Transplant Physicians’ Attitudes on Candidacy for Allogeneic Hematopoietic Cell Transplantation (HCT) in Older Patients: The Need for a Standardized Geriatric Assessment (GA) Tool

Background Despite improvements in conditioning regimens and supportive care having expanded the curative potential of HCT, underutilization of HCT in older adults persists (Bhatt VR et al, BMT 2017). Therefore, we conducted a survey of transplant physicians (TP) to determine their perceptions of the impact of older age (≥60 years) on HCT candidacy and utilization of tools to gauge candidacy. Methods We conducted a 23-item, online cross-sectional survey of adult physicians recruited from the Center for International Blood and Marrow Transplant Research between May and July 2019. Results 175/770 (22.7%) TP completed the survey; majority of respondents were 41-60 years old, male, and practicing in a teaching hospital. Over 75% were at centers performing ≥50 HCT per year. When considering regimen intensity, most (96%, n=168) had an upper age limit (UAL) for using a myeloablative regimen (MAC), with only 29 physicians (17%) stating they would consider MAC for patients ≥70 years. In contrast, when considering a reduced intensity/non-myeloablative conditioning (RIC/NMA), 8%, (n=13), 54% (n=93), and 20% (n=35) stated that age 70, 75, and 80 years respectively would be the UAL to use this approach, with 18% (n=31) reporting no UAL. TP agreed that Karnofsky Performance Score (KPS) could exclude older pts for HCT, with 39.1% (n=66), 42.6% (n=72), and 11.4% (n=20) requiring KPS of ≥70, 80, and 90, respectively. The majority (n=92, 52.5%) indicated an HCT-comorbidity index threshold for exclusion, mostly ranging from ≥3 to ≥ 5. Almost all (89.7%) endorsed the need for a better health assessment of pre-HCT vulnerabilities to guide candidacy for pts ≥60 with varied assessments being utilized beyond KPS (Figure 1). However, the majority of centers rarely (33.1%) or never (45.7%) utilize a dedicated geriatrician/geriatric-oncologist to assess alloHCT candidates ≥60 yrs. The largest barriers to performing GA included uncertainty about which tools to use, lack of knowledge and training, and lack of appropriate clinical support staff (Figure 2). Approximately half (n=78, 45%) endorsed GA now routinely influences candidacy. Conclusions The vast majority of TP will consider RIC/NMA alloHCT for patients ≥70 years. However, there is heterogeneity in assessing candidacy. Incorporation of GA into a standardized and easily applied health assessment tool for risk stratification is an unmet need. The recently opened BMT CTN 1704 may aid in addressing this gap

Chronic Graft-versus-Host Disease, Nonrelapse Mortality, and Disease Relapse in Older versus Younger Adults Undergoing Matched Allogeneic Peripheral Blood Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Analysis

•The increase in nonrelapse mortality with chronic graft-versus-host disease (cGVHD) did not differ based on age.•Relapse reduction with cGVHD was similar in older and younger adults.•Overall survival was increased with cGVHD in both older and younger adults.•Increased overall survival was observed with mild to moderate cGVHD but not with severe cGVHD. The effect of chronic graft-versus-host disease (cGVHD) on the risk of nonrelapse mortality (NRM) and relapse has not been specifically studied in older adults, who are increasingly undergoing allogeneic hematopoietic cell transplantation (alloHCT) and surviving long-term to develop cGVHD. In this Center for International Blood and Marrow Transplant Research (CIBMTR) analysis, we tested our hypothesis that the risk of NRM was higher with the development of cGVHD, particularly among older adults (age ≥60 years). We included 4429 adults age ≥40 years who underwent a first HLA-matched peripheral blood stem cell alloHCT for acute myelogenous leukemia or myelodysplastic syndrome between 2008 and 2017. We compared outcomes of 4 groups—older adults (≥60 years) and younger adults (40 to 59 years) with cGVHD and older and younger adults without cGVHD—to determine the effect of older age and cGVHD on various outcomes. We used Cox proportional hazard models to determine the risk of NRM, relapse, and overall survival (OS). We treated cGVHD as a time-dependent covariate. The severity of cGVHD was based on the CIBMTR clinical definitions. cGVHD was significantly associated with a higher risk of NRM and lower risk of relapse regardless of age. The risk of NRM was higher for older adults versus younger adults. Adults who developed cGVHD as a group had longer OS compared with age-matched cohorts without cGVHD. Older adults had worse OS regardless of cGVHD. Among adults with cGVHD, clinically moderate or severe cGVHD was associated with a significantly higher risk of NRM and lower risk of relapse; severe cGVHD was associated with shorter OS, whereas mild to moderate cGVHD was associated with longer OS. Among both younger and older adults, the development of cGVHD was associated with a higher risk of NRM, lower risk of relapse, and longer OS. Older adults had a higher risk of NRM, but the increased risk of NRM associated with cGVHD did not differ based on age. The development of mild to moderate cGVHD offered the most favorable balance between minimizing NRM and decreasing the risk of relapse. The relapse risk was lowest for adults with severe cGVHD, but high NRM resulted in shorter OS. Developing strategies to avoid clinically severe cGVHD is critically important. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc