6533b833fe1ef96bd129ba23

RESEARCH PRODUCT

Donor CD4 T cells convert mixed to full donor T-cell chimerism and replenish the CD52-positive T-cell pool after alemtuzumab-based T-cell-depleted allo-transplantation.

Eva WagnerEddy RoosnekTimo SchmittKlaus BenderRalf G. MeyerChristoph HuberAbdo KonurUdo F. HartwigKarin KolbeDaniela WehlerJulia HemmerlingWolfgang Herr

subject

CD4-Positive T-LymphocytesAntibodies NeoplasmLymphocytemedicine.medical_treatmentHematopoietic stem cell transplantation*Lymphocyte DepletionT-Lymphocyte SubsetsAlemtuzumabddc:616Transplantation Chimera/*immunologyHematopoietic Stem Cell TransplantationAntibodies MonoclonalHematologyMiddle Agedmedicine.anatomical_structureCD52 AntigenLymphocyte TransfusionAlemtuzumabmedicine.drug*GlycoproteinsAdultCD52T cellAntibodies Monoclonal/therapeutic useAntineoplastic AgentsCD4-Positive T-Lymphocytes/*transplantationAntibodies Monoclonal HumanizedLymphocyte DepletionAntigens CDAntigens NeoplasmmedicineAntibodies Neoplasm/therapeutic useHumans*Peripheral Blood Stem Cell TransplantationAgedCell ProliferationGlycoproteinsLymphocyte Transfusion/*methodsTransplantationPeripheral Blood Stem Cell TransplantationTransplantation Chimerabusiness.industryAntineoplastic Agents/therapeutic usemedicine.diseaseTransplantationGraft-versus-host disease*Antigens NeoplasmImmunology*Antigens CDbusinessCD8

description

Donor lymphocyte infusions (DLI) are used to resolve mixed T-cell chimerism (TCC) after allo-SCT despite a substantial risk of GVHD. We analyzed the impact of prophylactic CD8-depleted (CD8(depl)) DLI in 20 recipients of anti-CD52 alemtuzumab in vivo T-cell-depleted allografts with declining donor TCC after day +60. A total of 13 patients received CD8(depl) DLI and 7 patients did not. All but one of the DLI patients converted to complete donor T-cell chimeras, whereas only one non-DLI patient converted spontaneously. DLI induced transient acute GVHD in five and extensive chronic GVHD in two patients. These data suggest the use of CD8(depl) DLI as an effective treatment for mixed TCC, particularly in patients at high risk for GVHD. We also observed that the majority of reconstituting donor-derived T cells after alemtuzumab conditioning were CD52-negative. CD8(depl) DLI significantly increased the proportion of CD52-positive CD4 T cells, whereby their beneficial effect on reconstituting the post-transplant T-cell repertoire was shown.

10.1038/bmt.2009.212https://pubmed.ncbi.nlm.nih.gov/19684624