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.

Efficacy of Autologous and Allogeneic Hematopoietic Cell Transplantation in Waldenström Macroglobulinemia: A Systematic Review and Meta-analysis

“…36,37 Prediction and prevention of factors that lead to NRM following both allo-HCT and AHCT has also improved over the years. [38][39][40] As health care quality improvement initiatives, such as the Foundation for the Accreditation of Cellular Therapy, continue to gather data with the goal of improving outcomes in HCT, one can anticipate continued reductions in NRM. 41 Nevertheless, in selected patients, there appears to be a rationale for allo-HCT.…”

From frail to fit after allogeneic hematopoietic cell transplantation: Scope of the problem and a strength-based solution

“…Recipients of HCT can carry several risk factors for frailty including advanced age, polypharmacy, lack of regular exercise, isolation, malnutrition, and unintentional weight loss ( 1, 10 ). Risks traditionally associated with life-threatening complications following SCT have been substantially mitigated by innovations in supportive care.…”

Physically “fit” for allogeneic stem cell transplant?

“…With the increasing number of older adults receiving allogeneic HCT, there is an increased awareness of the importance of frailty and functionality prior to allogeneic HCT [ 1 ]. Ten to 33% of older adults are found to be frail prior to undergoing HCT [ 2 – 4 ]. In studies inclusive of all adults or younger adults, frailty is seen in 36% and 26%, respectively, prior to HCT, demonstrating that frailty is not limited to older adults [ 4 , 5 ].…”

“…Ten to 33% of older adults are found to be frail prior to undergoing HCT [ 2 – 4 ]. In studies inclusive of all adults or younger adults, frailty is seen in 36% and 26%, respectively, prior to HCT, demonstrating that frailty is not limited to older adults [ 4 , 5 ]. Frail adults have been shown to have decreased overall survival (OS), increased non-relapse mortality (NRM), and increased toxicities posttransplant [ 2 – 4 , 6 ].…”

“…In studies inclusive of all adults or younger adults, frailty is seen in 36% and 26%, respectively, prior to HCT, demonstrating that frailty is not limited to older adults [ 4 , 5 ]. Frail adults have been shown to have decreased overall survival (OS), increased non-relapse mortality (NRM), and increased toxicities posttransplant [ 2 – 4 , 6 ]. A major component of frailty includes an evaluation of impairments in instrumental activities of daily living (IADLs), activities required for individuals to live independently in the community.…”