Risk factors for graft-versus-host-disease after donor lymphocyte infusion following T-cell depleted allogeneic stem cell transplantation
IntroductionUnmodified donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation (alloSCT) can boost the beneficial Graft-versus-Leukemia (GvL) effect but may also induce severe Graft-versus-Host-Disease (GvHD). To improve the balance between GvL and GvHD, it is crucial to identify...
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| Format: | Article |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1335341/full |
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| author | Eva A. S. Koster Peter A. von dem Borne Peter van Balen Erik W. A. Marijt Jennifer M. L. Tjon Tjeerd J. F. Snijders Daniëlle van Lammeren Hendrik Veelken J. H. Frederik Falkenburg Constantijn J. M. Halkes Liesbeth C. de Wreede |
| author_facet | Eva A. S. Koster Peter A. von dem Borne Peter van Balen Erik W. A. Marijt Jennifer M. L. Tjon Tjeerd J. F. Snijders Daniëlle van Lammeren Hendrik Veelken J. H. Frederik Falkenburg Constantijn J. M. Halkes Liesbeth C. de Wreede |
| author_sort | Eva A. S. Koster |
| collection | DOAJ |
| description | IntroductionUnmodified donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation (alloSCT) can boost the beneficial Graft-versus-Leukemia (GvL) effect but may also induce severe Graft-versus-Host-Disease (GvHD). To improve the balance between GvL and GvHD, it is crucial to identify factors that influence the alloreactivity of DLI. MethodsWe investigated the effects of the presence of patient-derived antigen-presenting cells at time of DLI as estimated by the bone marrow (BM) chimerism status, lymphopenia as measured by the absolute lymphocyte count (ALC) at time of DLI, and the presence of a viral infection (de novo or reactivation) close to DLI on the risk of GvHD after DLI. The cohort consisted of patients with acute leukemia or myelodysplastic syndrome who prophylactically or pre-emptively received DLI as standard care after alemtuzumab-based alloSCT. In patients at high risk for relapse, DLI was administered at 3 months after alloSCT (n=88) with a dose of 0.3x106 or 0.15x106 T cells/kg in case of a related or unrelated donor, respectively. All other patients (n=76) received 3x106 or 1.5x106 T cells/kg, respectively, at 6 months after alloSCT. ResultsFor both DLIs, patients with reduced-intensity conditioning and an unrelated donor had the highest risk of GvHD. For DLI given at three months, viral infection within 1 week before and 2 weeks after DLI was an additional significant risk factor (hazard ratio (HR) 3.66 compared to no viral infection) for GvHD. At six months after alloSCT, viral infections were rare and not associated with GvHD. In contrast, mixed BM chimerism (HR 3.63 for ≥5% mixed chimerism compared to full donor) was an important risk factor for GvHD after DLI given at six months after alloSCT. ALC of <1000x106/l showed a trend for association with GvHD after this DLI (HR 2.05 compared to ≥1000x106/l, 95% confidence interval 0.94-4.45). Furthermore, the data suggested that the presence of a viral infection close to the DLI at three months or ≥5% mixed chimerism at time of the DLI at six months correlated with the severity of GvHD, thereby increasing their negative impact on the current GvHD-relapse-free survival. ConclusionThese data demonstrate that the risk factors for GvHD after DLI depend on the setting of the DLI. |
| first_indexed | 2024-04-25T00:15:06Z |
| format | Article |
| id | doaj.art-f91495ebee1a4669a0b7b64a4d0daa90 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-25T00:15:06Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f91495ebee1a4669a0b7b64a4d0daa902024-03-13T04:58:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13353411335341Risk factors for graft-versus-host-disease after donor lymphocyte infusion following T-cell depleted allogeneic stem cell transplantationEva A. S. Koster0Peter A. von dem Borne1Peter van Balen2Erik W. A. Marijt3Jennifer M. L. Tjon4Tjeerd J. F. Snijders5Daniëlle van Lammeren6Hendrik Veelken7J. H. Frederik Falkenburg8Constantijn J. M. Halkes9Liesbeth C. de Wreede10Department of Hematology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Hematology, Medical Spectrum Twente, Enschede, NetherlandsDepartment of Hematology, HagaZiekenhuis, The Hague, NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Hematology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Biomedical Data Sciences, Leiden University Medical Center, Leiden, NetherlandsIntroductionUnmodified donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation (alloSCT) can boost the beneficial Graft-versus-Leukemia (GvL) effect but may also induce severe Graft-versus-Host-Disease (GvHD). To improve the balance between GvL and GvHD, it is crucial to identify factors that influence the alloreactivity of DLI. MethodsWe investigated the effects of the presence of patient-derived antigen-presenting cells at time of DLI as estimated by the bone marrow (BM) chimerism status, lymphopenia as measured by the absolute lymphocyte count (ALC) at time of DLI, and the presence of a viral infection (de novo or reactivation) close to DLI on the risk of GvHD after DLI. The cohort consisted of patients with acute leukemia or myelodysplastic syndrome who prophylactically or pre-emptively received DLI as standard care after alemtuzumab-based alloSCT. In patients at high risk for relapse, DLI was administered at 3 months after alloSCT (n=88) with a dose of 0.3x106 or 0.15x106 T cells/kg in case of a related or unrelated donor, respectively. All other patients (n=76) received 3x106 or 1.5x106 T cells/kg, respectively, at 6 months after alloSCT. ResultsFor both DLIs, patients with reduced-intensity conditioning and an unrelated donor had the highest risk of GvHD. For DLI given at three months, viral infection within 1 week before and 2 weeks after DLI was an additional significant risk factor (hazard ratio (HR) 3.66 compared to no viral infection) for GvHD. At six months after alloSCT, viral infections were rare and not associated with GvHD. In contrast, mixed BM chimerism (HR 3.63 for ≥5% mixed chimerism compared to full donor) was an important risk factor for GvHD after DLI given at six months after alloSCT. ALC of <1000x106/l showed a trend for association with GvHD after this DLI (HR 2.05 compared to ≥1000x106/l, 95% confidence interval 0.94-4.45). Furthermore, the data suggested that the presence of a viral infection close to the DLI at three months or ≥5% mixed chimerism at time of the DLI at six months correlated with the severity of GvHD, thereby increasing their negative impact on the current GvHD-relapse-free survival. ConclusionThese data demonstrate that the risk factors for GvHD after DLI depend on the setting of the DLI.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1335341/fullallogeneic stem cell transplantationdonor lymphocyte infusiongraft-versus-host-diseaseacute myeloid leukemiaacute lymphoblastic leukemiamyelodysplastic syndrome |
| spellingShingle | Eva A. S. Koster Peter A. von dem Borne Peter van Balen Erik W. A. Marijt Jennifer M. L. Tjon Tjeerd J. F. Snijders Daniëlle van Lammeren Hendrik Veelken J. H. Frederik Falkenburg Constantijn J. M. Halkes Liesbeth C. de Wreede Risk factors for graft-versus-host-disease after donor lymphocyte infusion following T-cell depleted allogeneic stem cell transplantation Frontiers in Immunology allogeneic stem cell transplantation donor lymphocyte infusion graft-versus-host-disease acute myeloid leukemia acute lymphoblastic leukemia myelodysplastic syndrome |
| title | Risk factors for graft-versus-host-disease after donor lymphocyte infusion following T-cell depleted allogeneic stem cell transplantation |
| title_full | Risk factors for graft-versus-host-disease after donor lymphocyte infusion following T-cell depleted allogeneic stem cell transplantation |
| title_fullStr | Risk factors for graft-versus-host-disease after donor lymphocyte infusion following T-cell depleted allogeneic stem cell transplantation |
| title_full_unstemmed | Risk factors for graft-versus-host-disease after donor lymphocyte infusion following T-cell depleted allogeneic stem cell transplantation |
| title_short | Risk factors for graft-versus-host-disease after donor lymphocyte infusion following T-cell depleted allogeneic stem cell transplantation |
| title_sort | risk factors for graft versus host disease after donor lymphocyte infusion following t cell depleted allogeneic stem cell transplantation |
| topic | allogeneic stem cell transplantation donor lymphocyte infusion graft-versus-host-disease acute myeloid leukemia acute lymphoblastic leukemia myelodysplastic syndrome |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1335341/full |
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