ap-1903-reagent and Lymphoma--Large-Cell--Anaplastic

Adoptive transfer of donor-derived T lymphocytes expressing a safety switch may promote immune reconstitution in patients undergoing haploidentical hematopoietic stem cell transplant (haplo-HSCT) without the risk for uncontrolled graft versus host disease (GvHD). Thus, patients who develop GvHD after infusion of allodepleted donor-derived T cells expressing an inducible human caspase 9 (iC9) had their disease effectively controlled by a single administration of a small-molecule drug (AP1903) that dimerizes and activates the iC9 transgene. We now report the long-term follow-up of 10 patients infused with such safety switch-modified T cells. We find long-term persistence of iC9-modified (iC9-T) T cells in vivo in the absence of emerging oligoclonality and a robust immunologic benefit, mediated initially by the infused cells themselves and subsequently by an apparently accelerated reconstitution of endogenous naive T lymphocytes. As a consequence, these patients have immediate and sustained protection from major pathogens, including cytomegalovirus, adenovirus, BK virus, and Epstein-Barr virus in the absence of acute or chronic GvHD, supporting the beneficial effects of this approach to immune reconstitution after haplo-HSCT. This study was registered at www.clinicaltrials.gov as #NCT00710892.

Topics: Adolescent; Aspergillosis; Aspergillus fumigatus; Caspase 9; Child; Child, Preschool; Enzyme Induction; Female; Follow-Up Studies; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy, Adoptive; Lymphoma, Large-Cell, Anaplastic; Male; Myelodysplastic Syndromes; Organic Chemicals; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; T-Lymphocytes; Time Factors; Transgenes; Transplantation, Homologous; Treatment Outcome; Virus Diseases