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Burden and impact of multifactorial geriatric syndromes in allogeneic hematopoietic cell transplantation for older adults.

ABSTRACT: Multifactorial geriatric syndromes are highly prevalent in older patients with cancer. Because an increasing number of older patients undergo allogeneic hematopoietic stem cell transplantation (allo-HCT), we examined the incidence and impact of transplant-related geriatric syndromes using our institutional database and electronic medical records. We identified 527 patients age 60 years or older who had undergone first allo-HCT from 2001 to 2016 for hematologic malignancies. From the initiation of conditioning to 100 days posttransplant, new geriatric syndromes were predominantly delirium with a cumulative incidence of 21% (95% confidence interval [CI], 18%-25%) at day 100 followed by fall at 7% (95% CI, 5%-9%). In multivariable analyses of available pretransplant variables, fall within the last year, potentially inappropriate use of medication, thrombocytopenia, and reduced creatinine clearance were significantly associated with delirium; age older than 70 years and impaired activities of daily living were significantly associated with fall. In the 100-day landmark analysis, both delirium (hazard ratio [HR], 1.66; 95% CI, 1.09-2.52; P = .023) and fall (HR, 2.14; 95% CI, 1.16-3.95; P = .026) were significantly associated with increased nonrelapse mortality; moreover, fall (HR, 1.93; 95% CI, 1.18-3.14; P = .016), but not delirium, was significantly associated with reduced overall survival. Here, we establish baseline incidences and risk factors of common transplant-related geriatric syndromes. Importantly, we demonstrate significant associations of delirium and fall with inferior transplant outcomes. The burden and impact of transplant-related geriatric syndromes warrant the institution of patient-centered, preemptive, longitudinal, and multidisciplinary interventions to improve outcomes for older allo-HCT patients.

SUBMITTER: Lin RJ

PROVIDER: S-EPMC6325300 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Project description:Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative treatment for myelodysplastic syndrome (MDS). The proportion of MDS patients referred for transplantation evaluation, those undergoing transplantation, and the reasons for not undergoing transplantation are unknown. In this retrospective analysis, predefined HCT eligibility and indications criteria were applied to 362 unselected patients with newly diagnosed MDS seen by leukemia faculty between 2008 and 2015 at Memorial Sloan Kettering Cancer Center. Two hundred ninety-four patients (81%) were deemed eligible for transplantation and among these, transplantation was considered indicated in 244 (83%). Of these, 158 of 244 (65%) were referred for transplantation evaluation at a median of 3.9 months from diagnosis. Overall 120 of 362 (33%) underwent transplantation at a median of 7.7 months from diagnosis. Metastatic solid-organ malignancy was the major reason for transplantation ineligibility (54%), and death due to MDS, which occurred in 41% of candidates who did not undergo transplantation, was the major reason for not undergoing transplantation. Factors associated with a lower likelihood of referral for transplantation evaluation included age ≥65 (P < .001), ≥2 comorbidities (P = .008), intermediate-1/low risk MDS (P < .001), <5% blasts at diagnosis (overall P < .001), having Medicare/Medicaid health insurance (P < .001), not being married (P = .017), and diagnosis between 2008 and 2011 (P = .035). On multivariate analysis adjusting for all of the previous factors, diagnosis between 2008 and 2011 (P < .001), age ≥65 (P = .001), and <5% blasts at diagnosis (overall P = .031) were associated with a lower likelihood of referral for transplantation evaluation. Factors associated with a lower likelihood of undergoing transplantation included age ≥65 (P < .001), ≥2 comorbidities (P = .003), intermediate-1/low risk MDS (P < .001), <5% blasts (overall P < .001), very low/low/intermediate risk International Prognostic Scoring System-revised karyotype (P = .018), and having Medicare/Medicaid health insurance (P < .001). In multivariate analysis adjusting for all of the previous factors, age ≥65 (P = .021), presence of ≥2 comorbidities (P = .018), and <5% blasts (overall P = .011) were associated with a lower likelihood of undergoing transplantation. The results highlight that transplantation for MDS remains underutilized, particularly for candidates over the age of 65.

Project description:Allogeneic hematopoietic cell transplantation (alloHCT) provides cure for older patients with acute myeloid leukemia (AML); however, disease relapse remains a major concern. Based on recent data suggesting that younger donor age confers the greatest benefit for alloHCT with matched unrelated donors (MUDs), we attempted to answer a practical question: which donor type provides the best outcomes when an older patient with AML has a matched sibling donor (MSD, also older) versus the best MUD? This retrospective cohort registry study accessed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) in patients with AML age ≥ 50 years undergoing alloHCT from older MSDs (age ≥ 50 years) or younger MUDs (age ≤ 35 years) between 2011 and 2018. The study included common allograft types, conditioning regimens, and graft-versus-host disease (GVHD) prophylaxis. The primary outcome was relapse risk. Secondary outcomes included nonrelapse mortality (NRM), GVHD, disease-free survival (DFS), and overall survival. Among 4684 eligible patients, 1736 underwent alloHCT with an older MSD (median donor age, 60 years), and 2948 underwent alloHCT from a younger MUD (median donor age, 25 years). In multivariable analysis, compared to older MSDs, the use of younger MUDs conferred a decreased relapse risk (hazard ratio [HR], .86; P = .005) and a significantly lower adjusted 5-year cumulative incidence of relapse (35% versus 41%; P = .003), but was associated with an increased risk for chronic GVHD (HR, 1.18; 95% confidence interval [CI], 1.08 to 1.29; P = .0002) and greater NRM only in the earlier period of 2011 to 2015 (HR, 1.24; P = .016). The corresponding NRM rates were significantly lower in the more recent period of 2016 to 2018 (HR, .78; P = .017). The adjusted 5-year DFS probability was 44% (95% CI, 42% to 46%) with an alloHCT from younger MUDs compared to 41% (95% CI, 38% to 43%) with older MSDs (P = .04). In summary, for older patients with AML undergoing alloHCT, the use of younger MUDs is associated with decreased relapse risk and improved DFS compared with the use of older MSDs.

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Burden and impact of multifactorial geriatric syndromes in allogeneic hematopoietic cell transplantation for older adults.

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