Killer cell immunoglobulin-like receptor ligand mismatching and outcome after haploidentical transplantation with post-transplant cyclophosphamide.

Abstract

Haploidentical stem cell transplantation with T cell-replete grafts and post-transplant cyclophosphamide (PTCy) is increasingly used with encouraging outcome. Natural killer (NK) cell alloreactivity, predicted by missing killer cell immunoglobulin-like receptor (KIR) ligands in the recipient that are present in their donor improves outcome of T cell-depleted haploidentical transplants. We explored the role of KIR ligand mismatching in 444 acute leukemia patients after T cell-replete transplants with PTCy. Thirty-seven percent of all patients had KIR ligand mismatching. Patients were in first remission (CR1) (39%), second remission (CR2) (26%), or active disease (35%). Stem cell source was peripheral blood (PBSC, 46%) or bone marrow (54%). The 2-year relapse, non-relapse mortality (NRM), and survival rates were 36.0% (95% confidence interval (CI), 31.4-40.7), 23.9% (20.0-28.0), and 45.9% (40.8-51.0), respectively. Multivariate analysis identified acute myeloid leukemia compared with acute lymphoblastic leukemia (hazard ratio (HR) 0.55, P = 0.002), female gender (HR 0.72, P = 0.04), and good performance status (HR 0.71, P = 0.04) as factors associated with better survival, while advanced age (HR 1.13, P = 0.04), active disease (HR 3.38, P < 0.0001), and KIR ligand mismatching (HR 1.41, P = 0.03) as associated with worse survival. KIR ligand mismatching was associated with a trend for higher relapse but not with graft-versus-host disease or NRM. The KIR ligand-mismatching effect was more prominent in patients given PBSC. In conclusion, there is no evidence that KIR ligand mismatching results in better outcome in the PTCy setting.

• Authors: Avichai Shimoni, Myriam Labopin, Francesca Lorentino, Maria Teresa Van Lint, Yener Koc, Zafer Gülbas, Johanna Tischer, Benedetto Bruno, Didier Blaise, Pietro Pioltelli, Boris Afanasyev, Fabio Ciceri, Mohamad Mohty, Arnon Nagler
• Journal: Leukemia (Leukemia) Vol. 33 Issue 1 Pg. 230-239 (01 2019) ISSN: 1476-5551 [Electronic] England
• PMID: 29907809 (Publication Type: Journal Article)

Chemical References

• Immunosuppressive Agents
• Receptors, KIR
• Cyclophosphamide

Topics

• Adult
• Aged
• Cyclophosphamide (therapeutic use)
• Female
• Follow-Up Studies
• Graft vs Host Disease (genetics, immunology, mortality, therapy)
• Hematopoietic Stem Cell Transplantation (mortality)
• Histocompatibility
• Humans
• Immunosuppressive Agents (therapeutic use)
• Killer Cells, Natural (immunology)
• Leukemia, Myeloid, Acute (genetics, immunology, mortality, therapy)
• Male
• Middle Aged
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (genetics, immunology, mortality, therapy)
• Prognosis
• Receptors, KIR (genetics, immunology)
• Retrospective Studies
• Survival Rate
• Transplantation Conditioning
• Transplantation, Haploidentical
• Young Adult