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PURPOSE To report the incidence and risk factors for secondary neoplasm after transplantation for sickle cell disease. METHODS Included are 1,096 transplants for sickle cell disease between 1991 and 2016. There were 22 secondary neoplasms. Types included leukemia/myelodysplastic syndrome (MDS; n = 15) and solid tumor (n = 7). Fine-Gray regression models examined for risk factors for leukemia/MDS and any secondary neoplasm. RESULTS The 10-year incidence of leukemia/MDS was 1.7% (95% CI, 0.90 to 2.9) and of any secondary neoplasm was 2.4% (95% CI, 1.4 to 3.8). After adjusting for other risk factors, risks for leukemia/MDS (hazard ratio, 22.69; 95% CI, 4.34 to 118.66; P = .0002) or any secondary neoplasm (hazard ratio, 7.78; 95% CI, 2.20 to 27.53; P = .0015) were higher with low-intensity (nonmyeloablative) regimens compared with more intense regimens. All low-intensity regimens included total-body irradiation (TBI 300 or 400 cGy with alemtuzumab, TBI 300 or 400 cGy with cyclophosphamide, TBI 200, 300, or 400 cGy with cyclophosphamide and fludarabine, or TBI 200 cGy with fludarabine). None of the patients receiving myeloablative and only 23% of those receiving reduced-intensity regimens received TBI. CONCLUSION Low-intensity regimens rely on tolerance induction and establishment of mixed-donor chimerism. Persistence of host cells exposed to low-dose radiation triggering myeloid malignancy is one plausible etiology. Pre-existing myeloid mutations and prior inflammation may also contribute but could not be studied using our data source. Choosing conditioning regimens likely to result in full-donor chimerism may in part mitigate the higher risk for leukemia/MDS.

Mechanical circulatory support effectively treats adult cardiogenic shock. Whereas cardiogenic shock confers high mortality, acute limb ischemia is a known complication of mechanical circulatory support that confers significant morbidity. We compared our novel approach to peripheral mechanical circulatory support with a conventional femoral approach, with a focus on the incidence of acute limb ischemia.This was a retrospective cohort study of patients treated with mechanical circulatory support between January 1, 2015 and December 5, 2021 at our institution. Patients receiving any femoral peripheral venoarterial extracorporeal membrane oxygenation were compared with those receiving minimally invasive, peripherally inserted, concomitant right and left ventricular assist devices. These included the Impella 5.0 (Abiomed, Danvers, MA) left ventricular assist device and the ProtekDuo (LivaNova, London, UK) right ventricular assist device used concomitantly (Propella) approach. The primary outcome was incidence of acute limb ischemia. The baseline patient characteristics, hemodynamic data, and post-mechanical circulatory support outcomes were collected. Fisher exact test and Wilcoxon rank sum test was used for the categorical and continuous variables, respectively. Kaplan-Meier curves and log-rank test were used to estimate overall survival probabilities and survival experience, respectively.Fifty patients were treated with mechanical circulatory support at our institution for cardiogenic shock, with 13 patients supported with the novel Propella strategy and 37 with peripheral venoarterial extracorporeal membrane oxygenation. The baseline characteristics, including patient organ function and medical comorbidities, were similar among the groups. Nine patients suffered mortality in ≤48 hours of mechanical circulatory support initiation and were excluded. Twenty patients (69%) suffered acute limb ischemia in the peripheral venoarterial extracorporeal membrane oxygenation group; 0 patients receiving Propella suffered acute limb ischemia (P.001). The percentages of patients surviving to discharge in peripheral venoarterial extracorporeal membrane oxygenation and Propella groups were 24% and 69%, respectively (P = .007).Patients treated with the Propella experienced a lower incidence of acute limb ischemia compared with patients treated with peripheral venoarterial extracorporeal membrane oxygenation.

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).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.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.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.

Early autologous hematopoietic cell transplantation (AHCT) with post-transplant maintenance therapy is standard of care in multiple myeloma (MM). While short-term quality of life (QOL) deterioration after AHCT is known, the long-term trajectories and symptom burden after transplantation are largely unknown. Toward this goal, a secondary analysis of QOL data of the BMT CTN 0702, a randomized controlled trial comparing outcomes of three treatment interventions after a single AHCT (N = 758), was conducted. FACT-BMT scores up to 4 years post-AHCT were analyzed. Symptom burden was studied using responses to 17 individual symptoms dichotomized as 'none/mild' for scores 0-2 and 'moderate/severe' for scores of 3 or 4. Patients with no moderate/severe symptom ratings were considered to have low symptom burden at 1-year. Mean age at enrollment was 55.5 years with 17% African Americans. Median follow-up was 6 years (range, 0.4-8.5 years). FACT-BMT scores improved between enrollment and 1-year and remained stable thereafter. Low symptom burden was reported by 27% of patients at baseline, 38% at 1-year, and 32% at 4 years post-AHCT. Predictors of low symptom burden at 1-year included low symptom burden at baseline: OR 2.7 (1.8-4.1), p 0.0001; older age: OR 2.1 (1.3-3.2), p = 0.0007; and was related to being employed: OR 2.1 (1.4-3.2), p = 0.0004). We conclude that MM survivors who achieve disease control after AHCT have excellent recovery of FACT-BMT and subscale scores to population norms by 1-year post-transplant, though many patients continue to report moderate to severe severity in some symptoms at 1-year and beyond.

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.

7045 Background: The Center for International Blood and Marrow Transplant Research (CIBMTR) provides a validated 1-year Overall Survival (OS) calculator to estimate outcomes for individual patients prior to allogeneic Hematopoietic Cell Transplant (HCT) to inform risk. The calculator considers pre-HCT clinical and demographic characteristics, but not patient-reported outcome (PRO)s. Pre-HCT PRO scores have been associated with OS. We hypothesized that adding the baseline PRO score to the calculator will enhance its performance in predicting OS. Methods: In addition to established covariates,we considered pre-HCT PRO scores, collected on five (published) prospective randomized clinical trials performed through the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Measures used were the SF36 physical component score (PCS) and mental component score (MCS), and the FACT-BMT Trial outcome index (TOI). We also investigated inclusion of a single question from the SF36: In general, would you say your health is: excellent/very good/good vs fair/poor. Patients were ≥18. Results: 1,033 patients were included, 341 (33%) completed only the SF36, 339 (33%) only the FACT-BMT and 353 (34%) both, per study design. HCT occurred 2004-2014, and the population was diverse with respect to disease, stage, demographics, and transplant characteristics. When adjusted for clinical characteristics, the PCS was significantly predictive of mortality (HR=0.88, 95%CI 0.81-0.96, p=0.0021), while the MCS and TOI were not. The single general health question was also significantly associated with mortality (HR=0.52, 95%CI 0.35-0.74, p=0.0004). Addition of PRO scores to the calculator did not result in a significant change in the model’s predictive ability as measured by Harrell’s concordance statistic (Table). Conclusions: In this large analysis, we confirmed the significant, independent association of pre-HCT PRO scores with OS. We showed, for the first time in this setting, that a single general health question is as accurate as the full SF36 measure for predicting survival, but we did not find support for the hypothesis that adding PROs to the calculator improved its performance. Estimates of baseline PRO measure effect on mortality and model concordance statistics at 1-year post-HCT. [Table: see text]

Introduction: Allogeneic hematopoietic cell transplantation (HSCT) is a curative treatment option for children and adolescents with non-malignant disorders. Continued advances in HSCT have led to a growing population of long-term survivors. For these survivors, late occurring chronic health conditions or so-called "late effects" remain a challenge. We examined the cumulative incidence of selected late effects at 5- and 10-years post-HSCT in pediatric and adolescent patients transplanted for non-malignant diseases. Methods: A retrospective analysis using the Center for International Blood and Marrow Transplant Research (CIBMTR) database was performed. Eligible patients (1 - 20 years) underwent HSCT between 1995 and 2012 for treatment of non-malignant disorders including marrow failure, red cell disorders, and immunodeficiencies (Table). Late effects evaluated were: avascular necrosis (AVN), cataracts, diabetes, growth hormone deficiency, hypothyroidism, gonadal dysfunction, renal failure requiring dialysis, and neurologic events (stroke and seizure). The cumulative incidence of each late effect was calculated at 5-years and 10-years from date of first report post-HSCT. Results: Median follow up was 94.1 months. A total of 5,858 patients from 230 centers were included. Median age at HSCT was 5.5 years. The majority (65%) of the patients were White race/ethnicity and 9% were Black, 60% were male. Diagnoses included: Marrow failure disorders, hemoglobinopathies, immunodeficiencies and immune-dysregulation syndromes (Table). The majority (62%) of the cohort received myeloablative conditioning (MAC), and a minority (16%) received total body irradiation (TBI). Among all patients, 19% had chronic graft-versus-host-disease (GVHD). Cumulative incidence estimates at 5- and 10-years post-HSCT are presented in the Table. One-third (28%) of patients had at least one late effect. Cumulative incidence estimates at 10 years included stroke/seizures (11.2%), renal failure (7.7%), growth hormone deficiency/disturbance (7.6%), gonadal dysfunction (4.2%), hypothyroidism (4.1%), cataracts (2.9%), and AVN (1.4%). For AVN, renal failure, and stroke or seizures, incidence was stable between 5 and 10 years. For endocrine-associated late effects, incidence increased over time, nearly doubling from 5 to 10 years (Table). Across the cohort, the probability of growth hormone deficiency increased from 3.7% at 5-years, to 6.5% at 10-years. Similarly, hypothyroidism increased from 2.7% at 5-years, to 4.5% at 10 years. The cumulative incidence of treatment-associated diabetes was 3.1%, with most cases occurring in the first-year post-transplant. Finally, the probability of cataracts at 10 years was 2.9%, which was double the incidence at 5 years. Conclusions Among children and adolescents undergoing HSCT for non-malignant diseases, cumulative incidence of late effects was overall low, and did not exceed 12% at 10 years. The timing of late effect development differed, with the cumulative incidence of AVN, diabetes, renal failure, and seizure/stroke staying fairly stable after 5-years. Diabetes occurred most frequently in the first year, which may be a reflection of steroids or other medications to manage graft-versus-host-disease during the early-post transplant period. In contrast, the incidence of endocrine-associated late effects including growth disturbance, hypothyroidism, gonadal dysfunction and cataracts nearly doubled between 5 and 10-years post-transplant. Findings from this work further emphasize the need for long-term follow-up and screening for late effects, particularly diabetes, renal disease and neurologic symptoms early post-transplant, and cataracts and endocrinopathies over time. Figure 1 Figure 1. Disclosures Hamilton: Syndax: Membership on an entity's Board of Directors or advisory committees; Equilium: Membership on an entity's Board of Directors or advisory committees. Schoemans: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: personal fees , Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants and personal fees; Gilead: Other: travel grants; CIBMTR: Consultancy, Other: travel grants; Janssen: Membership on an entity's Board of Directors or advisory committees; BHS: Membership on an entity's Board of Directors or advisory committees, Other: travel grants and personal fees , Research Funding; Jazz Pharmaceuticals: Other: personal fees; Takeda: Other: personal fees. Phelan: Amgen Pharmaceuticals: Research Funding.

Introduction: It has been shown that racial/ethnic minorities have worse survival after matched unrelated donor allogeneic hematopoietic cell transplantation(allo-HCT) compared to Whites. Whether the racial disparity in allo-HCT outcomes persists in long-term survivors, and possibly may even be exacerbated in this population that frequently transitions back from the transplant center to their local healthcare providers, is unknown. In the current study we sought to compare long-term outcomes among one-year survivors, by race/ethnicity and socioeconomic status (SES), after allo-HCT reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Methods: The CIBMTR database was used to identify 5,473 patients with Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myeloid Leukemia (CML), or Myelodysplastic Syndrome (MDS) who received HCT between 2007-2017, who were alive and in remission for at least 1 year after allo-HCT. Study was restricted to patients transplanted in the United States. Cox regression model was used to determine association of ethnicity/race and SES with overall survival (OS), relapse, and treatment related mortality (TRM). Standardized mortality ratio (SMR) was calculated to compare mortality rates of the study patients to their general population peers matched on race/ethnicity, age and sex. Results: Patients were reported to be Non-Hispanic White (W) (n=4385), Non-Hispanic Black (B) (n=338), Hispanic (H) (n=516), and Asian (A) (n=234). Median follow up after 1 year allo-HCT (months): 69 W, 50 B, 59 H and 57 A (Table 1). Patient neighborhood poverty level was estimated from residential ZIP code at the time of allo-HCT. A ZIP code with ≥20% of persons below the federal poverty level was considered high poverty area. In multivariable analysis, we observed no significant differences in OS, relapse or TRM based on race or poverty level when adjusted for patient-, disease- and transplant-related covariates (Table 2). Conclusions: Our study highlights that among those who survived at least 1-year in remission after allo-HCT, previously reported disparities in post HCT outcomes based on racial/ethnic factors, are not evident in contemporary practice. This might suggest that previously recognized disparity in outcomes could be due to factors that mostly affect patients in their first year post HCT. Future studies are needed to identify these early adverse factors and implement strategies to mitigate them. Figure 1 Figure 1. Disclosures Blue: Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; WebMD: Consultancy. Wood: Pfizer: Research Funding; Teladoc: Consultancy; Koneksa Health: Consultancy, Current equity holder in publicly-traded company. Majhail: Incyte Corporation: Consultancy; Anthem, Inc: Consultancy. Saber: Govt. COI: Other.

Background There has been an increase in overall utilization as well as improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for most hematologic disorders over time. It is not known if these changes have impacted racial/ethnic minorities equally. In this study, we describe changes in the volume and rate of autologous (auto) and allogeneic (allo) HCT and examine trends in survival in different racial/ethnic groups from 2009 to 2018. Methods Data were obtained from the Center for International Blood and Marrow Transplant Research (CIBMTR) which collects patient data on most autologous and allogeneic HCT recipients in the US. We compared the number of auto and allo transplants in 4 different racial/ethnic groups: Non-Hispanic Whites (NHWs), African Americans (AAs), Hispanics and 'Others' across five 2-year cohorts from 2009 to 2018. 'Others' included Asians, Pacific Islanders and Native Americans as well as non-US residents. Since numbers in individual categories were too low to be meaningful, they were grouped together as 'Others'. Multi race individuals and those with either race or ethnicity missing were excluded. Cox proportional hazards models were used to examine trends in overall mortality after auto HCT in adult patients (for NHL, HD, and MM), and allo HCT among adult and pediatric patients (for AML, ALL, lymphoma including chronic lymphocytic leukemia, and MDS/MPD) in the 4 different racial ethnic groups over 5 study time periods. These models were adjusted for sociodemographic and clinical variables (age, sex, Karnofsky/Lansky score, HCT-comorbidity index, disease, disease status, geographic region, insurance, marital status, education, distance to the transplant center, median income derived from patient's ZIP code). Graft type, donor, conditioning, GVHD prophylaxis, donor-recipient CMV match and donor-recipient sex match were included for allo HCT models. Results A total of 80,080 (59,666 NHWs, 10,683 AAs, 7,110 Hispanics) patients received an auto HCT and 60,412 (44,272 NHWs, 4,964 AAs, 7,826 Hispanics) received an allo HCTs from 2009 to 2018. The volume of auto and allo transplants increased overall, as well as within each race/ethnicity group, over the study periods. In addition, there was a significant change in the proportion of patients in each racial/ethnic group undergoing an auto HCT, with a lower proportion of NHWs and increased proportion of minorities over time (from 78%, 12% and 8% in 2009 -2010 to 71%, 15% and 10% in 2017-2018 for NHWs, AAs and Hispanics respectively; p There was no significant difference in overall mortality amongst the three main racial ethnic groups, though there was decrease in mortality over time for auto HCT and adult allo HCT patients. In the allo HCT pediatric group, AAs had higher overall mortality as compared to NHWs across all time periods. (Table 2) Figure 1 shows temporal trends in two-year survival by race and ethnicity. Conclusions This large population-based study shows an improvement in the rates and survival of auto and allo HCT in adults over time. Changes in the proportion of different racial/ethnic groups undergoing HCT are higher than rate of change of population growth (3% decline for NHWs, no change in AAs and 2% increase in Hispanics from 2010 to 2019 per William H. Frey analysis of census population estimates released June 25, 2020). Progress is reflected in higher rates of increase in racial/ ethnic minority groups and comparable survival across the racial ethnic groups in our cohort as compared to two prior registry studies (Baker et al. JCO 2005 and Baker et al. BBMT 2009) for most HCT patients. However, in pediatric patients undergoing allo HCT, the gap in survival between NHWs and AAs has continued to persist over the years. With increasing diversity of the US population, we need to strengthen our efforts for improving access to, and outcomes of HCT to narrow the gap for all patients requiring HCT, irrespective of their sociodemographic characteristics. Figure 1 Figure 1. Disclosures Wood: Koneksa Health: Consultancy, Current equity holder in publicly-traded company; Teladoc: Consultancy; Pfizer: Research Funding. Ailawadhi: Karyopharm: Consultancy; AbbVie: Consultancy; Genentech: Consultancy; Takeda: Consultancy; GSK: Consultancy, Research Funding; Xencor: Research Funding; Cellectar: Research Funding; Medimmune: Research Funding; Ascentage: Research Funding; Pharmacyclics: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; BeiGene, Ltd.: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy. Saber: Govt. COI: Other.

Natural killer (NK) cell determinants predict relapse-free survival after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia, and previous studies have shown a beneficial graft-versus-leukemia effect in patients with juvenile myelomonocytic leukemia (JMML). However, whether NK cell determinants predict protection against relapse for JMML patients undergoing HCT is unknown. Therefore, we investigated NK cell-related donor and recipient immunogenetics as determinants of HCT outcomes in patients with JMML. Patients with JMML (age 0 to 3 (HR, 0.52; 95% CI, 0.29 to 0.95; P = .032), centromeric A/B score (HR, 0.57; 95% CI, 033 to 0.98; P = .041), and telomeric A/B score (HR, 0.58; 95% CI, 0.34 to 1.00; P = .048). To our knowledge, this is the first study analyzing the association of NK cell determinants and outcomes in JMML HCT recipients. This study identifies potential benefits of donor KIR-B genotypes in reducing aGVHD. Our findings warrant further study of the role of NK cells in enhancing the graft-versus-leukemia effect via recognition of JMML blasts.