Logan, Brent R.

Abstract Introduction: Graft Failure (GF) is a rare but devastating outcome of HCT. Primary GF (PGF), defined as a failure of neutrophil recovery by Day+28, is straightforward to diagnose. Diagnosing secondary GF (SGF) is more challenging, with its broad time-range, multiple confounding diagnoses, and lack of predictive biomarkers. In BMT CTN1703/1801, we analyzed patients receiving RIC HCT for heme malignancies with either Tac/MTX (n=159) or PT-Cy (n=165) GVHD prophylaxis. SGF was defined as donor chimerism <5% after initial donor engraftment. With Tac/MTX, there were 3 PGF and 1 SGF diagnoses. With PT-Cy, there were 4 PGF and 6 SGF. Median SGF diagnosis was Day +64 (range: Day+28-215). There were too few Tac/MTX patients to analyze SGF, but sufficient events with PT-Cy. To identify PT-Cy SGF predictors, we leveraged lymphocyte, T, B, and NK cell reconstitution analysis. In SGF we found an early, profound deficit in the reconstitution of all major lymphocyte populations, including total lymphocytes, T, B, and NK cells, as early as Day+28. This enabled the modeling of a SGF risk classifier based on the Absolute Lymphocyte Count (ALC). Methods: Clinical ALC measurements were performed on all SGF patients (n=6) and on non-GF controls with ALCs available (146 of 155 non-GF patients). Flow cytometry was performed on all PT-Cy SGF patients (n = 6) and from a subset of non-GF controls (n = 18: controls were chosen as patients without relapse or severe GVHD, to reduce confounders introduced by immunologic interventions, and for whom all samples, including from the graft infusion, were available). T, B, and NK counts, as well as T cell subsets, were compared (using Welch's T test) on Days 7, 14, 21, 28, 42, 63, 98, 180, 270, 365, 730, with SGF patients censored on the day of GF diagnosis. To interrogate the optimal ALC cutoff, the cumulative incidence of SGF was computed at Days +28 and +42, with death without GF as a competing risk. Results: We have previously demonstrated that, compared to Tac/MTX, PT-Cy patients exhibited an early decrease in reconstitution of all T cell populations (with normal NK and B cell reconstitution). Here we focused specifically on PT-Cy patients with or without SGF. Graft CD34 counts/kg were not different between SGF patients and non-GF patients (mean CD34/kg = 1.38 x10e6 (SGF) vs 0.67 x10e6 (non-GF, p = 0.61) However, even amidst the overarching early suppression in T cell reconstitution with PT-Cy, SGF patients could be easily distinguished from the larger PT-Cy cohort, based on more profound deficits in ALC, T, B and NK cells reconstitution, measured using 2 strategies: (1) SGF patients demonstrated significant early (Day +28) quantitative defects in the reconstitution of the ALC (mean +/- SEM 262+/-32 cells/µL (non-GF) vs 60 +/- 25 (SGF, p<0.0001), CD4 T cells (62 +/- 12 cells/µL vs 19+/-15, p=0.048), CD8 T cells (15 +/-3 cells/µL vs 3.5 +/-1 p=0.0009), all CD8 T cell subpopulations, as well as NK cells (116+/-31 cells/µL vs 2.9+/-1.4 cells/µL, p= 0.002) and B cells (3.5 +/-1.4 cells/µL vs 0.16+/-0.07 p =0.03). (2) In SGF, there was a significant deficit in the rate of rise of all major lymphocyte populations between Days 28-42-60 vs non-GF, including CD4 T cells (p<0.0001), CD8 T cells (p = 0.0002), B cells (p<0.0001), and NK cells (p =0.048). These discoveries suggested that a classifier could be identified to risk-stratify patients for SGF. We explored an ALC cutpoint, amenable to standard clinical lab analysis. A statistically significant threshold was identified at both Days+28 and +42, with Day+42 being most predictive: A threshold of 120 cells/µL was identified as optimal, with landmark analysis documenting a SGF rate of 34.7% below the cutpoint, and SGF of 1% above it (HR = 45.9, 95% CI 5.7 - 366). Conclusions: Despite the small number of events, PT-Cy patients with SGF demonstrated a distinctive reconstitution trajectory that encompassed an early, substantial, and sustained deficit in all lymphocyte counts, as well as a lack of their longitudinal expansion. This enabled the discovery of a candidate ALC biomarker cutpoint at Day+42 that could distinguish patients who were more likely to develop SGF. If confirmed, these data could generate a predictive biomarker for SGF, which would enable the design of trials evaluating early interventions (e.g. CD34+ boosts, DLI, modification of immunosuppression) to improve outcomes for these patients.

PURPOSE Public reporting of health care outcomes can have unintended effects such as inappropriate risk aversion in patient selection. METHODS The center-specific survival analysis annually assigns all hematopoietic cell transplantation (HCT) centers in the United States a +1, −1, or 0 score for observed outcomes that are above, below, or within a center-specific predicted range of outcome. For each index year (2012-2016), centers receiving a −1 score after 0 scores in the preceding 2 years were compared with contemporaneous centers with as-predicted outcomes (0 score). Changes in the patient population characteristics in the 3 years before versus the 3 years after the index years were compared between the newly below-expected centers (NBCs) and the controls. A multivariate model adjusted for baseline patient population characteristics and center volume. RESULTS No differences in patient selection behavior were identified when comparing the NBCs with the controls across eight key patient population characteristics. For the statistically modeled (predicted) 1-year overall survival (OS), reflecting a holistic measure of centers' patient population risk, we observed no statistically significant difference in change (−0.23% [95% CI, −1.4 to 0.9]; P = .70). The observed OS increased in both NBCs and controls by 0.9% and 4.5%, respectively, without statistically significant difference in change. CONCLUSION Centers receiving a −1 score were not observed to deviate significantly from patient selection trends in the HCT field. These findings suggest that public reporting of HCT outcomes in the United States does not result in unintended bias against HCT for high-risk patients.

PURPOSE The likelihood of finding a human leukocyte antigen (HLA)–matched unrelated donor (MUD) for hematopoietic cell transplantation can be predicted using a donor search prognosis score. Patients without a MUD may use alternative donors (haploidentical related, mismatched unrelated, or umbilical cord blood). METHODS This multicenter biological assignment trial was conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 1702). Eligibility criteria were broad to mirror clinical practice. The primary end point was 2-year survival from evaluability and compared between those Very Likely (>90%) and Very Unlikely (<10%) to find a MUD. All other patients, Less Likely to find a MUD, were enrolled in an observational arm. Transplant outcomes were compared for all three groups. RESULTS A total of 1,751 evaluable patients at 47 centers were Very Likely (54.7%), Less Likely (29.5%), and Very Unlikely (15.8%) to identify a MUD. Survival did not differ in univariate (hazard ratio [HR], 1.00 [95% CI, 0.82 to 1.21]; P = .98) or multivariate (HR, 1.07 [95% CI, 0.86 to 1.33]; P = .56) analyses between the Very Unlikely and Very Likely groups, measured through 2 years from the beginning of a search for a MUD or alternative donor. Of the transplanted patients (n = 1,179), MUD was used for 94% of the Very Likely, 38% of Less Likely, and 9% of Very Unlikely patients. Multivariate analyses showed no differences in relapse, treatment-related mortality, disease-free survival, and acute and chronic graft-versus-host diseases for the three search prognosis groups after transplantation. CONCLUSION Using a donor search prognosis strategy to prioritize an alternative donor for patients Very Unlikely to find a MUD resulted in survival and transplant outcomes that were not statistically different compared with those Very Likely to find a MUD.

Abstract We conducted a post hoc analysis of data from Blood and Marrow Transplant Clinical Trials Network 1506 (MORPHO), a randomized trial of gilteritinib vs placebo as posttransplantation maintenance for patients with FLT3-ITD–mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 comutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD negative before HCT, there was no difference in the cumulative incidence of relapse during follow-up between those receiving MAC vs RIC. NPM1 comutation was associated with the largest magnitude of relapse-free survival benefit from post-HCT gilteritinib, and in these participants, post-HCT gilteritinib in the setting of RIC appeared to be as effective as MAC at preventing relapse. MAC appeared superior to RIC in preventing relapse only in participants who were NPM1 wild type at diagnosis and FLT3-ITD MRD positive before HCT. Our findings suggest that only a subset of patients with FLT3-ITD AML undergoing HCT may benefit from MAC and that, similar to AML therapy before HCT, the intensity of the HCT regimen should be adapted according to the molecular features of the disease. This trial was registered at www.clinicaltrials.gov as #NCT02997202.

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for older adults with hematologic malignancies. Concerns on nonrelapse mortality (NRM) in older adults limit allo-HCT utilization. We executed a prospective, observational study BMT-CTN 1704 (Blood and Marrow Transplant Clinical Trials Network) enrolling allo-HCT recipients aged ≥60 years from 49 centers in the United States. We analyzed associations between 13 measurements of older adult health and NRM within 1 year to construct a comprehensive health assessment risk model (primary-CHARM) using multivariate Fine-Gray model and grouped penalized variable selection. Two machine learning (ML) models (Cox and pseudo-value boosting) were also explored. Models’ performances were compared using area under the curve (AUC), with bootstrap and cross-validation sampling to correct for optimism, decision curve analysis (DCA), calibration, and Brier scores. Among 1105 patients with median age of 67 (range, 60-82) years who received allo-HCT, NRM was 14.4% and overall survival (OS) 71.7% at 1 year. Factors statistically selected for inclusion in primary-CHARM were higher comorbidity burden, lower albumin, higher C-reactive protein, older age, higher weight-loss percentage, lower patient-reported performance score, and cognitive impairment. Primary-CHARM scores were independently associated with higher NRM (hazard ratio [HR], 2.72; P &lt; .0001) and worse OS (HR, 2.09; P &lt; .0001). Bootstrap bias–corrected AUC for primary-CHARM was 0.591. Comparing primary-CHARM with HCT-comorbidity index and 2 ML-CHARM models, calibration, Brier score, and DCA analysis favored primary-CHARM. Primary-CHARM, with mostly simple and readily available parameters, risk stratifies older adults for allo-HCT. Adopting primary-CHARM in practice may promote broader use of HCT by quantifying risk and enhance the design of strategies to improve outcomes. This trial was registered at www.ClinicalTrials.gov as #NCT03992352.

Abstract BMT CTN (Blood and Marrow Transplant Clinical Trials Network) 1506 (“MORPHO”) was a randomized study of gilteritinib compared with placebo as maintenance therapy after hematopoietic cell transplantation (HCT) for patients with FLT3-ITD–mutated acute myeloid leukemia (AML). A key secondary end point was to determine the impact on survival of before and/or after HCT measurable residual disease (MRD), as determined using a highly sensitive assay for FLT3-ITD mutations. Generally, gilteritinib maintenance therapy was associated with improved relapse-free survival (RFS) for participants with detectable peri-HCT MRD, whereas no benefit was evident for those lacking detectable MRD. We conducted a post hoc analysis of the data and found that the level of MRD detected with this approach correlated remarkably with RFS and relapse risk, and that MRD detectable at any level negatively affected RFS. In the placebo arm, 42.2% of participants with detectable FLT3-ITD MRD relapsed compared with 13.4% of those without detectable MRD. We found that 14.8% of participants had multiple FLT3-ITD clones detected as MRD and had worse survival irrespective of treatment arm. Finally, we examined the kinetics of FLT3-ITD clonal relapse or eradication and found that participants on the placebo arm with detectable MRD relapsed rapidly after HCT, often within a few weeks. MRD-positive participants on the gilteritinib arm relapsed either with FLT3 wild-type clones (assessed by capillary electrophoresis), after cessation of gilteritinib with persistent MRD, or on progression of multiclonal disease. These data demonstrate the potential of FLT3-ITD MRD to guide therapy with gilteritinib for this subtype of AML. This trial was registered at www.clinicaltrials.gov as #NCT02997202.

Background: A donor search prognosis score based on HLA type and race/ethnicity can classify patients into 3 groups based on the likelihood of finding an HLA-matched (8/8) unrelated donor (MUD): Very Likely (44% of the population), Likely (41%) and Very Unlikely (15%). Previous studies showed that &gt;90% of Very Likely, 26% of Likely and &lt;10% of Very Unlikely patients used a MUD for their hematopoietic cell transplants (HCT), with the rest using other donor sources (mismatched unrelated donor, cord blood, or haploidentical relative). For some patients, prolonged efforts to identify a MUD might be futile and delay HCT, leading to increased morbidity, greater chance for relapse and disease resistance, and worse HCT outcomes. BMT CTN 1702 (NCT03904134) was the first national study to track the entire donor search identification process. Designed as a biologic assignment study, the goal was to estimate and compare overall survival between two arms: patients who are Very Likely to find a MUD versus those who are Very Unlikely to find a MUD. It tested whether provision of a donor search prognosis score to centers could prevent prolonged futile searches for the Very Unlikely group and improve their transplant rates and outcomes, compared to the Very Likely group. Methods: Eligible diagnoses included acute leukemia, myelodysplastic syndromes, lymphoma, acquired aplastic anemia and sickle cell disease. Patients could be consented at any time after diagnosis until an unrelated donor search was started. Consented patients became evaluable only after it was determined that no appropriate HLA-identical siblings were available. The primary endpoint was survival time after the patient was declared evaluable, regardless of whether HCT occurred, and was compared between the Very Unlikely and Very Likely groups. The target enrollment was 1732 evaluable patients. Because this was a biologic assignment trial and not a randomized trial, formal comparisons of overall survival between the Very Likely and Very Unlikely groups were done using a covariate-adjusted Cox proportional hazards model. The following covariates were a priori specified for adjustment in the model, according to the statistical analysis plan: sex, age, Karnofsky Performance Score (KPS), race/ethnicity, disease, disease status, and interval from consent to evaluability. Results: 1751 evaluable patients were enrolled at 47 centers: 44% female, median age 59.4 years (range 0.6-81.3 years), 73% were non-Hispanic White, 10% Hispanic White, 8% Black, 5% Asian/Native Hawaiian/Pacific Islander, 0.5% American Indian/Alaska Native. Among the evaluable patients, 1181 received a HCT, 827 died, and 924 are still alive with or without HCT, with a median of 25 months of follow up (range=6-54 months [mos], inter-quartile range [IQR]=25-34 mos). The distribution was: 958 Very Likely, 517 Less Likely, and 276 Very Unlikely. Individuals in the Very Unlikely group were younger and were less likely to be non-Hispanic White. The unadjusted cumulative incidences of undergoing HCT by 6 mos and 2 years [yrs], in the Very Unlikely group were 51% and 61% vs. 60% and 69% in the Very Likely Group; after adjustment, there was not a significant difference in the likelihood of undergoing HCT (Dehn et al, submitted). There was no difference in median time from evaluability to HCT: 3.4 mos Very Unlikely and 3.3 mos Very Likely. Unadjusted survival rates from the time of evaluability for the Very Unlikely and the Very Likely groups were: 6 mos (85% vs 84%), 1 yr (69% vs. 69%) and 2 yrs (55% vs. 56%). In the multivariate Cox model, there was no significant difference in the risk of death (HR = 1.07 for Very Unlikely vs. Very Likely, 95% confidence interval 0.86-1.33, p=0.56) adjusting for significant clinical covariates: age, KPS, disease status, and time from consent to evaluability were all significantly associated with overall survival. There was no significant center effect and no interaction between donor search prognosis group and clinical covariates. Conclusion: In this large multicenter BMT CTN study, using the donor selection strategy described, there was no difference in adjusted time to HCT or survival for patients Very Likely versus Very Unlikely to find an 8/8 MUD. These results suggest that patients Very Unlikely to identify a MUD should proceed to HCT using the best available alternative donor rather than delaying HCT to try to identify a MUD.

PURPOSE Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 ( FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202 ) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

Background: BMT CTN 1506/MORPHO was a randomized study of the FLT3 inhibitor gilteritinib versus placebo as post-transplant (HCT) maintenance therapy for patients (pts) with FLT3-ITD acute myeloid leukemia (AML). Patients with FLT3-ITD AML in first remission underwent HCT and then were randomized, in double-blind fashion, to either gilteritinib or placebo for 24 months. The primary endpoint was relapse-free survival (RFS), and a pre-specified secondary endpoint was the effect of measurable residual disease (MRD) on survival as detected by a highly sensitive assay for FLT3-ITD mutations. In the primary analysis, while RFS was higher for pts randomized to gilteritinib, the difference did not reach the pre-determined threshold for significance (HR: 0.679; 95% CI: 0.459, 1.005; 2-sided p-value: 0.0518). However, in the secondary analysis, the 50.6% of pts who had MRD detectable pre- or post-HCT had significantly higher RFS with gilteritinib (HR of relapse or death=0.515, 95% CI: 0.316, 0.838, p = 0.0065). In this post-hoc analysis, we examined 1) the impact on RFS of different levels of FLT3-ITD variant allele frequency (VAF) pre-randomization (immediately before or after HCT but prior to randomization to gilteritinib or placebo); 2) the impact of the presence of multiple mutations detected as MRD pre-HCT; and 3) the eradication of FLT3-ITD clones detected post-HCT during follow up on gilteritinib or placebo. Methods: First-pull marrow aspirates were collected from pts at two time points pre-randomization (pre-HCT and between 30-90 days post-HCT), as well as at 3, 6, 12, 18, and 24 months post-randomization. For MRD detection (performed at Invivoscribe; San Diego, CA), 700 ng input DNA was amplified by polymerase chain-reaction (PCR) using 25 cycles and primers flanking exons 14 and 15 of FLT3, followed by next-generation sequencing (NGS) analysis of the amplicons. Variant allele frequency (VAF) was calculated as FLT3 mutant reads/total FLT3 reads. For pts with multiple FLT3-ITD mutations, the VAF used in analysis was the sum of the VAFs for each FLT3-ITD variant. The lower limit of blank (LOB) of the assay is estimated to be 1 x 10 -6 VAF. For terminology, VAF &gt; 1 x 10 -6 and &lt; 1 x 10 -5 is referred to as MRD6, VAF &gt; 1 x 10 -5 and &lt; 1 x 10 -4 is MRD5, VAF &gt; 1 x 10 -4 or greater is MRD4, and MRD0 equals no detectable MRD. Results: MRD was evaluated in 350/356 (98.3%) pts pre-HCT and 347/356 (97.5%) pts post-HCT. MRD was detected in 46% of pts pre-HCT and 19.9% prior to randomization, including 4.5% who did not have detectable MRD pre-HCT. The variant allele frequency (VAF) of detectable MRD ranged from a low of 1.09 x 10 -6 to a high of 3.0 x 10 -1. More than a single mutation was detected in 51 pts pre-HCT. Most of these 51 pts had 2 clones, but the total ranged from 2-9. The presence of more than one mutation detected as MRD immediately pre-HCT was associated with worse RFS compared with all other pts (MRD-positive with only one clone and MRD-negative), irrespective of treatment arm (Figure 1A; HR=2.428, 95% CI: 1.555, 3.792, P &lt; 0.001). There was no significant difference in age, mutation length, VAF, or karyotype between pts with more than one mutation and those with single mutations. However, if the VAFs of pts with multiple FLT3-ITD mutations were summed and treated as a single value, then the median VAF for pts with multiple mutations was higher than for those with single mutations (2.14 x 10 -4 vs. 3.12 x 10 -5). The VAF (including the summed VAFs of pts with multiple mutations) at multiple levels correlated very closely with RFS after HCT. To illustrate this quantitative effect of peri-HCT FLT3-ITD VAF on RFS, Kaplan-Meier analysis of pts on the placebo arm grouped by MRD level is displayed in Figure 1B. In the 71 pts with MRD detectable post-HCT, the MRD was eradicated in 69% of pts on gilteritinib versus 44% of pts on placebo. Conclusions Pts with multiple FLT3-ITD mutations have a worse prognosis, which may simply be a reflection of increased disease burden (VAF). The quantity of FLT3-ITD MRD appears to highly correlate with outcome. Gilteritinib appears to augment the effect of HCT, as evidenced by increased eradication of MRD post-HCT. These data illustrate the potential utility of the PCR-NGS FLT3-ITD MRD assay in the management of pts with FLT3-ITD AML.

Introduction Public reporting of outcomes drives healthcare improvement in many fields, including hematopoietic cell transplantation (HCT), although with possible unintended consequences. The Center for International Blood & Marrow Transplant Research (CIBMTR) publishes an annual Center-Specific Survival Analysis (CSA), which compares HCT centers' observed 1-year overall survival (OS) with their statistically modeled expected 1-year OS, with 95% confidence intervals (CI). Centers with OS within their 95% CI receive a 0 score, indicating as expected outcomes. Those with OS below / above their 95% CI receive a -1 / +1 score, indicating below / above expected OS, respectively. After a -1 report, centers may change their patient selection criteria, causing unintentional systematic exclusion of patient populations who could benefit from HCT. We analyzed how the CSA report influences patient selection practices among centers receiving a -1 score. Methods Centers receiving a -1 report between 2012 and 2016 that had ‘as expected’ survival in the preceding 2 years were classified as newly below expected OS centers (NBCs). The year of their -1 report was used as the index year. Centers with ‘as expected’ OS in the 3 years before and after each index year were identified as control centers, reflecting expected evolution of patient selection in the HCT field. The patient population variables analyzed are shown in Table 1. The difference in patient population characteristics in the 3 years before vs the 3 years after the index years defined the change in patient selection behavior at the NBCs and the controls. A multivariate model adjusting for baseline patient population characteristics and center size was used to compare the change in patient population from before and after the index year in the NBCs and that of the controls. The difference in differences (ΔinΔ) were calculated as ΔNBC - ΔControl. A significance threshold of p&lt;0.01 was used to account for multiple testing. Results After adjusting for overall trends, center size, and baseline patient population characteristics, no differences in patient selection behavior meeting the pre-specified threshold for statistical significance were identified when comparing the NBCs (n=24 centers) with the controls (n=195 centers). In the 3 years following the index years, 4,150 and 25,013 patients were transplanted at NBCs and controls, respectively. The proportion of patients receiving reduced intensity or non-myeloablative conditioning regimens decreased 4.1% in NBCs and increased 5.0% in controls, for a net difference of -9.1% (95% CI: -16.7% to -1.6%, p=0.02). All other patient characteristic proportions changed in the same direction at NBCs and controls, albeit to varying degrees (Table 1). In some high-risk characteristics, (e.g. HCT-CI &gt; 3), a greater increase was seen at NBCs vs controls (ΔinΔ 2.1% 95% CI: -2.8% to 6.9%, p=0.40). In others, (e.g. age 60+ years), a greater increase was seen at controls vs NBCs (ΔinΔ -2.6% 95% CI: -5.9% to 0.7%, p=0.12). To capture a holistic measure of centers' patient population risk, the predicted 1-year survival was compared in the NBCs vs controls using the logistic regression model generated for each year's CSA. The predicted OS increased by 3.08% and 3.30% in the NBCs and controls respectively, with no statistically significant difference (-0.23%, 95% CI: -1.4% to 0.9%, p=0.70, Figure 1). The observed overall survival (adjusted for predicted 1 year OS) also increased in both BECs and controls by 0.9% and 4.5% respectively, without statistically significant difference (-3.6%, 95% CI: -6.7% to -0.7%, p=0.02). Discussion For centers receiving a -1 report, no statistically significant changes were seen in patient population characteristics in the following 3 years when compared to centers with OS was as expected. There was variability in the changes in high-risk patient characteristics at the NBCs relative to the controls, and in some cases more patients with high-risk characteristics were selected at these centers compared to those at controls. The change in predicted overall survival at 1 year, a summary indicator of survival risk, was similar between BECs and control centers. Although the number of patients in centers with below expected OS was small, these findings suggest the public reporting of outcomes in HCT in the US does not unintentionally affect access to HCT for high-risk patients at NBCs.