Rizzo, J. Douglas

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.

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

Abstract INTRODUCTION: Obesity is increasingly common in the US and is frequently associated with co-morbid medical conditions that may increase the risk of HCT, often the optimal treatment for AML. HCT risk and outcomes for AML on the basis of body mass index (BMI) have not been well-characterized. Using data from the Center for International Blood and Marrow Transplant Research (CIBMTR), we have previously shown no significant difference in outcomes for autologous HCT for lymphoma among normal weight, overweight, and obese patients (pts) but worse outcomes for underweight pts (Navarro et al, BBMT 2006, 12(5): 541–51). Here, we compare outcomes by weight groups for AML patients who underwent autologous, related, or unrelated HCT. METHODS: Our final population included patients age ≥ 18 who underwent myeloablative unpurged autologous or allogeneic HCT for AML in 1st or 2nd complete remission, primary induction failure, or 1st relapse reported to the CIBMTR from 1995 to 2004. Cord blood HCTs were excluded. Four weight groups were defined based on BMI (BMI=weight (kg)/ height (m2)): underweight <18; normal=18–25; overweight >25–30; and obese >30. Treatment-related mortality (TRM), relapse, leukemia-free survival (LFS), and overall survival (OS) were compared using multivariable proportional hazards regression analysis accounting for patient, disease and HCT-related variables. RESULTS: We included 373 autologous, 2041 related, and 1801 unrelated transplant recipients. Patient-, disease-, and transplant characteristics were well-matched across weight groups and transplant types. Multivariable analysis examining risks (95% confidence intervals) relative to the normal weight group are: HCT Type Normal Underweight Overweight Obese -- =not done due to insufficient number of pts; NS=not significant; treatment failure = death or recurrence of disease. Autologous n=164 n=5 n=112 n=81 Death -- NS NS Treatment failure -- NS NS Relapse -- NS NS TRM -- NS NS Related Allogeneic n=1161 n=31 n=543 n=268 Death 1.86 (1.24–2.78) NS 1.23 (1.04–1.47) Treatment failure 2.08 (1.37–3.15) NS 1.19 (1.00–1.42) Relapse 2.02 (1.18–3.47) NS NS TRM 2.22 (1.17–4.22) NS 1.32 (1.02–1.70) Unrelated Allogeneic n=846 n=31 n=523 n=368 Death NS NS NS Treatment failure NS NS NS Relapse NS 0.82 (0.68–0.99) 0.76 (0.60–0.96) TRM NS NS NS CONCLUSIONS: There were no significant differences in risk of TRM, LFS, relapse or OS for normal weight, overweight or obese patient groups who received autologous HCT. Obese recipients of related HCT for AML had increased risk of death, treatment failure, and TRM, though the magnitude was small, an effect was not seen in the unrelated HCT group. Underweight patients who received a related, but not unrelated HCT, fared substantially worse than normal weight patients for all outcomes. It may be that the higher risk of the unrelated HCT procedure masks important but less obvious risks associated with being underweight whereas in the related donor HCT setting, such risks become manifest. Small numbers of patients limit the ability to better characterize this finding in underweight patients. Disproportionately, fewer transplants have been reported in underweight patients which suggest they experience disease and patient-related factors that preclude transplantation. No differences were observed for incidence of acute or chronic GVHD for any weight group. Overweight and obesity should not be a barrier to HCT; however, caution should be exercised in selecting underweight patients for HCT.

Abstract Few data are available on the outcomes of patients who fail to engraft following URD transplantation. We describe the results of 122 patients reported to the National Marrow Donor Program (NMDP) between 1990 and 2005, who received a second bone marrow (BM) or peripheral blood (PB) URD transplant after failing to achieve an absolute neutrophil count of ≥ 500/mm3 without evidence of recurrent disease. Patients were transplanted for leukemia (n=83), myelodysplastic disorders (n=16), severe aplastic anemia (n=20) and other disease (n=3). The median age at first transplant was 29 years. Approximately one third were in each age range, < 20 (33%), 20–40 (37%) and >40 (29%). The initial transplant was BM in 84% of patients while 51% received BM for the subsequent transplant. One hundred ten of these patients received two transplants, 11 received three and one received 4 transplants. Twenty four used a different donor whereas 98 used the original donor for the second transplant; 28 of these used cells that had been cryopreserved at the initial transplant date. Nearly two thirds of the patients received reduced intensity conditioning or no conditioning for the second transplant. Sixty one percent had ATG as a component of their second transplant. The median interval from first transplant to second transplant was 48 (range, 18–126) days. The median nucleated cell dose was 2 × 108/kg (range, <1–23) for the first transplant and 2 × 108/kg (range, <1–50) for the second. The median follow up of survivors after second transplant was 77 (range, 2–144) months. Univariate probabilities of outcomes for these patients after second transplant were: Outcome N eval Probability (95% CI) *cumulative incidence Neutrophil engraftment* 122 @ 28 days 43 (34–52) % @100 days 48 (39–57) % 30 day mortality 122 39 (31–48) % 100 day mortality 122 75 (67–82) % Overall survival (OS) @ 1 year 122 11 (6–17) % Treatment related mortality (TRM) @ 1 year* 99 86 (79–92) % Disease free survival (DFS) @ 1 year 99 7 (2–12) % Of the 122 patients analyzed, only 10 remain alive. The most common causes of death were graft failure or rejection (33%), organ failure/interstitial pnuemoniatis (22%), infection (15%), GVHD (14%) and recurrent disease (6%). Of the 37 patients who had persistent graft failure 21 (57%) died from infectious causes. We observed no differences between patients who received a graft from the same donor vs. different donor, fresh vs. cryopreserved cells, or small initial graft size vs. large initial graft size. Patients who received a T-cell depleted graft at the time of their first transplant had significantly worse survival at 1 year after their second transplant, 4% (95% CI, 0–11) compared to those patients who had a non T-cell depleted initial graft, 16% (95 % CI, 8–25)(P = 0.02). It appears that a second salvage transplant strategy may be effective in a small group of patients, although the overall DFS at 1 year of only 7% is disappointing. To improve these results, efforts might focus on early identification and treatment of those at highest risk for non engraftment to determine whether such a strategy can alter the natural history we have described.

Abstract Therapy-related myelodysplastic syndromes (t-MDSs) and acute myeloid leukemia (t-AML) have a poor prognosis with conventional therapy. Encouraging results are reported after allogeneic transplantation. We analyzed outcomes in 868 persons with t-AML (n = 545) or t-MDS (n = 323) receiving allogeneic transplants from 1990 to 2004. A myeloablative regimen was used for conditioning in 77%. Treatment-related mortality (TRM) and relapse were 41% (95% confidence interval [CI], 38-44) and 27% (24-30) at 1 year and 48% (44-51) and 31% (28-34) at 5 years, respectively. Disease-free (DFS) and overall survival (OS) were 32% (95% CI, 29-36) and 37% (34-41) at 1 year and 21% (18-24) and 22% (19-26) at 5 years, respectively. In multivariate analysis, 4 risk factors had adverse impacts on DFS and OS: (1) age older than 35 years; (2) poor-risk cytogenetics; (3) t-AML not in remission or advanced t-MDS; and (4) donor other than an HLA-identical sibling or a partially or well-matched unrelated donor. Five-year survival for subjects with none, 1, 2, 3, or 4 of these risk factors was 50% (95% CI, 38-61), 26% (20-31), 21% (16-26), 10% (5-15), and 4% (0-16), respectively (P < .001). These data permit a more precise prediction of outcome and identify subjects most likely to benefit from allogeneic transplantation.