Trends in Volumes and Survival After Hematopoietic Cell Transplantation in Racial/Ethnic Minorities.

There has been an increase in volume as well as improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have impacted racial/ethnic minorities equally. In this observational study from Center for International Blood and Marrow Transplant Research of 79,904 autologous (auto) and 65,662 allogeneic (allo) HCTs, we examined the volume and rates of change of auto HCT and allo HCT over time and trends in OS in 4 racial/ethnic groups: Non-Hispanic Whites (NHWs), Non-Hispanic African Americans (NHAAs), Hispanics across five 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs. NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (HR 1.13; 95% CI 1.04-1.22; p=0.004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; p<0.001 had a higher risk of mortality after alloHCT compared to NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT.Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics compared to NHWs. Survival after autoHCT and alloHCT improved over time, however NHAAs have worse OS after alloHCT which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT.

Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation: a CIBMTR analysis.

Patient-reported outcomes (PROs) capture subjective social determinants of health (SDOHs), which can affect health outcomes through the stress response pathway. The conserved transcriptional response to adversity (CTRA) is a stress-mediated proinflammatory transcriptomic pattern that has been linked to adverse hematopoietic cell transplant (HCT) outcomes. This study examined the association of pretransplant CTRA with patient-reported SDOHs in allogeneic HCT recipients. In this cross-sectional study, pre-HCT SDOH-related PROs included the 36-Item Short Form Health Survey and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT). CTRA was assessed by RNA sequencing of whole blood specimens, with mixed effects linear regression models relating CTRA expression to PRO scores while controlling for age, sex, race, disease, and performance status. Among 121 patients, the median age was 54 years, 42% were female, and 91% were White. CTRA was elevated in participants reporting lower scores on the FACT-BMT (P = .003), including the general (P = .003) and BMT-specific (P = .014) components. Effects were driven by the social well-being domain (P = .0001). This corresponded to an 8% to 15% difference in CTRA RNA expression across a 4 standard deviation range in patient-reported SDOHs. Ancillary bioinformatics analyses confirmed the association of well-being with reduced proinflammatory transcription pathway activity [cyclic AMP response element-binding protein, (CREB), NF-κB, and activating protein-1 (AP-1)]. In conclusion, HCT-treated patients who experience unfavorable social conditions show elevated CTRA expression in pretransplant blood samples. These data highlight the biologic sequelae of social well-being and community context and suggest a potential molecular mechanism for the impact of social gradients in HCT outcomes. Targeting this pathway could optimize outcomes in this high-risk population.

Racial and Socioeconomic Disparities in Long-Term Outcomes in ≥1 Year Allogeneic Hematopoietic Cell Transplantation Survivors: A CIBMTR Analysis.

Racial/ethnic minorities have demonstrated worse survival after allogeneic hematopoietic cell transplantation (HCT) compared to whites. Whether the racial disparity in HCT outcomes persists in long-term survivors and possibly may be even exacerbated in this population, which frequently transitions back from the transplant center to their local healthcare providers, is unknown. In the current study, we compared long-term outcomes among 1-year allogeneic HCT survivors by race/ethnicity and socioeconomic status (SES). The Center for International Blood and Marrow Transplant Research database was used to identify 5473 patients with acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, or myelodysplastic syndromes who underwent their first allogeneic HCT between 2007 and 2017 and were alive and in remission for at least 1 year after transplantation. The study was restricted to patients who underwent HCT in the United States. SES was defined using patient neighborhood poverty level estimated from the recipient's ZIP code of residence; a ZIP code with ≥20% of persons below the federal poverty level was considered a high poverty area. The primary outcome was to evaluate the associations of race/ethnicity and neighborhood poverty level with overall survival (OS), relapse, and nonrelapse mortality (NRM). Cox regression models were used to determine associations of ethnicity/race and SES with OS, relapse, and NRM. Standardized mortality ratios were calculated to compare mortality rates of the study patients and their general population peers matched on race/ethnicity, age, and sex. The study cohort was predominately non-Hispanic white (n = 4385) and also included non-Hispanic black (n = 338), Hispanic (n = 516), and Asian (n = 234) patients. Overall, 729 patients (13%) resided in high-poverty areas. Significantly larger proportions of non-Hispanic black (37%) and Hispanic (26%) patients lived in high-poverty areas compared to non-Hispanic whites (10%) and Asians (10%) (P < .01). Multivariable analysis revealed no significant associations between OS, PFS, relapse, or NRM and race/ethnicity or poverty level when adjusted for patient-, disease- and transplantation-related covariates. Our retrospective cohort registry study shows that among adult allogeneic HCT recipients who survived at least 1 year in remission, there were no associations between race/ethnicity, neighborhood poverty level, and long-term outcomes.

Reducing barriers of access and care related to hematopoietic cell transplantation and cellular therapy: The mission-driven role of the national marrow donor program.

The treatment of malignant and nonmalignant hematologic disorders continues to benefit from significant scientific advancement and progress in the use of hematopoietic cell transplantation and cellular therapies. However, barriers associated with receiving these lifesaving treatments and care remain, which necessitate innovative approaches to overcome, so all persons in need can receive these therapies. This article reviews barriers to receiving hematopoietic cell transplantation and cellular therapies, and highlights novel approaches taken by the National Marrow Donor Program in reducing barriers for all patients in need.

Impact of Public Reporting of Center-Specific Survival Analysis Scores on Patient Volumes at Hematopoietic Cell Transplant Centers.

The Center for International Blood and Marrow Transplant Research reports the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) at United States transplantation centers (TC) annually through its Center-Specific Survival Analysis (CSA). The CSA compares the actual 1-year overall survival (OS) and predicted 1-year OS rate after alloHCT at each TC, which is then reported as 0 (OS as expected), -1 (OS worse than expected), or 1 (OS better than expected). We evaluated the impact of public reporting of TC performance on their alloHCT patient volumes. Ninety-one TCs that serve adult or combined adult and pediatric populations and had CSA scores reported for 2012-2018 were included. We analyzed prior-calendar-year TC volume, prior-calendar-year CSA score, whether the CSA score had changed in the prior year from two years earlier, calendar year, TC type (adult only vs. combined adult and pediatric), and years of alloHCT experience for their impact on patient volumes. A CSA score of -1, as compared with 0 or 1, was associated with an 8% to 9% reduction in the mean TC volume (P < 0.001) in the subsequent year, adjusting for the prior year center volume. Additionally, being a TC neighboring an index TC with a -1 CSA score, was associated with a 3.5% increase in mean TC volume (P = 0.04). Our data show that public reporting of CSA scores is associated with changes in alloHCT volumes at TCs. Additional investigation into the causes of this shift in patient volume and the impact on outcomes is ongoing.

Enhancing Administrative Claims Data: Feasibility, Validation and Application of Linking Medicare Claims Data and National Marrow Donor Program Search Data.

PURPOSE: Administrative claims data provide real-world service utilization of acute myeloid leukemia (AML) treatment, but lacks insight into treatment delays or barriers. The National Marrow Donor Program (NMDP)/Be The Match Search (Search) data contains information on donor search, but lacks information on treatment received if allogeneic hematopoietic cell transplant (HCT) is not performed. We hypothesized that linking these two data sets would create a rich resource to define factors associated with receiving HCT that could not be evaluated with either data set alone. METHODS: A subset of 2010-2016 Medicare administrative claims data was linked with Search data. A total of 5,351 patients with AML age 65-74 years (HCT = 607, no HCT = 4,744) were identified using Medicare. These patients were then linked to 93,800 records with a donor search between 2009 and 2016. Patient date of birth, sex, disease, ZIP code, transplant center/hospital, and diagnosis date were used for matching. Exploratory analysis was conducted to identify predictors associated with receiving HCT for patients with AML who received a search. RESULTS: The data sets were successfully linked, showing high sensitivity and specificity. The final cohort included 5,085 patients with AML (HCT = 533, no HCT = 4,552). Of 97 patients who received HCT without a matched search, more than 85% received a related donor HCT. Of those not receiving HCT, 609 had a matched NMDP search and 3,943 did not have a matched NMDP search. Multivariate analysis showed time to search, age, diagnosis year, race/ethnicity, and neighborhood education status associated with receiving HCT. CONCLUSION: Methods herein demonstrate the feasibility of linking Search and Medicare data. Similar methods may be applied to answer critical questions regarding barriers to HCT, thereby identifying areas to improve access to care.

Trends in Allogeneic Hematopoietic Cell Transplantation Utilization and Estimated Unmet Need Among Medicare Beneficiaries with Acute Myelogenous Leukemia.

Allogeneic hematopoietic cell transplantation (alloHCT) is a resource-intensive procedure and the sole potentially curative treatment available for patients with acute myelogenous leukemia (AML). Although Medicare coverage may help address a major financial barrier to accessing alloHCT, there remains an unmet need for alloHCT owing to sociodemographic disparities. This study examined trends and factors associated with the utilization of alloHCT and the estimated unmet need for alloHCT among Medicare beneficiaries with AML. This retrospective cohort study included patients (age 65 to 74 years) with a diagnosis of AML identified in Medicare claims data from 2010 through 2016. To study trends in utilization, transplantation rates were calculated as the number of patients who underwent alloHCT within 180 days and 1 year of diagnosis (numerator) divided by the total number of patients with AML within each diagnosis year (denominator). A multivariable logistic regression was used to identify factors associated with the likelihood of undergoing alloHCT within 1 year of diagnosis. Two approaches were applied to estimate the unmet need for alloHCT. The first approach used claims data to identify the potential need for alloHCT among patients who achieved complete remission for at least 90 days. The second approach used established National Marrow Donor Program (NMDP) methodology, which considers estimates of risk level, response to treatment, comorbidity, and early mortality, to identify the potential and unmet need for alloHCT. The overall estimated need and unmet need from 2010 to 2015 and over different time periods were evaluated for both approaches. The alloHCT rate within 180 days of diagnosis increased from 8% in 2010 to 15.8% in 2016 (P < .001), and the 1-year alloHCT rate also increased over time, from 11.9% in 2010 to 20.0% in 2015 (P < .001). The likelihood of undergoing alloHCT within 1 year of diagnosis was associated with diagnosis year, age, race, geographic region, Elixhauser Comorbidity Index, and population-level median household income. Between 2010 and 2015, the claims data approach estimated a lower potential need for alloHCT compared with the NMDP methodology estimate (27% versus 36%); both approaches estimated that 43% to 44% of patients with a potential need for alloHCT had an unmet treatment need. Despite the differences in estimated potential need between the 2 approaches, both showed a sustained unmet need but with a downward trend over time. Our data show that utilization of alloHCT has increased over time among Medicare beneficiaries with AML. Two approaches of need analysis were conducted for validation of estimated need and unmet need for alloHCT using claim-identified remission status, given the lack of cytogenetics and molecular information in claims data. Both approaches to estimating the unmet need for alloHCT found a downward trend over time; however, there are differences in utilization of alloHCT by age, race, geographic region, comorbidity, and socioeconomic status, indicating disparities in access to alloHCT among Medicare beneficiaries with AML. This suggests the need for policy efforts, research, and continued education to improve access to alloHCT and to close the gap between the actual utilization of alloHCT and the unmet need.

Health-Related Quality of Life in Young Adult Survivors of Hematopoietic Cell Transplantation.

Young adults (YA), age 18 to 39 years, are at a stage of life that may make them more vulnerable than older adults to impairments in health-related quality of life (HRQOL) during and after hematopoietic cell transplantation (HCT). Health self-efficacy (HSE), the belief that one can implement strategies to produce a desired health outcome, has been associated with health outcomes in oncology research. Little is known about HRQOL or HSE in YA HCT survivors compared with older HCT survivors. Given the age-specific psychosocial challenges facing YA HCT recipients and research on non-transplant YA cancer survivors, we hypothesized that YA survivors would have worse post-HCT HRQOL compared with older adults, and that among YA HCT survivors, higher levels of HSE would be associated with higher levels of HRQOL and lower levels of cancer-related distress. This was a cross-sectional secondary analysis of 2 combined baseline datasets from multicenter studies of HCT survivors approached for participation in clinical trials of survivorship interventions. Participants from 20 transplantation centers in the United States were at 1 to 10 years post-HCT and age ≥18 years at the time of study enrollment, had no evidence of disease relapse/progression or subsequent malignancies, and could read English adequately to consent for and complete assessments. Medical record and patient-reported data were obtained for demographics and HCT-related clinical factors and complications (eg, total body irradiation, chronic graft-versus-host disease [cGVHD]). Participants completed surveys on HRQOL, including the Short-Form [SF]-12, HSE, and Cancer and Treatment Distress (CTXD), which includes 6 subscales and reports an overall mean score. On the SF-12, both the Mental Component Score (MCS) and Physical Component Score (PCS) were calculated. Two cohorts were compared: YAs (age 18 to 39 years at transplantation) and older adults (age ≥40 years at transplantation). Multiple linear regression analyses identified factors associated with HSE, PCS, MCS, and CTXD in YAs. In this analysis of 979 survivors, compared with the older adults, the YA participants had lower median mental health scores (SF-12 MCS: 48.40 versus 50.23; P = .04) and higher cancer-related distress (CTXD: .96 versus .85; P = .04), but better physical health (SF-12 PCS: 48.99 versus 47.18; P = .049). Greater overall cancer-related distress was driven by higher levels of uncertainty, financial concern, and medical demand subscales for YAs compared with older adults. Young adults also had lower HSE (2.93 versus 3.08; P = .0004). In a multivariate model, HSE was strongly associated with age group (P = .0005) after adjusting for multiple other transplantation-related factors. Among YAs, HSE was associated with the SF-12 MCS and PCS and the CTXD, and HSE remained significant after adjusting for other transplantation-related factors. Overall, the YA HCT survivors had lower mental health, increased cancer-related distress, and lower levels of HSE compared with the older adults. Although the direction of these effects cannot be determined with these data, the strong association between HSE and HRQOL among YAs suggests that targeting interventions to improve HSE may have broad impact on health outcomes.

The Impact of Pre-Apheresis Health Related Quality of Life on Peripheral Blood Progenitor Cell Yield and Donor's Health and Outcome: Secondary Analysis of Patient-Reported Outcome Data from the RDSafe and BMT CTN 0201 Clinical Trials.

There is a lack of evidence about how health-related quality of life (HRQoL), including psychosocial factors, might affect donation-related experiences and clinical markers in the context of hematopoietic stem cell donation. The broader literature suggests that psychological factors, including anxiety and depression, are associated with higher levels of inflammatory burden leading to poorer postprocedural outcomes including longer hospital stays and increased pain perception. In this study, we aimed to evaluate whether predonation HRQoL markers predict toxicity profile and stem cell yield after peripheral blood stem cell (PBSC) donation in healthy donors. The study population comprised adult granulocyte colony-stimulating factor mobilized PBSC-related donors (RD) (n = 157) and unrelated donors (URD) (n = 179) enrolled in the related donor safety study (RDSafe) and Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 clinical trials. Pre-donation HRQoL was assessed using the Short-Form-12 (SF-12) in RDSafe and SF-8 questionnaire in BMT CTN 0201 (higher score is better). The aims of this study were to (a) determine the impact of pre-donation HRQoL on peri-collection pain and acute toxicities experienced and (b) to investigate the pre-procedural HRQoL indicators on stem cells yield. URDs were younger than RDs (median age 35 versus 63). A higher proportion of RDs were female (50% versus 40%) and obese (41% versus 35%). A higher proportion of RD PBSC donations required 2 days or more of apheresis (44% versus 21%). More RD collections were lower volume procedures (<18L, 16% versus 28%), and required a central line (28% versus 11%). RDs were more likely to report pre-donation grade 1-2 pain (27% versus 8%) and other toxicities (16% versus 6%). Among RDs, a lower pre-donation physical component summary (PCS) score was associated with significantly more grade 2-4 pain at 1 month (P = .004) and at 1-year after donation (P = .0099) in univariable analyses. In multivariable analysis, pre-donation PCS remained significantly associated with grade 2-4 pain 1 month after donation (P = .0098). More specifically, RDs with predonation PCS scores in the highest quartile were less likely to report pain compared with donors with PCS scores in the lowest quartile (odds ratio 0.1; 95% confidence interval 0.01-0.83; P = .005). There was also a trend toward higher grade 2-4 pain at 1-year post-donation among RDs with lower predonation PCS score (P = .018). Among URDs, neither PCS nor mental component summary (MCS) scores were associated with pain or toxicities at any time point after donation based on the univariable analysis. Because of low rates of postdonation grade 2-4 pain and toxicities, multivariable analysis was not performed in the URD setting. Moreover, there was no correlation between preapheresis HRQoL score (PCS or MCS) and PBSC collection yield in either the RD or URD setting. Our study demonstrates that pre-donation HRQoL scores are significantly associated with the toxicity profile after PBSC donation in the RD setting, with adult RDs with lower predonation physical HRQoL experiencing higher levels of pain at 1 month and persisting up to 12 months after a PBSC collection procedure. There were no such associations found in URD. Our findings can help clinicians identify donors at higher risk of pain with donation, and lead to personalized information and interventions for specific donors. Lack of correlation between predonation HRQoL and stem cell yield may be due to a small sample size and warrants further evaluation.

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 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.

Breaking the Age Barrier: Physicians' Perceptions of Candidacy for Allogeneic Hematopoietic Cell Transplantation in Older Adults.

Despite continuing increases in the use of allogeneic hematopoietic cell transplantation (alloHCT) in older adults, no standardized geriatric assessment (GA) has been established to risk stratify for transplantation-related morbidity. We conducted a survey of transplant physicians to determine perceptions of the impact of older age (≥60 years) on alloHCT candidacy, and utilization of tools to gauge candidacy. This 23-item online cross-sectional survey was distributed to HCT physicians caring for adults in the United States between May and July 2019. Of the 770 invited HCT physicians, 175 (22.7%) completed the survey. The majority of respondents were age 41 to 60 years and male and practiced in a higher-volume teaching hospital. When considering regimen intensity, 29 physicians (17%) stated they would consider a myeloablative regimen for patients age ≥70 years, and 141 (82%) would consider reduced-intensity/nonmyeloablative conditioning for patients age ≥70 years. Almost all (90%) endorsed the need for a specialized assessment of pre-HCT vulnerabilities to guide candidacy decisions for older adults. Most physicians reported that their centers rarely (33%) or never (46%) use a dedicated geriatrician/geriatric-oncologist to assess alloHCT candidates age ≥60 years. Common barriers to performing a GA included uncertainty about which tools to use, lack of knowledge and training, and lack of appropriate clinical support staff. Many alloHCT physicians will consider alloHCT in patients up to age 75 years and not uncommonly in patients older than that. However, the application of tools and domains to assess candidacy in older adults varies widely. Incorporation of a standardized pretransplantation health assessment tool for risk stratification is a significant unmet need.

A Qualitative Analysis of State Medicaid Coverage Benefits for Allogeneic Hematopoietic Cell Transplantation (alloHCT) for Patients with Sickle Cell Disease (SCD).

Sickle cell disease (SCD) is the most common inherited hemoglobin disorder, affecting approximately 100,000 people in the United States. Allogeneic hematopoietic cell transplantation (alloHCT), also known as bone marrow transplant (BMT), is currently the only established curative option for SCD. However, alloHCT is an optional benefit under Medicaid. This study of alloHCT coverage for patients with SCD aims to understand the scope of state Medicaid coverage benefits and BMT financial coordinators' experience working with their state Medicaid programs. States estimated to have more than 50 newborns diagnosed with SCD in 2016 and at least one active BMT Clinical Trials Network (1503 [STRIDE 2], NCT02766465) transplant center (TC) were eligible to participate in this study. Qualitative, semi-structured interviews 30 to 60 minutes in length were conducted with BMT financial coordinators via telephone between May and October 2019. A total of 10 BMT financial coordinators from 10 TCs representing eight states (Florida, Georgia, Illinois, Michigan, New York, Pennsylvania, Texas, and Virginia) participated in the semi-structured interviews. Coordinators in all of the included states reported that alloHCT in children with SCD with a human leukocyte antigen-matched sibling donor was covered by their state Medicaid programs. However, only two states (Florida and Texas) had legislative policies mandating coverage of routine medical costs for patients in clinical trials. TCs in two states (Illinois and Pennsylvania) reported accepting out-of-state Medicaid insurance, but only one state (Michigan) covered both travel and lodging for the patient and one caregiver. Four themes emerged when coordinators were asked about their perspectives and experiences working with their corresponding state Medicaid programs: (1) state Medicaid eligibility criteria based on disability were perceived as being restrictive, and Medicaid reimbursement rates were reported to be low; (2) Medicaid fee-for-service plans were perceived as being more comprehensive and easier to navigate compared to comprehensive managed care (CMC) plans; (3) there is a need to address caregiver and financial assistance beyond the health care costs; and (4) completing the insurance authorization process leading up to alloHCT is critical, including peer-to-peer reviews. There is limited legislative policy to help ensure access to clinical trials and provide out-of-state benefits and travel and lodging for Medicaid enrollees with SCD. These data provide insight into potential areas that could influence changes in policy to enhance access to curative therapy for SCD.

Hematopoietic Cell Transplantation Outcomes among Medicaid and Privately Insured Patients with Sickle Cell Disease.

Compared with privately insured patients, recipients of Medicaid have been reported to have worse outcomes in several clinical conditions and following various surgical and medical procedures. However, the relationship between health insurance status and allogeneic hematopoietic cell transplantation (alloHCT) outcomes among patients with sickle cell disease (SCD) is not well described. We sought to compare alloHCT outcomes between patients with SCD who underwent alloHCT while enrolled on Medicaid versus those who underwent alloHCT while covered by private health insurance. We conducted a retrospective multicenter study using data reported to the Center for International Blood and Marrow Transplant Research. US patients enrolled on Medicaid or private insurance who underwent a first alloHCT for SCD between 2008 and 2018 were eligible for this study. The primary outcome was event-free survival (EFS), defined as time to death or graft failure. Secondary outcomes included overall survival (OS), graft failure, acute graft-versus-host disease (GVHD), and chronic GVHD. Univariate analysis was performed using the Kaplan-Meier method for EFS and OS. The proportion of patients with graft failure, acute GVHD, and/or chronic GVHD was calculated using the cumulative incidence estimator to accommodate competing risks (ie, death). Cox regression was used to identify factors associated with EFS, OS, graft failure, and acute and chronic GVHD. A total of 399 patients (Medicaid, n = 225; private insurance, n = 174) were included in this study. The median duration of follow-up was 34 months (range, 1.0 to 134.7 months) for the Medicaid group and 38.7 months (range, 0.3 to 139.3 months) for the private insurance group. Compared with the patients with private insurance, those on Medicaid had a significantly lower 3-year EFS (75.4% [95% confidence interval (CI), 69.4% to 81%] versus 82.2% [95% CI, 76.9% to 87.8%]; P = .0279) and a significantly higher 3-year cumulative incidence of graft failure (17.2% [95% CI, 12.5% to 22.5%] versus 10.5% [95% CI, 6.4% to 15.4%]; P = .0372). There were no significant between-group differences in 3-year OS (P = .6337) or in the cumulative incidence of acute GVHD (P = .4556) or chronic GVHD (P = .6878). Cox regression analysis after adjusting for other significant variables showed that the patients enrolled on Medicaid had a lower EFS (hazard ratio [HR], 2.36; 95% CI, 1.44 to 3.85; P = .0006) and a higher cumulative incidence of graft failure (HR, 2.57; 95% CI, 1.43 to 4.60; P = .0015), with no significant between-group differences in OS (HR, 0.99; 95% CI, 0.47 to 2.07; P = .9765), acute GVHD (HR, 0.94; 95% CI, 0.59 to 1.49; P = .7905), or cGVHD (HR, 0.98; 95% CI, 0.65 to 1.48; P = .9331). That EFS is worse in patients on Medicaid compared with privately insured individuals following alloHCT for SCD provides the rationale for research to better understand the mechanisms by which insurance status impacts alloHCT outcomes among patients with SCD.

Application and Evaluation of Survivorship Care Guides for Hematopoietic Cell Transplantation Recipients.

Hematopoietic cell transplantation (HCT) is a treatment for hematologic malignancies and disorders. Patients who receive HCT can face long-term physical and psychosocial effects. Survivorship care guides (care guides), which describe screening and preventive care practices were mailed to allogenic HCT recipients at clinically important timepoints (6, 12, and 24 months after HCT). The primary objective of this study was to evaluate how patients perceived and used the care guides. A cross-sectional, time-series survey was sent to all National Marrow Donor Program/Be The Match allogeneic HCT recipients from September 2012 to November 2016 after the care guides were sent; patients or caregivers could respond. Respondents who returned all 3 surveys were included (554 patients; 65 caregivers), for an overall response rate of 13% (maintenance rate of 45%). The majority of patients and caregivers strongly agreed or agreed that the care guides helped them understand that post-HCT care is important to staying healthy and that they were more familiar with recommended tests at check-up appointments. Most patients who did not share the care guides with their doctors at any of the timepoints believed their doctor knew which tests were needed. Results from this study can help inform and guide development of future tools and evaluations of educational resources for patients after HCT. Tools and educational resources, such as survivorship care guides, have the potential to help empower patients to be more knowledgeable and to understand and advocate for their survivorship care needs.

Healthcare Costs of Treating Privately Insured Patients with Acute Myeloid Leukemia in the United States from 2004 to 2014: A Generalized Additive Modeling Approach.

OBJECTIVES: The primary objective of this study was to predict healthcare cost trajectories for patients with newly diagnosed acute myeloid leukemia (AML) receiving allogeneic hematopoietic cell transplantation (alloHCT), as a function of days since chemotherapy initiation, days relative to alloHCT, and days before death or last date of insurance eligibility (LDE). An exploratory objective examined patients with AML receiving chemotherapy only. METHODS: We used Optum's de-identified Clinformatics® Data Mart Database to construct cumulative cost trajectories from chemotherapy initiation to death or LDE (through 31 December 2014) for US patients aged 20-74 years diagnosed between 1 March 2004 and 31 December 2013 (n = 187 alloHCT; n = 253 chemotherapy only). We used generalized additive modeling (GAM) to predict expected trajectories and bootstrapped confidence intervals (CIs) at user-specified intervals conditional on dates of alloHCT and death or LDE relative to chemotherapy initiation. RESULTS: Expected costs (in 2017 values) for a hypothetical patient receiving alloHCT 60 days after chemotherapy initiation and followed for 5 years were $US572,000 (95% CI 517,000-633,000); $US119,000 (95% CI 51,000-192,000); $US102,000 (95% CI 0-285,000); $US79,000 (95% CI 0-233,000), for years 1-4, respectively, and either $US494,000 (95% CI 212,000-799,000) or $US108,000 (95% CI 0-230,000) in year 5, whether the patient died or was lost to follow-up on day 1825, respectively. CONCLUSIONS: Rates of cost accrual varied over time since chemotherapy initiation, with accelerations around the time of alloHCT and death. GAM is a potentially useful approach for imputing longitudinal costs relative to treatment initiation and one or more intercurrent, clinical, or terminal events in randomized controlled trials or registries with unrecorded costs or for dynamic decision-analytic models.

Information Needs for Treatment Decision-making of Hematopoietic Cell Transplant Patients 65 Years or Older and Caregivers.

Hematopoietic cell transplantation (HCT) is a complex and potentially life-threatening treatment option for patients with hematologic malignant and non-malignant diseases. Advances have made HCT a potentially curative treatment option for patients 65 years of age and older (older patients), and patient education resources should be adapted to meet their needs. To better understand the information needs of older patients and their caregivers for HCT treatment decision-making, the National Marrow Donor Program® (NMDP)/Be The Match® conducted a qualitative comprehensive needs assessment. Focus groups, offered in person or by phone, were conducted with older HCT patients and primary caregivers of older HCT patients at three transplant centers in the USA that were selected based on the number of older adults treated and geographic diversity. The one-hour, semi-structured discussions were recorded and transcribed verbatim. The analysis was performed with the NVivo 10 software for identification of conceptual themes. Five telephone and six in person focus groups of patients (n = 35) and caregivers (n = 10) were conducted. Themes that emerged included the following: (1) the need for tailored resources with age-specific recovery expectations; (2) the need for the right amount of information at the right times; and (3) the benefit of peer support. Effective patient education supports learning and treatment decision-making. As HCT increasingly becomes a treatment option for older patients, tailored educational resources are needed. These focus group results can inform and guide the development of new educational resources for older adults with hematologic diseases considering and planning for HCT.

Engaging hematopoietic cell transplantation patients and caregivers in the design of print and mobile application individualized survivorship care plan tools.

PURPOSE: INSPIRE (INteractive Survivorship Program with Information and REsources) is an online health program that includes a mobile app, website, health action plan, and individualized survivorship care plans for adult hematopoietic cell transplant (HCT) survivors. The INSPIRE program integrates two previously effective randomized control trials that tested an internet-based program and patient-centered survivorship care plans for HCT survivors. METHODS: Three focus groups were conducted with a total of 22 participants (20 patients, 2 caregivers/patient advocates) to explore patient and caregiver preferences and to optimize the patient-centered emphasis of INSPIRE. Adult (age > 18 years at the time of study entry) HCT recipients had to be at least 1-year post-HCT to participate; caregivers/patient advocates were also eligible. Participants had to be able to communicate in English, could have any diagnosis, transplant type, or donor source, and could have had multiple transplants. RESULTS: All patient participants received an allogeneic HCT; average time since HCT was 8 years (range 2-22 years). The majority of participants were female (77.3%). Overall, the tools were well received by participants in this study, particularly the personalized features of all the tools. Major themes included interest in having the ability to tailor features to individual needs, and an interest in tracking information over time. DISCUSSION: Engaging patients and caregivers is invaluable to optimize tools designed to improve HCT survivorship care. Print, online, and mobile-based tools, tailored to individual patients' treatment history and requisite follow-up care, can provide otherwise unavailable expertise and guidelines for care.

Addressing Knowledge Gaps in Acute Myeloid Leukemia to Improve Referral for Hematopoietic Cell Transplantation Consultation.

BACKGROUND: Outcomes after hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) are better when HCT is performed during first complete remission (CR1). This study aimed to identify and address knowledge gaps that affect the timely referral of patients for HCT consultation. METHODS: A mixed-methods educational needs assessment included a national survey and focus groups consisting of hematologists/oncologists. An educational intervention of 3 webinars addressed identified knowledge gaps. RESULTS: A total of 150 hematologists/oncologists were recruited for the survey, of whom 20 participated in focus groups. Physicians in practice 0 to 10 years were 4.2 times more likely to refer for HCT consultation in CR1 than those with >10 years in practice (P=.0027). Physicians seeing ≤10 patients with AML in the past year were 3.7 times more likely to refer for HCT consultation in CR1 than those seeing >10 patients (P=.0028). Knowledge gaps included (1) improper classification of molecular/cytogenetic results for risk stratification, (2) lack of understanding that disease stage impacts outcomes, and (3) use of chronologic age alone for referral decision-making. Combined attendance for the webinars was 1,098 clinicians; >74% of participants indicated that they would apply the knowledge they gained in clinical practice. Trends were observed toward improvement in identifying favorable-risk AML, from 48% to 60% (n=85; P=.12); improvement in identifying 2 poor-risk cytogenetic/molecular abnormalities, with the percentage of respondents indicating chromosome 7 deletion increasing from 51% to 70% (n=53; P=.05) and that of respondents indicating TP53 mutation increasing from 42% to 62% (n=62; P=.03); and improvement in identifying which patients with AML aged >60 years were most likely to benefit from HCT based on cytogenetic/molecular features, with the percentage of correct responses increasing from 66% to 81% (n=62; P=.07). CONCLUSIONS: The webinars met the educational needs of learners and improved knowledge gaps. This study provided novel insights into the learning needs of clinicians who care for patients with AML and a roadmap for future educational interventions.

Reimbursement, Utilization, and 1-Year Survival Post-Allogeneic Transplantation for Medicare Beneficiaries With Acute Myeloid Leukemia.

BACKGROUND: The economics of allogeneic hematopoietic cell transplantation (alloHCT) for older patients with acute myeloid leukemia (AML) affects clinical practice and public policy. To assess reimbursement, utilization, and overall survival (OS) up to 1 year post-alloHCT for Medicare beneficiaries aged 65 years or older with AML, a unique merged dataset of Medicare claims and national alloHCT registry data was analyzed. METHODS: Patients diagnosed with AML undergoing alloHCT from 2010 to 2011 were included for a retrospective cohort analysis with generalized linear model adjustment. One-year post-alloHCT reimbursement included Medicare, secondary payer, and beneficiary copayments (no coinsurance) (inflation adjusted to 2017 dollars). Cost-to-charge ratios were applied to estimate department-specific inpatient costs. Cox proportional hazards regression models were utilized to identify risk factors of 1-year OS post-alloHCT. RESULTS: A total of 250 patients met inclusion criteria. Mean total reimbursement was $230 815 (95% confidence interval [CI] = $214 381 to $247 249) 1 year after alloHCT. Pharmacy was the most- costly inpatient service category. Adjusted mean total reimbursement was statistically higher for patients who received cord blood grafts (P = .01), myeloablative conditioning (P < .0001), and alloHCT in the Northeast and West (P = .03). Mortality increased with age (hazard ratio [HR] = 1.08, 95% CI = 1.0 to 1.17), poorer Karnofsky performance score (<90% vs ≥90%, HR = 1.60, 95% CI = 1.08 to 2.35), and receipt of myeloablative conditioning (HR = 1.88, 95% CI = 1.21 to 2.92). CONCLUSIONS: This merged dataset allowed adjustment for a richer set of patient- and HCT-related characteristics than claims data alone. The finding that nonmyeloablative conditioning was associated with lower reimbursement and improved OS 1 year post-alloHCT warrants further investigation.

Caregiver availability and patient access to hematopoietic cell transplantation: social worker perspectives inform practice.

PURPOSE: Hematopoietic cell transplantation (HCT) often involves a long hospitalization and recovery period, with patients generally required to have a caregiver. This study aimed to identify transplant center (TC) requirements for a caregiver, describe challenges that impact caregiver availability, and identify potential solutions. METHODS: An exploratory sequential mixed-methods approach was used. Qualitative data was obtained from focus groups of TC social workers in the United States (US) (three focus groups; n = 15 total participants). Results informed the development of a national, web-based survey that was administered to the primary social worker contact at TCs in the National Marrow Donor Program (NMDP)/Be The Match Network (n = 133). RESULTS: Respondents included social workers from adult (n = 47) and pediatric (n = 19) TCs (response rate = 49%). The majority (89%) of both adult and pediatric TCs required a caregiver for a patient to proceed to transplant, but requirements varied in length of time, formality, transplant type, and HCT setting. Regardless of transplant type or patient population, social workers identified loss of caregiver income as the greatest challenge to caregiver availability, with the most common solution being allowing patients to have multiple caregivers throughout the transplant course. DISCUSSION: Caregiver availability is an important concern for patients considering and receiving HCT, and may be a barrier proceeding to HCT when a caregiver is unavailable. Results from this study highlight caregiver availability barriers and solutions of TCs across the US. These results can inform TCs about other center experiences with caregiver availability and identify potential practice changes for individual TCs.