KIR-ligand incompatibility in the graft-versus-host direction improves outcomes after umbilical cord blood transplantation for acute leukemia.

Abstract

Donor killer cell immunoglobulin-like receptor (KIR)-ligand incompatibility is associated with decreased relapse incidence (RI) and improved leukemia-free survival (LFS) after haploidentical and HLA-mismatched unrelated hematopoietic stem cell transplantation. We assessed outcomes of 218 patients with acute myeloid leukemia (AML n=94) or acute lymphoblastic leukemia (n=124) in complete remission (CR) who had received a single-unit unrelated cord blood transplant (UCBT) from a KIR-ligand-compatible or -incompatible donor. Grafts were HLA-A, -B or -DRB1 matched (n=21) or mismatched (n=197). Patients and donors were categorized according to their degree of KIR-ligand compatibility in the graft-versus-host direction by determining whether or not they expressed HLA-C group 1 or 2, HLA-Bw4 or HLA-A3/-A11. Both HLA-C/-B KIR-ligand- and HLA-A-A3/-A11 KIR-ligand-incompatible UCBT showed a trend to improved LFS (P=0.09 and P=0.13, respectively). Sixty-nine donor-patient pairs were HLA-A, -B or -C KIR-ligand incompatible and 149 compatible. KIR-ligand-incompatible UCBT showed improved LFS (hazards ratio=2.05, P=0.0016) and overall survival (OS) (hazards ratio=2.0, P=0.004) and decreased RI (hazards ratio=0.53, P=0.05). These results were more evident for AML transplant recipients (2-year LFS and RI with or without KIR-ligand incompatibility 73 versus 38% (P=0.012), and 5 versus 36% (P=0.005), respectively). UCBT for acute leukemia in CR from KIR-ligand-incompatible donors is associated with decreased RI and improved LFS and OS.

• Authors: R Willemze, C A Rodrigues, M Labopin, G Sanz, G Michel, G Socié, B Rio, A Sirvent, M Renaud, L Madero, M Mohty, C Ferra, F Garnier, P Loiseau, J Garcia, L Lecchi, G Kögler, Y Beguin, C Navarrete, T Devos, I Ionescu, K Boudjedir, A-L Herr, E Gluckman, V Rocha, Eurocord-Netcord and Acute Leukaemia Working Party of the EBMT
• Journal: Leukemia (Leukemia) Vol. 23 Issue 3 Pg. 492-500 (Mar 2009) ISSN: 1476-5551 [Electronic] England
• PMID: 19151783 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA Antigens
• Receptors, KIR

Topics

• Acute Disease
• Adolescent
• Adult
• Aged
• Child
• Child, Preschool
• Cord Blood Stem Cell Transplantation
• Female
• Graft vs Leukemia Effect (immunology)
• HLA Antigens (immunology)
• Herpesvirus 4, Human (physiology)
• Histocompatibility
• Humans
• Incidence
• Infant
• Killer Cells, Natural (immunology)
• Leukemia (immunology, therapy, virology)
• Male
• Middle Aged
• Receptors, KIR (immunology)
• Remission Induction
• Retrospective Studies
• Transplantation, Homologous (immunology)
• Treatment Outcome
• Virus Activation
• Young Adult