Access and Referral Barriers to Autologous and Allogeneic Hematopoietic Cell Transplantation in Adult Patients with Cancer: A Systematic Review with a Specific Focus on Geriatric Population
Authors: Loh Kah Poh , Tan Jian Liang , McHugh Colin M. , Liesveld Jane L. , O'Dwyer Kristen M. , Becker Michael W. , Mendler Jason H. , Aljitawi Omar S. , Klepin Heidi D. , Stock Wendy , Wildes Tanya , Artz Andrew S , El-Jawahri Areej , Majhail Navneet S. 
Published: October 2019

Abstract
Introduction:
Hematopoietic cell transplantation (HCT) advances in reduced intensity conditioning, donor identification, and supportive care have led to its increased use over the last few decades. HCT is a complex process that requires coordination at multiple levels, and there may be disparities in its utilization. To better understand these access disparities, we conducted a systematic review of studies that assessed barriers to referral and/or receipt of HCT. Additionally, we focused on a subgroup of older patients (aged ≥65 at transplant), who we hypothesized would be at higher risk for access barriers to HCT.
Methods:
A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched for articles published in English from PubMed, Embase, Cumulative Index for Nursing and Allied Health, and Cochrane Central Register of Controlled Trials between the database inception and January 12th, 2018. Inclusion criteria were: 1) clinical trials, observational, qualitative, cross-sectional, or mixed-method study designs; 2) study assessed barriers to HCT or factors associated with referral for or receipt of HCT (except for country-specific economic factors as these are less likely to be targetable), 3) included patients ≥18 years with cancer. Narrative review articles and abstracts without full text were excluded. Two authors independently reviewed all titles and abstracts (N=3,262) and assessed studies for full-text eligibility (N=153). A third reviewer resolved any discrepancies. Eighteen studies met eligibility criteria and an additional 5 studies (not identified on our search strategy) were included on review of the bibliographies. Literature on subgroup of patients aged ≥65 was also assessed.
Results:
Among the 23 studies included, 16 were published after 2010. Studies were retrospective (N=18; 14 from registry data), cross-sectional (N=4; 2 from registry data), and mixed-method (N=1), and primarily conducted in the US (N=21). Barriers were assessed at the patient level (N=19; sample size ranged from 350 to 38,420), healthcare professional level (N=3; 1 study assessed both patients and healthcare professionals), or country level (N=2). Fourteen studies included some information on age of the patients and 10 studies included some patients aged 60 and above. Seventeen studies only included patients with hematologic malignancies. Age was the most common barrier identified (N=16 out of 16 studies identified older age as a barrier). Fourteen studies showed that older age was associated with lower odds of referral for or receipt of HCT, and the remaining 2 studies provided descriptive data showing lower percentages of patients receiving HCT compared to the younger age groups. Table 1 shows other potential barriers or factors associated with lower referral for or receipt of HCT at the patient, disease, physician, and organizational levels. These included race (N=14 out of 16 studies identified non-white race as a barrier), insurance or financial capacity (N=11/12), comorbidity (N=8/9), gender (N=7/17; primarily female), disease status (N=5/5), patient preferences (N=5/5), time of diagnosis (N=5/5), cancer type (N=4/6), and socioeconomic status (N=4/5). Only one study evaluated factors associated with receipt of HCT in a subgroup of patients ≥65 years. Older age, female gender, and a diagnosis of leukemia other than acute myeloid leukemia were associated with lower odds of receiving HCT.
Conclusions:
There are limited prospective studies evaluating access barriers to HCT in adult patients with cancer. Older age is the most commonly reported barrier to both autologous and allogeneic HCT, although studies have not addressed specific mechanisms for this disparity. In addition, other potential barriers identified such as gender, race, insurance status, and comorbidity have not been well studied in the context of older age. While some barriers may be difficult to intervene upon (e.g. comorbidity, disease status, performance status), many are amenable to interventions (e.g. socioeconomic status, distance to transplant center, social support). With the increasing trend for HCT in older patients, there is a critical need for prospective studies that better describe these access barriers and their mechanisms in order to design future interventions to reduce disparities in HCT access.
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Disclosures
Liesveld: Onconova: Other: DSMB; Abbvie: Honoraria. Aljitawi:Medpace: Consultancy; The University of Rochester Medical Center: Patents & Royalties: Pending patent related to decellularized Wharton's jelly matrix. Klepin:Genentech Inc: Consultancy. Stock:Jazz Pharmaceuticals: Consultancy. Wildes:Janssen: Research Funding. Majhail:Incyte: Honoraria; Anthem, Inc.: Consultancy; Atara: Honoraria.