D’Souza, Anita

Abstract Abstract 1238 Background: SNPs within genes encoding factor XI (F11), fibrinogen genes (FGA, FGG) and other candidate genes within the procoagulant, anticoagulant, fibrinolytic, innate immunity and endocrine pathways have been reported as associated with VTE. However, the independent risk of VTE associated with many of these SNPs after controlling for factor V Leiden, Prothrombin G20210A and ABO blood group non-O carrier status is uncertain. Objective: To replicate candidate gene SNPs previously reported as associated with VTE. Methods: As part of a large replication study, we included 17 SNPs previously reported as associated with VTE in a custom Illumina Golden gate (total n=1093 SNPs) genotyping array. We genotyped 1270 non-Hispanic adults of European ancestry with objectively-diagnosed VTE (cases; no cancer, venous catheter or antiphospholipid antibodies) and 1302 controls (frequency-matched on case age, gender, race, MI/stroke status). Genotyping results from high-quality control DNA (SNP call rate ≥ 95%) was used to generate a cluster algorithm. The primary outcome was VTE status, a binary measure. The covariates were age at interview or blood sample collection, sex, stroke and/or MI status, and state of residence. To adjust for population stratification, we performed the multidimensional scaling (MDS) analysis option in PLINK v 1.07 to identify outliers in our population using the ancestry informative markers. We tested for an association between each SNP and VTE using unconditional logistic regression, adjusting for age, sex, stroke/MI status, state of residence and ABO rs514659 (in high linkage disequilibrium with non-O blood type). The analyses were corrected for multiple comparisons using an extension of false discovery rates. The false discovery rate (reported as a Q-value) is an analogue measure of the p-value that takes into account the number of statistical tests and estimates the expected proportion of false positive tests incurred when a particular SNP is significant. All analyses were performed using PLINK v 1.07. Results: MDS gave no evidence of population stratification. Genotyping was unsuccessful for two of the 17 SNPs. We found significant associations between VTE and SNPs in F11, FGG, TC2D and FGA (Table). However, the false discovery rates for all significant SNPs except F11 rs3756008 were >0.05, suggesting that the observed associations were likely falsely positive due to multiple comparisons. Even at a false discovery rate of Q-value=0.0099, one would expect ∼13 SNPs (0.0099 × 1302 SNPs) to be falsely associated with VTE due to multiple comparisons. Consequently, even our observed association between F11 rs3756008 and VTE remains tentative. Conclusions: We were unable to replicate reported associations between 15 SNPs and VTE. Our results emphasize the necessity of replication studies in different populations to confirm reported associations of SNPs with VTE. Disclosures: Heit: Daiichi Sankyo: Consultancy, Honoraria.

Key Points There was no difference in overall survival after allogeneic transplant between patients aged 55-64 years and patients ≥65 years. Age alone should not be a determinant for allogeneic transplant eligibility among older non-Hodgkin lymphoma patients.

572 Background: Single-center observational studies have established the use of single or tandem SCT to salvage relapsed GCT but randomized trials are lacking. We analyzed outcomes and prognostic factors in 2,395 male SCT recipients for relapsed GCT between 1990 and 2015. Methods: Recipients of single or tandem SCT reported to the Center for International Blood and Marrow Transplant Research were identified. Outcomes were compared by SCT year: 1990-94 (N = 288), 1995-99 (N = 351), 2000-04 (N = 376), 2005-09 (N = 509) and 2010-15 (N = 871). A recent subset (n = 267, 2000-2015) with detailed disease- and transplant-related data was further analyzed with a multivariate (MVA) Cox proportional hazards model. Results: Median age at SCT was 31 (11-76) years and 49% received SCT within 12 months of diagnosis consistent with early relapse/primary refractory GCT. 26% had primary extragonadal GCT; 1,167 (49%) had intent to tandem transplant (TT). The median follow up was 51 (3-313) months. Day 100 non-relapse mortality was statistically similar at 8% in 1990-94 (vs. 4% in 2010-15) but 3-year progression-free survival (PFS) improved from 24 (18-31)% in 1990-94 to 47 (43-50)% in 2010-15 (p < 0.0001) and 3-year survival (OS) from 35 (29-40)% to 54 (50-57)% in 2010-15 (p < 0.0001). Compared with single SCT, TT recipients were younger 31 (16-62) vs 34 (13-76), with lower Hematopoietic Cell Transplantation-Comorbidity Index, more likely to undergo SCT after 1 line of chemotherapy (28% vs 9%), and within 1 year of diagnosis (51% vs 38%). TT was preferred over single SCT over time (48% of SCT were TT in 2000-04 vs. 81% in 2010-15). In MVA, non-seminoma histology, residual tumor at SCT, receipt of > 1 line of pre-SCT chemotherapy and single SCT (vs. TT), were associated with worse PFS and OS. Year of SCT was not significant when adjusted for these covariates. Conclusions: In this large longitudinal cohort, improvements in PFS and OS were observed in recent years. SCT earlier in disease course and tandem SCT were associated with superior outcomes. These data involving a large cohort reported from 225 centers confirm specialized centers’ date in a real-world setting.

Key Points Over the last decade, allogeneic HCT has been increasingly administered in the United States to adults aged 70 and older with hematologic malignancies. Allogeneic transplant outcomes were reasonable; high comorbidity and ablative conditioning regimens were associated with inferior outcomes.

BACKGROUNDRace/ethnicity remains an important barrier in clinical care. The authors investigated differences in the receipt of autologous hematopoietic cell transplantation (AHCT) among patients with multiple myeloma (MM) and outcomes based on race/ethnicity in the United States.METHODSThe Center for International Blood and Marrow Transplant Research database was used to identify 28,450 patients who underwent AHCT for MM from 2008 through 2014. By using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results 18 registries, the incidence of MM was calculated, and a stem cell transplantation utilization rate (STUR) was derived. Post‐AHCT outcomes were analyzed among patients ages 18 to 75 years who underwent melphalan‐conditioned peripheral cell grafts (N = 24,102).RESULTSThe STUR increased across all groups from 2008 to 2014. The increase was substantially lower among Hispanics (range, 8.6%‐16.9%) and non‐Hispanic blacks (range, 12.2%‐20.5%) compared with non‐Hispanic whites (range, 22.6%‐37.8%). There were 18,046 non‐Hispanic whites, 4123 non‐Hispanic blacks, and 1933 Hispanic patients. The Hispanic group was younger (P < .001). Fewer patients older than 60 years underwent transplantation among Hispanics (39%) and non‐Hispanic blacks (42%) compared with non‐Hispanic whites (56%). A Karnofsky score <90% and a hematopoietic cell transplantation comorbidity index score >3 were more common in non‐Hispanic blacks compared with Hispanic and non‐Hispanic whites (P < .001). More Hispanics (57%) versus non‐Hispanic blacks (54%) and non‐Hispanic whites (52%; P < .001) had stage III disease. More Hispanics (48%) versus non‐Hispanic blacks (45%) and non‐Hispanic whites (44%) had a very good partial response or better before transplantation (P = .005). Race/ethnicity did not impact post‐AHCT outcomes.CONCLUSIONSAlthough the STUR increased, it remained low and was significantly lower among Hispanics followed by non‐Hispanic blacks compared with non‐Hispanic whites. Race/ethnicity did not impact transplantation outcomes. Efforts to increase the rates of transplantation for eligible patients who have MM, with an emphasis on groups that underuse transplantation, are warranted. Cancer 2017;123:3141–9. © 2017 American Cancer Society.

BACKGROUNDTo evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post‐transplantation.METHODSWe analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre‐HCT depression requiring treatment versus those without pre‐HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post‐HCT using Poisson models. We also compared the incidence of grade 2‐4 acute and chronic graft‐versus‐host disease (GVHD) in allogeneic HCT.RESULTSThe study included 1116 (15%) patients with pre‐transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre‐transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04‐1.23; P = 0.004) and a higher incidence of grade 2‐4 acute GVHD (HR, 1.25; 95% CI, 1.14‐1.37; P < 0.0001), but similar incidence of chronic GVHD. Pre‐transplant depression was associated with fewer days‐alive‐and‐out‐of‐the hospital (means ratio [MR] = 0.97; 95% CI, 0.95‐0.99; P = 0.004). There were 512 (13.5%) patients with Pre‐transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre‐transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98‐1.34; P = 0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97‐0.99; P = 0.002).CONCLUSIONPre‐transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre‐transplant depression represent a population that is at risk for post‐transplant complications. Cancer 2017;123:1828–1838. © 2017 American Cancer Society.

Summary For diffuse large B‐cell lymphoma ( DLBCL ) patients progressing after autologous haematopoietic cell transplantation (auto HCT ), allogeneic HCT (allo HCT ) is often considered, although limited information is available to guide patient selection. Using the Center for International Blood and Marrow Transplant Research ( CIBMTR ) database, we identified 503 patients who underwent allo HCT after disease progression/relapse following a prior auto HCT . The 3‐year probabilities of non‐relapse mortality, progression/relapse, progression‐free survival ( PFS ) and overall survival ( OS ) were 30, 38, 31 and 37% respectively. Factors associated with inferior PFS on multivariate analysis included Karnofsky performance status ( KPS ) <80, chemoresistance, auto HCT to allo HCT interval <1‐year and myeloablative conditioning. Factors associated with worse OS on multivariate analysis included KPS <80, chemoresistance and myeloablative conditioning. Three adverse prognostic factors were used to construct a prognostic model for PFS , including KPS <80 (4 points), auto HCT to allo HCT interval <1‐year (2 points) and chemoresistant disease at allo HCT (5 points). This CIBMTR prognostic model classified patients into four groups: low‐risk (0 points), intermediate‐risk (2‐5 points), high‐risk (6‐9 points) or very high‐risk (11 points), predicting 3‐year PFS of 40, 32, 11 and 6%, respectively, with 3‐year OS probabilities of 43, 39, 19 and 11% respectively. In conclusion, the CIBMTR prognostic model identifies a subgroup of DLBCL patients experiencing long‐term survival with allo HCT after a failed prior auto HCT .

Purpose Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. Patients and Methods Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). Results Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m2 or greater were associated with worsened OS. Conclusion Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality and excellent 5-year survival. The risk-benefit ratio for autotransplantation has changed, and randomized comparison with nontransplantation approaches is again warranted.

ObjectiveReview Mayo Clinic experience of localized tongue amyloidosis.Study DesignCase series with retrospective chart review.SettingAcademic medical center.Subjects and MethodsCases of localized tongue amyloidosis were identified from the dysproteinemia database at the Mayo Clinic in Rochester, Minnesota. Electronic records were reviewed with focus on presenting symptoms, laboratory results (ie, serum or urine immunoelectrophoresis, bone marrow biopsy, and fat aspirate analysis), treatment modality, and status of disease at follow‐up.ResultsSix cases of localized tongue amyloidosis presented to the Mayo Clinic between 1969 and 2011. Mean patient age was 69 years (range, 43‐90). Patients presented with asymptomatic tongue mass(es). Biopsy of the tongue mass in all patients showed amyloid on Congo red stains. Work‐up for systemic amyloidosis, including bone marrow biopsy, fat aspiration, and serum and urine protein immunoelectrophoresis, was negative for all 6 patients, nor was there other organ involvement. Two patients underwent resection of the lesions, and the remaining patients elected for observation. Recurrence requiring repeat excision occurred in 1 of the patients that underwent resection. Repeat evaluation for systemic involvement was performed in 3 patients 1 to 3 years after the initial diagnosis. None of these patients went on to develop systemic involvement.ConclusionsLocalized tongue amyloidosis remains a rare diagnosis and requires exclusion of systemic involvement. Localized lesions may be observed or resected; however, recurrence may occur with resection. Patients with localized tongue amyloidosis do not appear to be at increased risk of developing systemic involvement.