Monocyte Subpopulation Recovery as Predictors of Hematopoietic Cell Transplantation Outcomes

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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 1 2019

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Cell Transplantation
Monocytes
Survival
Transplants
Fetal Blood
Recurrence
Disease-Free Survival
Mortality
Stem Cells
Graft vs Host Disease
Hematologic Neoplasms

Keywords

  • HCT outcomes
  • Monocyte subpopulations

PubMed: MeSH publication types

  • Journal Article

Cite this

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title = "Monocyte Subpopulation Recovery as Predictors of Hematopoietic Cell Transplantation Outcomes",
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.",
keywords = "HCT outcomes, Monocyte subpopulations",
author = "Turcotte, {Lucie M} and Qing Cao and Cooley, {Sarah A} and Curtsinger, {Julie M} and Holtan, {Shernan G} and Xianghua Luo and Ashely Yingst and Weisdorf, {Daniel J} and Blazar, {Bruce R} and Miller, {Jeffrey S} and Wagner, {John E} and Verneris, {Michael R}",
year = "2019",
month = "5",
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doi = "10.1016/j.bbmt.2019.01.003",
language = "English (US)",
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pages = "883--890",
journal = "Biology of Blood and Marrow Transplantation",
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TY - JOUR

T1 - Monocyte Subpopulation Recovery as Predictors of Hematopoietic Cell Transplantation Outcomes

AU - Turcotte, Lucie M

AU - Cao, Qing

AU - Cooley, Sarah A

AU - Curtsinger, Julie M

AU - Holtan, Shernan G

AU - Luo, Xianghua

AU - Yingst, Ashely

AU - Weisdorf, Daniel J

AU - Blazar, Bruce R

AU - Miller, Jeffrey S

AU - Wagner, John E

AU - Verneris, Michael R

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

KW - HCT outcomes

KW - Monocyte subpopulations

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U2 - 10.1016/j.bbmt.2019.01.003

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SN - 1083-8791

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