title: Fetal-maternal microchimerism enhances the survival effect of interleukin-2-activated haploidentical peripheral blood stem cell treatment in patients with advanced solid cancer.
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.
authors.affiliation: Cancer Biotherapy Center, Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Jinpu
authors.initials: J
authors.lastname: Yu
authors.forename: Shui
authors.initials: S
authors.lastname: Cao
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Baozhu
authors.initials: B
authors.lastname: Ren
authors.forename: Xiumei
authors.initials: X
authors.lastname: An
authors.forename: Naining
authors.initials: N
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Qi
authors.forename: Xiubao
authors.initials: X
authors.lastname: Ren
mesh_terms: D000293:Adolescent; D000328:Adult; D032721:Adult Children; D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D000368:Aged; D046528:Chimerism; D018572:Disease-Free Survival; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000628:therapy*; D010290:Parents; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D011247:Pregnancy; D011379:Prognosis; D016016:Proportional Hazards Models; D011788:Quality of Life; D054340:Receptors, KIR / Q000276:immunology; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007376:Interleukin-2; D054340:Receptors, KIR