Brazauskas, Ruta

Importance Limited granular data exist on breast cancer in transgender, nonbinary, and/or gender-diverse (TGD) individuals. Objective To describe patient demographic and tumor clinicopathological variables, clinically relevant risk factors, method of breast cancer detection, treatment characteristics, and locoregional outcomes and to estimate a 5-year breast cancer–specific survival (BCSS). Design, Setting, and Participants This cohort study obtained data on patients treated from 1990 to 2023 from 22 US academic medical centers using institutional databases, electronic medical records, and tumor registries. Included participants were TGD individuals 18 years or older with stage 0 to IV breast cancer. A comparative breast cancer cohort was selected from the 2016 to 2021 Surveillance, Epidemiology, and End Results Program (SEER) breast cancer dataset. Data were analyzed from January to October 2025. Exposure Breast cancer. Main Outcomes and Measures Estimated 5-year BCSS and locoregional recurrence rates. Wilcoxon rank sum and χ 2 tests were used to compare continuous and categorical variables. Kaplan-Meier analysis was used to estimate 5-year BCSS. Results A total of 112 TGD persons (median [IQR] age at diagnosis, 42.5 [36.5-51.0] years; 104 individuals [92.9%] were assigned female at birth) with breast cancer and 1 with bilateral disease were included in the analysis. Forty-three patients (38.4%) used gender-affirming hormone therapy before diagnosis. Among the entire cohort, 58 patients (51.8%) detected their own breast cancer, 68 (60.7%) had a familial breast cancer history, and 16 (14.3%) had a pathogenic germline variant. Tumors were predominantly hormone receptor positive (96 [85.7%]) and early stage (29 [25.7%] ductal carcinoma in situ [DCIS]; 51 [45.1%] stage I). The TGD cohort, compared with patients with breast cancer in the SEER dataset (N = 480 915), was younger (median [IQR] age, 42.5 [36.5-51.0] years vs 62.0 [52.0-72.0] years), had a higher proportion of persons assigned male at birth (8 [7.1%] vs 3522 [0.7%]), more often had progesterone receptor–positive disease (89 [79.5%] vs 335 491 [69.8%]), and presented with earlier-stage disease (eg, DCIS: 29 [25.9%] vs 79 604 [16.6%]). With a median (IQR) follow-up time for the TGD cohort of 38 (24-74) months, 5-year BCSS was favorable at 96.2% (95% CI, 85.3%-99.0%). Conclusions and Relevance This cohort study of TGD patients with breast cancer found that this population was young and often detected their own tumors via self-examination, suggesting opportunities to improve early detection through screening for individuals at elevated risk. Although short-term BCSS appeared favorable, prospective research is essential to define evidence-based guidelines and elucidate long-term outcomes.

Abstract Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancy, can be effectively treated with allogeneic hematopoietic cell transplantation (HCT). Older age at HCT and mismatched donors are known to affect overall survival (OS). However, the influence of specific clinical manifestations or WAS variant class on OS and factors associated with event-free survival (EFS) remain incompletely defined. We analyzed outcomes of 308 patients with WAS who underwent HCT at 37 institutions of the Primary Immune Deficiency Treatment Consortium from 1990 to 2018. With a median follow-up of 5.3 years, the 5-year OS and EFS were 87.2% and 79.7%, respectively. Age ≥5 years, donor type, and a pre-HCT history of severe infection had a negative impact on OS and EFS, whereas pre-HCT autoimmunity had no impact. Reduced-intensity regimens were associated with lower T-cell and myeloid donor chimerism, particularly when non–busulfan-based regimens were used. Low myeloid donor chimerism was associated with lower platelet counts. Mixed chimerism was not consistently associated with post-HCT autoimmunity. Patients with class I (exon 1-2 missense and intron 5 hot spot variants) and class II variants (all others) had similar pre-HCT clinical symptom severity and no difference in OS, EFS, or platelet recovery post-HCT. In conclusion, our study showed excellent long-term OS and EFS after HCT for WAS, highlighting the importance of early HCT, before the development of severe infections. We confirmed that HCT using busulfan-based conditioning was associated with improved donor chimerism and platelet recovery. This trial was registered at www.clinicaltrials.gov as NCT02064933.

ABSTRACTBackgroundIn this study, we compared outcomes of intensified myeloablative conditioning regimens using large registry data from Japan (Japanese Society for Transplantation and Cellular Therapy) and the United States (Center for International Blood and Marrow Transplant Research).MethodsAdult patients who underwent their first myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia in remission between 2010 and 2018 using conditioning regimens of cyclophosphamide plus total‐body irradiation (CY/TBI), CY/TBI+cytarabine (AraC), or CY/TBI+etoposide (VP16) were included.ResultsThe acute myeloid leukemia (AML) cohort (N = 480, 38.8%) indicated that overall survival (OS) was poorer in CY/TBI+AraC (hazard ratio [HR] 1.46, p < 0.001) and CY/TBI+VP16 (HR 1.39, p = 0.059) compared to CY/TBI. Relapse was not suppressed, while treatment‐related mortality (TRM) was significantly higher (HR 1.78 and 1.74, p < 0.001 and 0.018, respectively). In the acute lymphoblastic leukemia (ALL) cohort (N = 3901, 61.2%), OS was comparable among these regimens. With intensified regimens, relapse was significantly suppressed in CY/TBI+VP16 (HR 0.74, p = 0.005), while TRM was higher (HR 1.21, p = 0.077). No interactions were observed regarding the country.ConclusionIn AML adding AraC and VP16 to CY/TBI had an adverse effect on OS. Conversely, in ALL, adding VP16 or AraC to CY/TBI did not affect survival, but the addition of VP16 reduced the risk of relapse.Clinical Trial RegistrationThe authors have confirmed clinical trial registration is not needed for this submission.

ImportanceUtilization of hematopoietic cell transplantation (HCT) for hematologic cancers previously demonstrated race, ethnicity, and age-based disparities.ObjectiveTo evaluate utilization over time by race, ethnicity, and age to determine if disparities persist in light of recent significant increases in HCT volume.Design, Setting, and ParticipantsThis US population-based retrospective cohort study includes patients who received transplants from January 2009 to December 2018. Data collection and cleaning occurred from February 2019 to November 2021, and data analysis occurred from January 2022 to October 2023. Method 1 restricted the analysis to Surveillance, Epidemiology and End Results (SEER) reporting areas for cases and transplants. Method 2 applied SEER age-, race-, and ethnicity-specific incidence rates to corresponding US census population and included all transplants reported to the Center for International Blood and Marrow Transplant Research. Race and ethnicity groups were hierarchically defined as Hispanic (any race), non-Hispanic White, non-Hispanic Black, and non-Hispanic Other (Asian and American Indian).ExposureReceipt of HCT.Main Outcomes and MeasuresUtilization rate of autologous or allogeneic HCT for patients with hematologic cancers by age, race, and ethnicity.ResultsFrom 2009 to 2018, 136 280 HCTs were analyzed for 6 hematologic cancers comprising 16.7% pediatric/adolescent/young adults (0-39 years), 83.3% adults (40-84 years), 58% male, 10.3% Hispanic, 11.4% non-Hispanic Black, 3.8% non-Hispanic Other, and 74.5% non-Hispanic White patients, with 49 385 allogeneic and 86 895 autologous HCTs performed. HCT utilization increased over time for all disease, age, race, and ethnic groups. From 2017 to 2018, adult (40-84 years) allogeneic transplant utilization for acute myeloid leukemia and myelodysplastic syndrome (MDS) was similar for Hispanic and non-Hispanic White or Other patients but was lower for non-Hispanic Black patients (acute myeloid leukemia: 19% vs 13%; MDS: 9%-10% vs 5%). Similarly, autologous transplant utilization for lymphoma was similar for all race and ethnicity groups; however, autologous transplant for multiple myeloma was highest for non-Hispanic White patients and lower for all other groups (31% vs 26%-27%). In patients aged 0 to 39 years, utilization of allogeneic transplant for acute lymphoblastic leukemia was highest in Hispanic patients, followed by non-Hispanic White, Black, and Other races (acute lymphoblastic leukemia: 19%, 18%, 17%, and 16%, respectively).Conclusions and RelevanceIn this cohort study of autologous and allogeneic transplant utilization for hematologic cancers, disparities persisted for non-Hispanic Black patients. Hispanic, non-Hispanic Other, and younger age groups had increased utilization over time that was on par with non-Hispanic White patients in the most recent cohort.

Abstract There has been an increase in volume as well as an improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have affected racial/ethnic minorities equally. In this observational study from the Center for International Blood and Marrow Transplant Research of 79 904 autologous (auto) and 65 662 allogeneic (allo) HCTs, we examined the volume and rates of change of autoHCT and alloHCT over time and trends in OS in 4 racial/ethnic groups: non-Hispanic Whites (NHWs), non-Hispanic African Americans (NHAAs), and Hispanics across 5 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.04-1.22; P = .004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; P &lt; .001) had a higher risk of mortality after alloHCT than NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT. Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics than in NHWs. Survival after autoHCT and alloHCT improved over time; however, NHAAs have worse OS after alloHCT, which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT.

Abstract Study Design: Cross-sectional study. Objectives: To determine etiologic factors related to spinal cord injury (SCI) severity and to assess factors related to benefit from care in individuals seen for SCI in six Eastern and South-eastern Asian countries. Setting: Care centers in Bangladesh, India, Malaysia, Nepal, Sri Lanka, and Thailand. Methods: Data from multiple centers collected between October 2015 and February 2021 were analyzing using descriptive statistics and logistic regression. Results: Among 2,634 individuals, the leading cause of SCIs was falls (n=1410, 54%). Most single-level SCIs occurred in the thoracic spine (n=977, 39%). Greater than half of SCIs (n=1423, 54%) were graded American Spinal Injury Association Impairment Scale (AIS) A. Thoracic SCIs accounted for 53% (n=757) of all single-level AIS A SCIs, and the percentage of thoracic SCIs graded AIS A (78%) was significantly higher than cervical (51%), lumbar (24%), sacral (8%), and multiple level (15%) SCIs (p<0.001). Regression analyses isolated predictive factors both of SCI severity and inpatient improvement. Four factors predicted injury severity: age, spinal region, injury etiology, and country of residence. Four factors also predicted inpatient improvement: age, spinal region, AIS grade on intake, and country of residence. Conclusions: Falls were the leading cause of traumatic SCIs, most of which occurred from ≥1 meter. The thoracic spine was the most commonly injured region, and thoracic SCIs were associated with both increased injury severity and poorer recovery. Age, spinal region, and country were each predictive factors of both SCI severity and inpatient improvement. Sponsorship: Mayo Clinic Global Health Program

Abstract 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&lt;0.001). Similar trends were observed for allo HCT: from 76%, 8% and 12% in 2009-2010 to 71%, 9% and 14% in 2017-2018 of all allo HCTs for NHWs, AAs and Hispanics respectively; p&lt;0.001. While there was an increase in the rate of transplants over the years across all racial/ethnic groups, the rate was higher in AAs and Hispanics as compared to NHWs (Table 1). 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.

Abstract 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.

Abstract 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.