Hematopoietic Stem-Cell Transplantation: Exploring the Latest Advances and Gaps in Disparities, Psychosocial and Symptom Management Interventions, and Chronic Graft-Versus-Host Disease Care.

Although allogeneic hematopoietic cell transplantation (HCT) offers a potential for cure for many patients with advanced hematologic malignancies and bone marrow failure or immunodeficiency syndromes, it is an intensive treatment and accompanied by short- and long-term physical and psychological symptoms requiring specialized care. With substantial advances in therapeutic approaches for HCT and supportive care, HCT survivors experience less morbidity and mortality. However, disparities in both HCT access and outcomes persist, and HCT survivors and their caregivers often lack access to much-needed psychosocial care. Additionally, more medical and psychosocial resources are needed to holistically care for HCT survivors with chronic graft-versus-host disease (GVHD). Hence, this chapter focuses on three areas pertaining to advances and gaps in HCT care: disparities in access to and outcomes of HCT, psychosocial and physical symptom management with supportive care interventions, and GVHD prevention and management.

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.

Projected Impact of Omidubicel-onlv on Racial/Ethnic Disparities in Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) Outcomes in Hematologic Malignancies.

INTRODUCTION: In a phase III clinical trial (NCT02730299), omidubicel-onlv, a nicotinamide-modified allogeneic hematopoietic progenitor cell therapy, showed rapid hematopoietic and immune recovery compared with standard umbilical cord blood (UCB) transplant across all racial/ethnic groups. METHODS: A decision-tree model was used to project the effect of omidubicel-onlv availability on addressing health disparities in allogeneic hematopoietic cell transplantation (allo-HCT) access and outcomes for patients with hematologic malignancies. The model used a hypothetical population of 10,000 allo-HCT-eligible US adults, for whom matched related donors were not available. Patients received matched or mismatched unrelated donor, haploidentical, UCB transplant, or no transplant. Scenarios with omidubicel-onlv use of 0% (status quo), 10%, 15%, 20%, and 30% were modeled on the basis of proportional reductions in other allo-HCT sources or no transplant by racial/ethnic group. RESULTS: Increased omidubicel-onlv use was associated with a higher proportion of patients undergoing allo-HCT, decreased time to allo-HCT, decreased 1-year non-relapse mortality, and increased 1-year overall survival, particularly among racial minorities. In the scenario modeling 20% omidubicel-onlv use, the proportion of Black patients receiving allo-HCT increased by 129%; increases were also observed in Asian (64%), Hispanic (45%), and other (42%) patient groups. Modeled time to allo-HCT improved among transplanted patients (23%) from 11.4 weeks to 8.8 weeks. One-year OS in the overall population increased by 3%, with improvements ranging from 3% for White patients to 5% for Black patients. CONCLUSION: This study demonstrates that broad access to omidubicel-onlv could increase access to allo-HCT and improve outcomes for patients, with the greatest benefits seen among racial/ethnic minority groups.

Family-Focused Facilitated Fitness: Feasibility and Acceptability of a Couple-Based Physical Activity Intervention for Hematopoietic Cell Transplant Recipients and Their Caregiving Partners.

Reductions in physical activity (PA) are common among patients following hematopoietic cell transplantation, and a risk factor for poor physical functioning. PA among spouses/cohabiting partners, who frequently serve as the patient's primary caregiver, may also be reduced due to caregiving demands and limited bandwidth for self-care. In addition, the patient-caregiver relationship can be compromised, and communication patterns disrupted. All PA interventions in the hematopoietic cell transplantation setting have focused entirely on patients, ignoring an opportunity to synergistically engage and benefit the caregiver as well. We sought to test feasibility and acceptability of a couple-based intervention entitled Family-Focused Facilitated Fitness (FFFF), designed to improve PA as assessed by daily step counts among both patients undergoing hematopoietic cell transplantation and their caregivers. Guided by interdependence and communal coping perspectives, FFFF is an 8-week, remotely-delivered intervention that provides training in communication skills and joint problem-solving to help patients and caregivers support one another in PA. Participants are also given a Fitbit to track their steps and weekly individualized step prescription based on the 75th percentile ranked value of their last 7 recorded daily step counts. A priori benchmarks for feasibility and acceptability in this single-arm pilot were as follows: 50% of eligible couples would agree to participate, 70% of couples would attend all 8 sessions, 80% of participants would provide valid Fitbit wear data 4/7 days/ week, and among sessions reviewed for treatment fidelity, 85% of treatment protocol elements would be covered. Couples were recruited prior to transplant. Among 26 couples approached and deemed eligible, 17 enrolled (65% agreement) and completed baseline assessment. Three couples later withdrew after transplantation but prior to receiving the intervention, resulting in 14 couples commencing the intervention, on average 21 days post-transplant. Four couples subsequently discontinued due to medical complications (n = 3) or caregiver schedule (n = 1). Among the 10 couples who completed the intervention, the percentage of participants meeting our benchmark of valid Fitbit wear at least 4 days per week was 85% in week 1, 90% in weeks 2 to 7, and 80% in week 8. Treatment fidelity was 95% on average across 24 sessions reviewed (3 cases). Treatment satisfaction scores were uniformly high across multiple dimensions, with all means above 4 on the 1 to 5 scale. Daily step counts among those attending all 8 intervention sessions increased from 2249 ± 302 steps/day in week 1 to 4975 ± 1377 steps/day in week 8 among patients, and from 8676 ± 3760 steps/day in week 1 to 9838 ± 3723 steps/day in week 8 among caregivers. Qualitative feedback indicated perceived mental and physical health benefits of the program. Participants also offered suggestions for adaptations to accommodate medical setbacks and constraints. All a priori feasibility benchmarks were met or exceeded. Results offer promise for utility of the program to engage and leverage patient-caregiver dyads to increase PA following transplant. An investigation using a randomized controlled design will be necessary to adequately examine change over time relative to control and its possible impact on clinical and patient-reported outcomes.

Lung Injury Prediction Model in Bone Marrow Transplantation: A Multicenter Cohort Study.

Rationale: Pulmonary complications contribute significantly to nonrelapse mortality following hematopoietic stem cell transplantation (HCT). Identifying patients at high risk can help enroll such patients into clinical studies to better understand, prevent, and treat posttransplantation respiratory failure syndromes. Objectives: To develop and validate a prediction model to identify those at increased risk of acute respiratory failure after HCT. Methods: Patients underwent HCT between January 1, 2019, and December 31, 2021, at one of three institutions. Those treated in Rochester, MN, formed the derivation cohort, and those treated in Scottsdale, AZ, or Jacksonville, FL, formed the validation cohort. The primary outcome was the development of acute respiratory distress syndrome (ARDS), with secondary outcomes including the need for invasive mechanical ventilation (IMV) and/or noninvasive ventilation (NIV). Predictors were based on prior case-control studies. Measurements and Main Results: Of 2,450 patients undergoing stem cell transplantation, there were 1,718 hospitalizations (888 patients) in the training cohort and 1,005 hospitalizations (470 patients) in the test cohort. A 22-point model was developed, with 11 points from prehospital predictors and 11 points from posttransplantation or early (<24-h) in-hospital predictors. The model performed well in predicting ARDS (C-statistic, 0.905; 95% confidence interval [CI], 0.870-0.941) and the need for IMV and/or NIV (C-statistic, 0.863; 95% CI, 0.828-0.898). The test cohort differed markedly in demographic, medical, and hematologic characteristics. The model also performed well in this setting in predicting ARDS (C-statistic, 0.841; 95% CI, 0.782-0.900) and the need for IMV and/or NIV (C-statistic, 0.872; 95% CI, 0.831-0.914). Conclusions: A novel prediction model incorporating data elements from the pretransplantation, posttransplantation, and early in-hospital domains can reliably predict the development of post-HCT acute respiratory failure.

Venetoclax and hypomethylating agent combination therapy in newly diagnosed acute myeloid leukemia: Genotype signatures for response and survival among 301 consecutive patients.

Venetoclax + hypomethylating agent (Ven-HMA) is currently the standard frontline therapy for older/unfit patients with newly diagnosed acute myeloid leukemia (ND-AML). Our objective in the current retrospective study of 301 adult patients (median age 73 years; 62% de novo) with ND-AML was to identify molecular predictors of treatment response to Ven-HMA and survival; European LeukemiaNet (ELN) genetic risk assignment was favorable 15%, intermediate 16%, and adverse 69%. Complete remission, with (CR) or without (CRi), count recovery, was documented in 182 (60%) patients. In multivariable analysis, inclusive of mutations only, "favorable" predictors of CR/CRi were NPM1 (86% vs. 56%), IDH2 (80% vs. 58%), and DDX41 (100% vs. 58%) and "unfavorable" TP53 (40% vs. 67%), FLT3-ITD (36% vs. 63%), and RUNX1 (44% vs. 64%) mutations; significance was sustained for each mutation after adjustment for age, karyotype, and therapy-related qualification. CR/CRi rates ranged from 36%, in the presence of unfavorable and absence of favorable mutation, to 91%, in the presence of favorable and absence of unfavorable mutation. At median follow-up of 8.5 months, 174 deaths and 41 allogeneic stem cell transplants (ASCT) were recorded. In multivariable analysis, risk factors for inferior survival included failure to achieve CR/CRi (HR 3.4, 95% CI 2.5-4.8), adverse karyotype (1.6, 1.1-2.6), TP53 mutation (1.6, 1.0-2.4), and absence of IDH2 mutation (2.2, 1.0-4.7); these risk factors were subsequently applied to construct an HR-weighted risk model that performed better than the ELN genetic risk model (AIC 1661 vs. 1750): low (n = 130; median survival 28.9 months), intermediate (n = 105; median 9.6 months), and high (n = 66; median 3.1 months; p < .001); survival in each risk category was significantly upgraded by ASCT. The current study identifies genotype signatures for predicting response and proposes a 3-tiered, CR/CRi-based, and genetics-enhanced survival model for AML patients receiving upfront therapy with Ven-HMA.

TP53 variant allele frequency and therapy-related setting independently predict survival in myelodysplastic syndromes with del(5q).

Among 210 patients with myelodysplastic syndromes (MDSs) with del(5q), molecular information was available at diagnosis or at least 3 months before leukaemic transformation in 146 cases. Multivariate analysis identified therapy-related setting (p = 0.02; HR 2.3) and TP53 variant allele frequency (VAF) ≥22% (p < 0.01; HR 2.8), but not SF3B1 mutation (p = 0.65), as independent risk factors for survival. Median survival was 11.7 versus 4 years (5/10-year survival 73%/52% vs. 42%/14%) in the absence (N = 112) versus presence (N = 34) of ≥1 risk factors; leukaemia-free survival was affected by TP53 VAF ≥22% (p < 0.01). Such information might inform treatment decision-making in MDS-del(5q) regarding allogeneic stem cell transplant.

Reappraisal of mast cell leukemia based on a single institution review of 16 cases: Mast cell morphology determines clinical outcome.

Cytologic abnormalities of atypical mast cells in mastocytosis. The mature mast cells have oval-shaped nuclei, cytoplasmic hypogranulation and spindle-shaped cytology. or well-differentiated displaying a round nucleus with condensed chromatin, and abundant dense cytoplasmic granulations. Immature mast cells include promastocytes and metachromatic blast-like forms.

Venetoclax duration (14 vs. 21 vs. 28 days) in combination with hypomethylating agent in newly diagnosed acute myeloid leukemia: Comparative analysis of response, toxicity, and survival.

Overall survival and response rates of 270 patients with newly diagnosed acute myeloid leukemia receiving venetoclax (Ven) plus hypomethylating agent, stratified by Ven dosing schedule (Cycle 1 Ven 14 vs. 21 vs. 28 days).

Financial hardship for patients with cancer and caregivers at end of life in the USA: narrative review.

BACKGROUND: Patients and their families face financial hardship during cancer treatment, which may intensify at end of life (EOL) due to increased symptoms and care needs. We undertook a narrative literature review to describe the current understanding of the causes, impacts and factors associated with financial hardship at EOL. We identify gaps in research, policy and clinical practice and propose steps to mitigate financial hardship for patients and caregivers at EOL. METHODS: We conducted a Medline search to identify US studies since 2000 that examined EOL financial hardship for patients with cancer and their caregivers. RESULTS: Twenty-seven adult and four paediatric studies met review criteria. Adults with cancer and their caregivers face significant financial hardship at EOL and in bereavement, especially due to employment changes and informal caregiving time costs. Financial hardship may be higher for younger caregivers and for patients who are uninsured, low income, rural, with high symptom burdens or with certain cancer types. The few paediatric studies showed high financial hardship and employment impact lasting well beyond a child's death. CONCLUSIONS: There is limited literature examining financial hardship at EOL in the USA, especially in paediatrics. Priorities for future research include longitudinal studies in diverse populations of patients with cancer and informal caregivers using standardised financial hardship measures. Policies to address financial hardship at EOL, especially with hospice care, should include insurance coverage for family caregiving and medical leave policies. There is need for increased financial hardship screening at EOL and in bereavement and a need for financial navigation interventions.

Exploring social determinants of health and physical activity levels in older adults living with mild cognitive impairment and dementia in the Upper Midwest of the United States.

BACKGROUND: Physical activity can improve physical health for people living with mild cognitive impairment (MCI) and dementia and may have cognitive benefits. Identifying modifiable social factors inhibiting physical activity among this group is needed. We sought to examine the relationship between reported physical activity levels and social determinants of health (SDOH) in a population of older adults living with MCI or dementia. METHODS: This descriptive study included people with a diagnosis of MCI or dementia followed by Community Internal Medicine at Mayo Clinic (Rochester, Minnesota, United States), aged over 55 years, who had a clinic visit between June 1, 2019 and June 30, 2021 and had completed a SDOH questionnaire. We focused on 8 SDOH domains: education, depression, alcohol use, stress, financial resource strain, social connections, food insecurity, and transportation needs. Data were analyzed based on physical activity level (inactive, insufficiently active, sufficiently active). SDOH domains were compared according to physical activity level using the χ2 test and multinomial logistic regression. RESULTS: A total of 3224 persons with MCI (n = 1371) or dementia (n = 1853) who had completed questions on physical activity were included. Of these, 1936 (60%) were characterized as physically inactive and 837 (26%) insufficiently active. Characteristics associated with an increased likelihood of physical inactivity were older age, female sex, obesity, lower education, dementia diagnosis, screening positive for depression and increased social isolation (p < 0.001). CONCLUSIONS: Physical inactivity is common among people living with MCI and dementia. Physical activity levels may be influenced by many factors, highlighting potential areas for intervention.

Proceedings of the 2023 Second Annual ASTCT-NMDP ACCESS Initiative Workshop.

Here the proceedings from the Second Annual American Society for Transplantation and Cellular Therapy (ASTCT) and National Marrow Donor Program (NMDP) ACCESS Initiative are reviewed to inform the hematopoietic cell transplantation (HCT) and cellular therapy (CT) ecosystem about progress and direction of the collaborative. Highlights from the meeting, including updates on the progress of projects from the Awareness, Poverty, and Racial Inequity Committees, are presented. The ACCESS Initiative continues to evolve and will remain dependent on the HCT/CT ecosystem's continued dedication to reduce barriers and improve outcome disparities for all patients in need of HCT/CT.

Allogeneic hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: a CIBMTR analysis.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes.

Relationships Among Health Insurance Literacy, Financial Toxicity, and Sociodemographic Factors in Patients With Cancer.

PURPOSE: The objective of the study was to describe the prevalence of health insurance literacy (HIL) and investigate how patient-reported outcome measures assessing HIL are related to financial toxicity in patients with cancer. METHODS: We assessed HIL and financial toxicity in 404 patients enrolled between December 2019 and January 2021 at two medical centers in the United States. We conducted exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to explore and test the relationships among the factors and items. We fit structural equation models (SEMs) to find the relationships among the factors and sociodemographic/clinical characteristics. RESULTS: The EFA revealed items loaded on four factors: knowledge about health insurance, confidence related to HIL (HIL confidence), information-seeking behavior related to health insurance, and financial toxicity. The four-factor CFA model had good fit statistics (comparative fit index, 0.960; Tucker-Lewis index, 0.958; root mean square error of approximation, 0.046; and standardized root mean square residual, 0.086). In SEM, income, education level, and race positively predicted knowledge about health insurance. Knowledge about health insurance and number of total lines of cancer treatment was positively associated with HIL confidence. Higher income, older age, and HIL confidence were associated with less financial toxicity. Higher levels of financial toxicity, HIL confidence, and knowledge were associated with greater information-seeking behavior. CONCLUSION: Our findings showed how different aspects of HIL are related to financial toxicity even after adjustment for sociodemographic and clinical characteristics. Future studies should investigate the longitudinal relationships among these factors to help develop interventions to mitigate financial toxicity.

Financial Hardship in Childhood Cancer Survivors Treated with Hematopoietic Cell Transplantation: A Report from the Childhood Cancer Survivor Study.

Long-term survivors of childhood cancer are at risk for financial hardship. However, it is not known if HCT leads to an incremental change in financial hardship for survivors who received it versus those who did not. We examined financial outcomes among adult survivors of childhood cancer who had undergone HCT. Using a cross-sectional survey in the Childhood Cancer Survivor Study population between 2017 and 2019, self-reported financial hardship was compared between survivors who received HCT, survivors treated without HCT ("non-HCT"), and siblings and categorized into 3 domains: material hardship/financial sacrifices, behavioral, and psychological hardship. The standardized score of each domain of financial hardship was calculated by adding the item responses and dividing by the standard deviation among siblings. Multivariable linear and logistic regression were used to evaluate associations between sociodemographic characteristics, cancer diagnosis, post-treatment complications, and financial hardship among survivors. The mean adjusted score for each hardship domain was not significantly different between HCT survivors (n = 133) and non-HCT survivors (n = 2711); mean differences were .18 (95% confidence interval [CI], -.05 to .41) for material hardship/financial sacrifices, .07 (95% CI, -.18 to .32) for behavioral hardship, and .19 (95% CI, -.04 to .42) for psychological hardship. Within specific items, a higher proportion of survivors treated with HCT reported greater financial hardship compared to non-HCT survivors. HCT survivors also had significantly higher mean domain scores compared to sibling controls (n = 1027) in all domains. Household income and chronic health conditions, but not HCT, were associated with financial hardship among all survivors. Adult survivors of childhood cancer treated with HCT do not report greater overall financial hardship compared to non-HCT survivors but do report greater overall financial hardship compared to sibling controls. Surveillance and intervention may be necessary for all survivors regardless of HCT status.

Assessing Medicaid Coverage for Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy: A Project from the American Society for Transplantation and Cellular Therapy and the National Marrow Donor Program ACCESS Initiative.

The American Society for Transplantation and Cellular Therapy (ASTCT) and the National Marrow Donor Program (NMDP) formed the ACCESS Initiative to address and reduce barriers to hematopoietic cell transplantation (HCT) and cellular therapy (CT) to ensure equal access and outcomes for all patients in need. The 3 committees, addressing awareness, poverty, and racial and ethnic inequity, defined pilot projects focusing on addressing relevant barriers to HCT/CT. Because many socioeconomically disadvantaged HCT/CT recipients receive care through state Medicaid programs, the Poverty Committee conducted a Medicaid scan of all 50 US states with the following objectives: to define beneficiary coverage for allogeneic and autologous HCT and chimeric antigen receptor (CAR) T cell therapy; to define support for travel, temporary lodging, and meals for both beneficiaries and caregivers; and to determine search and cell acquisition payment procedures. Here we summarize the results of the Medicaid scan and highlight significant variations and gaps in coverage for HCT/CT recipients. We also provide an initial roadmap for addressing gaps in Medicaid support for HCT and CAR-T therapy recipients.

Multiple Myeloma: Current Clinical Landscape and Compounding Costs.

PURPOSE OF REVIEW: The treatment landscape of multiple myeloma (MM) has evolved resulting in MM becoming a chronic condition. The costs of MM therapies are substantial and compound as patients remain on long-term maintenance therapies and progress through multiple lines of high-cost therapies. MM predominantly impacts the elderly population insured by Medicare; here, we analyze how these costs impact patients and the Medicare trust fund. RECENT FINDINGS: With the recent passing of the Inflation Reduction Act (IRA), we postulate how costs may be impacted and debate future policy initiatives that may result in sustainability. The IRA will impact drug pricing and likely reduce the costs of some treatments used in MM; there is still a lot of room for policy reform to reduce financial toxicity to patients and prevent depletion of the Medicare trust fund.