Chimerism-based pre-emptive immunotherapy with fast withdrawal of immunosuppression and donor lymphocyte infusions after allogeneic stem cell transplantation for pediatric hematologic malignancies

Biol Blood Marrow Transplant. 2015 Apr;21(4):729-37. doi: 10.1016/j.bbmt.2014.12.029. Epub 2015 Jan 31.

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.

Trial registration: ClinicalTrials.gov NCT01036009.

Keywords: Adoptive immunotherapy chimerism; Minimal residual disease; Pediatric leukemia.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Allografts
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / prevention & control*
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunosuppression Therapy*
  • Infant
  • Lymphocyte Transfusion*
  • Male
  • Survival Rate
  • Transplantation Chimera*

Associated data

  • ClinicalTrials.gov/NCT01036009