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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalLeukemia
DOIs
Publication statusAccepted/In press - Jun 15 2018

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Shimoni, A., Labopin, M., Lorentino, F., van Lint, M. T., Koc, Y., Gülbas, Z., Tischer, J., Bruno, B., Blaise, D., Pioltelli, P., Afanasyev, B., Ciceri, F., Mohty, M., & Nagler, A. (Accepted/In press). Killer cell immunoglobulin-like receptor ligand mismatching and outcome after haploidentical transplantation with post-transplant cyclophosphamide. Leukemia, 1-10. https://doi.org/10.1038/s41375-018-0170-5