Immune Reconstitution in Recipients of Photodepleted HLA-Identical Sibling Donor Stem Cell Transplantations: T Cell Subset Frequencies Predict Outcome

• Published in: Biology of blood and marrow transplantation 2011-12, Vol.17 (12), p.1846-1854
• Main Authors: McIver, Zachariah A, Melenhorst, Jan J, Grim, Andrew, Naguib, Nicholas, Weber, Gerrit, Fellowes, Vicki, Khuu, Hahn, Stroncek, David S, Leitman, Susan F, Battiwalla, Minoo, Barrett, A. John
• Format: Article
• Language: English
• Subjects: CD4 central memory; CD4-CD8 Ratio; Female; GVHD; Hematology, Oncology and Palliative Medicine; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - immunology; HLA Antigens - immunology; Humans; Lymphocyte Depletion - methods; Male; Photodepletion; Photosensitizing Agents - therapeutic use; Rhodamines - therapeutic use; Siblings; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; TH9402; Tissue Donors; Transplantation; Treatment Outcome
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2011.05.017

We evaluated an ex vivo photodepletion (PD) technique to selectively deplete graft-versus-host disease (GVHD) alloreacting T cells given to 24 human leukocyte antigen (HLA)-identical sibling stem cell transplantation (SCT) recipients. Donor lymphocytes were activated by 72-hour exposure to irradiated in vitro expanded recipient T lymphocytes and pulsed with a TH9402 photosensitizer. Alloactivated T cells preferentially retaining the photosensitizer were eliminated by light exposure. The PD product showed an inverted CD4+ /CD8+ ratio with greatest depletion occurring in the CD4+ naive and central memory populations. In contrast, the CD8+ naive and effector cells were relatively conserved, reflecting the differential extrusion of TH9402 by T cell subsets. Cytomegalovirus reactive T cells were reduced in the PD product and in recipient blood 100 days after SCT when compared with contemporaneous HLA-identical sibling donor T cell-depleted SCT recipients. Although PD SCT recipients experienced similar absolute lymphocyte counts during the first 100 days after SCT, they achieved 100% donor T cell chimerism more rapidly and had higher CD8+ naive T cell counts early after SCT. SCT recipients of PD products with the lowest CD4 central memory content had the highest risk of developing chronic GVHD (cGVHD) ( P = .04) and a poorer survival ( P = .03). Although the persistence of CD8+ naive T cells may have contributed to important antileukemia responses resulting in a relatively low relapse rate, our findings emphasize the role of donor memory T cells and CD4 cells in establishing immune competence post-SCT. Although PD is associated with excellent outcomes in the haploidentical setting, the low frequency of alloactivations in HLA-matched pairs makes the PD approach used by our group for allodepletion in HLA-matched sibling transplantations an inefficient technique.