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Abstract Background: International Working Group (IWG) has set criteria in 2003 for response assessment in patients with AML; at which time intensive chemotherapy was the main therapy (Cheson, JCO 2003). Hypomethylating agents (HMA) were approved shortly after for the treatment of elderly AML (Fenaux, JCO 2009; Dombret et al Blood 2015). Although few patients achieve a deep response, the majority will have stable disease (SD), some of which could last several months while patients continue to receive HMA and gain clinical benefit. We hereby describe outcomes for patients who achieve SD with HMA for the treatment of elderly unfit AML patients. Methods: A total of 56 AML patients' data from Feb 2007 to June 2015 at Mayo Clinic were reviewed after appropriate IRB approval was obtained. All cases had their bone marrow slides reviewed at our institution. Patients were considered for our study if they received HMA as frontline therapy for their AML. Patients who received HMAs after induction chemotherapy failure or for their MDS were excluded. Response was identified based on 2003 IWG AML response criteria. Patients with SD were categorized into short-lasting (<6 cycles of HMA, cohort 1) or long-lasting (≥6 cycles of HMA, cohort 2) SD.Prognostic factors were analyzed by univariate and multivariate analyses. Survival estimates were calculated using Kaplan-Meier curves and univariate and multivariate analyses was based on log-rank testing using JMP software version 10. Results: i) Characteristics: Fifty six AML patients were treated with HMA as frontline therapy with median age of 76 years (range, 59-91), 68% of which were males. Therapy related AML (T-AML) was seen in 2% of the cases. Cytogenetics were favorable risk in 2%, intermediate in 62%, and poor in 36%. Complete remission (CR) was found in 10 (18%) patients, CR with incomplete count recovery in 3 (5%), partial remission (PR) in 3 (5%) patients. Forty patients were non-responders (SD). ii) Characteristics of HMA SD cohorts: Upon comparison of cohort 1 versus cohort 2 there was no statistical significance in median age, white blood count, absolute neutrophil count, platelets, peripheral blood and bone marrow blasts, bone marrow cellularity and sex. Median number of cycles was expectedly higher in cohort 2 vs 1 (9 vs 2, p<0.0001). Intermediate cytogenetic risk was more common in cohort 2 vs 1 (90% vs 43%, p=0.006), while poor risk was more common in cohort 1 vs 2 (57% vs 10%, p=0.006). Only 10% had complex karyotype in cohort 2 compared to 50% in cohort 1 (p=0.017). NPM1 mutation was absent in all cases, while FLT3 mutation was present 30% in cohort 1 and 25% in cohort 2 (p = 0.9). Decitabine was more commonly given in cohort 1 vs cohort 2 (80% vs 50%, p =0.07). iii) Clinical outcome of HMA SD cohorts : Median overall survival was higher in long-lasting SD patients (cohort 2) vs short-lasting SD (18 vs 4 months, p = 0.0002). Upon multivariate analysis, both age (p <0.0001) and long-lasting SD (p =0.01) were statistically significant for overall survival but not cytogenetics risk grouping nor type of HMA administered. Conclusions: Standard response criteria for AML by IWG were developed for intensive chemotherapy and do not apply to newer agents, specifically HMA. Stable disease (SD) could be meaningful to some elderly AML patients when treated with HMA. Intermediate cytogenetics and azacitidine use were more frequent in patients with long-lasting SD. Long-lasting SD did confer a survival benefit in elderly AML patients. Newer response criteria for assessing novel agents' efficacy are needed in this population. Figure Figure. Disclosures Tibes: Italfarmaco S.p.A.: Consultancy, Honoraria. Foran:pfizer: Honoraria; Millennium Pharmaceuticals, Inc.: Research Funding; medscape: Honoraria; karyopharm: Honoraria; novartis: Honoraria; boehringer ingelheim: Research Funding; agios: Research Funding; Cellerant: Research Funding. Al-Kali:Novartis: Research Funding; Celgene: Research Funding.

Abstract Introduction: Depression is associated with increased mortality among healthy individuals and patients with various medical conditions including cardiovascular disease and cancer. The impact of an existing diagnosis of depression prior to autologous and allogeneic hematopoietic stem cell transplantation (HCT) on clinical outcomes including overall survival has not been studied. Methods: We analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry to compare overall survival and hospital-length-of-stay during the first 100 days after autologous (n= 3786) or allogeneic (n = 7433) HCT for adult (≥ 18 years) patients with hematologic malignancies with an existing diagnosis of pre-transplant depression requiring treatment vs. those without pre-transplant depression. Data regarding an existing diagnosis of pre-transplant depression requiring treatment were collected from medical chart reviews and reported to the CIBMTR. Data for autologous and allogeneic HCT were analyzed separately. Using Cox proportional hazards regression models adjusting for patient-, disease-(including the disease risk index for allogeneic HCT), donor-(for allogeneic HCT), and transplant-related variables, we compared overall survival between patients with or without pre-transplant depression. To account for early deaths, we compared the number of days alive and out of the hospital in the first 100 days post-transplantation using Poisson models adjusting for patient-, disease-, and transplant-related variables. Among patients undergoing allogeneic HCT, we also compared the risk of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD among patients with or without pre-transplant depression using Cox proportional hazard regression analyses controlling for significant confounders. Results: We included 1116 (15%) patients with pre-transplant depression and 6317 (85%) patients without pre-transplant depression who underwent allogeneic HCT between 2008 and 2012. Patients with pre-transplant depression were similar to those without pre-transplant depression with regards to age, disease distribution, disease risk index, time from diagnosis to transplant, conditioning regimen, receipt of total body irradiation, graft type, donor type, and donor source, but they were more likely to be female, white, divorced, less educated, not working full-time, and had lower performance status and higher number of comorbid conditions. In multivariable analyses, pre-transplant depression was associated with higher overall mortality (HR 1.13, 95% CI 1.04-1.23, p = 0.004) and higher risk of grade II-IV acute GVHD (HR 1.25, 95%CI 1.14-1.37, p < 0.0001), but similar risk of chronic GVHD (HR 1.06, 95% CI 0.96-1.16, p = 0.26). 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). Among patients undergoing autologous HCT, we included 512 (13.5%) patients with pre-transplant depression and 3274 (86.5%) patients without pre-transplant depression between 2007 and 2012. Patients with pre-transplant depression were similar to those without pre-transplant depression with regards to disease distribution, disease status prior to HCT, time from diagnosis to transplant, conditioning regimen, and year of transplant, but they were slightly younger, more likely be to female, white, divorced, less educated, not working full-time, and had lower performance status and higher number of comorbid conditions. Pre-transplant depression in autologous HCT recipients was not associated with overall survival in multivariable analyses (HR 1.15, 95% CI 0.98-1.34, p = 0.096), but was significantly associated with fewer days alive and out of the hospital (MR = 0.98, 95% CI 0.97-0.99, p = 0.002). Conclusion: Pre-transplant depression was associated with higher mortality and higher risk of acute GVHD among patients undergoing allogeneic HCT. Moreover, pre-transplant depression is associated with a longer hospital-length-of stay during the first 100 days after autologous and allogeneic HCT. Therefore patients with pre-transplant depression represent a highly vulnerable population at risk for post-transplant mortality and complications, and they may benefit from more intensive interventions to mitigate the risk of depression on their post-transplant outcomes. Disclosures Chen: Bayer: Consultancy, Research Funding. Lee:Bristol-Myers Squibb: Consultancy; Kadmon: Consultancy. Hahn:Novartis: Equity Ownership; NIH/NHLBI: Research Funding.

Abstract BMT CTN 0201 was a randomized study of unrelated donor bone marrow (BM) vs. peripheral blood (PB) (N=551) in hematopoietic cell transplantation (HCT) for hematologic malignancies. The primary analysis after 2 years of follow up showed similar survival, disease-free survival and treatment-related mortality between the graft types. There was a higher rate of graft failure with bone marrow (9% vs. 3%, p=0.002) and a higher rate of chronic GVHD with peripheral blood (53% vs. 41%, p=0.01). (Anasetti et al, NEJM 2012) Patient reported outcomes (PROs) were collected from patients > 16 years old at enrollment and 0.5, 1, 2 and 5 years after transplantation with the Functional Assessment of Cancer Therapies - Bone Marrow Transplant (FACT-BMT), Mental Health Inventory (MHI), and Lee chronic graft-versus-host disease (cGVHD) symptom scale. At 5 years, 102 BM and 93 PB participants were alive and eligible for the quality of life (QOL) study. Clinically meaningful differences (changes in scores that are noticeable to patients) were considered 0.5 x standard deviation of the total population based on the distribution method. Results: Data as of 5/25/15 were analyzed. 70% completed the pre-randomization assessment, and 74-78% of adult survivors completed the 5 year assessment. Age < 30 at transplant and high risk disease were associated with missing 5 year data, but not graft source. Response rates at 0.5, 1 and 2 years were 28-43% of survivors. There are no differences in any of the primary QOL scores in the first two years after HCT using univariate comparisons, although missing data severely limit conclusions during this period. At 5 years, the FACT-Trial Outcome Index (TOI), the MHI Psychological Well-Being, and the cGVHD symptom scale scores are all significantly better for BM patients, although only the latter two are still significant after adjustment for multiple testing (p<0.0125 because of 4 primary QOL variables). Results were similar when tested in multivariate models adjusting for baseline patient-reported scores and also imputing missing values based on patient characteristics (Table). Of the 7 chronic GVHD subscales, symptoms in the eye, lung, and energy were significantly better with BM (p<0.01). A diagnosis of cGVHD was highly associated with patient-reported cGVHD symptoms but not with QOL or psychological status. Inclusion of extensive cGVHD in the multivariate models did not change the significance of PRO differences suggesting that differences in cGVHD incidence do not explain the PRO findings. With a median follow up of 73 months for survivors, no difference in survival between PB and BM is observed (p=0.84, Figure). Conclusion: At 5 years after transplant, recipients of unrelated donor BM have better psychological well-being and less burdensome chronic GVHD symptoms than recipients of PB. Survival rates are similar. Table. Comparisons of primary QOL variables at 5 years, adjusted for QOL values at baseline and missing data using inverse probability weighting using significant clinical characteristics. QOL scale Bone marrow (n=102) Peripheral blood (n=93) P value Clinically significant difference* Difference between BM and PB (95% CI) FACT-BMT TOI, mean +/- SE (higher scores better) 76.7 +/- 1.6 (n=79) 70.5 +/- 1.9 (n=69) 0.014 8.5 6.2 (1.3-11.1) MHI - Psychological well-being, mean +/- SE (higher scores better) 78.9 +/- 1.7 (n=80) 72.2 +/- 1.9 (n=72) 0.011 8.4 6.7 (1.6-11.8) MHI-Psychological Distress, mean +/- SE (lower scores better) 16.0 +/- 1.3 (n=80) 19.0 +/- 1.5 (n=71) 0.128 6.5 -3.0 (-6.8,0.9) Chronic GVHD symptoms, mean +/- SE (lower scores better) 13.1 +/- 1.5 (n=80) 19.3 +/- 1.6 (n=72) 0.004 7.1 -6.3 (-10.5, -2.0) SE, standard error *0.5 x STD Figure 1. Figure 1. Disclosures Lee: Bristol-Myers Squibb: Consultancy; Kadmon: Consultancy. Maziarz:Athersys: Consultancy, Patents & Royalties, Research Funding; Novartis: Consultancy.

Abstract Abstract 3606 Background: Cytogenetic abnormalities are important prognostic indicators in CLL. At Mayo Clinic, CLL FISH analyses are derived from buffy coat samples not purified for lymphocytes. Scoring is therefore performed on consecutive qualifying nuclei regardless of cell size, shape or morphology. This scoring may not reflect the percent of abnormal nuclei of the affected cell type, but rather the entire population of cells present in the sample. We sought to determine whether the percent abnormal nuclei in only the affected cell type (e.g. lymphocytes) of patients with CLL differed from that of the general cell population. Scoring only B-lymphocytes could increase the sensitivity of the test in patients with low B-cell counts, either early in their disease or after treatment. Cell sorting techniques could be used to reach this goal but can be expensive, labor intensive and add to completion time. We propose a “Poor Man's Cell Sorting” technique based on cell morphology when stained with 4',6-diamidino-2-phenylindole (DAPI). In CLL samples, both round and so called “lobed” cells are seen by DAPI staining but we hypothesize that the CLL B-cells typically present as perfectly round in shape (Fig. 1). Thus our hypothesis: if only the round cells are scored for a genetic defect, would this more accurately represent the malignant leukemic B-cell population and allow for enhanced disease status by FISH? Methods: After IRB approval, we identified 87 CLL patients (75% male; 25% female, mean age 62.4 y, range 43–89 y) in the Mayo Clinic CLL Database, who were seen at Mayo Clinic between March, 2002 - July, 2010. We selected patients known to have low level FISH abnormalities and who therefore should have a significant population of both lymphocytes and neutrophils. Selection criteria included <20×106 B-cells per microliter (by flow cytometry) of peripheral blood and ≤40% of interphase nuclei expressing a specific FISH abnormality. Although most of the 87 patients exhibited more than one FISH abnormality, we focused on only one FISH defect per patient for this study. The original specimen (slide or fixed cell pellet) was rescored for % abnormal nuclei among 100 consecutive round and 100 consecutive lobed (or multilobular) nuclei, using DAPI to identify nuclear architecture. These scores were compared to each other and to the original clinical FISH analysis (scored for 200 consecutive nuclei and not selected for nuclear morphology). Results: Among 87 cases, FISH signals were scored for 6q-(1), 11q-(9), +12(15), 13q-(58), 17p-(2) and 2 IGH rearrangements. In 86/87 cases, the abnormal lobed nuclei did not have FISH defects. One patient exhibited 35% +12 by clinical assay, 52% +12 in the round nuclei, and 11% by lobed nuclei. For all cases, the mean percentage of abnormal nuclei was greater in the round cells (46%) vs original scoring (23.6%). In 79/87 patients (91%), the % of abnormal nuclei was greater in the round cells vs original FISH (mean increase 24.3%; range 1.5–57%). One patient's score was the same in round cells vs original, and 7 patients exhibited fewer abnormal nuclei in the round cells vs original. For these 7 cases, the mean % abnormal nuclei was 5.6% for round nuclei vs 8.4% for original score (score differences ranged from 1 – 5.5%). Overall, by univariate regression analysis, round cells (p=0.0043) have a better correlation with % B-cells, ascertained by flow cytometry, than either the current clinical approach (p=0.0462) or the lobed-cell approach (p=0.4058). Discussion: In virtually all cases (99%), the abnormal FISH patterns were confined to the round nuclei, and the lobed nuclei were virtually always normal by FISH. For patients with <20×106 lymphocytes, selecting for round nuclei uniformly resulted in identification of a higher percentage of abnormal cells. Further studies, including comparison of our round nucleus approach to CLL FISH analysis to actual sorted B-lymphocyte cell selection and the association of this leukemic restricted estimation of abnormal FISH levels to clinical outcome are necessary. Given our findings, we believe that estimating FISH defects restricted to the leukemic B-cell population will become an important adjunct to cytogenetic analysis for patients with low lymphocyte counts, including those in clinical remission and those with minimal residual disease. Disclosures: No relevant conflicts of interest to declare.

Abstract Genetic analysis has an increasing role in the diagnosis, classification, and management of patients with CLL. Although translocations involving the IgH locus are well characterized in B-cell malignancies such as follicular cell lymphoma, their frequency and significance in CLL are less well defined. We studied a series of patients with a clinical diagnosis of CLL using a FISH probe set including IgH. Methods: FISH was performed on blood using a DNA probe set designed to detect common chromosome anomalies associated with CLL and translocations involving IgH. Patients with an IgH abnormality were further studied using FISH probes sets for IgH and cyclin D1, BCL-2, BCL-3, BCL-6, BCL-11a, c-MYC, MALT-1, c-MAF, FGFR-3 or PAX-5. The clinical presentation, pathology, and flow cytometric immunophenotype was reviewed in patients with various translocations involving IgH. Results: Between 1/1/03 and 6/15/04, samples from 1032 patients with a clinical diagnosis of CLL were analyzed by FISH. Of these, 76 patients (7%) had translocations involving the IgH locus. Sixty one patients had a single translocation partner gene (cyclin D1 45%, BCL-2 24%, BCL-3 8%, c-MYC 2.5%, or BCL-11a 1.3%). Two patients had two independent clones (cyclin D1 and BCL-2; BCL-3 and BCL-11a). In 13 pts (17%) we could not identify the translocation partner. Thirty five (46%) of the 76 patients with IgH translocations had been seen at Mayo Clinic Rochester and had clinical and laboratory data for detailed review. Among these 35 patients, 16 (45%) had fusion of IgH and cyclin D1 and were diagnosed with mantle cell lymphoma (MCL). The immunophenotype of the monoclonal B cells was typical of MCL (CD5+, CD23-) in 6 patients and typical of CLL (CD5+, CD23+) in 4 patients. Six MCL patients had non-diagnostic immunophenotypes: CD5-, CD 23+ (n = 3) and CD5-, CD23- (n = 3). Twelve (34%) of the 35 patients had the IGH/BCL-2 fusion gene. Of these, 3 patients had leukemic phase follicular lymphoma, one had both CLL and MCL, and 8 had the diagnostic immunophenotype of CLL. The remaining 7 patients (19%) had a variety of translocation partners: BCL-3 (n = 1), BCL-3 and BCL-11a (n = 1), c-MYC (n = 2), and unknown (n = 3). The patients with a translocation involving BCL-3 had a typical CLL immunophenotype. Discussion: The IgH FISH probe detected a molecular defect in 7% of patients with a circulating monoclonal B cell population. In patients with a CLL immunophenotype, use of the IgH probe identified the IgH/cyclin D1 translocation characteristic of MCL in 4 patients, a finding of major clinical significance. Interestingly, after exclusion of MCL patients, more than 4% patients with CLL had other translocations involving IgH, a proportion comparable with other better defined chromosomal abnormalities in CLL. Although IgH/BCL-2 translocation is usually associated with follicular lymphoma, we identified 8 patients with CLL and this translocation. Translocations involving BCL-3 had been described before in CLL with an “atypical” immunophenotype. In contrast both of our patients with BCL-3 had typical phenotypes. Translocations involving IgH and BCL-11a have not been previously described. We conclude that FISH studies using the IgH probe improve the precision of diagnosis in CLL and could also have prognostic value.

Abstract Background Although the clinical importance of del 17p13 in patients with chronic lymphocytic leukemia (CLL) is well recognized, the implications of when this defect is identified are less clearly defined. In particular, the distinction between the identification of del 17p13 at the time of diagnosis and secondary acquisition of del 17p13 during the course of the disease are poorly characterized. Methods We identified all patients with CLL cared for at the Mayo Clinic between 1/1/2000 and 12/31/2012 who underwent baseline fluorescence in-situ hybridization (FISH) testing prior to receiving treatment. The Results of repeat FISH testing were reviewed to identify cases with clinically ascertained clonal evolution. Results A total of 1757 patients with newly diagnosed CLL were seen at Mayo Clinic prior to receiving treatment. Among these, 1243 had FISH testing performed prior to treatment and within 36 months of diagnosis. The median time from diagnosis to initial FISH was 0.8 months (11.5 to 35.4 months). The Results of baseline FISH testing among these patients is as follows: 486 (39%) had del 13q14, 234 (19%) had trisomy 12, 115 (9%) had del 11q23, 59 (5%) had del 17p13, 15 (1%) had other (e.g., del6q) and 334 (37%) had no abnormalities detected. Among these patients, 344 (28%) underwent repeat FISH testing during the course of their disease. Repeat FISH testing was typically performed for clinical suspicion of karyotype evolution or prior to therapy selection in patients with a long time interval between first prognostic FISH and initiation of treatment. Among these 344 patients, 41 (12%) acquired new cytogenetic abnormalities on repeat FISH. Classification of these 344 patients by the Dohner classification at diagnosis and time of follow-up FISH is shown in Table 1. Among the 41 pts who acquired a new FISH detectable genetic abnormality, the newly acquired defect resulted in a change in Dohner FISH risk category for 39 patients including 15/41 (37%) who acquired a del 17p13. Baseline clinical and prognostic characteristics of patients who developed clonal evolution to those who did not are shown in Table 2. Patients with unmutated immunoglobulin heavy chain (IGHV) gene mutation status (p<0.0001) and CD49d (p=0.003) expression were more likely to experience clonal evolution. Among the 319 patients who did not have del 17p13 on baseline FISH, 15 (5%) acquired del 17p13 during the course of their disease. The overall survival from the date del 17p13 was identified is shown for those with del 17p13 at diagnosis (n=59) compared to those who acquired del 17p13 later in the course of the disease (n=15) in Figure 1A. Similarly, among 339 patients who did not have del 6q23 on baseline FISH, 9 (3%) acquired del 6q23 during the course of their disease. The overall survival from the date del 6q23 was identified is shown for those with del 6q23 at diagnosis (n=11) and those who acquired del 6q23 later in the course of the disease (n=9) in Figure 1B. Conclusion Acquired cytogenetic evolution is clinically ascertained by FISH during the course of the disease in approximately 12% of patients. The newly acquired defects in these patients result in a change in Dohner classification for in >90% of these patients including ∼37% who acquire del 17p13. The clinical implications of del 17p13 is influenced by the timing of ascertainment with markedly shorter survival for those who acquire del 17p13 during the course of the disease relative to those with this defect at diagnosis. Disclosures: Shanafelt: Genentech: Research Funding; Glaxo-Smith-Kline: Research Funding; Cephalon: Research Funding; Hospira: Research Funding; Celgene: Research Funding; Polyphenon E International: Research Funding.

Abstract Background: In 2006 Lenalidomide received FDA approval for myelodysplasia (MDS) with interstitial deletion 5q [del(5q)] based on conventional cytogenetic (CC) results before and after treatment. In clinical practice, FISH studies of interphase nuclei with probes for EGR1 are widely used to detect del(5q), but it is not known whether this method has similar efficacy as CC. Thus, we compared CC and FISH results for various forms of del(5q). Methods: We selected 145 patients (pts) in our cytogenetic database with del(5q). These pts had various forms of del(5q) and were representative of our clinical practice. This series included 9 pts with MDS that were studied before and after treatment with Lenalidomide. CC studies were done using standard procedures to analyze 20 metaphases from bone marrow. FISH studies were done on the same specimens using stored left-over cells and standard procedures for EGR1 (5q31.2) and D5S23/D5S721 (5p15.2). The cutoff for del(5q) for FISH was <6.0% based on 200 nuclei. Results: Among 145 pts, 104 were referred for MDS, 9 acute myeloid leukemia, 9 lymphoproliferative disorders, 7 myeloproliferative disorders and 16 without clinical information. A total of 116 pts had breakpoints at del(5)(q13q33), 17 del(5)(q15q33), 8 del(5)(q11.2~q31q31~q35), 3 del(5)(q22q33) and 1 del(5)(q13q22). Del(5q) was detected in 144 pts by both CC and FISH. One pt had del(5)(q13q22) in 20/20 metaphases but was normal by FISH. Percent abnormal cells by FISH was lower in 135/145 pts compared to CC (mean difference 22.5 ± 19.6, range −42 to 98). For 9 pts with MDS, 29 specimens were collected before and after treatment with Lenalidomide: 7 achieved complete cytogenetic remission (four relapsed) and 2 showed a decrease in percent abnormal metaphases. Results of CC and FISH for these 9 pts were concordant for detection of del(5q) and trend of tumor burden due to treatment for 28/29 specimens. The discordant specimen was collected 222 days after treatment; results of CC were normal but FISH was abnormal in 19% of nuclei. Among the 29 specimens, percent abnormal cells by FISH was lower than CC in 27 (mean difference 13.9% ± 22.5, range −19.0 to 73.5). Each of the 9 treated pts had only del(5q) prior to treatment, and was detected by both FISH and CC. After treatment, FISH did not detect a separate cytogenetic clone involving deletion 20q without del(5q) in 2 pts nor did it identify development of other anomalies in 3 pts. Conclusions: Results of CC and FISH were mostly concordant, but differed in 4 respects. First, 1/145 pts was normal by FISH but had del(5q) by CC. This pt had unusual breakpoints that did not result in loss of EGR1. Second, percentage of cells with del(5q) was usually lower by FISH than CC. This observation is likely related to a different mitotic rate of cells with del(5q) versus normal cells. Third, 1 specimen was abnormal by FISH but normal by CC after treatment, but 2 subsequent specimens were concordant. This discrepancy was likely due to interference of mitosis of del(5q) cells and residual non-proliferating disease. Fourth, 2 treated pts developed a separate cytogenetic clone without del(5q) and 3 developed other anomalies that could not be detected by FISH. We believe FISH for EGR1 is useful in clinical practice, but not a substitute for CC.

Abstract 44 patients with relapsed or refractory CD20+ NHL were enrolled on a phase I trial of dose-escalated 90YZ followed by high-dose BEAM and autotransplant in which the 90YZ dose was patient-specific based on dosimetry. 90YZ doses were calculated to deliver cohort-defined radiation doses (100–1700 cGy) to critical organs (liver, lung or kidney) with 3–6 patients per cohort. On D-22, rituximab (R) 250 mg/m2 was infused followed by 111In Zevalin®. Imaging was performed immediately and at 4, 24, 72 and 144 hours; dosimetry was performed on D-15. On D-14, R was followed immediately by 90YZ at the cohort-prescribed dose. On D-6 through D-1, patients received high-dose BEAM. On D0, a minimum of 2.0 × 106 CD 34+ cells/kg was infused and G-CSF 5 μg/kg SQ daily begun. The median age was 54 (range: 25–73) years. NHL histologic subtypes were as follows: 16% mantle cell, 57% diffuse aggressive, 11% low-grade and 16% transformed. 43% had recieved 3 or more chemotherapy regimens, and 70% had received R either alone or in combination with chemotherapy. The toxicity profile was similar to that associated with high-dose BEAM. The most common grade III/IV toxicities were infection, fever, stomatitis, nausea, vomiting, diarrhea. One patient experienced transient veno-occlusive disease at the 700 cGy dose level. Two dose-limiting toxicities occurred at the 1700 cGy dose level: one patient with grade 4 stomatitis died of pneumonia and sepsis on D+10, and one patient experienced septic emboli to the lung on D+13. Engraftment occurred at a median of 10 days (range: 8–18 ) to granulocytes ≥ 500/μL, and 21 days (range: 11–40 days) to platelets ≥20,000/μL. One heavily pretreated patient developed MDS on D+291 and expired of sepsis on D+483. With a median follow-up of 21 months, the three year overall and progression-free survivals are 52% and 37%, respectively. 90YZ Zevalin ® Dosing for Cohorts 5–9 (median;range) Cohort (cGy) Total Dose (mCi) mCi/kg 900(n=3) 28(27–37) 0.3(0.3–0.4) 1100(n=5) 51(29–65) 0.6(0.5–0.8) 1300(n=5) 61(39–98) 0.6(0.5–1.1) 1500(n=6) 73(51–99) 0.9(0.5–1.4) 1700(n=3) 98(82–104) 1.2(1.1–1.2) For dosimetry-based trials, 1500 cGy to the critical organ (nearly always liver) is the recommended dose. Although patient-specific doses calculated to deliver a cohort-prescribed absorbed radiation dose to the critical organ were highly variable, the two dose-limiting toxicities ocurred at nearly identical doses (1.14, 1.20 mCi/kg) when calculated according to weight. Whereas eight other patients safely received at least twice the conventional 0.4 mCi/kg dose, 0.8 mCi/kg is the recommended dose for phase II studies, if dosing is to be based on weight and not dosimetry. Outcomes are encouraging given the high-risk patient population. A phase III trial will be required to establish whether or not the addition of 90YZ to high-dose BEAM improves outcomes in NHL patients undergoing autotransplant.

PURPOSE In a professional setting, the introduction of female speakers without their professional title may have an impact on the public’s perception of the female speaker. We examined how professional titles were used during speakers’ introductions at the ASCO Annual Meeting. METHODS We conducted a retrospective, observational study of video-archived speaker introductions at the 2017 and 2018 ASCO Annual Meetings. A “professional address” was defined as the professional title followed by the speaker’s full name or last name. Multivariable logistic regressions were used to identify factors associated with the form of address. RESULTS Of 2,511 videos reviewed, 781 met inclusion criteria. Female speakers were addressed less often by their professional title compared with male speakers (62% v 81%; P < .001). Males were less likely to use a professional address when introducing female speakers compared with females when introducing male speakers (53% v 80%; P < .01). When women performed speaker introductions, no gender differences in professional address were observed (75% v 82%; P = .13). Female speakers were more likely to be introduced by first name only (17% v 3%; P < .001). Male introducers were more likely to address female speakers by first name only compared with female introducers (24% v 7%; P < .01). In a multivariable regression including gender, degree, academic rank, and geographic location of the speaker’s institution, male speakers were more likely to receive a professional address compared with female speakers (odds ratio, 2.43; 95% CI, 1.71 to 3.47; P < .01). CONCLUSION When introduced by men, female speakers were less likely to receive a professional address and more likely to be introduced by first name only compared with their male peers.

Abstract Abstract 2852 Background: The 18-item Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF, Scherber et al Blood 2011) given in conjunction with the 9-item Brief Fatigue Inventory (BFI, Mendoza et al Cancer 1999) is a patient-completed questionnaire for assessing symptoms in persons with MPNs. The MPN-SAF has been translated and validated in 9 languages to date. The Total Symptom Score (TSS) is computed from 10 of the most pertinent MPN-SAF items to assess symptom burden in MPN patients and to evaluate response to therapy. Psychometric properties of the TSS have been previously reported (Emanuel et al Blood 2012). The purpose of this analysis is to compare MPN-SAF symptoms and psychometric properties of the TSS across 9 languages in an international sample. Methods: Data were collected in an international cohort of subjects with MPNs. Surveyed symptoms included fatigue, early satiety, abdominal pain and discomfort, inactivity, headaches, concentration, dizziness, extremity tingling, insomnia, sexual problems, mood changes, cough, night sweats, pruritus, bone pain and fever on a 0 (absent) to 10 (worst imaginable) scale. TSS was computed using the published scoring algorithm on a 0 (all symptoms absent) to 100 (all symptoms worst imaginable) scale. Demographic and disease-related data including disease type, gender, and age had to be present to be included in analysis. Demographics were compared across languages groups using ANOVA and chi-squared tests. Symptoms and TSS were compared across language groups using a general linear model adjusting for disease type, age, and gender with post-hoc Tukey pairwise comparisons. Internal consistency and factor structure of the TSS were investigated overall and within language groups using Cronbach's alpha and principal-axis factoring analysis. Results: Subject Demographics and Disease Type: 1,851 subjects with polycythemia vera (PV N=655), essential thrombocythemia (ET N=769) and myelofibrosis (MF N=427; 286 primary MF, 61 PV-MF, 80 ET-MF) were prospectively enrolled and administered the MPN-SAF and BFI in 1 of 9 languages: English [UK] 55, English [US] 102, Italian 186, Swedish 114, German 112, French 457, Spanish 192, Dutch 236, and Chinese 397. Age (median 61, range, 15–94) and gender (55% F) were typical. Disease type and age varied across language groups (both p <0.001). MPN-SAF Symptoms and TSS: Symptom frequencies ranged from 19% (fever) to 88% (fatigue) overall with mean severities ranging from 0.4 (SD=1.3, fever) to 4.3 (SD=2.3, fatigue). Fatigue had the highest mean severity among all symptoms within each language group. Overall, mean TSS was 21.5 (SD=16.7) with the Swedish (mean=18.1, SD=15.2) and Dutch (mean=27.6, SD=17.1) cohorts reporting the lowest and highest unadjusted TSS means, respectively. When comparing symptom items across languages (adjusting for disease type, age, and gender), concentration and sexual problems had the most statistically significant pairwise differences (11 and 10, respectively, out of a possible 36) followed by dizziness and overall quality of life (9 each, out of a possible 36). No statistically significant pairwise differences were observed for abdominal discomfort, headache, extremity tingling, or insomnia. For the TSS, the Dutch cohort appeared to statistically significantly differ (all p <0.05) with all other languages except the English cohorts. All other TSS pairwise comparisons were not statistically significant. TSS Internal Consistency and Factor Structure: The TSS had excellent internal consistency overall (Cronbach's alpha 0.83) as well as within language groups (Cronbach's alpha 0.81–0.86). Overall factor analysis identified a single underlying construct among the 10 TSS items. Factor loadings ranged from 0.41 for fever to 0.73 for inactivity. A single factor solution was appropriate for each language group with factor loadings ranging from 0.18 to 0.85. Conclusion: This analysis suggests that the available translations of the MPN-SAF are generally acceptable for use in a broad context. The TSS demonstrated acceptable internal consistency and similar factor structure across all language groups. Most symptom and TSS comparisons between languages were not statistically significant, but for the few which differed, further studies are needed to evaluate whether these variances are due to disease-related factors or due to linguistic or cultural influences present in the cohorts. Disclosures: Kiladjian: Novartis: Honoraria, Research Funding; Celgene: Research Funding; Shire: Honoraria. Griesshammer:Shire: Honoraria. Roy:Novartis, BMS: Speakers Bureau. Harrison:Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding. Passamonti:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mesa:Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding.