A Phase 2 Trial of KIR-Mismatched Unrelated Donor Transplantation Using in Vivo T Cell Depletion with Antithymocyte Globulin in Acute Myelogenous Leukemia: Children's Oncology Group AAML05P1 Study

Stella M. Davies, Robert Iannone, Todd A. Alonzo, Yi Cheng Wang, Robert Gerbing, Sandeep Soni, E. Anders Kolb, Soheil Meshinchi, Paul J. Orchard, Linda J. Burns, Shalini Shenoy, Wing Leung

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1 Scopus citations

Abstract

Patients with acute myelogenous leukemia (AML) who undergo killer immunoglobulin-like receptor (KIR)-mismatched haploidentical hematopoietic stem cell transplantation (HSCT) have improved survival. Children's Oncology Group AAML05P1 is a prospective phase 2 trial of unrelated donor (URD) HSCT in which KIR typing of donors was available to the treating physician at donor selection, aiming to determine feasibility (defined as the ability to obtain donor samples from URDs and obtain KIR data before transplantation) of prospective selection of KIR-mismatched donors and effect on outcomes. Patients age ≤30 years with high-risk AML at presentation or relapsed AML were eligible; the study accrued 90 evaluable patients. After enrollment, as many as 5 potential URD samples were KIR-typed (including gene expression) in a central laboratory and results reported to the treating physician, who made the final donor selection. Cases were categorized as KIR-matched or KIR-mismatched using different published strategies. Overall survival (OS), disease-free survival (DFS), and relapse did not differ significantly by KIR mismatch status. Acute graft-versus-host disease (GVHD) was significantly lower in recipients of KIR-mismatched stem cells (35% versus 60%; P = .027). We examined DFS according to time to natural killer (NK) receptor recovery after HSCT. NK p44 recovery was significantly associated with KIR mismatch and with decreased DFS and increased relapse risk in multivariate Cox analysis (P = .006 and. 009, respectively). We show that prospective selection of URD according to KIR type was feasible, acute GVHD was reduced, but survival did not differ using any model of KIR mismatch. However, the study enrolled mostly matched transplants, so ligand-ligand mismatch was rare, and thus the sample size was insufficient to determine potential benefit according to this model. Cord blood recipients demonstrated a trend toward improved DFS with KIR mismatch, but the study was not powered to detect a difference in this small subset of patients. Our data suggest that recovery of NK receptor expression might influence DFS after HSCT.

Original languageEnglish (US)
Pages (from-to)712-717
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume26
Issue number4
DOIs
StatePublished - Apr 2020

Bibliographical note

Funding Information:
Financial disclosure: This work was supported by National Clinical Trials Network (NCTN) Operations Center Grant U10 CA180886, NCTN Statistics and Data Center Grants U10 CA180899 and R01 CA120583 (to W.L.), St Baldrick's Foundation, and the Andrew McDonough B+ Foundation.

Funding Information:
Financial disclosure: This work was supported by National Clinical Trials Network (NCTN) Operations Center Grant U10 CA180886, NCTN Statistics and Data Center Grants U10 CA180899 and R01 CA120583 (to W.L.), St Baldrick's Foundation, and the Andrew McDonough B+ Foundation. Conflict of interest statement: S.M.D. has served as a consultant for Novartis and has received research support from Alexion and Prolacta. W.L. is currently a part-time employee of Miltenyi Biotec. R.I. was a full-time employee of Merck and Company and AstraZeneca during the study and is currently a full-time employee of Jazz Pharmaceuticals. Authorship statement: S.M.D. R.I. and W.L. designed the study, analyzed data, and wrote and approved the manuscript. T.A. Y.W. and R.G. developed datasets, performed statistical analyses and edited and approved the manuscript. S.S. E.A.K. S.M. P.J.O. L.J.B. and S.S. analyzed data and edited and approved the manuscript. Financial disclosure: See Acknowledgments on page 717.

Publisher Copyright:
© 2019 American Society for Transplantation and Cellular Therapy

Keywords

  • AML
  • KIR match
  • KIR mismatch
  • Pediatric transplantation

PubMed: MeSH publication types

  • Clinical Trial, Phase II
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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