Early posttransplantation donor-derived invariant natural killer T-cell recovery predicts the occurrence of acute graft-versus-host disease and overall survival.
Invariant natural killer T (iNKT) cells can experimentally dissociate GVL from graft-versus-host-disease (GVHD). Their role in human conventional allogeneic hematopoietic stem cell transplantation (HSCT) is unknown. Here, we analyzed the post-HSCT recovery of iNKT cells in 71 adult allografted patients. Results were compared with conventional T- and NK-cell recovery and correlated to the occurrence of GVHD, relapse, and survival. We observed that posttransplantation iNKT cells, likely of donor origin, recovered independently of T and NK cells in the first 90 days after HSCT and reached greater levels in recipient younger than 45 years (P = .003) and after a reduced-intensity conditioning regimen (P = .03). Low posttransplantation iNKT/T ratios (ie, < 10(-3)) were an independent factor associated with the occurrence of acute GVHD (aGVHD; P = .001). Inversely, reaching iNKT/T ratios > 10(-3) before day 90 was associated with reduced nonrelapse mortality (P = .009) without increased risk of relapse and appeared as an independent predictive factor of an improved overall survival (P = .028). Furthermore, an iNKT/T ratio on day 15 > 0.58 × 10(-3) was associated with a 94% risk reduction of aGVHD. These findings provide a proof of concept that early postallogeneic HSCT iNKT cell recovery can predict the occurrence of aGVHD and an improved overall survival.
Hematology and Bone Marrow Transplantation Department, Saint Antoine Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP) 184, Paris, France.
Marie-Thérèse
MT
Rubio
Lucia
L
Moreira-Teixeira
Emmanuel
E
Bachy
Marie
M
Bouillié
Pierre
P
Milpied
Tereza
T
Coman
Felipe
F
Suarez
Ambroise
A
Marcais
David
D
Sibon
Agnès
A
Buzyn
Sophie
S
Caillat-Zucman
Marina
M
Cavazzana-Calvo
Bruno
B
Varet
Michel
M
Dy
Olivier
O
Hermine
Maria
M
Leite-de-Moraes
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D020544:Graft vs Leukemia Effect / Q000276:immunology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology; D012008:Recurrence; D012307:Risk Factors; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous