Monocyte Subpopulation Recovery as Predictors of Hematopoietic Cell Transplantation Outcomes

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5 Scopus citations

Abstract

Monocyte recovery after hematopoietic cell transplantation (HCT)has been correlated with overall survival (OS). However, monocytes are heterogeneous and consist of classic (CD14 ++ CD16 - ), intermediate (CD14 + CD16 + ), and nonclassic (CD14 + CD16 ++ )subpopulations, with unique functional properties. We hypothesized that monocyte subpopulation reconstitution would vary based on allogeneic stem cell source and would be associated with outcomes. We studied monocyte subpopulation recovery at days 28, 60, 100, 180, and 365 post-HCT among 202 patients with hematologic malignancy. Significant differences in absolute monocyte count (AMC)and monocyte subpopulation counts at days 60 and 100 were identified based on stem cell source (all P <.01), with more robust recovery in umbilical cord blood (UCB)recipients. Using 2-fold cross-validation, optimal cutpoints were calculated for day 28 AMC and monocyte subpopulations based on OS. These were used to calculate hazard ratios for OS, disease-free survival (DFS), relapse, transplant-related mortality (TRM), and acute and chronic graft-versus-host disease. OS and DFS were superior when AMC and classic monocyte recovery were above optimal cutpoints (all P <.03). Relapse was reduced for those with AMC (P <.01)and classic (P =.05)monocyte counts above optimal cutpoints. TRM was also reduced when classic (P =.02)monocyte count exceeded optimal cutpoints. Intermediate and nonclassic monocyte recovery were not associated with outcomes. In summary, hematopoietic cell source is associated with monocyte subpopulation recovery, with the early robust recovery in UCB recipients. Recovery of AMC and classic monocytes were prognostic for survival, relapse, and TRM. These indicators may identify patients at increased risk for post-HCT failure and guide therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)883-890
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number5
DOIs
StatePublished - May 2019

Bibliographical note

Funding Information:
Financial disclosure: This work was supported in part by National Institutes of Health (NIH) grant P30 CA77598 using the Translational Therapy Laboratory Shared Resource of the Masonic Cancer Center, University of Minnesota . The Translational Therapy Lab processed specimens, stained and acquired cells on an LSRII flow cytometer (BD Biosciences: San Jose, CA), and analyzed data using FlowJo (FlowJo LLC: Ashland, OR). Additional support was provided by NIH/ National Cancer Institute grant 5P01CA065493 (to Q.C., S.A.C., J.C., X.L., D.J.W., B.R.B., J.S.M., J.E.W., and M.R.V.), NIH grant R01 HL56067 , the Children's Cancer Research Fund (Minneapolis, MN), and the National Center for Advancing Translational Sciences of the NIH Award ( UL1TR000114 , to L.M.T.).

Funding Information:
Financial disclosure: This work was supported in part by National Institutes of Health (NIH) grant P30 CA77598 using the Translational Therapy Laboratory Shared Resource of the Masonic Cancer Center, University of Minnesota. The Translational Therapy Lab processed specimens, stained and acquired cells on an LSRII flow cytometer (BD Biosciences: San Jose, CA), and analyzed data using FlowJo (FlowJo LLC: Ashland, OR). Additional support was provided by NIH/National Cancer Institute grant 5P01CA065493 (to Q.C., S.A.C., J.C., X.L., D.J.W., B.R.B., J.S.M., J.E.W., and M.R.V.), NIH grant R01 HL56067, the Children's Cancer Research Fund (Minneapolis, MN), and the National Center for Advancing Translational Sciences of the NIH Award (UL1TR000114, to L.M.T.). Financial disclosure: See Acknowledgments on page 7.

Publisher Copyright:
© 2019 American Society for Blood and Marrow Transplantation

Keywords

  • HCT outcomes
  • Monocyte subpopulations

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