Dynamic Graft-versus-Host Disease-Free, Relapse-Free Survival

Multistate Modeling of the Morbidity and Mortality of Allotransplantation

Shernan G Holtan, Lin Zhang, Todd E De For, Nelli Bejanyan, Mukta Arora, Armin Rashidi, Aleksandr Lazaryan, Florence Kotiso, Bruce R Blazar, John E Wagner, Claudio G Brunstein, Margaret L MacMillan, Daniel J. Weisdorf

Research output: Contribution to journalArticle

Abstract

Graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) represents complete, ideal recovery after allogeneic hematopoietic cell transplantation (HCT). However, as originally proposed, this composite endpoint does not account for the possibility that HCT complications may improve after treatment. To more accurately estimate survival with response to GVHD and relapse after HCT, we developed a dynamic multistate GRFS (dGRFS) model with outcomes data from 949 patients undergoing their first allogeneic HCT for hematologic malignancy at the University of Minnesota. Because some patients were successfully treated for GVHD and relapse, dGRFS was higher than the originally defined time-to-event GRFS at 1 year (37.0 versus 27.6%) through 4 years (37.4% versus 22.2%). Mean survival without failure events was .52 years (95% confidence interval, .45 to .58 year) greater in dGRFS compared with the originally defined GRFS. Patient age (P< .001), disease risk (P < .001), conditioning intensity (P = .007), and donor type (P = .003) all significantly influenced dGRFS. The multistate model of dGRFS closely estimates the continuing and prevalent severe morbidity and mortality of allogeneic HCT. To serve the greater HCT community in more accurately modeling recovery from transplantation, we provide our R code for determination of dGRFS with annotations in Supplementary Materials.

Original languageEnglish (US)
Pages (from-to)1884-1889
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number9
DOIs
StatePublished - Sep 1 2019

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Cell Transplantation
Graft vs Host Disease
Morbidity
Recurrence
Survival
Mortality
Hematologic Neoplasms
Transplantation
Tissue Donors
Confidence Intervals

Keywords

  • Allogeneic hematopoietic cell transplantation
  • GRFS
  • Graft-versus-host disease
  • Multistate modeling
  • Relapse

Cite this

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title = "Dynamic Graft-versus-Host Disease-Free, Relapse-Free Survival: Multistate Modeling of the Morbidity and Mortality of Allotransplantation",
abstract = "Graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) represents complete, ideal recovery after allogeneic hematopoietic cell transplantation (HCT). However, as originally proposed, this composite endpoint does not account for the possibility that HCT complications may improve after treatment. To more accurately estimate survival with response to GVHD and relapse after HCT, we developed a dynamic multistate GRFS (dGRFS) model with outcomes data from 949 patients undergoing their first allogeneic HCT for hematologic malignancy at the University of Minnesota. Because some patients were successfully treated for GVHD and relapse, dGRFS was higher than the originally defined time-to-event GRFS at 1 year (37.0 versus 27.6{\%}) through 4 years (37.4{\%} versus 22.2{\%}). Mean survival without failure events was .52 years (95{\%} confidence interval, .45 to .58 year) greater in dGRFS compared with the originally defined GRFS. Patient age (P< .001), disease risk (P < .001), conditioning intensity (P = .007), and donor type (P = .003) all significantly influenced dGRFS. The multistate model of dGRFS closely estimates the continuing and prevalent severe morbidity and mortality of allogeneic HCT. To serve the greater HCT community in more accurately modeling recovery from transplantation, we provide our R code for determination of dGRFS with annotations in Supplementary Materials.",
keywords = "Allogeneic hematopoietic cell transplantation, GRFS, Graft-versus-host disease, Multistate modeling, Relapse",
author = "Holtan, {Shernan G} and Lin Zhang and {De For}, {Todd E} and Nelli Bejanyan and Mukta Arora and Armin Rashidi and Aleksandr Lazaryan and Florence Kotiso and Blazar, {Bruce R} and Wagner, {John E} and Brunstein, {Claudio G} and MacMillan, {Margaret L} and Weisdorf, {Daniel J.}",
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T1 - Dynamic Graft-versus-Host Disease-Free, Relapse-Free Survival

T2 - Multistate Modeling of the Morbidity and Mortality of Allotransplantation

AU - Holtan, Shernan G

AU - Zhang, Lin

AU - De For, Todd E

AU - Bejanyan, Nelli

AU - Arora, Mukta

AU - Rashidi, Armin

AU - Lazaryan, Aleksandr

AU - Kotiso, Florence

AU - Blazar, Bruce R

AU - Wagner, John E

AU - Brunstein, Claudio G

AU - MacMillan, Margaret L

AU - Weisdorf, Daniel J.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) represents complete, ideal recovery after allogeneic hematopoietic cell transplantation (HCT). However, as originally proposed, this composite endpoint does not account for the possibility that HCT complications may improve after treatment. To more accurately estimate survival with response to GVHD and relapse after HCT, we developed a dynamic multistate GRFS (dGRFS) model with outcomes data from 949 patients undergoing their first allogeneic HCT for hematologic malignancy at the University of Minnesota. Because some patients were successfully treated for GVHD and relapse, dGRFS was higher than the originally defined time-to-event GRFS at 1 year (37.0 versus 27.6%) through 4 years (37.4% versus 22.2%). Mean survival without failure events was .52 years (95% confidence interval, .45 to .58 year) greater in dGRFS compared with the originally defined GRFS. Patient age (P< .001), disease risk (P < .001), conditioning intensity (P = .007), and donor type (P = .003) all significantly influenced dGRFS. The multistate model of dGRFS closely estimates the continuing and prevalent severe morbidity and mortality of allogeneic HCT. To serve the greater HCT community in more accurately modeling recovery from transplantation, we provide our R code for determination of dGRFS with annotations in Supplementary Materials.

AB - Graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) represents complete, ideal recovery after allogeneic hematopoietic cell transplantation (HCT). However, as originally proposed, this composite endpoint does not account for the possibility that HCT complications may improve after treatment. To more accurately estimate survival with response to GVHD and relapse after HCT, we developed a dynamic multistate GRFS (dGRFS) model with outcomes data from 949 patients undergoing their first allogeneic HCT for hematologic malignancy at the University of Minnesota. Because some patients were successfully treated for GVHD and relapse, dGRFS was higher than the originally defined time-to-event GRFS at 1 year (37.0 versus 27.6%) through 4 years (37.4% versus 22.2%). Mean survival without failure events was .52 years (95% confidence interval, .45 to .58 year) greater in dGRFS compared with the originally defined GRFS. Patient age (P< .001), disease risk (P < .001), conditioning intensity (P = .007), and donor type (P = .003) all significantly influenced dGRFS. The multistate model of dGRFS closely estimates the continuing and prevalent severe morbidity and mortality of allogeneic HCT. To serve the greater HCT community in more accurately modeling recovery from transplantation, we provide our R code for determination of dGRFS with annotations in Supplementary Materials.

KW - Allogeneic hematopoietic cell transplantation

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KW - Multistate modeling

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SN - 1083-8791

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