Fetal-maternal microchimerism enhances the survival effect of interleukin-2-activated haploidentical peripheral blood stem cell treatment in patients with advanced solid cancer

Cancer Biother Radiopharm. 2010 Dec;25(6):741-6. doi: 10.1089/cbr.2010.0770.

Abstract

Killer immunoglobulin-like receptor (KIR)-ligand incompatibility in the graft-versus-host direction is associated with improved outcome in patients receiving hematopoietic stem cell transplants. Fetal-maternal microchimerism has been suggested to mediate acquired fetal-maternal tolerance. The goal of this study was to determine the clinical efficacy of KIR-ligand incompatibility and fetal-maternal microchimerism for interleukin-2-activated haploidentical peripheral blood stem cells (haplo-PBSCs) treatment for patients with advanced solid cancer. Forty-two (42) patients with advanced stage of solid cancer and refractory to standard chemotherapy were treated with haplo-PBSCs donated by their parents or children. Human leukocyte antigen typing, fetal-maternal microchimerism status, and engraftment were detected. Clinical outcomes including overall survival (OS), progression-free survival (PFS), and Karnofsky Performance Status (KPS) level were evaluated. Patients receiving haplo-PBSCs treatment with KIR-ligand incompatibility in the graft-versus-host direction had higher probability of OS (26.8 ± 3.1 months) and PFS (13.4 ± 1.3 months) when compared with those with KIR ligand compatibility (OS: 17.4 ± 3.0 months, p < 0.05 and PSF: 8.0 ± 0.9 months, p < 0.05). Further, OS (31.2 ± 4.3 months), PFS (14.7 ± 2.2 months), and KPS increase (27 points) in the microchimerism-positive group was improved compared with that in the microchimerism-negative group (OS: 16.9 ± 3.8 months, p < 0.01, PFS: 5.6 ± 1.4 months, p < 0.01, and KPS increase: 15 points, p < 0.01). Therefore, KIR-ligand incompatibility and fetal-maternal microchimerism are associated with better outcome for haplo-PBSCs treatment.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Adult Children
  • Adult Stem Cells / cytology
  • Adult Stem Cells / drug effects
  • Adult Stem Cells / transplantation*
  • Aged
  • Chimerism*
  • Disease-Free Survival
  • Female
  • HLA Antigens / immunology*
  • Humans
  • Interleukin-2 / pharmacology*
  • Kaplan-Meier Estimate
  • Karnofsky Performance Status
  • Male
  • Maternal-Fetal Exchange / immunology*
  • Middle Aged
  • Neoplasms / diagnosis
  • Neoplasms / therapy*
  • Parents
  • Peripheral Blood Stem Cell Transplantation / adverse effects
  • Peripheral Blood Stem Cell Transplantation / methods*
  • Pregnancy
  • Prognosis
  • Proportional Hazards Models
  • Quality of Life
  • Receptors, KIR / immunology
  • Risk Factors
  • Treatment Outcome
  • Young Adult

Substances

  • HLA Antigens
  • Interleukin-2
  • Receptors, KIR