Phase II Study of Sequential Infusion of Donor Lymphocyte Infusion and Cytokine-Induced Killer Cells for Patients Relapsed after Allogeneic Hematopoietic Stem Cell Transplantation

Biol Blood Marrow Transplant. 2017 Dec;23(12):2070-2078. doi: 10.1016/j.bbmt.2017.07.005. Epub 2017 Jul 13.

Abstract

Seventy-four patients who relapsed after allogeneic stem cell transplantation were enrolled in a phase IIA study and treated with the sequential infusion of donor lymphocyte infusion (DLI) followed by cytokine-induced killer (CIK) cells. Seventy-three patients were available for the intention to treat analysis. At least 1 infusion of CIK cells was given to 59 patients, whereas 43 patients received the complete cell therapy planned (58%). Overall, 12 patients (16%) developed acute graft-versus-host disease (aGVHD) of grades I to II in 7 cases and grades III to IV in 5). In 8 of 12 cases, aGVHD developed during DLI treatment, leading to interruption of the cellular program in 3 patients, whereas in the remaining 5 cases aGVHD was controlled by steroids treatment, thus allowing the subsequent planned administration of CIK cells. Chronic GVHD (cGVHD) was observed in 11 patients (15%). A complete response was observed in 19 (26%), partial response in 3 (4%), stable disease in 8 (11%), early death in 2 (3%), and disease progression in 41 (56%). At 1 and 3 years, rates of progression-free survival were 31% and 29%, whereas rates of overall survival were 51% and 40%, respectively. By multivariate analysis, the type of relapse, the presence of cGVHD, and a short (<6 months) time from allogeneic hematopoietic stem cell transplantation to relapse were the significant predictors of survival. In conclusion, a low incidence of GVHD is observed after the sequential administration of DLI and CIK cells, and disease control can be achieved mostly after a cytogenetic or molecular relapse.

Keywords: Cytokine-induced killer (CIK) cells; DLI; Passive immunotherapy; Relapse after allo-BMT.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Cytokine-Induced Killer Cells / transplantation*
  • Female
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Lymphocyte Transfusion / adverse effects
  • Lymphocyte Transfusion / methods*
  • Male
  • Middle Aged
  • Prognosis
  • Recurrence
  • Remission Induction
  • Survival Analysis
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult