Optimal Donor Selection Across Multiple Outcomes For Hematopoietic Stem Cell Transplantation By Bayesian Nonparametric Machine Learning.

Allogeneic hematopoietic cell transplantation (HCT) is one of the only curative treatment options for patients suffering from life-threatening hematologic malignancies; yet, the possible adverse complications can be serious even fatal. Matching between donor and recipient for 4 of the HLA genes is widely accepted and supported by the literature. However, among 8/8 allele matched unrelated donors, there is less agreement among centers and transplant physicians about how to prioritize donor characteristics like additional HLA loci (DPB1 and DQB1), donor sex/parity, CMV status, and age to optimize transplant outcomes. This leads to varying donor selection practice from patient to patient or via center protocols. Furthermore, different donor characteristics may impact different post transplant outcomes beyond mortality, including disease relapse, graft failure/rejection, and chronic graft-versus-host disease (components of event-free survival, EFS). We develop a general methodology to identify optimal treatment decisions by considering the trade-offs on multiple outcomes modeled using Bayesian nonparametric machine learning. We apply the proposed approach to the problem of donor selection to optimize overall survival and event-free survival, using a large outcomes registry of HCT recipients and their actual and potential donors from the Center for International Blood and Marrow Transplant Research (CIBMTR). Our approach leads to a donor selection strategy that favors the youngest male donor, except when there is a female donor that is substantially younger.

Long-term Outcomes of Peripheral Blood Stem Cell Unrelated Donors Mobilized with Filgrastim.

Allogeneic hematopoietic cell transplantation is a life-saving procedure used to treat of a variety of devastating diseases. It requires hematopoietic stem cells collected via filgrastim mobilized peripheral blood stem cells or bone marrow harvest from volunteer unrelated donors. There is a paucity of safety data regarding donors' long-term adverse events. This prospective, observational study combined peripheral blood stem cell donors enrolled on the NMDP Investigational New Drug trial and bone marrow donors between July 1, 1999, and September 30, 2015. The primary objective was to describe the long-term incidence of myeloid malignancies. Secondary objectives included describing the long-term incidence of lymphoid malignancies, non-hematologic malignancies, autoimmune disorders, and thrombotic events. 21643 donors (14530 peripheral blood stem cells and 7123 bone marrow) were included. The incidence rate of myeloid disorders per 100000 person years in donors of peripheral blood stem cells was 2.53 (95% CI: 0.82-7.84) and in donors of bone marrow it was 4.13 (95% CI: 1.33-12.8). The incidence rate ratio of peripheral blood stem cells /bone marrow donors was 0.61 (95% CI: 0.12-3.03; p=0.55). The incidence of other malignancies, autoimmunity, and thrombosis did not differ between donor types. This comprehensive study of long-term effects of filgrastim in unrelated donors of peripheral blood stem cells provides strong evidence that donors who receive filgrastim are not at increased risk of these events compared to bone marrow donors. It also provides reassurance to current donors undergoing stem cell mobilization as well as individuals considering joining stem cell registries such as NMDP.

Severity and organ distribution of chronic graft-versus-host disease with posttransplant cyclophosphamide-based versus methotrexate/calcineurin inhibitor-based allogeneic hematopoietic cell transplantation.

The reduced risk of chronic graft-versus-host-disease (GVHD) with posttransplant cyclophosphamide (ptCy) in the setting of haploidentical related donor and more recently, with HLA-matched related and matched and mismatched unrelated donor allogeneic transplantation has been established. There is, however, paucity of data to show if ptCy impacts chronic GVHD pathogenesis, its phenotype and evolution after HCT regardless of the donor status. We examined the differences in chronic GVHD incidence and presentation in 314 consecutive patients after receiving their first allogeneic transplantation (HCT) using ptCy-based GVHD prophylaxis (ptCy-HCT; n = 120; including 95 with haploidentical related donor) versus conventional calcineurin inhibitor-based prophylaxis (CNI-MUD; n = 194) between 2012 and 2019. The 1-year cumulative incidence of all-grade chronic GVHD and moderate/severe chronic GVHD was 24% and 12%, respectively, after ptCy-HCT and 40% and 23% in the CNI-MUD recipients (p = 0.0003 and 0.007). Multivariable analysis confirmed that use of CNI-based GVHD prophylaxis and peripheral blood stem cell graft as the risk factors for chronic GVHD. The cumulative incidence of visceral (involving ≥1 of the following organs: liver, lungs, gastrointestinal tract, serous membranes) chronic GVHD was significantly higher with CNI-MUD vs. ptCy-HCT (27% vs. 15% at 1 year, p = 0.009). The incidence of moderate/severe visceral chronic GVHD was 20% in CNI-MUD group vs. 7.7% in the ptCy-HCT group at 1 year (p = 0.002). In addition, significantly fewer ptCy-HCT recipients developed severe chronic GVHD in ≥3 organs (0.8%) vs. 8.8% in the CNI-MUD group at 1-year posttransplant (p = 0.004). There was no significant different in relapse, non-relapse mortality, and relapse-free and overall survival between the two groups. Further investigation is needed to confirm that reduced risk and severity of chronic GVHD, less visceral organ distribution with ptCy-HCT leads to improved quality of life.

Incorporating patient-reported outcome data into a predictive calculator for allogeneic hematopoietic cell transplantation recipients.

BACKGROUND: The Center for International Blood and Marrow Transplant Research (CIBMTR) provides a 1-year overall survival calculator to estimate outcomes for individual patients before they undergo allogeneic hematopoietic cell transplantation (HCT) to inform risk. The calculator considers pre-HCT clinical and demographic characteristics, but not patient-reported outcomes (PROs). Because pre-HCT PRO scores have been associated with post-HCT outcomes, the authors hypothesized that adding PRO scores to the calculator would enhance its predictive power. METHODS: Clinical data were obtained from the CIBMTR and the Blood and Marrow Transplant Clinical Trials Network. The PRO measures used were the 36-Item Short Form Survey (SF-36) and the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation. One thousand thirty-three adult patients were included. RESULTS: When adjusted for clinical characteristics, the SF-36 physical component score was significantly predictive of 1-year survival (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.81-0.95; p = .0015), whereas the mental component score was not (HR, 1.02; 95% CI, 0.95-1.10; p = 0.6396). The baseline single general health question on the SF-36 was also significantly associated with mortality (HR, 1.91 for those reporting fair/poor health vs. good, very good, or excellent health; 95% CI, 1.33-2.76; p = .0005). The addition of PRO scores to the calculator did not result in a significant change in the model's predictive ability. Self-reported pre-HCT scores were strongly predictive of self-reported health status (odds ratio, 3.35; 95% CI, 1.66-6.75; p = .0007) and quality of life (odds ratio, 3.24; 95% CI, 1.93-5.41; p < .0001) after HCT. CONCLUSIONS: The authors confirmed the significant, independent association of pre-HCT PRO scores with overall survival, although adding PRO scores to the survival calculator did not improve its performance. They also demonstrated that a single general health question was as accurate as the full measure for predicting survival, an important finding that may reduce respondent burden and promote its inclusion in routine clinical practice. Validation of these findings should be performed.

Comparison of Vital Status, Cause of Death, and Follow-Up after Hematopoietic Cell Transplantation in Linked Center for International Blood and Marrow Transplant Research and California Cancer Registry Data, 1991 to 2018.

Assessing outcomes following hematopoietic cell transplantation (HCT) poses challenges due to the necessity for systematic and often prolonged patient follow-up. Linking the HCT database of the Center for International Blood and Marrow Transplant Research (CIBMTR) with cancer registry data may improve long-term outcome ascertainment, but the reliability of mortality data in death certificates from cancer registries among HCT recipients remains unknown. We compared the classification of vital status and primary cause of death (COD), as well as the length of follow-up between the CIBMTR and California Cancer Registry (CCR) to assess the possibility of supplementing the CIBMTR with cancer registry data. This retrospective study leveraged a linked CIBMTR-CCR dataset. We included patients who were California residents at the time of HCT and received a first allogeneic (allo) or autologous (auto) HCT for a hematologic malignancy diagnosed during 1991-2016. Follow-up was through 2018. We analyzed 18,450 patients (alloHCT, n = 8232; autoHCT, n = 10,218). The Vital status agreement was 97.7% for alloHCT and 97.2% for autoHCT. Unknown COD was higher in CIBMTR (12.9%) than in CCR (1.6%). After excluding patients with unknown COD information, the overall agreement of primary COD (cancer versus noncancer) was 53.7% for alloHCT and 83.2% for autoHCT. This agreement was lower within the first 100 days post-HCT (alloHCT, 31.0%; autoHCT, 54.6%). Compared with CIBMTR, deaths due to cancer were higher in CCR (alloHCT, 90.0%; autoHCT, 90.1% versus alloHCT, 47.3%; autoHCT, 82.5% in CIBMTR). CIBMTR reports more frequently noncancer-related deaths, including graft-versus-host disease and infections. The cumulative incidence of cancer-specific mortality at 20 years differed, particularly for alloHCT (CCR, 53.7%; CIBMTR, 27.6%). The median follow-up among alive patients was longer in CCR (alloHCT, 6.0 years; autoHCT, 4.7 years) than in CIBMTR (alloHCT, 5.0 years; autoHCT, 3.8 years). Our findings highlight the completeness of vital status data in CIBMTR but reveal substantial disagreement in primary COD. Consequently, caution is required when interpreting HCT studies that use only death certificates to estimate cause-specific mortality outcomes. Improving the accuracy of COD registration and follow-up completeness by developing communication pathways between cancer registries and hospital-based cohorts may enhance our understanding of late effects and long-term outcomes among HCT survivors.

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.

Prevalence of Sleep Aid Medication Use in Patients Receiving a Hematopoietic Cell Transplant on an Inpatient Unit.

BACKGROUND AND OBJECTIVES: There is a lack of research regarding the use of sleep aids after hematopoietic stem cell transplantation (HCT). We describe the prevalence of sleep aid administration in the HCT unit and identify associations with patient or clinical characteristics. PATIENTS AND METHODS: In this retrospective analysis of sequential inpatient HCTs from July 1 to December 31, 2016 we describe whether and when patients were prescribed sleep aid medications. Chi-square tests determined significant differences between patient characteristics, sleep aid prescription, and time of prescription. RESULTS: Of the 225 patients identified, 193 (86%) were prescribed sleep aids. Significantly more women received prescriptions for sleep aids (90.4%) than men (81%; P = .047). One hundred patients (44%) received prescriptions exclusively while in the hospital. CONCLUSION: Findings show a high prevalence of sleep medication use in patients undergoing inpatient HCT, primarily during hospitalization. Future efforts toward standardized recommendations to optimize peri-transplant sleep would help clinicians and patients.

Clinical impact of cryopreservation of allogeneic hematopoietic cell grafts during the onset of the COVID-19 pandemic.

At the onset of the COVID-19 pandemic, the National Marrow Donor Program mandated the cryopreservation of hematopoietic cell grafts from volunteer unrelated donors because of numerous patient and donor safety concerns and logistical hurdles. Using the Center for International Blood and Marrow Transplant Research outcomes database, we report the impact of cryopreservation on overall survival (OS) and other outcomes within 1 year after hematopoietic cell transplantation (HCT). We analyzed 1543 recipients of cryopreserved allografts receiving HCT at US centers during the first 6 months of the pandemic and compared them with 2499 recipients of fresh allografts during a 6-month period in 2019. On multivariable regression analysis, we observed no difference in the OS (P = .09), nonrelapse mortality (P = .89), graft-versus-host disease (GVHD), or GVHD- and relapse-free survival (P = .58) in recipients of cryopreserved vs fresh allografts. Disease-free survival (DFS) was lower in the cryopreserved allograft recipients (P = .006) because of a higher risk of relapse (P = .01) compared with the fresh allograft recipients. Primary graft failure was higher (P = .01), and the risk of chronic GVHD was lower (P = .001) with cryopreservation compared with fresh grafts. In conclusion, although there was no negative impact of cryopreservation on OS, relapse was higher, and DFS was lower than that with no cryopreservation. Fresh grafts are recommended as the pandemic-related logistical hurdles resolve. Cryopreservation should be considered an option for patients when fresh grafts are not feasible.

Real-World Data Showing Trends and Outcomes by Race and Ethnicity in Allogeneic Hematopoietic Cell Transplantation: A Report from the Center for International Blood and Marrow Transplant Research.

The use of HLA-mismatched donors could enable more patients with ethnically diverse backgrounds to receive allogeneic hematopoietic cell transplantation (HCT) in the United States. However, real-world trends and outcomes following mismatched donor HCT for diverse patients remain largely undefined. We conducted this study to determine whether the use of mismatched donor platforms have increased the access to allogeneic HCT for ethnically diverse patients, particularly through the application of novel graft-versus-host disease (GVHD) prophylaxis regimens, and whether outcomes for diverse patients are comparable to those of non-Hispanic White patients. This observational cross-sectional study used real-world data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. All patients receiving their first allogeneic HCT in the United States between 2009 and 2020 were included, with a focus on transplantations performed in 2020. Data from patients undergoing allogeneic HCT using bone marrow, peripheral blood, or cord blood from HLA-matched or mismatched related and unrelated donors were analyzed. Specifically, relative proportion of allogeneic HCT was generated as percentage of total for donor type and for patient age, disease indication, GVHD prophylaxis, and race and ethnicity. Causes of death were summarized using frequencies, and the Kaplan-Meier estimator was used for estimating overall survival. Compared to matched related donor and matched unrelated donor HCT, more ethnically diverse patients received mismatched unrelated donor, haploidentical donor, and cord blood HCT. Although matched unrelated donor remains the most common donor type, the use of haploidentical donors has increased significantly over the last 5 years. Paralleling this increase in haploidentical HCT is the increased use of post-transplantation cyclophosphamide (PTCy) as GVHD prophylaxis. Relative to previous transplantation eras, the most contemporary era is associated with the highest survival rates following allogeneic HCT irrespective of patient race and ethnicity. Nonetheless, disease relapse remains the primary cause of death for both adult and pediatric allogeneic HCT recipients by donor type and across all patient racial/ethnic groups. Ethnically diverse patients are undergoing allogeneic HCT at higher rates, largely through the use of alternative donor platforms incorporating PTCy. Maintaining access to potential life-saving allogeneic HCT using alternative donors and novel GVHD prophylaxis strategies and improving HCT outcomes, particularly disease relapse, remain urgent clinical needs.

Association of ABO mismatch with the outcomes of allogeneic hematopoietic cell transplantation for acute leukemia.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). While many factors influence the outcomes of allo-HCT, the independent impact of donor-recipient ABO mismatching remains unclear. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified patients aged ≥18 years with AML or ALL who underwent allo-HCT between 2008 and 2018. Our objectives were to analyze the outcomes of allo-HCT based on the donor-recipient ABO status (match, minor mismatch, major mismatch, bidirectional mismatch). Among 4946 eligible patients, 2741 patients (55.4%) were ABO matched, 1030 patients (20.8%) had a minor ABO mismatch, 899 patients (18.1%) had a major ABO mismatch, and 276 patients (5.6%) had a bidirectional ABO mismatch. In multivariable analyses, compared to ABO matched allo-HCT, the presence of a major ABO mismatch was associated with worse overall survival (HR 1.16, 95% CI 1.05-1.29; p = 0.005), inferior platelet engraftment (HR 0.83, 95% CI 0.77-0.90; p < 0.001), and higher primary graft failure (HR 1.60, 95% CI 1.12-2.30, p = 0.01). Relapse, acute graft versus host disease (GVHD) grades III-IV and chronic GVHD were not significantly associated with ABO status. While donor age was not significantly associated with outcomes, older recipient age was associated with worse survival and non-relapse mortality. Our study demonstrates that donor-recipient ABO status is independently associated with survival and other post-transplantation outcomes in acute leukemia. This underscores the importance of considering the ABO status in donor selection algorithms and its impact in acute leukemia.

Multi-Stakeholder Qualitative Interviews to Inform Measurement of Patient Reported Outcomes After CAR-T.

Toxicities after chimeric antigen receptor T cell (CAR-T) therapy are well known, yet the patient experience during and after CAR-T therapy has not been well described outside of the trial setting. We explored the patient experience after CAR-T therapy to inform the patient-reported outcomes (PRO) measurement approach for the Center for International Blood and Marrow Transplant Research (CIBMTR). We recruited (1) adult patients diagnosed with a hematologic malignancy 14 days to 6 months after receiving a commercial CAR T cell product who had agreed to be contacted by the CIBMTR, (2) caregivers of those patients, and (3) clinical experts in CAR-T therapy. Telephone interviews were conducted following a semistructured guide that included open-ended questions about symptoms and functioning. We conducted a systematic content analysis of each transcript using prespecified codes representing common domains of health, as well as open coding for emergent themes. Forty patients at 29 centers, 15 of their caregivers, and 15 experts from 9 centers participated, representing diversity with respect to age, sex, race/ethnicity, and years in practice (experts). Patients, caregivers, and experts shared largely consistent impressions of the patient experience after CAR-T therapy. Commonly described themes included anxiety, cognitive dysfunction, depression, fatigue, pain, impaired physical function, gastrointestinal symptoms, sexual dysfunction, sleep difficulties, need for support, financial impact, hospitalization, communication with healthcare providers, and the COVID-19 pandemic. Limitations in patients' ability to participate in social roles and activities was the most prevalent theme, found in nearly all interviews. In the setting of CAR-T therapy, a multidimensional approach to PRO measurement is needed that includes physical, mental, and social health, as well as the financial impact of this novel treatment. High-quality existing PRO tools are available to measure these concepts. Results will inform the CIBMTR measurement of PROs after CAR-T therapy and may be applicable to other CAR-T studies that aim to represent patient experiences.

Unrelated Stem Cell Donor HLA Match Likelihood in the US Registry Incorporating HLA-DPB1 Permissive Mismatching.

Donor-recipient HLA matching at the DPB1 locus improves the outcomes of hematopoietic stem cell transplantation (HCT). Retrospective outcome studies found that in HCTs matched for all 8 alleles of the A, B, C, and DRB1 loci at high resolution (8/8 match), few transplantations were also allele-matched at the DPB1 locus. DPB1 allele matching was once thought to be logistically impractical; however, a DPB1-permissive mismatch model based on T cell epitope (TCE) reactivity expands the proportion of suitable donors. To understand the likelihood of finding a DPB1-permissive donor, we sought to expand population genetic match likelihood models for the US unrelated donor registry, the National Marrow Donor Program (NMDP). After extending HLA haplotype frequency estimates to include the DPB1 locus, our models found that the likelihood of having a DPB1-permissive donor was not much lower than likelihood of 8/8 matching. A maximum of 5 additional donors would need to be typed to find a more optimal DPB1-permissive donor at least 90% of the time. Linkage disequilibrium patterns between the DPB1 locus and other classical HLA loci varied markedly by haplotype and population, indicating that the known recombination hotspot between DQ and DP gene complexes has not had a uniform impact; thus, DPB1-permissive donors are easier to identify within minority populations. DPB1 TCE categories were highly predictable from HLA typing at other loci when imputed with extended haplotype frequency data. Our overall results indicate that registry search strategies that seek a more optimally matched HCT donor encompassing HLA-DPB1 permissibility are likely to be highly productive.

Health-Related Quality of Life Outcomes in Older Hematopoietic Cell Transplantation Survivors.

The use of hematopoietic cell transplantation (HCT) has been increasing in older patients. However, the levels if distress, psychosocial functioning, and health-related quality of life (HRQOL) among older HCT survivors remains largely unknown. In this secondary analysis using data from 2 randomized controlled trials, we analyzed baseline Cancer and Treatment Distress (CTXD) and Confidence In Survivorship Information (CSI) surveys of HCT survivors who were age ≥60 years at the time of transplantation and alive and disease-free ≥1 year post-autologous or -allogeneic HCT. We analyzed associations of these parameters with the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores of the 12-Item Short Form Survey (SF-12) and a healthcare adherence (HCA) scale, after adjusting for transplantation and patient demographic factors. A total of 567 patients were included. The median patient age at HCT was 65 years, and 68% of the patients underwent autologous HCT. The median CTXD score was .7 (mild), and the greatest distress was reported in the "health burden" subscale. The median CSI score was 1.4 (moderate-high), with the lowest confidence reported in the "late effects" subscale. We found negative Spearman correlations between CTXD score and SF-12 PCS (P = -.59) and MCS (P = -.54) and positive Spearman correlations between CSI score and SF-12 PCS (P = .23) and MCS (P = .30). The median HCA scale score was high at .8. Male sex, autologous HCT, increased distress level, and worse CSI score were associated with lower use of preventive care. Older survivors experienced a low level of distress and moderate-high level of CSI at ≥1 year post-HCT. As lower distress and higher CSI were associated with improved HRQOL and optimized preventive HCA, CTXD/CSI measures can be used to individualize the care of older adult HCT survivors.

Three-Year Outcomes in Recipients of Mismatched Unrelated Bone Marrow Donor Transplants Using Post-Transplantation Cyclophosphamide: Follow-Up from a National Marrow Donor Program-Sponsored Prospective Clinical Trial.

The use of post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis has resulted in reductions in GVHD and improved outcomes in allogeneic hematopoietic cell transplantation (HCT) using HLA-mismatched related donors. We report the 3-year outcomes of the first multicenter prospective clinical trial using PTCy in the setting of mismatched unrelated donor (MMUD) bone marrow HCT. The study enrolled 80 patients, treated with either myeloablative conditioning (MAC; n = 40) or reduced-intensity conditioning (RIC; n = 40), with the primary endpoint of 1-year overall survival (OS). The median follow-up for this study was 34 months (range, 12 to 46 months) in the RIC group and 36 months (range, 18 to 49 months) in the MAC group. Three-year OS and nonrelapse mortality were 70% and 15%, respectively, in the RIC group and 62% and 10% in the MAC group. No GVHD was reported after 1 year. The incidence of relapse was 29% in the RIC group and 51% in the MAC group. OS did not differ based on HLA match grade (63% in the 7/8 strata and 71% in the 4 to 6/8 strata). These encouraging outcomes, which were sustained for 3 years post-HCT, support the continued exploration of MMUD HCT using a PTCy platform. Important future areas to address include relapse reduction and furthering our understanding of optimal donor selection based on HLA and non-HLA factors.

Health-related quality of life in reduced-intensity hematopoietic cell transplantation based on donor availability in patients aged 50-75 with advanced myelodysplastic syndrome: BMT CTN 1102.

For myelodysplastic syndrome (MDS), allogeneic hematopoietic cell transplantation (alloHCT) is the only available curative therapy. The Blood and Marrow Transplant Clinical Trials Network study 1102 (BMT CTN 1102, NCT02016781) was a multicenter, biologic assignment trial based on matched donor availability in adults aged 50-75 with higher risk de novo MDS who were candidates for reduced-intensity conditioning (RIC) alloHCT. The primary analysis showed that those who received alloHCT had a survival benefit, but whether this is at the cost of worse quality of life (QOL) has not been described in detail. English- and Spanish-speaking trial participants completed the Functional Assessment of Cancer Therapy-General (FACT-G), the SF-36, and the EQ-5D, at enrollment, every 6 months until 24 months, and 36 months. We compared patient-reported outcome (PRO) scores between study arms using an inverse probability weighted-independent estimating equation (IPW-IEE) model. Between January 2014 and November 2018, 384 subjects (median age 66.7 years, range: 50.1-75.3) enrolled at 34 centers. PRO completion rates were generally high at 65%-78%. The PRO trajectories for both arms were similar, with most decreasing or stable from baseline to 6 months and improving thereafter. Baseline PRO scores were the most consistent independent predictors of subsequent QOL outcomes and survival, even after controlling for clinical and patient-level factors. For older adults with MDS, the survival advantage associated with donor availability and alloHCT did not come at the cost of worse QOL. These results should reassure older patients and clinicians who prefer a curative approach to treating MDS.

Patient-reported cognitive function among hematopoietic stem cell transplant and cellular therapy patients: a scoping review.

PURPOSE: Cognitive dysfunction is a known complication following cellular therapies (CT), which can be assessed through performance based and patient-reported measures. We performed a systematic scoping review to assess self-reported cognitive function measures used among adult CT patients and describe long-term results, including associations with clinical outcomes. METHODS: Library databases were searched from inception to February 2020 according to PRISMA guidelines. Additional studies were identified through reference lists and trial protocols. Two members of the research team screened titles and abstracts and resolved discrepancies. Articles that met eligibility criteria continued to full-text review, with 25% double screening. Articles were removed if they (1) were not original research, peer-reviewed articles; (2) were the wrong disease, age, or treatment-specific patient population; (3) did not use patient-reported outcomes; (4) did not separately report cognitive function outcomes. RESULTS: Of the1952 articles, 56 were included. Twenty-one patient-reported measures of cognitive function were used; most frequently the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30), which includes a two-item cognitive function subscale (57%; n = 32). Thirteen studies collected performance-based and self-reported measures and of those (n = 6) who assessed associations found moderate correlations (range r = .13-.58). Longitudinal patterns showed declines in cognitive function soon after treatment (< 1 month) returning to baseline at 1 year. Cognitive function was often associated with other quality of life measures, chiefly depression (n = 5). CONCLUSIONS: EORTC-QLQ-C30 is the most commonly used to measure, though there remain numerous measures used, including several measures with little previous validation and investigator developed items.

Relationship between work performance and quality of life in long-term survivors of pediatric and adolescent hematopoietic cell transplant.

PURPOSE: To assess work status, missed time at work (absenteeism), work performance (presenteeism), and their relationship with quality of life (QOL) among long-term survivors of childhood hematopoietic cell transplant (HCT). METHODS: A single-center cross-sectional survey study of adult survivors of childhood allogeneic HCT (performed between 1985 and 2010). Work and QOL data were captured using the World Health Organization Health and Work Performance Questionnaire and the National Institutes of Health Patient Reported Outcomes Measurement Information System (PROMIS), respectively. Higher absenteeism and presenteeism scores meant higher missed time at work and productivity, respectively. PROMIS domains were scored on a T-score metric with a mean score of reference population at 50 and standard deviation of 10. Univariate linear regression was performed to study factors associated with increase in PROMIS scores. RESULTS: Forty-four survivors completed the survey. Median ages at HCT and survey were 11 years (interquartile range [IQR] 7-13) and 30 years (IQR 26-34), respectively. Seventy-three percent were working, 23% were unemployed, and 4% were students. Employed survivors reported less pain and sleep disturbance. Higher absolute presenteeism was associated with less pain interference and more satisfaction with social roles and activities and physical function. Higher relative presenteeism was associated with less cognitive concerns. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: We found significant associations between survivors' work status, performance, and QOL. Our findings provide an important insight on the implications of work outcomes on HCT survivors' physical, mental, and social health and emphasize the importance of longitudinal assessment of work status, performance, and QOL.

Sickle Cell Transplantation Evaluation of Long-term and Late Effects Registry (STELLAR) to Compare Long-term Outcomes After Hematopoietic Cell Transplantation to Those in Siblings Without Sickle Cell Disease and in Nontransplanted Individuals With Sickle Cell Disease: Design and Feasibility Study.

BACKGROUND: There are sparse data on the long-term and late effects of hematopoietic cell transplantation (HCT) for sickle cell disease (SCD). OBJECTIVE: This study aims to establish an international registry of long-term outcomes post-HCT for SCD and demonstrate the feasibility of recruitment at a single site in the United States. METHODS: The Sickle Cell Transplantation Evaluation of Long-Term and Late Effects Registry (STELLAR) was designed to enroll patients with SCD ≥1 year post-HCT, their siblings without SCD, and nontransplanted controls with SCD to collect web-based participant self-reports of health status and practices by using the Bone Marrow Transplant Survivor Study (BMTSS) surveys, health-related quality of life (HRQOL) using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Profile-25 or Pediatric Profile-29 survey, chronic graft-versus-host disease (cGVHD) using the symptom scale survey, daily pain using an electronic pain diary, the economic impact of HCT using the financial hardship survey, sexual function using the PROMIS Sexual Function SexFSv2.0 survey, and economic productivity using the American Time Use Survey (ATUS). We also piloted retrieval of clinical data previously submitted to the Center for International Blood and Marrow Transplant Research (CIBMTR); recorded demographics, height, weight, blood pressure, waist and hip circumferences, timed up and go (TUG) test, and handgrip test; and obtained blood for metabolic screening, gonadal function, fertility potential, and biorepository of plasma, serum, RNA, and DNA. RESULTS: Of 100 eligible post-HCT patients, we enrolled 72 (72%) participants aged 9-38 (median 17) years. We also enrolled 19 siblings aged 5-32 (median 10) years and 28 nontransplanted controls with SCD aged 4-46 (median 22) years. Of the total 119 participants, 73 (61%) completed 85 sets of surveys and 41 (35%) contributed samples to the biorepository. We completed ATUS interviews of 28 (24%) participants. We successfully piloted retrieval of data submitted to the CIBMTR and expanded recruitment to multiple sites in the United States, Canada, the United Kingdom, and Nigeria. CONCLUSIONS: It is feasible to recruit subjects and conduct study procedures for STELLAR in order to determine the long-term and late effects of HCT for SCD. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36780.