Hematopoietic Cell Transplant–Related Toxicities and Mortality in Frail Recipients

Merve Pamukcuoglu, Smita Bhatia, Daniel J Weisdorf, Todd E De For, Celalettin Ustun, Manju Nayar, Shernan G Holtan, Najla El Jurdi, Bharat Thyagarajan, Claudio G Brunstein, Veronika Bachanova, Erica D Warlick, Ben Severseike, Hok Sreng Te, Troy C Lund, Mukta Arora

Research output: Contribution to journalArticle

Abstract

Frailty is a state characterized by diminished physiologic reserve and increased vulnerability to stress and adversely affects outcomes in older patients. We aimed to determine the relationship between pre–hematopoietic cell transplant (HCT) frailty and grades 3 to 4 nonhematologic toxicities (Common Terminology Criteria for Adverse Events, version 5.0) and mortality in HCT recipients within 1 year after HCT and also examined whether age at HCT moderated that association. In a prospective longitudinal study of 117 patients aged ≥ 40 years undergoing HCT, we performed formal pre-HCT geriatric assessments. Frailty was assessed using Fried's criteria. Post-HCT toxicities were abstracted through medical record reviews. The prevalence of pre-HCT frailty was 21% and was not different in younger (40 to 59 years) versus older (≥60 years) HCT recipients. Overall, frail recipients (versus nonfrail) had a higher cumulative incidence of any grades 3 to 4 nonhematologic toxicity (86% [95% confidence interval {CI}, 62% to 100%] versus 70% [95% CI, 57% to 83%), P =.03) and more organ-specific grades 3 to 4 toxicities, such as non-neutropenic infections (38% [95% CI, 17% to 59%] versus 13% [95% CI, 6% to 20%], P <.01), nervous system disorders (19% [95% CI, 3% to 35%] versus 4% [95% CI, 0 to 8%], P =.02), and pneumonia (38% [95% CI, 17% to 59%] versus 10% [95% CI, 4% to 17%], P <.01). Frail recipients were 1.9-fold (95% CI, 1.1 to 3.4) more likely to develop any grades 3 to 4 toxicities (P =.03), 4-fold more likely to suffer non-neutropenic infections (95% CI, 1.4 to 11) and pneumonia (95% CI, 1.4 to 12; both P =.01), and 8.6-fold (95% CI, 1.6 to 45.3) more likely to suffer nervous system disorders (P =.01). Frail allogeneic HCT recipients also had a 3.1 times (95% CI,.9 to 9.7; P =.06) higher risk of overall mortality as compared with nonfrail allogeneic HCT recipients. The higher toxicity and mortality observed in frail allogeneic recipients needs to be monitored with high attention. Studies focusing on interventions to reduce frailty and manage morbidities are needed.

Original languageEnglish (US)
JournalBiology of Blood and Marrow Transplantation
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Confidence Intervals
Mortality
Nervous System Diseases
Pneumonia
Geriatric Assessment
Infection
Terminology
Medical Records
Longitudinal Studies
Prospective Studies
Morbidity
Transplants
Incidence

Keywords

  • Frailty
  • HCT toxicities
  • Mortality in frail recipient

PubMed: MeSH publication types

  • Journal Article

Cite this

@article{6537896716ea4ab396ca4f52f7844316,
title = "Hematopoietic Cell Transplant–Related Toxicities and Mortality in Frail Recipients",
abstract = "Frailty is a state characterized by diminished physiologic reserve and increased vulnerability to stress and adversely affects outcomes in older patients. We aimed to determine the relationship between pre–hematopoietic cell transplant (HCT) frailty and grades 3 to 4 nonhematologic toxicities (Common Terminology Criteria for Adverse Events, version 5.0) and mortality in HCT recipients within 1 year after HCT and also examined whether age at HCT moderated that association. In a prospective longitudinal study of 117 patients aged ≥ 40 years undergoing HCT, we performed formal pre-HCT geriatric assessments. Frailty was assessed using Fried's criteria. Post-HCT toxicities were abstracted through medical record reviews. The prevalence of pre-HCT frailty was 21{\%} and was not different in younger (40 to 59 years) versus older (≥60 years) HCT recipients. Overall, frail recipients (versus nonfrail) had a higher cumulative incidence of any grades 3 to 4 nonhematologic toxicity (86{\%} [95{\%} confidence interval {CI}, 62{\%} to 100{\%}] versus 70{\%} [95{\%} CI, 57{\%} to 83{\%}), P =.03) and more organ-specific grades 3 to 4 toxicities, such as non-neutropenic infections (38{\%} [95{\%} CI, 17{\%} to 59{\%}] versus 13{\%} [95{\%} CI, 6{\%} to 20{\%}], P <.01), nervous system disorders (19{\%} [95{\%} CI, 3{\%} to 35{\%}] versus 4{\%} [95{\%} CI, 0 to 8{\%}], P =.02), and pneumonia (38{\%} [95{\%} CI, 17{\%} to 59{\%}] versus 10{\%} [95{\%} CI, 4{\%} to 17{\%}], P <.01). Frail recipients were 1.9-fold (95{\%} CI, 1.1 to 3.4) more likely to develop any grades 3 to 4 toxicities (P =.03), 4-fold more likely to suffer non-neutropenic infections (95{\%} CI, 1.4 to 11) and pneumonia (95{\%} CI, 1.4 to 12; both P =.01), and 8.6-fold (95{\%} CI, 1.6 to 45.3) more likely to suffer nervous system disorders (P =.01). Frail allogeneic HCT recipients also had a 3.1 times (95{\%} CI,.9 to 9.7; P =.06) higher risk of overall mortality as compared with nonfrail allogeneic HCT recipients. The higher toxicity and mortality observed in frail allogeneic recipients needs to be monitored with high attention. Studies focusing on interventions to reduce frailty and manage morbidities are needed.",
keywords = "Frailty, HCT toxicities, Mortality in frail recipient",
author = "Merve Pamukcuoglu and Smita Bhatia and Weisdorf, {Daniel J} and {De For}, {Todd E} and Celalettin Ustun and Manju Nayar and Holtan, {Shernan G} and Jurdi, {Najla El} and Bharat Thyagarajan and Brunstein, {Claudio G} and Veronika Bachanova and Warlick, {Erica D} and Ben Severseike and Te, {Hok Sreng} and Lund, {Troy C} and Mukta Arora",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.bbmt.2019.07.030",
language = "English (US)",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Hematopoietic Cell Transplant–Related Toxicities and Mortality in Frail Recipients

AU - Pamukcuoglu, Merve

AU - Bhatia, Smita

AU - Weisdorf, Daniel J

AU - De For, Todd E

AU - Ustun, Celalettin

AU - Nayar, Manju

AU - Holtan, Shernan G

AU - Jurdi, Najla El

AU - Thyagarajan, Bharat

AU - Brunstein, Claudio G

AU - Bachanova, Veronika

AU - Warlick, Erica D

AU - Severseike, Ben

AU - Te, Hok Sreng

AU - Lund, Troy C

AU - Arora, Mukta

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Frailty is a state characterized by diminished physiologic reserve and increased vulnerability to stress and adversely affects outcomes in older patients. We aimed to determine the relationship between pre–hematopoietic cell transplant (HCT) frailty and grades 3 to 4 nonhematologic toxicities (Common Terminology Criteria for Adverse Events, version 5.0) and mortality in HCT recipients within 1 year after HCT and also examined whether age at HCT moderated that association. In a prospective longitudinal study of 117 patients aged ≥ 40 years undergoing HCT, we performed formal pre-HCT geriatric assessments. Frailty was assessed using Fried's criteria. Post-HCT toxicities were abstracted through medical record reviews. The prevalence of pre-HCT frailty was 21% and was not different in younger (40 to 59 years) versus older (≥60 years) HCT recipients. Overall, frail recipients (versus nonfrail) had a higher cumulative incidence of any grades 3 to 4 nonhematologic toxicity (86% [95% confidence interval {CI}, 62% to 100%] versus 70% [95% CI, 57% to 83%), P =.03) and more organ-specific grades 3 to 4 toxicities, such as non-neutropenic infections (38% [95% CI, 17% to 59%] versus 13% [95% CI, 6% to 20%], P <.01), nervous system disorders (19% [95% CI, 3% to 35%] versus 4% [95% CI, 0 to 8%], P =.02), and pneumonia (38% [95% CI, 17% to 59%] versus 10% [95% CI, 4% to 17%], P <.01). Frail recipients were 1.9-fold (95% CI, 1.1 to 3.4) more likely to develop any grades 3 to 4 toxicities (P =.03), 4-fold more likely to suffer non-neutropenic infections (95% CI, 1.4 to 11) and pneumonia (95% CI, 1.4 to 12; both P =.01), and 8.6-fold (95% CI, 1.6 to 45.3) more likely to suffer nervous system disorders (P =.01). Frail allogeneic HCT recipients also had a 3.1 times (95% CI,.9 to 9.7; P =.06) higher risk of overall mortality as compared with nonfrail allogeneic HCT recipients. The higher toxicity and mortality observed in frail allogeneic recipients needs to be monitored with high attention. Studies focusing on interventions to reduce frailty and manage morbidities are needed.

AB - Frailty is a state characterized by diminished physiologic reserve and increased vulnerability to stress and adversely affects outcomes in older patients. We aimed to determine the relationship between pre–hematopoietic cell transplant (HCT) frailty and grades 3 to 4 nonhematologic toxicities (Common Terminology Criteria for Adverse Events, version 5.0) and mortality in HCT recipients within 1 year after HCT and also examined whether age at HCT moderated that association. In a prospective longitudinal study of 117 patients aged ≥ 40 years undergoing HCT, we performed formal pre-HCT geriatric assessments. Frailty was assessed using Fried's criteria. Post-HCT toxicities were abstracted through medical record reviews. The prevalence of pre-HCT frailty was 21% and was not different in younger (40 to 59 years) versus older (≥60 years) HCT recipients. Overall, frail recipients (versus nonfrail) had a higher cumulative incidence of any grades 3 to 4 nonhematologic toxicity (86% [95% confidence interval {CI}, 62% to 100%] versus 70% [95% CI, 57% to 83%), P =.03) and more organ-specific grades 3 to 4 toxicities, such as non-neutropenic infections (38% [95% CI, 17% to 59%] versus 13% [95% CI, 6% to 20%], P <.01), nervous system disorders (19% [95% CI, 3% to 35%] versus 4% [95% CI, 0 to 8%], P =.02), and pneumonia (38% [95% CI, 17% to 59%] versus 10% [95% CI, 4% to 17%], P <.01). Frail recipients were 1.9-fold (95% CI, 1.1 to 3.4) more likely to develop any grades 3 to 4 toxicities (P =.03), 4-fold more likely to suffer non-neutropenic infections (95% CI, 1.4 to 11) and pneumonia (95% CI, 1.4 to 12; both P =.01), and 8.6-fold (95% CI, 1.6 to 45.3) more likely to suffer nervous system disorders (P =.01). Frail allogeneic HCT recipients also had a 3.1 times (95% CI,.9 to 9.7; P =.06) higher risk of overall mortality as compared with nonfrail allogeneic HCT recipients. The higher toxicity and mortality observed in frail allogeneic recipients needs to be monitored with high attention. Studies focusing on interventions to reduce frailty and manage morbidities are needed.

KW - Frailty

KW - HCT toxicities

KW - Mortality in frail recipient

UR - http://www.scopus.com/inward/record.url?scp=85071496867&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071496867&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2019.07.030

DO - 10.1016/j.bbmt.2019.07.030

M3 - Article

C2 - 31394273

AN - SCOPUS:85071496867

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

ER -