combination of anti-thymocyte globulin (ATG), post-transplantation cyclophosphamide (PTCy), cyclosporine/tacrolimus, mycophenolate mofetil, or methotrexate, have been taken up. As more research is needed to establish the most beneficial form of therapy, haplo-HSCT is currently considered an alternative donor strategy for pediatric and adult patients with complications like viral and bacterial infections, invasive fungal disease, and GVHD. Full article
(This article belongs to the Special Issue Hematological Malignancies: Molecular Mechanisms and Therapy)
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10 pages, 707 KiB  
Communication
Post-Transplant Cyclophosphamide versus Anti-Thymocyte Globulin in Patients with Hematological Malignancies Treated with Allogeneic Hematopoietic Stem Cell Transplantation from Haploidentical and Matched Unrelated Donors: A Real-Life Experience
by Bianca Serio, Gabriella Storti, Matteo D’Addona, Lidia Santoro, Camilla Frieri, Danilo De Novellis, Luana Marano, Giovanna De Santis, Roberto Guariglia, Ilenia Manfra, Eleonora Urciuoli, Serena Luponio, Serena Marotta, Denise Morini, Michela Rizzo, Fausto Palmieri, Nicola Cantore, Valentina Giudice, Antonio Maria Risitano and Carmine Selleri
Hematol. Rep. 2024, 16(2), 234-243; https://doi.org/10.3390/hematolrep16020023 - 17 Apr 2024
Viewed by 1708
Abstract
Background: Post-transplant cyclophosphamide (PTCY) is widely used as graft versus host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplant (HSCT) recipients, with reported clinical benefits in patients who underwent transplant from a matched unrelated donor (MUD). However, real-life data on clinical efficacy [...] Read more.
Background: Post-transplant cyclophosphamide (PTCY) is widely used as graft versus host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplant (HSCT) recipients, with reported clinical benefits in patients who underwent transplant from a matched unrelated donor (MUD). However, real-life data on clinical efficacy and safety of PTCY in haploidentical and MUD transplantations are still poor. Methods: In our real-life retrospective observational study, we included a total of 40 consecutive adult patients who underwent haploidentical or MUD HSCT for various hematological malignancies and who received PTCY (n = 24) or ATG (n = 16) as GvHD prophylaxis at Hematology Units from hospitals of Salerno and Avellino, Italy, and clinical outcomes were compared. Results: We showed protective effects of PTCY against disease relapse with the relapse rate after transplantation of 16% versus 50% in the ATG arm (p = 0.02). All-cause mortality was lower (36% vs. 75%; p = 0.02) and the 2-year overall survival was slightly superior in patients administered PTCY (61% vs. 42%; p = 0.26). Conclusions: We support the use of PTCY, even in a real-life setting; however, the optimization of this protocol should be further investigated to better balance relapse prevention and GvHD prophylaxis. Full article
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