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Sickle cell disease (SCD) is a lifelong burdensome disorder of heterogenic expression. This study investigated the longer-term economic burden of severe presentation of SCD. As SCD treatment landscapes evolve toward curative intent gene therapies, understanding how SCD-associated costs may change over the patient lifetime will be important for medical decision-making. Patients with severe presentation of SCD (presence of acute vaso-occlusive events [VOEs] or history of stroke and/or other disease-related sequelae), were identified within the MarketScan Commercial and Medicare Supplemental and Multi-state Medicaid Databases from 1/1/2010 to 12/31/2018. The first SCD claim served as the index date and patients were followed over a 5-year post-period. Clinical characteristics and healthcare resource utilization and costs were assessed over follow-up for eligible cohorts of commercial and Medicaid patients with severe SCD presentation and age-based subgroups (via Medicaid (79.2%), qualified for the analysis. Patients evidenced persistent VOEs over follow-up; prevalence of most comorbidities increased with age. Mean total healthcare costs over the 5-year follow-up were $275,143 (SD± $406,770) and $362,728 (SD± $620,189) in the commercial and Medicaid samples, respectively. Disease severity, assessed by the number of VOEs and utilization of inpatient and emergency services, peaked in the 18–30 year group in both samples. These groups also evidenced the highest mean healthcare costs over the 5-year follow-up at $344,776 (SD± $434,521) and $671,321 (SD± $938,764) in the commercial and Medicaid samples respectively. Results indicate high clinical need and economic burden among patients with severe presentation of SCD. These findings not only highlight the need for improved therapeutic options to limit or prevent disease progression, but also start to provide insight on lifetime costs of SCD that will be needed in the evaluation of emerging curative intent therapies.

Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassemia. However, the role that adherence to ICT plays in health-related outcomes is less well known. Our objectives were to identify adherence rates of ICT, and to assess methods of measurement, predictors of adherence, and adherence-related health outcomes in the literature published between 1980 and 2020. Of 543 articles, 43 met the inclusion criteria. Studies measured ICT adherence, predictors, and/or outcomes associated with adherence. Most studies were across multiple countries in Europe and North America (

The medical needs of individuals with sickle cell disease (SCD) are complex. Patients with SCD experience complications such as recurrent pain episodes and increased hospitalizations. Over 70% of AYA and their parents seek medical information from the Internet; 83% inquire on sites that have interactive/social features, such as Facebook or Twitter, yet accuracy remains unclear. Our objective was to assess the accuracy of the SCD-information posted on social media. We hypothesized that most of the posted information is inaccurate. We coded one month of threads from two common SCD Facebook groups (Sickle Cell Warriors Unity and Sickle Cell Anemia) to identify the purpose of each post and the accuracy of medical information posted. Amongst both social media sites, there were 487 posts. Most of the posts were directed toward socializations (

Purpose To examine the relations between patient-reported outcomes (PROs) within a conceptual model for adults with sickle cell disease (SCD) ages 18 – 45 years enrolled in the multi-site Sickle Cell Disease Implementation Consortium (SCDIC) registry. We hypothesized that patient and SCD-related factors, particularly pain, and barriers to care would independently contribute to functioning as measured using PRO domains. Methods Participants (N = 2054) completed a 48-item survey including socio-demographics and PRO measures, e.g., social functioning, pain impact, emotional distress, and cognitive functioning. Participants reported on lifetime SCD complications, pain episode frequency and severity, and barriers to healthcare. Results Higher pain frequency was associated with higher odds of worse outcomes in all PRO domains, controlling for age, gender and site (OR range 1.02–1.10, 95% CI range [1.004–1.12]). Reported history of treatment for depression was associated with 5 of 7 PRO measures (OR range 1.58–3.28 95% CI range [1.18–4.32]). Fewer individual barriers to care and fewer SCD complications were associated with better outcomes in the emotion domain (OR range 0.46–0.64, 95% CI range [0.34–0.86]). Conclusions Study results highlight the importance of the biopsychosocial model to enhance understanding of the needs of this complex population, and to design multi-dimensional approaches for providing more effective interventions to improve outcomes.

It is not known whether obesity has a differential effect on allogeneic haematopoietic cell transplantation outcomes with alternative donor types. We report the results of a retrospective registry study examining the effect of obesity [body mass index (BMI) 30] on outcomes with alternative donors (haploidentical related donor with two or more mismatches and receiving post-transplant cyclophosphamide [haplo] and cord blood (CBU)] versus matched unrelated donor (MUD). Adult patients receiving haematopoietic cell transplantation for haematologic malignancy (2013-2017) (N = 16 182) using MUD (n = 11 801), haplo (n = 2894) and CBU (n = 1487) were included. The primary outcome was non-relapse mortality (NRM). The analysis demonstrated a significant, non-linear interaction between pretransplant BMI and the three donor groups for NRM: NRM risk was significantly higher with CBU compared to haplo at BMI 25-30 [hazard ratio (HR) 1.66-1.71, p 0.05] and MUD transplants at a BMI of 25-45 (HR, 1.61-3.47, p 0.05). The results demonstrated that NRM and survival outcomes are worse in overweight and obese transplant recipients (BMI ≥ 25) with one alternative donor type over MUD, although obesity does not appear to confer a uniform differential mortality risk with one donor type over the other. BMI may serve as a criterion for selecting a donor among the three (MUD, haplo and CBU) options, if matched sibling donor is not available.

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.

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.

The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients. However, clinical trials employing auto-HSCT followed by lenalidomide maintenance have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in MM patients following auto-HSCT using CIBMTR registry data. Adult MM patients who underwent first auto-HSCT in the United States with melphalan conditioning regimen from 2011 to 2018 and received maintenance therapy were included (n=3,948). At a median follow up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (HR 2.62, P

Background eHealth tools such as patient portals and personal health records, also known as patient-centered digital health records, can engage and empower individuals with chronic health conditions. Patients who are highly engaged in their care have improved disease knowledge, self-management skills, and clinical outcomes. Objective We aimed to systematically review the effects of patient-centered digital health records on clinical and patient-reported outcomes, health care utilization, and satisfaction among patients with chronic conditions and to assess the feasibility and acceptability of their use. Methods We searched MEDLINE, Cochrane, CINAHL, Embase, and PsycINFO databases between January 2000 and December 2021. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Eligible studies were those evaluating digital health records intended for nonhospitalized adult or pediatric patients with a chronic condition. Patients with a high disease burden were a subgroup of interest. Primary outcomes included clinical and patient-reported health outcomes and health care utilization. Secondary outcomes included satisfaction, feasibility, and acceptability. Joanna Briggs Institute critical appraisal tools were used for quality assessment. Two reviewers screened titles, abstracts, and full texts. Associations between health record use and outcomes were categorized as beneficial, neutral or clinically nonrelevant, or undesired. Results Of the 7716 unique publications examined, 81 (1%) met the eligibility criteria, with a total of 1,639,556 participants across all studies. The most commonly studied diseases included diabetes mellitus (37/81, 46%), cardiopulmonary conditions (21/81, 26%), and hematology-oncology conditions (14/81, 17%). One-third (24/81, 30%) of the studies were randomized controlled trials. Of the 81 studies that met the eligibility criteria, 16 (20%) were of high methodological quality. Reported outcomes varied across studies. The benefits of patient-centered digital health records were most frequently reported in the category health care utilization on the “use of recommended care services” (10/13, 77%), on the patient-reported outcomes “disease knowledge” (7/10, 70%), “patient engagement” (13/28, 56%), “treatment adherence” (10/18, 56%), and “self-management and self-efficacy” (10/19, 53%), and on the clinical outcome “laboratory parameters,” including HbA1c and low-density lipoprotein (LDL; 16/33, 48%). Beneficial effects on “health-related quality of life” were seen in only 27% (4/15) of studies. Patient satisfaction (28/30, 93%), feasibility (15/19, 97%), and acceptability (23/26, 88%) were positively evaluated. More beneficial effects were reported for digital health records that predominantly focus on active features. Beneficial effects were less frequently observed among patients with a high disease burden and among high-quality studies. No unfavorable effects were observed. Conclusions The use of patient-centered digital health records in nonhospitalized individuals with chronic health conditions is potentially associated with considerable beneficial effects on health care utilization, treatment adherence, and self-management or self-efficacy. However, for firm conclusions, more studies of high methodological quality are required. Trial Registration PROSPERO (International Prospective Register of Systematic Reviews) CRD42020213285; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=213285

Infertility secondary to chemotherapy, myeloablative conditioning regimens prior to stem cell transplantation, radiation therapy, and/or surgery is an important cause of morbidity and psychosocial distress among pediatric cancer patients. Known options exist for fertility preservation; however, knowledge among providers varies. We conducted a pilot study with an educational intervention over one-hour for hematology-oncology faculty, fellows, and advanced practice providers. Participants completed pre-/post-test assessment on fertility preservation knowledge. Participants' pretest mean (SD) score was 53% (17%), which significantly increased to 72% (11%) in the post-test (p = 0.0004). We demonstrated that a fertility education intervention could improve knowledge regarding infertility risk assessment and fertility preservation options.

Background Hydroxyurea therapy is effective for reducing complications related to sickle cell disease (SCD) and is recommended by National Health Lung and Blood Institute care guidelines. However, hydroxyurea is underutilized, and adherence is suboptimal. We wanted to test a multilevel mobile health (mHealth) intervention to increase hydroxyurea adherence among patients and improve prescribing among providers in a multicenter clinical trial. In the first 2 study sites, participants were exposed to the early phases of the COVID-19 pandemic, which included disruption to their regular SCD care. Objective We aimed to describe the impact of the COVID-19 pandemic on the implementation of an mHealth behavioral intervention for improving hydroxyurea adherence among patients with SCD. Methods The first 2 sites initiated enrollment 3 months prior to the start of the pandemic (November 2019 to March 2020). During implementation, site A clinics shut down for 2 months and site B clinics shut down for 9 months. We used the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework to evaluate the implementation and effectiveness of the intervention. mHealth implementation was assessed based on patients’ daily app use. Adherence to hydroxyurea was calculated as the proportion of days covered (PDC) from prescription records over the first 12 and 24 weeks after implementation. A linear model examined the relationship between app usage and PDC change, adjusting for baseline PDC, lockdown duration, and site. We conducted semistructured interviews with patients, health care providers, administrators, and research staff to identify factors associated with mHealth implementation and effectiveness. We used a mixed methods approach to investigate the convergence of qualitative and quantitative findings. Results The percentage of patients accessing the app decreased after March 15, 2020 from 86% (n=55) to 70% (n=45). The overall mean PDC increase from baseline to week 12 was 4.5% (P=.32) and to week 24 was 1.5% (P=.70). The mean PDC change was greater at site A (12 weeks: 20.9%; P=.003; 24 weeks: 16.7%; P=.01) than site B (12 weeks: −8.2%; P=.14; 24 weeks: −10.3%; P=.02). After adjustment, PDC change was 13.8% greater in those with increased app use after March 15, 2020. Interview findings indicated that site B’s closure during COVID-19 had a greater impact, but almost all patients reported that the InCharge Health app helped support more consistent medication use. Conclusions We found significant impacts of the early clinic lockdowns, which reduced implementation of the mHealth intervention and led to reduced patient adherence to hydroxyurea. However, disruptions were lower among participants who experienced shorter clinic lockdowns and were associated with higher hydroxyurea adherence. Investigation of added strategies to mitigate the effects of care interruptions during major emergencies (eg, patient coaching and health navigation) may “insulate” the implementation of interventions to increase medication adherence. Trial Registration ClinicalTrials.gov NCT04080167; https://clinicaltrials.gov/ct2/show/NCT04080167 International Registered Report Identifier (IRRID) RR2-10.2196/16319

Social determinants of health, including poverty, contribute significantly to health outcomes in the United States; however, their impact on pediatric hematopoietic cell transplantation (HCT) outcomes is poorly understood. We aimed to identify the association between neighborhood poverty and HCT outcomes for pediatric allogeneic HCT recipients in the Center for International Blood and Marrow Transplant Research database. We assembled 2 pediatric cohorts undergoing first allogeneic HCT from 2006 to 2015 at age ≤18 years, including 2053 children with malignant disease and 1696 children with nonmalignant disease. Neighborhood poverty exposure was defined a priori per the US Census definition as living in a high-poverty ZIP code (≥20% of persons below 100% federal poverty level) and used as the primary predictor in all analyses. Our primary outcome was overall survival (OS), defined as the time from HCT until death resulting from any cause. Secondary outcomes included relapse and transplantation-related mortality (TRM) in malignant disease, acute and chronic graft-versus-host disease, and infection in the first 100 days post-HCT. Among children undergoing transplantation for nonmalignant disease, neighborhood poverty was not associated with any HCT outcome. Among children undergoing transplantation for malignant disease, neighborhood poverty conferred an increased risk of TRM but was not associated with inferior OS or any other transplantation outcome. Among children with malignant disease, a key secondary finding was that children with Medicaid insurance experienced inferior OS and increased TRM compared with those with private insurance. These data suggest opportunities for future investigation of the effects of household-level poverty exposure on HCT outcomes in pediatric malignant disease to inform care delivery interventions.

BACKGROUND: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. METHODS: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. RESULTS: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). CONCLUSIONS: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization. ispartof: CURRENT ONCOLOGY vol:27 issue:6 pages:E596-E606 ispartof: location:Switzerland status: published

Background The association of community factors and outcomes after hematopoietic cell transplantation (HCT) has not been comprehensively described. Using the County Health Rankings and Roadmaps (CHRR) and the Center for International Blood and Marrow Transplant Research (CIBMTR), this study evaluated the impact of community health status on allogeneic HCT outcomes. Methods This study included 18,544 adult allogeneic HCT recipients reported to the CIBMTR by 170 US centers in 2014-2016. Sociodemographic, environmental, and community indicators were derived from the CHRR, an aggregate community risk score was created, and scores were assigned to each patient (patient community risk score [PCS]) and transplant center (center community risk score [CCS]). Higher scores indicated less healthy communities. The impact of PCS and CCS on patient outcomes after allogeneic HCT was studied. Results The median age was 55 years (range, 18-83 years). The median PCS was -0.21 (range, -1.37 to 2.10; standard deviation [SD], 0.42), and the median CCS was -0.13 (range, -1.04 to 0.96; SD, 0.40). In multivariable analyses, a higher PCS was associated with inferior survival (hazard ratio [HR] per 1 SD increase, 1.04; 99% CI, 1.00-1.08; P = .0089). Among hematologic malignancies, a tendency toward inferior survival was observed with a higher PCS (HR, 1.04; 99% CI, 1.00-1.08; P = .0102); a higher PCS was associated with higher nonrelapse mortality (NRM; HR, 1.08; 99% CI, 1.02-1.15; P = .0004). CCS was not significantly associated with survival, relapse, or NRM. Conclusions Patients residing in counties with a worse community health status have inferior survival as a result of an increased risk of NRM after allogeneic HCT. There was no association between the community health status of the transplant center location and allogeneic HCT outcomes.

Poor medication adherence is associated with reduced drug effectiveness, poor health-related quality of life, increased morbidity and mortality, and increased healthcare utilization and cost. Including the patient's voice is essential in understanding barriers to adherence. Useful patient-reported adherence measures are brief, inexpensive, non-invasive; can indicate barriers to adherence; and can be incorporated in electronic health records. The NIH Patient-Reported Outcomes Measurement Information System (PROMIS®) includes high-quality, freely available patient-reported measures covering many important constructs in patient-centered research but does not include a medication adherence measure. To fill this gap, we developed the PROMIS Medication Adherence Scale (PMAS) using the rigorous PROMIS instrument development guidelines. To develop the PMAS, we first conducted a review of the reviews, which enabled us to identify content areas relevant to medication adherence behavior. Then, we conducted qualitative research to elicit patients' views of and experiences with medication adherence. This process identified the following important content areas to guide item writing: extent medication is taken, knowledge of medication regimen, beliefs about medication, remembering to take medication, skipping due to side effects, skipping due to feeling better, and cost of medications. Based on the results of these activities, we wrote items and aimed to retain 1-2 items per content area. The final item set included 9 total adherence items, which were then refined through intensive comprehension and translatability review, as well as cognitive interviews. Future steps include testing the PMAS's validity.

Sickle cell disease (SCD) is one of the most common inherited blood disorders. Deoxygenated hemoglobin S (HbS) polymerizes and causes anemia and various end organ effects. Voxelotor acts by increasing HbS oxygen affinity, decreasing anemia and hemolysis. Voxelotor is approved for use in individuals with SCD age 4 years and older. Phase 3 trials demonstrated an increase in hemoglobin levels and a decrease in markers of hemolysis; however, data or benefits related to clinical and quality of life outcomes are relatively limited and varied across different studies. This review summarizes the published clinical trials and research studies focused on the use of voxelotor in SCD to provide an evidence-based practical guide for hematology providers on its utilization in clinical settings, including physicians and independent licensed practitioners.

Sickle cell disease (SCD) state level surveillance data are limited. We performed a retrospective review of emergency department (ED) visits and hospitalizations from individuals with SCD in Illinois (2016-2020) using the Illinois Health and Hospital Association's Comparative Health Care and Hospital Data Reporting Services. There were 48,094 outpatient ED visits and 31,686 hospitalizations. Most visits (67%) occurred in Cook County, were covered by public insurance (77%) and were from individuals with medium high (40.3%) or high (36.1%) poverty levels. SCD healthcare utilization remains high and surveillance data may inform SCD program development and resource allocation at the state level.AbbreviationsCDCCenters for Disease Control and PreventionEDEmergency DepartmentFDAFoodDrug AdministrationICDInternational Classification of DiseasesILIllinoisSCDSickle cell disease.

Background. Sickle cell disease (SCD) is a hemoglobinopathy with increasing global prevalence resulting in pain episodes and multiorgan complications. Complications of SCD have been shown to adversely impact health-related quality of life (HRQOL) comprised of physical, social, and emotional domains; hence, HRQOL measures can serve as an effective evaluator of disease burden. Hydroxyurea (HU) and other disease-modifying therapies have demonstrated to significantly improve clinical outcomes in patients with SCD. Medication adherence is an essential mediator of the clinical benefits of these therapies; low adherence has been shown to increase disease burden and healthcare utilization. This systematic literature review intends to determine the association between adherence to disease-modifying therapies and HRQOL in patients with SCD. Methods. We found a total of 12 articles involving 788 participants, which included both patients with SCD and caregivers/parents. Adherence was measured using self-report instruments, laboratory markers, such as fetal hemoglobin and mean corpuscular volume, and mHealth medication trackers. HRQOL was measured using self-report instruments. Results. All studies demonstrated a correlation between higher HU adherence and better HRQOL scores. Higher HU adherence was associated with lower pain impact, less frequent pain episodes, less fatigue, and improved physical function and mobility, reflecting better physical HRQOL outcomes. Higher adherence was also associated with improved emotional response, decreased anxiety and depressive symptoms, and better social functioning and peer relationships. In addition, our findings indicated that having less frequent barriers to HU adherence was associated with better HRQOL scores. No studies evaluated HRQOL outcomes in relation to adherence to l-glutamine, voxelotor, or crizanlizumab. Conclusions. Optimizing HU adherence has the potential to improve HRQOL in patients with SCD in addition to reducing healthcare utilization and improving treatment satisfaction. Addressing barriers to HU adherence can positively strengthen the relationship between adherence and HRQOL to potentially improve patient outcomes.

BACKGROUND: Hydroxyurea is the primary treatment for sickle cell anemia (SCA), yet real-world implementation in high-income settings is suboptimal. Variation in prescribed hydroxyurea dose and patient adherence in these settings can both affect actual exposure to hydroxyurea. Quantifying the contributions of hydroxyurea dose and medication adherence to the relationship between hydroxyurea exposure and hematologic parameters could inform strategies to optimize exposure and improve outcomes. PROCEDURE: We evaluated the relationship between hydroxyurea exposure, defined by average prescribed dose and adherence, and hematologic parameters using data from children with SCA who were enrolled in two prospective hydroxyurea adherence studies. Hydroxyurea adherence was assessed by video directly observed therapy or electronic pill bottle and medication administration record. Average prescribed dose was abstracted from prescriptions in patients’ electronic medical record. Participants with a hydroxyurea exposure >20mg/kg/day and ≤20 mg/kg/day were included in the higher and lower exposure groups, respectively. RESULTS: Forty-five participants are included in the analysis (56% male; median age 12 years (range 2–19); 98% Black). Higher exposed participants (n=23) were prescribed a higher dose (27.2 vs. 24.4 mg/kg/day, P=0.002) and had better adherence (0.92 vs. 0.71, P=

Importance Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear. Objective To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs. Design, Setting, and Participants This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020. Interventions/Exposures Allo-HCT from an older MSD (donor age ���50 years) or a younger MUD (donor age ���35 years). Main Outcomes and Measures The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival. Results Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P���=���.02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P���=���.07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P���

Chronic graft-versus-host disease (cGVHD) occurs in up to 25% of children following allogeneic hematopoietic cell transplantation (HCT) and continues to be a major cause of late morbidity and poor quality of life among long-term survivors of pediatric HCT. Late effects (LEs) of HCT are well documented in this population, and cGVHD has been identified as a risk factor for subsequent neoplasms (SNs) and several nonmalignant LEs (NM-LEs); however, the reported correlation between cGVHD and LEs varies among studies. We compared LEs occurring ≥2 years following childhood HCT for a hematologic malignancy in 2-year disease-free survivors with and without cGVHD and further evaluated the association of cGVHD features on the development of LEs. This systematic retrospective analysis used data from the Center of International Blood and Marrow Transplant Research (CIBMTR) on a large, representative cohort of 1260 survivors of pediatric HCT for hematologic malignancy to compare first malignant LEs and NM-LEs in those with a diagnosis of cGVHD and those who never developed cGVHD. The cumulative incidences of any first LE, SN, and NM-LE were estimated at 10 years after HCT, with death as a competing risk for patients with cGVHD versus no cGVHD. Cox proportional hazards models were used to evaluate the impact of cGVHD and its related characteristics on the development of first LEs. The estimated 10-year cumulative incidence of any LE in patients with and without cGVHD was 43% (95% CI, 38% to 48.2%) versus 32% (95% confidence interval [CI], 28.5% to 36.3%) (P.001), respectively. The development of cGVHD by 2 years post-HCT was independently associated with any LE (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.68; P = .001) and NM-LE (HR, 1.37; 95% CI, 1.10 to 1.70; P = .006), but not SN (HR, 1.30; 95% CI, .73 to 2.31; P = .38). cGVHD-related factors linked with the development of an NM-LE included having extensive grade cGVHD (HR, 1.60; 95% CI, 1.23 to 2.08; P = .0005), severe cGVHD (HR, 2.25; 95% CI, 1.60 to 3.17; P.0001), interrupted onset type (HR, 1.57; 95% CI, 1.21 to 2.05; P = .0008), and both mucocutaneous and visceral organ involvement (HR, 1.59; 95% CI, 1.24 to 2.03; P = .0002). No significant association between cGVHD-specific variables and SN was identified. Finally, the duration of cGVHD treatment of cGVHD with systemic immunosuppression was not significantly associated with SNs or NM-LEs. cGVHD was more closely associated with NM-LEs than with SNs among survivors of pediatric HCT for hematologic malignancy. In this analysis, the development of SNs was strongly associated with the use of myeloablative total body irradiation. cGVHD-related characteristics consistent with a state of greater immune dysregulation were more closely linked to NM-LEs.

Background : Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GvHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies, such as prostate, penile, and testicular cancer. They may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. Objective : Here, we provide a systematic review of male-specific late effects in a collaboration between transplant physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research, and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Study Design : We utilized systematic review methodology to summarize incidence, risk factors, screening, prevention and treatment of these complications and provide consensus evidence-based recommendations for clinical practice and future research. Results : Most of the evidence regarding male GvHD is still based on limited data, precluding strong therapeutic recommendations. We therefore recommend to systematically screen for male genital GvHD regularly and report it to large registries to allow for a better understanding. Future research should also address treatment since little published evidence is available to date. Male-specific endocrine consequences of HCT include hypogonadism which may also affect bone health. Since the evidence is scarce, current recommendations for hormone substitution and/or bone health treatment are based on similar principles as for the general population. Following HCT, sexual health decreases and this topic should be addressed at regular intervals. Future studies should focus on interventional strategies to address sexual dysfunction. Infertility remains prevalent in patients having undergone myeloablative conditioning, which warrants offering sperm preservation in all HCT candidates. Most studies on fertility rely on descriptive registry analysis and surveys, hence the importance of reporting post-HCT conception data to large registries. Although the quality of evidence is low, the development of cancer in male genital organs does not seem more prevalent than in the general population; however, subsequent malignancies in general seem to be more prevalent in males than females, and special attention should be given to skin and oral mucosa. Conclusion : Male-specific late effects, probably more under-reported than female-specific complications, should be systematically considered during the regular follow-up visits of male survivors who have undergone HCT. Care of patients with male-specific late effects warrants close collaboration between transplant physicians and specialists from other involved disciplines. Future research should be directed towards better data collection on male-specific late effects and on studies about the interrelationship between these late effects, to allow the development of evidence based effective management practices.

Allogeneic hematopoietic cell transplantation (HCT) can cure many nonmalignant conditions, but concern for morbidity and mortality remains. To help physicians estimate patient-specific transplant mortality risk, the HCT comorbidity index (HCT-CI) is used. However, pediatric physicians use the HCT-CI less frequently than adult counterparts. We used the Center for International Blood and Marrow Transplant Research database to expand the HCT-CI comorbidity definitions to be more inclusive of children and adolescent and young adult (AYA) patients, adding history of mechanical ventilation, history of invasive fungal infection, assessment of chronic kidney disease (CKD) by estimated glomerular filtration rate, expanding the definition of obesity, and adding an underweight category. A total of 2815 children and AYAs (40 years old) who received first allogeneic HCT for nonmalignant diseases from 2008 to 2017 were included to create an expanded youth nonmalignant HCT-CI (expanded ynHCT-CI) and a simplified non-malignant (simplified ynHCT-CI) HCT-CI. The expanded comorbidities occurred frequently-history of mechanical ventilation (9.6%), history of invasive fungal infection (5.9%), mild CKD (12.2%), moderate/severe CKD (2.1%), obesity (10.9%), and underweight (14.5%). Thirty-nine percent of patients had an increase in their comorbidity score using the expanded ynHCT-CI, leading to a redistribution of scores: ynHCT-CI score 0 (35%), 1-2 (36.4%), and ≥3 (28.6%). Patients with an increase in their comorbidity score had an increased hazard of mortality compared to those whose score remained the same (hazard ratio = 1.41; 95% confidence interval, 1.01-1.98). Modifications to the HCT-CI can benefit children and AYA patients with nonmalignant diseases, creating a risk assessment tool that is clinically relevant and better captures comorbidity in this younger population.

Patients with sickle cell disease (SCD) have significant impairment in their quality of life across the life span as a consequence of serious disease burden with several SCD-related complications. A number of disease-modifying therapies are currently available, yet long-term clinical benefits in real-world settings remain unclear. Over the past few years, a number of important initiatives have been launched to optimize clinical trials in SCD in different ways, including: (1) established panels through a partnership between the American Society of Hematology (ASH) and the US Food and Drug Administration; (2) the ASH Research Collaborative SCD Clinical Trials Network; (3) the PhenX Toolkit (consensus measures for Phenotypes and eXposures) in SCD; and (4) the Cure Sickle Cell Initiative, led by the National Heart, Lung, and Blood Institute. Electronic patient-reported outcomes assessment is highly recommended, and patient-reported outcomes (PROs) should be evaluated in all SCD trials and reported using Standard Protocol Items Recommendations for Interventional Trials guidelines. Patient-centered outcomes research (PCOR) approaches and meaningful stakeholder engagement throughout the process have the potential to optimize the execution and success of clinical trials in SCD with considerable financial value. This article reviews several clinical trial considerations in SCD related to study design and outcomes assessment as informed by recent initiatives as well as patient-centered research approaches and stakeholder engagement. A proposed hematology stakeholder-engagement framework for clinical trials is also discussed.

ObjectivesSickle cell disease (SCD) leads to chronic and acute complications that require specialised care to manage symptoms and optimise clinical results. The National Heart Lung and Blood Institute (NHLBI) evidence-based guidelines assist providers in caring for individuals with SCD, but adoption of these guidelines by providers has not been optimal. The objective of this study was to identify barriers to treating individuals with SCD.MethodsThe SCD Implementation Consortium aimed to investigate the perception and level of comfort of providers regarding evidence-based care by surveying providers in the regions of six clinical centres across the USA, focusing on non-emergency care from the providers’ perspective.ResultsRespondents included 105 providers delivering clinical care for individuals with SCD. Areas of practice were most frequently paediatrics (24%) or haematology/SCD specialist (24%). The majority (77%) reported that they were comfortable managing acute pain episodes while 63% expressed comfort with managing chronic pain. Haematologists and SCD specialists showed higher comfort levels prescribing opioids (100% vs 67%, p=0.004) and managing care with hydroxyurea (90% vs 51%, p=0.005) compared with non-haematology providers. Approximately 33% of providers were unaware of the 2014 NHLBI guidelines. Nearly 63% of providers felt patients’ medical needs were addressed while only 22% felt their mental health needs were met.ConclusionsA substantial number of providers did not know about NHLBI’s SCD care guidelines. Barriers to providing care for patients with SCD were influenced by providers’ specialty, training and practice setting. Increasing provider knowledge could improve hydroxyurea utilisation, pain management and mental health support.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To identify and assess the effects of digital behavioural interventions focused on behavioural change in people with SCD on: medication adherence or disease management (such as managing acute and chronic pain), or both, on health- and other-related outcomes;specific subgroups defined by age (i.e. children, adolescents and adults) and type of modality or delivery (e.g. cell phone, the Internet).

During transition from pediatrics to adult health care, young adults with sickle cell disease (SCD) face increased risk of severe morbidities and premature mortality.1 Sickle cell disease complications can be mitigated with hydroxyurea use.2 However, successful alleviation and prevention of SCD morbidities is contingent on initiation of and continued adherence to hydroxyurea therapy.3,4 With higher frequency of SCD-related complications among young adults, we examined the prevalence of hydroxyurea prescription among patients aged 18 to 25 years using statewide claims data. Understanding the patterns of hydroxyurea use in this patient population is key to potentially preventing the high burden of the disease accumulating among young adults.