Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens

• Published in: Blood 2010-05, Vol.115 (19), p.3869-3878
• Main Authors: Warren, Edus H., Fujii, Nobuharu, Akatsuka, Yoshiki, Chaney, Colette N., Mito, Jeffrey K., Loeb, Keith R., Gooley, Ted A., Brown, Michele L., Koo, Kevin K.W., Rosinski, Kellie V., Ogawa, Seishi, Matsubara, Aiko, Appelbaum, Frederick R., Riddell, Stanley R.
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Adult; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Clinical Trials and Observations; Cytotoxicity, Immunologic; Dermis - cytology; Dermis - immunology; Fibroblasts - immunology; Flow Cytometry; Graft vs Host Disease; Graft vs Leukemia Effect - immunology; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation; Humans; Immunoenzyme Techniques; Leukemia - immunology; Leukemia - therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Middle Aged; Minor Histocompatibility Antigens - immunology; Myelodysplastic Syndromes - immunology; Myelodysplastic Syndromes - therapy; Neoplasm Recurrence, Local; T-Lymphocytes - transplantation; T-Lymphocytes, Cytotoxic; Treatment Outcome; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2009-10-248997

The adoptive transfer of donor T cells that recognize recipient minor histocompatibility antigens (mHAgs) is a potential strategy for preventing or treating leukemic relapse after allogeneic hematopoietic cell transplantation (HCT). A total of 7 patients with recurrent leukemia after major histocompatibility complex (MHC)–matched allogeneic HCT were treated with infusions of donor-derived, ex vivo–expanded CD8+ cytotoxic T lymphocyte (CTL) clones specific for tissue-restricted recipient mHAgs. The safety of T-cell therapy, in vivo persistence of transferred CTLs, and disease response were assessed. Molecular characterization of the mHAgs recognized by CTL clones administered to 3 patients was performed to provide insight into the antileukemic activity and safety of T-cell therapy. Pulmonary toxicity of CTL infusion was seen in 3 patients, was severe in 1 patient, and correlated with the level of expression of the mHAg-encoding genes in lung tissue. Adoptively transferred CTLs persisted in the blood up to 21 days after infusion, and 5 patients achieved complete but transient remissions after therapy. The results of these studies illustrate the potential to selectively enhance graft-versus-leukemia activity by the adoptive transfer of mHAg-specific T-cell clones and the challenges for the broad application of this approach in allogeneic HCT. This study has been registered at http://clinicaltrials.gov as NCT00107354.