ALBERT

Description: Background: The discovery that gut microbial dysbiosis correlated with prognosis, immune reconstitution and development of graft-versus-host disease (GVHD) in patients undergoing allogeneic stem cell transplantation (allo-SCT) highlights the clinical relevance of the gut microbiome in shaping anti-tumor immune responses. Treatment of allo-SCT patients with antibiotics has recently been associated with increased GVHD mortality (Routy et al. 2017). Based on these studies and the association of distinct gut bacteria with increased efficacy to PD-1 blockade in patients with solid tumors (Derosa et al. 2018), we performed a retrospective analysis to determine if infection treated with antibiotics affected the outcomes of multiple myeloma (MM) patients after autologous SCT (ASCT). Methods: A list of all MM patients treated at our institution between January 2012 through December 2015 was obtained and 1095 patients were identified. A comprehensive review of the electronic medical record (EMR) of the first 142 who received ASCT was performed. Information was collected from diagnosis to the date of last contact. Baseline characteristics, treatment history, transplant course, antibiotic treatment, and infection severity using common terminology criteria for adverse event (CTCAE) version 4 were reviewed. Prophylactic antibiotics were excluded. Response was measured and defined using the International Myeloma Working Group Criteria. Progression free survival (PFS) and overall survival (OS) were estimated using log rank tests. Cox hazard stepwise regression model examined for multiple factors affecting PFS and OS using the Akaike information criterion. Results: Of the 142 patients, 93 (65%) were Durie Salmon (DS) III, 20 (14%) were Revised International Staging System (R-ISS) III, 44 (31%) had high-risk cytogenetics, and 76 (54%) were male. The median age at diagnosis was 60. Although there was a similar frequency of DS III (67% vs 61%) and high-risk cytogenetics (35% vs 25%) among patients in the antibiotic and non-antibiotic treated groups, there was an over-representation of R-ISS 3 (19% v 4%) patients in the antibiotic-treated group. Treatment with antibiotics was associated with decreased median PFS (2.38 vs 6.58 years (yrs), p =0.00003) (Figure 1a) and decreased median OS (7.43 vs 17.39 yrs, p =

Description: Abstract 4517 Oral mucositis is a common toxicity associated with many cancer therapies and has been correlated with risk for infection, mortality, and extended hospital stay. Prophylactic use of a supersaturated calcium phosphate mouth rinse (SSCPR, Caphosol..) was found in a phase III study to reduce the frequency, intensity, and duration of oral mucositis in patients (pts) undergoing allogeneic or autologous hematopoietic stem cell transplantation (Papas, et al. Bone Marrow Transpl 2003;31:705). That study also found a faster time to recovery of an absolute neutrophil count (ANC) ≥0.2×109/l, but not for other engraftment endpoints, possibly a result of the mixed pt population studied. We performed a single-center retrospective review of a uniform population of pts

Description: Chronic GVHD (cGVHD) is a major risk factor in patients receiving allogeneic hematopoietic cell transplantation (HCT), and is a complicated syndrome with a combination of autoimmune-like features and a range of multiorgan manifestations. Currently, efforts are being made to standardize the criteria for diagnosis and staging of cGVHD, but there is little understanding of the pathogenesis of the disease, associated biomarkers, and the immune perturbations that may result. Reconstitution of the T cell repertoire after allo-HCT often takes several months to a year, and may be significantly impaired or skewed in patients who develop cGVHD. We thus sought to assess the immune T cell status of cGVHD patients by TCR Vβ CDR3-size spectratype analysis. A cohort of 9 patients who underwent allo-HCT (PBMC n=7; BM n=2) were enrolled in the study. The underlying diseases in these patients were CML (n=1), AML (n=4), ALL (n=1), CLL (n=1), and MM (n=2). Patients received either reduced intensity or myeloablative conditioning before transplantation, and 8 of the 9 had a previous history of acute GVHD. Furthermore, the patients did not have evidence of infectious disease. PBMC was collected from each patient at one time point ranging from 2 wk to 3 yr from the time they were diagnosed with cGVHD. The onset of cGVHD ranged from 100 d to 3 yr post-HCT (median of 5 mo). Flow cytometric analysis was performed on peripheral blood lymphocytes from 7 of the 9 patients to analyze recovery of different subpopulations. PCR amplification of the CDR3 region of 21 TCR Vβ genes was used to analyze the diversity of the T cell repertoire. The PCR products were run on a sizing gel to separate the CDR3-lengths, and further analyzed by ABI GeneMapper software. Flow cytometric analysis revealed diverse percentages of CD4+ and CD8+ T cells among the 7 patients tested, which were correlated with the post-HCT period. Two patients who received HCT, 4 and 9 months before blood sampling, had only 3% and 4% CD4+ and 3% and 9% CD8+ T cells in their PBMC sample, respectively. On the other hand, the remaining 5 patients, who were all at later time points post-HCT, had CD4+ and CD8+ T cell percentages within normal range. One patient had a ratio close to the normal 2:1 CD4/CD8 ratio, two patients had a 1:1 ratio, and four had inverse CD4/CD8 ratios. Based on CDR3-size spectratype analysis, we determined the recipient TCR-Vβ complexity index within each resoluble family, which represented the percentage of the number of peaks found for each Vβ relative to that found in the average corresponding Vβ family of 10 healthy donors. We considered Vβ to be fully complex if the complexity index exceeded 85%. The results indicated that 41 to 88% of resolved Vβ in all 9 patients were fully complex, with the lower range corresponding to those patients sampled early post-HCT. Vβ 1, 2, 4, 6, 8, 12, and 13 families revealed the best recovery in all patients, even in patients after 4-mo post-HCT. Importantly, extensive skewing of the repertoire within most of the TCR Vβ families were found in all 9 recipients, suggesting that there were active heterogenous T cell responses in those patients with cGVHD. As to what these T cell responses were directed to remains to be seen, and could theoretically involve autoantigens, alloantigens, tumor antigens, or sub-detectable infectious agents. In any case, the presence of a wide-ranging T cell response in these patients may serve as an important new diagnostic indicator for cGVHD.

Description: Background: TA-TMA is a life-threatening complication of hematopoietic cell transplantation (HCT), usually manifested as a combination of non-immune mediated hemolytic anemia, thrombocytopenia and end-organ dysfunction (renal, neurologic and/or hypertension). Reported mortality rates following TA-TMA are high (50-75%; Gavriilaki et al, Bone Marrow Transplantation 2017). It is more commonly associated with allogeneic HCT, however, may infrequently occur with autologous HCT. Traditionally, treatment for TA-TMA consisted in removing possible offending agents (calcineurin inhibitors, sirolimus) and/or instituting total plasma exchange (PLEX). These approaches have not resulted in significant improvement in the natural history of TA-TMA, with complete resolution in 12-20% of pts (Mulay et al, J Clin Apher 2015). Recent evidence of alternate complement pathway activation has been implicated in the pathophysiology of TA-TMA (Jodele et al, Blood 2013). Eculizumab (ECU) is an anti-C5 monoclonal antibody, approved for treatment of PNH and aHUS, which has been used anecdotally as treatment for TA-TMA. Most reports consist of pediatric patients. In this analysis, we evaluated consecutive cases of adult recipients of HCT who developed TA-TMA and have received ECU therapy at our institution. Methods: We reviewed electronic records of consecutive patients who presented with a diagnosis of TA-TMA (non-immune hemolytic anemia plus worsening thrombocytopenia and end-organ dysfunction) and were treated with ECU between 2015 and 2017 at our institution. Univariate and bivariate statistics were calculated for the sample; Fisher's exact tests and Wilcoxon rank sum tests were utilized to test for differences across groups. Results: Table 1 shows the baseline characteristics of these pts. A total of 15 pts were included in the analysis; 2/3 were female and the median age was 62. ECU was given according to the usual schedule for aHUS (900 mg IV weekly x 4, 1200 mg every other week starting on week 5). Median time from TA-TMA diagnosis to initiation of ECU was 2 days. All patients received prophylaxis for Neisseria meningitides with ciprofloxacin and antifungal prophylaxis at initiation of ECU. Three (20%) pts received PLEX prior to ECU. Seven (47%) patients were receiving tacrolimus at diagnosis, however, levels were not within toxic range (3.7-7.9 ng/mL). Median time post-HCT for development of TA-TMA was 135 days. Median LDH, hemoglobin, platelet count and creatinine at TA-TMA diagnosis were 1724 U/L, 7.3 g/dL, 33,000/mcL and 1.7 mg/dL, respectively. Ten (66.6%) patients had acute kidney injury and 7 (46.6%) pts had neurologic manifestations. Eight (53.3%) pts had evidence of GVHD concurrent with TA-TMA diagnosis. Ten (63.3%) pts developed systemic infections during their TA-TMA treatment. No pts developed meningitis or fungal infections. Median follow-up was 4.5 months after initiation of ECU. Eight (53.3%) patients had complete resolution of TA-TMA (i.e. resolution of hemolytic anemia, thrombocytopenia and end-organ damage), 4 of these 8 pts were recipients of autologous HCT. Median time to resolution was 98 days and median cumulative ECU dose was 10,200 mg (range 4800-36400mg). An additional 2 pts (13%) presented clinical improvement without complete resolution of TA-TMA. Mortality secondary to TA-TMA or its complications was 33%. Median time to death was 31 days. The most common cause of mortality were infectious complications. Median survival for the entire cohort was 130 days (range 6-833 days, Figure). LDH 〉1300 U/L; more than one organ involvement, allogeneic HCT, use of tacrolimus and early (

Description: Chronic graft-versus-host disease (GVHD) is likely caused by donor T lymphocytes. Because unmodified blood stem cell grafts contain one log more T lymphocytes than unmodified marrow grafts, we evaluated the incidence of chronic GVHD in previously reported 37 blood stem cell recipients and 37 computer-matched historical control marrow recipients (Bensinger et al, Blood 88:2794, 1996). All patients have been followed until death, relapse, or occurrence of chronic GVHD or for a minimum of 2 years. In a univariable proportional hazards regression model, the relative risk of developing clinical chronic GVHD (includes clinical limited and clinical extensive disease) by 2 years posttransplant among the peripheral blood stem cell recipients compared with the marrow recipients was 2.22 (95% confidence interval, 1.04 to 4.74; P = .039). For clinical extensive chronic GVHD, the relative risk was 2.37 (95% confidence interval, 1.07 to 5.29; P = .035). In multivariable analyses, considering also the covariables of patient age, patient cytomegalovirus serostatus, and donor cytomegalovirus serostatus, the relative risks of clinical chronic GVHD and clinical extensive chronic GVHD were also greater than 2 (P 〈 .05). We conclude that the transplantation of unmanipulated filgrastim-mobilized blood stem cells may result in a relatively high incidence of chronic GVHD.

Description: Abstract 3453 Individuals undergoing allogeneic transplantation receive multiple red blood cell transfusions both as part of the transplant procedure and as part of the pre-transplant care of the underlying disease. Therefore these patients may be at risk for complications of transfusional iron overload. Several studies have noted that individuals entering the transplant with baseline elevated serum ferritin values have decreased overall survival and higher rates of disease relapse. Whether the iron is a direct contributor to inferior outcomes or is a marker of more advanced disease (thereby requiring greater transfusions) is unclear. Little is known about the incidence and consequences of iron overload among long-term survivors of allogeneic transplantation. Methods: Using Kaplan-Meier and Cox regression analyses, we performed a single center, retrospective cohort study of consecutive allogeneic transplants performed at Hackensack University Medical Center from January 2002 through June 30, 2009 to determine the association between serum ferritin (measured approximately 1 yr post allogeneic transplant) and overall survival. Results: During the study time frame, 637 allogeneic transplants (Donor Lymphocyte Infusion procedures excluded) were performed at our center and 342 (54%) survived ≥ one year. Among 1-year survivors 240 (70%) had post-transplant serum ferritin values available for review, including 132 (55%) allogeneic sibling, 68 (28%) matched unrelated, and 40 (17%) mismatched unrelated donor transplants. The median post-transplant ferritin value among 1-year survivors of allogeneic transplant was 628 ng/ml (95% CI 17, 5010), with 93 (39%) above 1000 ng/ml and 40 (17%) above 2500 ng/ml. The median post-transplant ferritin levels varied by underlying hematologic disease (aplastic anemia = 1147, acute leukemia = 1067, MDS = 944, CLL = 297, CML = 219, lymphoma = 123, multiple myeloma = 90). The Kaplan-Meier projected 5-year survival rate was 76% for the cohort that had survived one year and had available ferritin values. Fifty late deaths have occurred; causes of late death were disease relapse (n=37, 74%), GVHD (n=7, 14%), infection (n=4, 8%), cardiac (n=1, 2%) and second malignancy (n=1, 2%). The 1-year post-transplant serum ferritin value was a significant predictor of long term survival. Using a cut-off ferritin value of 1000 ng/ml, the 5-year projected survivals were 85% (95 CI 75%-91%) and 64% (95% CI 52–73%) for the low and high ferritin cohorts respectively (Figure, log-rank p

Description: Abstract 4569 Background: Oral mucositis is a common toxicity associated with cancer therapies and increases risk for infection, mortality, and extended hospital stay. Prophylactic use of a supersaturated calcium phosphate mouth rinse (SSCPR, Caphosol®) was found in a phase III study to reduce the frequency, intensity, and duration of oral mucositis in patients (pts) undergoing allogeneic or autologous hematopoietic stem cell transplantation (Papas, et al. Bone Marrow Transpl 2003;31:705). That study also found a faster time to recovery of an absolute neutrophil count (ANC) ≥0.2×109/l, but not for other engraftment endpoints, likely a result of the mixed pt population studied. Objective: A single-center retrospective review of two uniform populations undergoing autologous peripheral blood stem cell transplantation (PBSCT) to determine if an effective regimen of mucositis prophylaxis results in faster engraftment and shorter hospital stays. Methods: Two different uniform population of pts ≤70 years of age with Hodgkin or non-Hodgkin lymphoma (HL/NHL) and multiple myeloma (MM) undergoing PBSCT between 1/1/07 and 12/31/09 (Table 1). MM pts were conditioned with single dose melphalan (N= 16 with 140 mg/m2; N= 203 with 200 mg/m2). HL/NHL pts were conditioned with BEAM. Oral ice chips were given during the melphalan infusion for all pts. Filgrastim, 5 ug/kg, was given on days +3, +5, +7, +9 and then daily until granulocyte engraftment. A regimen of oral hygiene using sodium bicarbonate (NaHCO3) tooth cleaning after each meal with as needed rinsing was encouraged. SSCPR was added to this regimen in May 2008 with pts instructed to rinse 4-times daily after teeth cleaning and as needed. Granulocyte engraftment was defined as the first day with a rising ANC ≥0.5×109/l, and platelet engraftment was defined as the first day of a rising platelet count ≥20×109/l. Prospective scoring of mucositis was not performed and the use of intravenous fluconazole, ciprofloxacin, and/or acyclovir prophylaxis was recorded as a surrogate indicator of severe mucositis. Engraftment times and time to hospital discharge were estimated using the method of Kaplan and Meier, and the groups were compared using the log-rank test. The Mann-Whitney U test was used to assess differences in median values of age and CD34 cells infused, and Fisher's Exact test was used to assess the significance of differences categorical parameters. Results: No differences were found between the control and study populations for age, gender, diagnosis, or CD34+ cell content of the graft (Table 1). For the HL/NHL control group one pt failed to engraft and was censored at the time of infusion of backup PBSC. In the MM groups no pts failed to engraft. No pts for either diagnosis were censored for death or relapse before hospital discharge. For both populations, pts using SSCPR achieved the primary endpoints of engraftment and were discharged home a median of 1 day faster than the respective control group pts (Table 2). 18 pts in the HL/NHL control group and 20 pts in the SSCPR group experienced febrile neutropenia (p=1.0) and 4 pts in each group were given intravenous medications (p=1.0). 73 pts in the MM control group and 53 pts in the SSCPR group experienced febrile neutropenia (p=0.22). 11 pts in the control group and 10 pts in the SSCPR group were given intravenous medications (p=1.0). These retrospective data of sequentially treated cohorts suggest that an effective regimen of mucositis prophylaxis may result in faster engraftment and shorter hospital stays with fewer days of antibiotics and cytokines. This retrospective study lacks detail regarding the incidence of mild/moderate mucositis and a mechanism of this action cannot be discerned from these data. Disclosures: Rowley: EUSA Pharmaceautical: Speakers Bureau.

Description: Abstract 3131 Introduction: Although MCL is reported to be an FDG-avid NHL subtype, PET-CT is not currently recommended in the modified IWG criteria (Chesen et al, JCO 2007) to stage, survey and assess treatment response in MCL. PET-CT is however frequently used for these purposes in clinical practice in MCL. Although convincing data exists regarding the prognostic utility of PET-CT imaging in Hodgkin Lymphoma (interim & post treatment) and DLBCL (post treatment), its prognostic utility both during treatment and immediately following treatment have not systematically been evaluated in a large MCL patient cohort to support its use in clinical practice. Methods: We conducted a two-center (JTCC & UPenn), retrospective cohort study to examine the prognostic utility of pre-treatment (PET-1), interim-treatment (PET-2 after 2–3 treatment cycles) and post-treatment PET-CT (PET-3) imaging in a uniform MCL patient cohort undergoing dose-intensive chemotherapy (R-HCVAD) or high-dose chemotherapy followed by autologous stem (ASCT) cell rescue in the 1st line setting. The primary study endpoints were PFS and OS. PET-CT images were centrally reviewed for the purposes of this study using standardized response criteria proposed by the Imaging Subcommittee of International Harmonization Project in Lymphoma (Juweid et al, JCO 2007). Radiologists were blinded to clinical outcomes at the time of PET-CT review and results were dichotomized at each time point and their concomitant SUV max at a suspected site of disease was recorded. Result: 82 pts (median age 61, range 35–95) with advanced stage (98% stage IV) MCL with PET-CT data were identified for this analysis. Of these, 57 pts were treated with R-HCVAD (50) or ASCT (7) in the first-line setting. 154 PET-CT scans were reviewed. Overall treatment response rate (IWG) was 93% (76% CR + 17%PR). With median follow-up of 23 months (disease progression) and 27 months (overall survival), 3 year PFS and OS estimates were 70% (CI 53–82%) and 82% (CI 65–91%) respectively. Median baseline characteristics: WBC 7.4, ECOG PS 1, LDH/ULN .82, Ki-67 (MIB-1) 28% (range 10–90%), MIPI 3.5 (31% intermediate risk, 19% high risk). 20% and 30% of pts were blastoid variant and leukemic phase at diagnosis respectively. Pre-treatment PET-CTs were FDG-avid in 92% of MCL patients with a median SUV max of 7.8 (range 2.4–36.7) at a suspected site of disease. Pre-treatment PET-CT SUV max was positively associated with high Ki-67 (variance-weighted least-squares regression, p=.01). PET-2 and PET-3 were positive in 34% and 18% of patients respectively. Kaplan Meier and Cox regression survival analyses were used to test the association between PET-CT and survival. Interim PET-CT status was not associated with PFS (HR 1.1, CI .4-3.6, p=.8) or OS (HR .8, CI .15-4.6, p=.8). Post treatment PET-CT status was statistically significantly associated with PFS (HR 5.4, CI 2.0–14.5, p=.001, Harrell's C =.70, Figure) and trended towards significant for OS (HR 3.2, CI .8-11.9, p=.1). Post treatment PET-CT status remained an independent predictor of PFS in multivariate analysis which included MIPI score, blastoid variant and Ki-67. Conclusion: Our cohort is the first large series of MCL patients treated essentially with R-HCVAD examining the correlation between PET-CT and outcome in the front-line setting. A positive PET-CT following the completion of therapy identifies patients with an inferior PFS and a trend towards inferior OS. These data do not support the prognostic utility of PET-CT in pre-treatment (no upstaging) and interim treatment settings. This information should be incorporated into the design of future prospective clinical trials. We are currently examining the relationship of novel computer-assisted quantitative FDG-PET/CT measures of total tumor volume and total tumor metabolic burden with clinical outcome in patients with mantle cell lymphoma. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Though overall Hodgkin lymphoma (HL) carries one of the best outcomes among lymphoma, about 40% of patients relapse and/or fail to respond to initial therapy. Out of those about half can be cured with salvage therapy followed by high dose therapy and autologous stem cell transplantation (ASCT) while eligible patients who fail and/or relapse after HDT-ASCT are offered nonmyeloablative stem cell transplantation. Achieving a negative PET response prior to ASCT correlate with superior outcome in HL regardless of their clinical presentation. More recently novel therapies have emerged in the field from brentuximab vedotin approved in r/r setting in HL as well as checkpoint inhibitors currently in trials with very promising results. This study analyzed a cohort of HL pts transplanted at our institution over the last 5 years to identify potential new patterns in the evolving landscape of HL. Methods: We performed a retrospective analysis of r/r HL pts referred to our center for salvage therapy at our institution between 2009 and 2014 using the Blood and Bone marrow transplant database at HUMC. Results: A total of 66 patients with r/r HL transplanted at HUMC were identified. Baseline characteristics were as follows: male 57%, female 43%, median age 36.8y (range 16-66), Frontline therapy was ABVD in all but one pt who received Gemzar, Vinorelbine, Doxil; and 27% pts received consolidation w/ radiation. Median time to relapse was 7mo (range 0.93-87mo), stage at first relapse I-0, II-33%, III-20%, IV-23%, NA 24%. The salvage regimen used was ICE in 54 pts, brentuximab vedotin in 8 pts and HCVAD in 4 pts. Involved field radiation was used in 10% at salvage prior to HDT-ASCT. Responses after first salvage were as follows: PET-CR 59%, CT-CR 5%, PR-14%, PD-12%, NA-10%. As per our practice, pts not in CR after first salvage continue to the next salvage until they reach a CR. Pts not in CR after 2 lines of salvage were considered for allogeneic stem transplantation (alloSCT). Conditioning regimen was BEAM prior to ASCT, reduced intensity (fludarabine-based) prior to alloSCT. Source of allo stem cells was: MRD in 7 pts, MUD in 3 pts, haploidentical donor in 2 pts. A total of 59 pts had ASCT, 6 pts had alloSCT as first transplant (primary refractory), while 6 pts underwent alloSCT for relapse after ASCT. Disease status post first transplant was as follows: PET-CR 76%, CT-CR 17%, PR-1%, PD-6%. All 6 alloSCT pts are alive in remission, while 13 out of 59 ASCT pts have relapsed, 7 relapses occurred within the first year, 3 within the second year post ASCT. Out of 6pts with alloSCT after ASCT relapse, 4 pts are alive in CR, one died from PD, one died from PTLD (in CR from HL). After a median follow up of 24.5 mo (3.7-70), the 3y PFS and OS are 73% and 95% respectively. For CR and PR after first salvage to SCT pts, median PFS and OS has not been reached. For SD/PD after first salvage therapy pts median PFS is 14.5mo, median OS 47mo. No significant difference in mPFS and mOS is seen in pts who received one vs more than one salvage therapy prior to ASCT or had radiation as part of frontline or salvage therapy. Conclusion: We report on a consecutive series of high-risk r/rHL. Our results demonstrate an improved outcome compared to historical data. Pts requiring more than one salvage prior to SCT while having mPFS of only 14.5 mo, have prolonged survival at median 47 mo. While the number is small, selected young pts with high risk relapsed HL may benefit from alloSCT. Strategy of requiring CR prior to SCT, and alloSCT (instead of ASCT) in pts requiring more than 2 consecutive salvage regimens, availability of novel agents, diminishing use of RT may have contributed to observed improved outcomes. Disclosures Feldman: Pharmacyclics/JNJ: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau. Vesole:Idera Pharmaceuticals: Research Funding; Celgene Corporation: Speakers Bureau. Skarbnik:Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Speakers Bureau; Gilead Sciences: Honoraria, Speakers Bureau. Goy:Acerta: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/JNJ: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Description: Introduction: The outcome of MCL patients (pts) has improved over the last three decades, although this is debated outside clinical trials (Chandran, Leuk Lymphoma Aug 2012; Smith, Br J Cancer. April 2015). The Mantle Cell International Prognostic Index (MIPI) (Hoster, Blood Jan 2008) is based on 4 variables which predict survival: age (host factor), PS (tumor/host), LDH (tumor burden) and WBC (leukemic phase). The additional value of including co-morbidities into risk stratification has not been fully explored. Methods: Using the COTA database we retrospectively analyzed MCL cases treated at John Theurer Cancer Center and the affiliated practices of Regional Cancer Care Associates from 2004 to 2016. Clinical and treatment characteristics, including calculation of the CCI index (Charlson J Chronic Diseases 1987) were captured via the COTA platform by extracting data from the electronic health records. Results: 490 pts with MCL were evaluated and full longitudinal data from diagnosis is currently reported on 195 subjects. Pts characteristics included: male (66.15%), med age (65, range 34-94), stage IV (87%), LDH (elevated 26%; median 197, range 112-7950), MIPI (low 38%, interm 32%, high 30%), Ki-67 (≥30%: 51%, 86 NA), blastoid variant (16%, 35 NA), SOX-11 positive (87%, 143 NA), 17p abnormalities (p53 del or overexpression/mutation (24%, 88 NA) and b-2 microglobulin (b-2m) 〉 3 mg/L (52%). Frontline therapy consisted of R-Hyper-CVAD (with or without bortezomib on study) (36%), R-HyperCVAD or R-CHOP followed by high-dose therapy followed by autologous stem cell transplantation (ASCT) (9%), BR alone (8%), BR+ maintenance (8%), R-CHOP alone (4%), Rituximab (3%), R-BAC (3%), BR+ Ibrutinib vs placebo (2%), radiation (2%), R-Lenalidomide (1%), R-CHOP + maintenance (1%), other treatments (10%) while 10% of patients were treated expectantly Seventeen pts underwent ASCT consolidation (15 auto vs 2 allo (del17p/blastoid at presentation). Overall and progression free survival was computed using Kaplan Meier curves and significance tested using log-rank tests. The 5y OS for this entire cohort was 81. Overall, dose-intensive strategies (with or without ASCT) approach was associated with a 23 mo difference in PFS (median 74 mo, range 0-111 mo (intensive) vs median 51 mo, range 2-57 mo for the non-intensive group (p=0.37). The median OS was not reached for either group, with a 5y OS of 88% in intensive vs. 71% non-intensive regimens (p=0.14). Using MIPI as stratification, low/intermediate risk pts had similar outcome in intensive and non-intensive therapy groups (5y OS 88% vs 71%; p=0.13). Pts with high MIPI had a 5 year OS of 80% in the intensive therapy group vs 46% for non-intensive group (p=0.376). The CCI scores for the whole cohort were 0 in 16 pts (8%), 1-3 in 81 pts (41%), and ≥ 4 in 98 pts (50%). Baseline CCI score (pre-treatment) was highly predictive of outcome with a 5y OS of 90% in CCI 0-3 vs 62% in CCI 3+ (p=0.001) (Figure 1). CCI did not predict complete response rate (CR) to induction therapy (CCI 0-3 94% vs CCI 3+ 80%). The median MIPI scores were 5.7 for CCI 0-3 and 6.3 for CCI 3+. Age is a component of both indexes but more heavily weighted in the CCI. Adding CCI to MIPI defined a subset of pts among the high MIPI group who did better than expected with a 5y OS of 88% in combined high MIPI / CCI 0-3 vs 31% for high MIPI / CCI 4+/ (p=0.03). b-2m (cut-off 3mg/L) correlated with 5y OS 93% vs 80%; (p=0.04) as previously reported but did not add to MIPI or CCI risk stratification. Ki-67 (30% cut-off) was marginally associated with OS: 5-y 89% vs 77% (p=0.06). Conclusions: Our cohort is consistent with the improvement of MCL outcome comparing to historical controls and illustrates the importance of comorbidities captured at baseline. A combined CCI-MIPI approach might help identify pts who can still benefit from current therapy approaches in spite of age. Among the high MIPI score group, CCI further refines cohorts with significantly different outcomes. Figure 1 Figure 1. FIgure 2 FIgure 2. Disclosures Goy: Acerta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Other: Research funding for clinical trials through institution; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; COTA: Membership on an entity's Board of Directors or advisory committees; Janssen/Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Research funding for clinical trials through institution, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Research funding for clinical trials through institution. Wu:COTA: Employment. Hansen:COTA: Employment. Arunajadai:COTA: Employment. Protomastro:COTA: Employment. Valentinetti:COTA: Employment. Murphy:COTA: Employment. Smith:COTA: Employment. Pe Benito:COTA: Employment. Hasan:COTA: Employment. Suryadevara:COTA: Employment. Feldman:Seattle Genetics: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Pharmacyclics: Speakers Bureau; Celgene: Speakers Bureau. Skarbnik:Pharmacyclics: Consultancy; Genentech: Speakers Bureau; Seattle Genetics: Speakers Bureau; Gilead Sciences: Speakers Bureau; Abbvie: Consultancy. Leslie:Celgene: Speakers Bureau; Seattle Genetics: Speakers Bureau. Pecora:COTA: Employment, Equity Ownership. Goldberg:Bristol Myers Squibb, Novartis: Speakers Bureau; Neostem: Equity Ownership; Novartis: Consultancy; COTA Inc: Employment; Pfizer: Honoraria.