Functional immune reconstitution after allogeneic hematopoietic stem cell transplantation in myeloablative and non-myeloablative conditioned patients
Abstract Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a treatment modality for several hematological and immune-driven diseases. A conditioning regimen precedes transplantation. These comprise myeloablative (MA) conditioning consisting of chemotherapeutics often in combination wi...
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2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-06718-y |
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| author | Patrick Terrence Brooks Lia Minculescu Rebecca Svanberg Teglgaard Hans Jakob Hartling Jose Antonio Salado-Jimena Lone Smidstrup Friis Brian Kornblit Ida Schjødt Søren Lykke Petersen Niels Smedegaard Andersen Susanne Dam Nielsen Jens Lundgren Hanne Vibeke Marquart Lars Klingen Gjaerde Henrik Sengeløv Sisse Rye Ostrowski |
| author_facet | Patrick Terrence Brooks Lia Minculescu Rebecca Svanberg Teglgaard Hans Jakob Hartling Jose Antonio Salado-Jimena Lone Smidstrup Friis Brian Kornblit Ida Schjødt Søren Lykke Petersen Niels Smedegaard Andersen Susanne Dam Nielsen Jens Lundgren Hanne Vibeke Marquart Lars Klingen Gjaerde Henrik Sengeløv Sisse Rye Ostrowski |
| author_sort | Patrick Terrence Brooks |
| collection | DOAJ |
| description | Abstract Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a treatment modality for several hematological and immune-driven diseases. A conditioning regimen precedes transplantation. These comprise myeloablative (MA) conditioning consisting of chemotherapeutics often in combination with high-dose total body irradiation (TBI), while non-myeloablative (NMA) conditioning regimens use reduced dosage of chemotherapy and TBI allowing allo-HCT to patients who would otherwise not be eligible for treatment. While cellular immune reconstitution in allo-HCT patients has been well studied, differences between MA and NMA conditioned patients including the functional status of the immune system post-transplantation remains unclear. Seventy-seven patients undergoing allo-HCT were included in the main study, only including patients receiving peripheral blood stem cell grafts, no ATG treatment and no other GVHD prophylaxis than tacrolimus + methotrexate or cyclosporine + MMF + sirolimus (median age 59; IQR: 48–65). The cohort consisted of 34 patients receiving MA conditioning and 43 NMA conditioned patients. As a proxy for post-transplantation immune function, we analyzed stimulated cytokine release patterns in whole-blood samples from MA and NMA patients before and after transplantation alongside major immune cell phenotypes and T cell chimerism on day 28 after transplantation. Notably, among patients receiving grafts from peripheral blood apheresis, MA patients exhibited higher T cell counts, and elevated CD3/CD28-stimulated cytokine release compared to NMA patients. Assessment of associations between cytokine release and immune cell concentration associations indicated that variation in T cell or other immune cell concentrations between the cohorts could not account for differences in CD3/CD28-stimulated cytokine release. Meanwhile, LPS- and R848-stimulated cytokine release was associated with innate immune cell subtypes. A secondary study amongst MA conditioned patients further revealed that those who received fludarabine and treosulfan (n = 35) had higher T cell concentration and stimulated immune function compared to patients receiving more intense MA regimens (n = 15). These findings highlight the complex impact conditioning has on immune function after allo-HCT. Further analyses of T cell compartments and myeloid/lymphoid innate cells are needed to further understand the functional differences observed between conditioning groups and the potential impact on clinical outcomes. |
| format | Article |
| id | doaj-art-c98a747082bb4a6b8dcf5e9aaa9f1fd7 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-c98a747082bb4a6b8dcf5e9aaa9f1fd72025-08-20T03:37:22ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-06718-yFunctional immune reconstitution after allogeneic hematopoietic stem cell transplantation in myeloablative and non-myeloablative conditioned patientsPatrick Terrence Brooks0Lia Minculescu1Rebecca Svanberg Teglgaard2Hans Jakob Hartling3Jose Antonio Salado-Jimena4Lone Smidstrup Friis5Brian Kornblit6Ida Schjødt7Søren Lykke Petersen8Niels Smedegaard Andersen9Susanne Dam Nielsen10Jens Lundgren11Hanne Vibeke Marquart12Lars Klingen Gjaerde13Henrik Sengeløv14Sisse Rye Ostrowski15Department of Clinical Immunology, Copenhagen University HospitalDepartment of Clinical Immunology, Copenhagen University HospitalDepartment of Clinical Immunology, Copenhagen University HospitalDepartment of Clinical Immunology, Copenhagen University HospitalDepartment of Clinical Immunology, Copenhagen University HospitalDepartment of Hematology, Copenhagen University Hospital - RigshospitaletDepartment of Hematology, Copenhagen University Hospital - RigshospitaletDepartment of Hematology, Copenhagen University Hospital - RigshospitaletDepartment of Hematology, Copenhagen University Hospital - RigshospitaletDepartment of Hematology, Copenhagen University Hospital - RigshospitaletDepartment of Infectious Diseases, Copenhagen University Hospital - RigshospitaletDepartment of Infectious Diseases, Copenhagen University Hospital - RigshospitaletDepartment of Clinical Immunology, Copenhagen University HospitalDepartment of Hematology, Copenhagen University Hospital - RigshospitaletDepartment of Hematology, Copenhagen University Hospital - RigshospitaletDepartment of Clinical Immunology, Copenhagen University HospitalAbstract Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a treatment modality for several hematological and immune-driven diseases. A conditioning regimen precedes transplantation. These comprise myeloablative (MA) conditioning consisting of chemotherapeutics often in combination with high-dose total body irradiation (TBI), while non-myeloablative (NMA) conditioning regimens use reduced dosage of chemotherapy and TBI allowing allo-HCT to patients who would otherwise not be eligible for treatment. While cellular immune reconstitution in allo-HCT patients has been well studied, differences between MA and NMA conditioned patients including the functional status of the immune system post-transplantation remains unclear. Seventy-seven patients undergoing allo-HCT were included in the main study, only including patients receiving peripheral blood stem cell grafts, no ATG treatment and no other GVHD prophylaxis than tacrolimus + methotrexate or cyclosporine + MMF + sirolimus (median age 59; IQR: 48–65). The cohort consisted of 34 patients receiving MA conditioning and 43 NMA conditioned patients. As a proxy for post-transplantation immune function, we analyzed stimulated cytokine release patterns in whole-blood samples from MA and NMA patients before and after transplantation alongside major immune cell phenotypes and T cell chimerism on day 28 after transplantation. Notably, among patients receiving grafts from peripheral blood apheresis, MA patients exhibited higher T cell counts, and elevated CD3/CD28-stimulated cytokine release compared to NMA patients. Assessment of associations between cytokine release and immune cell concentration associations indicated that variation in T cell or other immune cell concentrations between the cohorts could not account for differences in CD3/CD28-stimulated cytokine release. Meanwhile, LPS- and R848-stimulated cytokine release was associated with innate immune cell subtypes. A secondary study amongst MA conditioned patients further revealed that those who received fludarabine and treosulfan (n = 35) had higher T cell concentration and stimulated immune function compared to patients receiving more intense MA regimens (n = 15). These findings highlight the complex impact conditioning has on immune function after allo-HCT. Further analyses of T cell compartments and myeloid/lymphoid innate cells are needed to further understand the functional differences observed between conditioning groups and the potential impact on clinical outcomes.https://doi.org/10.1038/s41598-025-06718-yHematopoietic stem cellsBone marrow transplantationConditioningTruCultureImmune stimulationImmune function |
| spellingShingle | Patrick Terrence Brooks Lia Minculescu Rebecca Svanberg Teglgaard Hans Jakob Hartling Jose Antonio Salado-Jimena Lone Smidstrup Friis Brian Kornblit Ida Schjødt Søren Lykke Petersen Niels Smedegaard Andersen Susanne Dam Nielsen Jens Lundgren Hanne Vibeke Marquart Lars Klingen Gjaerde Henrik Sengeløv Sisse Rye Ostrowski Functional immune reconstitution after allogeneic hematopoietic stem cell transplantation in myeloablative and non-myeloablative conditioned patients Scientific Reports Hematopoietic stem cells Bone marrow transplantation Conditioning TruCulture Immune stimulation Immune function |
| title | Functional immune reconstitution after allogeneic hematopoietic stem cell transplantation in myeloablative and non-myeloablative conditioned patients |
| title_full | Functional immune reconstitution after allogeneic hematopoietic stem cell transplantation in myeloablative and non-myeloablative conditioned patients |
| title_fullStr | Functional immune reconstitution after allogeneic hematopoietic stem cell transplantation in myeloablative and non-myeloablative conditioned patients |
| title_full_unstemmed | Functional immune reconstitution after allogeneic hematopoietic stem cell transplantation in myeloablative and non-myeloablative conditioned patients |
| title_short | Functional immune reconstitution after allogeneic hematopoietic stem cell transplantation in myeloablative and non-myeloablative conditioned patients |
| title_sort | functional immune reconstitution after allogeneic hematopoietic stem cell transplantation in myeloablative and non myeloablative conditioned patients |
| topic | Hematopoietic stem cells Bone marrow transplantation Conditioning TruCulture Immune stimulation Immune function |
| url | https://doi.org/10.1038/s41598-025-06718-y |
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