Pophali, Priyanka A.

e19039 Background: In patients with lymphoma, lactate dehydrogenase (LDH) is an important prognostic marker. Serum lactate can also be elevated due to hypermetabolism from aggressive lymphoma. We have observed critically ill lymphoma patients with elevated serum lactate who had a delay in the diagnosis and treatment of their underlying lymphoma because the cause of the elevated lactate was presumed to be infection. This clinical observation led us to perform a study to evaluate the relationship between serum lactate and LDH levels in lymphoma patients. Methods: We used the Mayo Clinic Lymphoma Database to search for patients with lymphoma and elevated lactate during a recent two year time period, January 2014 through December 2015. Fifty patients met these initial criteria and underwent medical chart review. The patients were divided into two groups – those with documented infection (SepsisLA group) and those without infection (all cultures negative) where the elevated lactate was due to lymphoma hypermetabolism (LymLA group). The Wilcoxon/Kruskal-Wallis test was used to compare the SepsisLA and LymLA groups. Kaplan-Meier analysis was used to estimate survival. Results: The mean age of the 66 patients was 65 ± 14.8 years and 60% were male. At the time of presentation, the mean lactate and LDH values were 4.5 ± 2.81mmol/L (UNL < 2 mmol/L) and 835.1 ± 1741.4 U/L (UNL < 222 U/L), respectively. 64% (32/50) of patients had elevated LDH values. After review, 32 (64%) patients were in the SepsisLA group; 18 (36%) were in the LymLA group. DLBCL was the most common disease type in both the SepsisLA (50%; 16/32) and LymLA (88%; 16/18). The sepsisLA and LymLA groups were not significantly different in terms of age, sex, lactate levels, or maxSUV on PET scan (N = 13). However, patients in the LymLA group did have higher LDH values (p = 0.02) compared to those with SepsisLA. Patients with LymLA had a reduced overall survival (OS) (1.45 median months) compared to those with SepsisLA (7.83 median months) p = 0.02. Conclusions: This study demonstrates that the level of lactate elevation is not helpful indiscriminating SepsisLA vs LymLA; however an elevated LDH with elevated lactate is more likely LymLA. Lymphoma pts with LymLA had an inferior survival compared to SepsisLA. We are unable to define the true incidence and prognostic value of elevated serum lactate in lymphoma; this will require a prospective study with fresh samples. In summary, lymphoma activity can masquerade as infection with elevated lactate. Once sepsis is ruled out, treatment for the lymphoma should not be delayed as this presentation portends poor prognosis.

Abstract MYC amplification (amp) is a marker of poor prognosis in many non-hematologic malignancies. While MYC translocations in B cell lymphoma (BCL) have been extensively studied, little is known about the significance of MYC amp. Recent studies describe increased MYC copy numbers (3-10 copies/cell) to be associated with more aggressive BCL. The WHO 2017 does not include MYC amp in the definition of high-grade BCL (HGBCL) with MYC and BCL2 and/or BCL6 rearrangement ("double-hit lymphoma", DHL). However, it also states that high-level MYC amp occurring together with a MYC rearrangement, and concurrent with BCL2 rearrangement likely has a similar clinical impact as classic DHL. Although increased MYC copy number is commonly identified by routine fluorescence in situ hybridization (FISH) testing in BCL, the experience of our large cytogenetics reference laboratory suggests that high-level MYC amp, defined as uncountable MYC signals, is far less common. Therefore, we sought to characterize the clinical, pathologic and cytogenetic features of patients with BCL showing high-level MYC amp. The Mayo Clinic cytogenetic database was retrospectively reviewed for all cases of BCL with high-level MYC amp seen by FISH from January 2010 - February 2018. All FISH studies reported as MYC amp were re-reviewed by a cytogeneticist to verify the level of amp and the MYC probes involved. Pathology was reviewed by two independent hematopathologists. Clinical information was collected through chart review. Survival analysis was performed using Kaplan-Meier curves and the Wilcoxon rank-sum test. FISH analysis for MYC aberrations identified 44/9715 (0.45%) cases with high-level MYC amp. Of cases with available H&E, the most common morphology was diffuse large BCL (DLBCL) (82%; 28/34), followed by HGBCL (15%; 5/34) and plasmablastic BCL (3%; 1/34). Hans cell of origin (COO) algorithm immunohistochemistry (IHC) identified 21/25 (84%) germinal center B-cell-like (GCB), and 4/25 (16%) non-GCB cases. 21/27 (78%) cases were BCL2+ by IHC. MYC+ by IHC was ≥40% in 21/28 (75%) and <40% in 7/28 (25%) cases. 9/17 (53%) were "double expressers" (DEL) by IHC. MYC amp probe signals appeared in a cloud-like distribution (CLD) in 31 (70%) or in a single homogenous staining region (HSR) in 13 (30%) [Figure 1A]. Among 38 cases with amp in a MYC break-apart probe, 21 (55%) had amp of 5' alone, 15 (40%) of intact and 2 (5%) of the 3' probe alone. 7/44 (16%) had MYC translocations (5 IGH; 2 non-IGH). BCL2 rearrangement was seen in 15/39 (38%) cases, and BCL6 rearrangement in 3/36 (8%). Only 2/44 (4%) cases met the current WHO 2017 definition of DHL. Clinical data was available for 20 cases. Median age at diagnosis was 64.5 (range 25-88) years with M:F of 1.5:1. Only 1/14 (7%) had bone marrow while 16/18 (88.8%) had other extranodal sites of involvement (8 gastrointestinal). The clinical presentation was heterogeneous: 13 de novo, 3 post-transplant, 3 transformed from low grade and 1 mediastinal BCL. 9/14 had an elevated LDH, median 387 (225 - 2063) U/L. R-CHOP was the most common first line therapy in 12/17 (70%). At median follow-up of 18.2 (range 0.4 - 88.9) months, 9 patients had died, 3 were in relapse and 8 remained in first complete remission. Lymphoma relapse/progression was the most common cause of death in 7/9 (78%). The median overall survival (OS) was 29.3 months [Figure 1B]. There was no statistically significant difference in OS by morphologic classification (DLBCL vs HGBCL, p=0.6), double expresser (Yes/No, p=0.19), COO (GCB vs non-GCB, p=0.08), MYC amp pattern (HSR vs CLD, p=0.48), MYC amp probe (3' vs 5' vs intact, p=0.31), MYC rearrangement (Yes/No, p=0.1), or MYC amp with concurrent BCL2/BCL6 rearrangement (Yes/No ,p=0.2). To our knowledge, this is the first study to characterize the clinical, pathologic and cytogenetic features of BCL with strictly-defined high level MYC amp identified by FISH. The 5' signal alone, or the intact MYC probe are most frequently amplified, and two distinct patterns of amp can be seen. Predominant extra nodal involvement is an important clinical observation. These cases are usually DLBCL, GCB type, and infrequently have concurrent MYC/BCL2/BCL6 rearrangement. Our study suggests that BCL with high-level MYC amp may have an aggressive disease course regardless of MYC, BCL2 and BCL6 gene rearrangement status. A larger series is necessary to further understand the clinical significance of high-level MYC amp in BCL. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Abstract Background: Lymphoma survivors are at risk for long term and late effects which may negatively impact quality of life (QOL). Few studies have assessed the impact of change in health behaviors (physical activity (PA), alcohol and smoking) on QOL, specifically in lymphoma survivors. Methods: Patients were prospectively enrolled <9 months of diagnosis into the Lymphoma SPORE Molecular Epidemiology Resource cohort. At baseline and 3-year follow-up (FU3), patients self-reported QOL, smoking, alcohol use and PA. At FU3, survivors reported change in health behaviors since diagnosis. The Godin Leisure Score Index (LSI) was calculated as a measure of PA (Pophali et al. ASH 2017); modeled by tertile. QOL was measured via FACT-G; the total and sub-scales [emotional (EWB), functional (FWB), physical (PWB), and social/family well-being (SFWB)] scores were transformed to a 0-100 scale. Patients who completed <80% of QOL questions were excluded. The association of QOL with health behaviors was evaluated using Kruskal-Wallis test (categorical) and Spearman's rank correlation (continuous). Results: At baseline, 2805 participants were evaluable for QOL of which 2025 were evaluable at FU3. The median age at diagnosis was 62 (IQR 52-69) years. Majority were males (N=1148, 56.8%), with advanced stage III-IV disease (N=941, 62%) and ECOG performance status <2 (N=1935, 96%). At baseline, smoking status was current (N=237), former (N=802), never (N=1310) or not available (NA, N= 456). Current smokers had a significantly lower median QOL scores compared to former and never smokers for EWB (75 vs 79 vs 79, p<0.01), FWB (71 vs 79 vs 79, p<0.01), PWB (86 vs 89 vs 89, p=0.02), SFWB (86 vs 90 vs 89, p=0.02) and total FACT-G (67 vs 82 vs 82, p<0.01). The median number of pack years smoked among current &former smokers was 15.6 (range 0.5-126). There was a significant negative correlation of pack years smoked with FWB (p=0.05), and total FACT-G (p=0.04). At FU3, current smokers had significantly lower median scores compared to former and never smokers for FWB (80 vs 86 vs 86, p=0.01), PWB (89 vs 93 vs 93, p<0.01) and total FACT-G (82 vs 86 vs 87, p<0.01). EWB (83 vs 88 vs 88, p=0.12) and SFWB (83 vs 86 vs 86, p=0.12) were also lower than never and former smokers but not statistically significant. Smoking status was decreased (N=30), increased (N=0) and unchanged (N=1439) at FU3. There was no association of change in smoking with change in QOL. At baseline, alcohol use status was current (N=1189), former (N=506), never (N=518) and NA (N=592). Current alcohol users had the highest FWB (79 vs 75 vs 75, p<0.01) vs former and never users. Former users vs current and never users had the lowest PWB (86 vs 89 vs 89, p<0.01), SFWB (88 vs 89 vs 92, p<0.01) and total FACT-G (80 vs 83 vs 82, p<0.01). EWB was similar in all 3 groups. Among current & former alcohol users, the average number of drinks/week was 3.4. There was no association of the number of drinks/week with QOL except positive correlation with PWB (p=0.01). At FU3, alcohol use was reported as increased (N=40), decreased (N=312) and no change (N=875). There was no association between change in alcohol use and change in QOL. At baseline, participants with PA in the high vs low LSI tertile had significantly better median scores for FWB (79 vs 75, p=0.01), SFWB (93 vs 89, p<0.01) and total FACT-G (83 vs 82, p<0.01). At FU3, participants in the high vs low LSI tertile had significantly better scores on all subscales and total FACT-G with a significant positive correlation between the continuous LSI and QOL (FACT-G total and subscales). PA was reported as increased (N=107), decreased (N=394) and no change (N=495). There was a significant association of increase in PA with change in PWB (p<0.01), EWB (p=0.01), FWB (p<0.01) and total FACT-G (p<0.01) from baseline to FU3, but not with change in SFWB (p=0.06). In a sensitivity analysis, QOL was modeled for health behaviors in the subset of patients with QOL assessed prior to treatment; results were consistent with the QOL in all patients. Conclusions: Health behaviors in lymphoma survivors are significantly associated with QOL: better QOL is associated with not smoking, more PA, and moderate alcohol use. Current alcohol consumption, as opposed to former alcohol use, may be related to overall health status. An increase in PA after lymphoma diagnosis is associated with an increase in the QOL. Thus, modification of health behaviors has the potential to impact QOL in lymphoma survivors. Figure. Figure. Disclosures Cerhan: Celgene: Research Funding; Nanostring: Research Funding; Jannsen: Other: Scientific Advisory Board.

Abstract Background: The frequency of preventive health practices (PHP), including age-appropriate screening for malignancies and immunizations, and compliance with PHP guidelines in lymphoma survivors is not known. We hypothesized that lymphoma survivors are more compliant with PHP than the general population but PHP rates may differ based on patient, disease and treatment characteristics. Methods: We identified eligible lymphoma patients from the SPORE Molecular Epidemiology Resource (MER) cohort, in which they were prospectively enrolled within <9 months of diagnosis. Survivors self-reported their PHP (colon, breast, and prostate cancer screening and influenza immunization) in the 3-year follow-up questionnaire (FU3). Per US Preventative Task Force guidelines, survivors were considered eligible for colon cancer screening if they were >50 years and compliant if they had fecal occult blood test <1 year or sigmoidoscopy/colonoscopy <10 years of FU3. Eligible female survivors age 50-75 were considered compliant if they had a mammogram after lymphoma diagnosis. Since USPTF recommended against PSA for prostate cancer screening in 2012, males aged 55-69 prior to 2012 were eligible and considered compliant if PSA test was <1 years of FU3. Survivors who received influenza vaccine <1 year of FU3 were considered compliant. Chi-square test was used to compare characteristics of compliant vs non-compliant patients; p value <0.05 was considered statistically significant. Results: Of 4248 lymphoma patients enrolled in the MER from 2002 to 2012, 2038 participants completed FU3. 1105 (54%) were male. The median age at diagnosis was 61 (IQR 51-69) years. There were equal numbers of indolent (N=1002) and aggressive (N=995) histologies with follicular (N=515, 25%) and diffuse large B-cell (N=427, 21%) being the most common. Majority (N=1221, 60%) had advanced stage (Ann Arbor III-IV) disease. 469 (23%) had events prior to FU3 and majority 1777 (88%) had received lymphoma treatment prior to FU3. Of 2038 survivors who completed FU3, 1576 (79%) reported having colon cancer screening in their lifetime. 1328 (91%) of 1570 eligible survivors were compliant, 124 (9%) were not and 118 had missing information. Survivors of age >60 years (93% vs 88%, p<0.001), those with indolent lymphomas (93% vs 90%, p=0.046), or diagnosed between 2010-2012 (94% vs 90% 2002-2009, p=0.007) were more likely to be compliant. There was no difference in colon cancer screening by sex, events prior to FU3 or treatment prior to FU3. 872 (96%) of 933 female survivors reported having a breast exam and 836 (91%) had a mammogram at least once in their lifetime. 495 (96%) of 561 eligible female survivors were compliant, 23 (4%) were not and 43 had missing information. There was no difference in mammographic screening based on age (<=60 vs >60), histology (indolent vs aggressive), events prior to FU3, treatment prior to FU3 or year of diagnosis (2010-2012 vs 2002-2009). 737 (78%) of 1105 male survivors had a PSA test at least once in their lifetime. 115 (71%) of 216 eligible men were compliant, 47 (29%) were not and 54 had missing information. There was no difference in PSA screening by age (<=60 vs >60), histology (indolent vs aggressive), events prior to FU3, and treatment prior to FU3. 1818/2038 (90%) survivors had received an influenza vaccine in their lifetime. 1567 (81%) were compliant, 373 (19%) were not and 98 had missing information. Survivors >60 years of age (87% vs 75%, p<0.001) and those with indolent lymphoma (83% vs 78%, p=0.015) were more likely to be compliant. There was no difference in influenza vaccination by sex, events prior to FU3, treatment prior to FU3, and year of diagnosis (2010-2012 vs 2002-2009). As a comparison in the US general population [Figure], between 2002-2015 the highest rates published by the Center for Disease Control are 62% for colon cancer screening (2015), 75% for mammography (insured, 2003) and influenza vaccination 42% (2015). Per the American Cancer Society, the highest rate of PSA screening was 54% (2010). Conclusion: Lymphoma survivors have high compliance with PHP recommendations compared to the general population. Although older individuals and those with indolent histologies were more likely to receive influenza vaccination and colon cancer screening, this difference was not seen in breast and prostate cancer screening practices. Lymphoma treatment and events did not seem to affect the frequency of PHP among survivors. Figure. Figure. Disclosures Cerhan: Nanostring: Research Funding; Jannsen: Other: Scientific Advisory Board; Celgene: Research Funding.

AbstractThe impact of physical activity (PA) on lymphoma survival is not known. The association of PA and change in PA with overall (OS), lymphoma‐specific (LSS) and event‐free (EFS) survival was evaluated in a prospective cohort of newly diagnosed lymphoma patients (2002‐2012). We calculated Leisure Score Indexes (mLSI) from the self‐reported usual adult PA (baseline) and at 3‐years post‐diagnosis (FU3), grouping patients by active vs insufficiently active by the American Cancer Society PA guidelines. Associations of PA with survival were assessed using hazard ratios (HRs) and 95% confidence intervals (CI) from Cox models stratified by lymphoma subtype, adjusted for age, sex, baseline BMI, and comorbidity score with change scores further adjusted for baseline PA. Three thousand sixty participants were evaluable at baseline and 1371 at FU3. Active patients had superior survival from baseline [HR (CI): OS 0.82 (0.72‐0.94); LSS 0.74 (0.61‐0.90); EFS 0.92 (0.82‐1.02)] and FU3 [HR (CI): OS 0.64 (0.46‐0.88); LSS 0.32 (0.18‐0.59); EFS 0.82 (0.61‐1.10)] compared to insufficiently active. An increase in mLSI from baseline to FU3 (vs stable mLSI) was associated with superior OS (HR = 0.70, CI 0.49‐1.00) and LSS (HR = 0.49, CI 0.26‐0.94).The continuous change in mLSI at FU3 was significantly associated with OS, LSS and EFS; maintained across subgroups and appeared linear. Higher PA among lymphoma patients at diagnosis and 3 years is significantly associated with OS, LSS, and EFS. Increasing PA after diagnosis is significantly associated with improved OS and LSS supporting an important role for PA in lymphoma survivorship and the need for intervention trials.

e13083 Background: CNS involvement from low grade B-cell NHL is rare and has only been reported as case series. The distribution, demographics and outcomes of patients with low grade B-cell CNS NHLs have not been well characterized. Methods: The NCDB represents ~70% of cancer cases in the United States. Using the 2004-2013 NCDB extranodal NHL database, we identified all CNS B-cell NHLs based on ICD-O-3 site and histology codes. Primary or secondary CNS involvement could not be determined. Results: Out of 9435 CNS NHL cases, 475 [5.03%] had low grade histologies. In this group, the median age at diagnosis was 58 years [range 19-89]. Majority of the cases were female [56%], White, non-Hispanic [72%], privately insured [53%], with no comorbidities [74%] and treated in academic/research programs [38%]. Site of CNS disease was not specified in 22%. HIV status was known in 318 cases (6.3% positive). The brain [44%] was the most common site of involvement followed by spinal cord [19%] and meninges [15%]. Follicular lymphoma (FL) [48%] was the most common histology overall followed by marginal zone (MZL) [37%], small lymphocytic (SLL) [8%] and lymphoplasmacytic lymphomas (LPL) [7%]. MZL was the most common histology in the brain [44%] and meninges [61%] while FL was most common in the spinal cord [77%] and nervous system, NOS [69%]. Cranial nerves and eye (retina/optic nerve) involvement was very rare [2 and 1 case each- both MZL]. The overall survival (OS) of CNS B-cell NHL was significantly better if histology was low grade vs other [5-year OS 74% vs 32%, P < 0.0001]. Among CNS low grade B-cell NHLs, 5-year OS varied by histology [MZL 83%, FL 75%, LPL 56% and SLL 50%, P = 0.0003] and site of disease [spinal cord 89%, meninges 78% and brain 63%, P = 0.03] in addition to age at diagnosis and co-morbidities on both uni- and multivariate analysis. Survival was not influenced by sex, race, insurance, year of diagnosis, facility type or location. Conclusions: CNS involvement with low grade B-cell NHL is rare but has a relatively good outcome with most patients surviving beyond 5 years. FL and MZL are the more common low grade histologies. Both histology and disease site are important factors affecting survival.

1573 Background: There are no epidemiologic studies of SWM due to lack ofICD codes specific for smoldering status. Methods: The NCDB represents ~70% of cancer cases in the US. It records the time to initial treatment or reasons for not receiving treatment. Using the 2004-2012 database, we estimated the overall proportion of new adult WM cases that are smoldering and analyzed outcomes according to socio-geo-demographic subgroups. Patients who were recommended treatment (irrespective of administration status) or died within 120 days of diagnosis were considered to have active WM while those who did not require treatment and had follow-up ≥120 days after diagnosis were considered to have SWM. Results: 2322 (28%) of 8302 patients diagnosed with WM were SWM. Median age at diagnosis was 71 (range 28-90) years. Median age did not change significantly during 2004-2012 (P = 0.83) but the proportion of smoldering disease decreased with time (P = 0.02). The proportions of SWM according to socio-geo-demographic subgroups are shown in the Table. Conditional survival (given survival to 4 months) at 5-years was 66% vs. 70% and at 10-years was 38% vs. 46% for active WM vs. SWM, respectively. The OS for SWM was significantly better among females and those who were younger, privately insured, with less co-morbidities and residing closer to a health facility. However, the OS did not differ by racial groups or era of diagnosis 2004-2008 vs 2009-2012. On multivariate analysis, sex, age group and co-morbidity index were significant factors affecting OS while race, insurance, distance from health facility and era of diagnosis were not. Conclusions: Approximately 28% of WM cases in the US are smoldering at diagnosis. The prevalence of SWM varied among socio-geo-demographic subgroups. Sex, age and co-morbidities significantly affect survival of SWM. [Table: see text]

95 Background: While PA is known to improve quality of life in lymphoma pts, its impact on OS is not known. We studied the effect of PA on OS in lymphoma pts enrolled at diagnosis in the Iowa/Mayo Molecular Epidemiology Resource. Methods: Godin Leisure Score Index (LSI; Range 0-50) was calculated based on level of PA pre-diagnosis (baseline) and 3 years post diagnosis (FU3), with pts grouped by tertile into high, moderate, or low PA. At FU3, pts also reported perceived change in PA since diagnosis. OS was measured as time from assessment (baseline or FU3) until death from any cause. Associations between LSI tertiles and OS were assessed using Cox models adjusted for lymphoma subtype, age and sex. Results: PA level was available for 3060 pts at baseline and 1371 pts at FU3. 95% had an ECOG performance status < 2, 37% had an aggressive subtype, 29% had BMI ≥ 30, and 54% were age > 60. Indolent lymphoma pts with higher PA at baseline had no difference in OS. Higher PA at FU3 had improved OS (moderate vs low HR 0.63, CI 0.42-0.93; high vs low HR 0.53, CI 0.33-0.86). Pts with BMI < 30 who had higher PA at baseline showed no difference in OS. Higher PA at FU3 had improved OS for pts with BMI < 30 (moderate vs low HR 0.68 CI, 0.48-0.98; high vs low HR = 0.41, CI 0.26-0.64). For pts > 60 years, high vs low baseline PA showed improved OS (HR 0.77, CI 0.63-0.93). Higher PA at FU3 (moderate vs low HR 0.68 CI 0.48-0.96, high vs low HR 0.53 CI 0.34-0.83) was associated with OS. At FU3, compared to no change, perceived reduction of PA was associated with worse OS for indolent lymphoma (HR 2.13, CI 1.56-2.91), BMI < 30 (HR 1.95, CI 1.45-2.62), BMI > 30 (HR 2.00, CI 1.21-3.30), age ≤ 60 (HR 3.06, CI 1.72-5.46), and age > 60 (HR 1.98, CI 1.52-2.58). Perceived increase in PA was not associated with OS. Higher PA in pts with aggressive lymphoma, BMI ≥30, and age < 60 was not significantly associated with OS but trended similarly. All results were similar when analyzing by continuous LSI score. Conclusions: Higher levels of PA, especially at FU3, were associated with superior OS. The effect was more pronounced in pts with indolent lymphoma, BMI < 30, or age > 60. Perceived reduction in PA was associated with worse outcomes. PA should be incorporated into lymphoma survivorship plans.