title: Chimerism-based pre-emptive immunotherapy with fast withdrawal of immunosuppression and donor lymphocyte infusions after allogeneic stem cell transplantation for pediatric hematologic malignancies.
abstract: The presence of increasing host chimerism or persistent mixed chimerism (MC) after hematopoietic stem cell transplantation for leukemia in children is a predictor of relapse. To reduce the risk of relapse, we prospectively studied post-transplantation chimerism-based immunotherapy (IT) using fast withdrawal of immunosuppression (FWI) and donor lymphocyte infusions (DLI) in children with early post-transplantation MC. Forty-three children with hematologic malignancies at 2 institutions were enrolled prospectively in this study from 2009 until 2012 and were followed for a mean of 42 (SD, 10) months. Twelve patients (28%) were assigned to the observation arm based on the presence of graft-versus-host disease (GVHD) or full donor chimerism (FDC), and 5 (12%) sustained early events and could not undergo intervention. Twenty-six (60%) patients with MC were assigned to IT with FWI, which started at a median of 49 days (range, 35 to 85 days) after transplantation. Fourteen patients proceeded to DLI after FWI. Toxicities of treatment included GVHD, which developed in 19% of patients undergoing intervention, with 1 of 26 (4%) dying from GVHD and 1 (4%) still requiring therapy for chronic GVHD 21 months after DLI. Patients with MC undergoing IT had similar 2-year event-free survival (EFS) (73%; 95% confidence interval (CI), 55% to 91%) compared with patients who achieved FDC spontaneously (83%; 95% CI, 62% to 100%); however, because 50% of all relapses in the IT occurred later than 2 years after transplantation, the EFS declined to 55% (95% CI, 34% to 76%) at 42 (SD, 11) months. There were no late relapses in the observation group. EFS in the entire cohort was 58% (95% CI, 42% to 73%) at 42 (SD, 11) months after transplantation. Evidence of disease before transplantation remained a significant predictor of relapse, whereas development of chronic GVHD was protective against relapse.
authors: Allergy Immunology and Blood and Marrow Transplant Division at Benioff Children's Hospital at University of California San Francisco, San Francisco, California. Electronic address: hornb@peds.ucsf.edu.
authors: Biljana
authors: B
authors: Horn
authors: Department of Blood and Marrow Transplantation, All Children's Hospital, St. Petersburg, Florida.
authors: Aleksandra
authors: A
authors: Petrovic
authors: Allergy Immunology and Blood and Marrow Transplant Division at Benioff Children's Hospital at University of California San Francisco, San Francisco, California.
authors: Justin
authors: J
authors: Wahlstrom
authors: Allergy Immunology and Blood and Marrow Transplant Division at Benioff Children's Hospital at University of California San Francisco, San Francisco, California.
authors: Christopher C
authors: CC
authors: Dvorak
authors: Immunogenetics and Transplantation Laboratory, University of California San Francisco, San Francisco, California.
authors: Denice
authors: D
authors: Kong
authors: UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
authors: Jimmy
authors: J
authors: Hwang
authors: Allergy Immunology and Blood and Marrow Transplant Division at Benioff Children's Hospital at University of California San Francisco, San Francisco, California.
authors: Jueleah
authors: J
authors: Expose-Spencer
authors: Department of Blood and Marrow Transplantation, All Children's Hospital, St. Petersburg, Florida.
authors: Michael
authors: M
authors: Gates
authors: Allergy Immunology and Blood and Marrow Transplant Division at Benioff Children's Hospital at University of California San Francisco, San Francisco, California.
authors: Morton J
authors: MJ
authors: Cowan
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007165:Immunosuppression Therapy; D007223:Infant; D017710:Lymphocyte Transfusion; D008297:Male; D015996:Survival Rate; D018183:Transplantation Chimera
keywords: Adoptive immunotherapy chimerism; Minimal residual disease; Pediatric leukemia