ALBERT

Description: Background: Lower total CD34+ cell dose and increased HLA-mismatch are known predictors of engraftment failure and higher transplant related mortality (TRM) in cord blood (CB) recipients. To compensate for cell dose, double unit grafts (DUCBT) are commonly used in adult. However, in the majority of patients (pts), only one of the two CB units engrafts. Identification of the factors that predict which unit will engraft remains elusive, although increased recipient-donor HLA-matching and larger CD3+ cell dose have been associated with the predominating unit in a single center retrospective analysis (Ramirez et al, 2012). Historically, CB units are selected by maximizing matching at the HLA-A and -B antigen and -DRB1 allelic level. Evidence supports that matching at HLA-C appears to decrease TRM, and many clinicians incorporate HLA-C antigen matching into unit selection. It is unclear, however, if HLA-C matching predicts the engrafting unit in DUCBT. This study retrospective study evaluates whether HLA-C matching is associated with the winning CB unit. Design: Clinical data was reviewed from all pts with a hematologic malignancy receiving a DUCBT at Moffitt Cancer Center between November 13, 2009 and August 29, 2013. Chimerism studies identified the predominating unit (〉 65% single unit) between day 21 and day 28. Subsequent chimerism analyses performed at a median of day 100 confirmed unit predominance. Unit selection required intermediate resolution antigen match at HLA-A, -B, -C, and high resolution allele match at -DRB1. Units were a minimum of 4/8 matched to the patient and each other with a minimum cell dose of 1.5 x 107 total nucleated cell dose (TNC) /kg. Serology for donor specific antibodies against both units was negative. Results: Excluding 6 pts who were missing HLA-C typing on one or both CB units, 54 pts with hematologic malignancies (ALL=6, MDS/AML=29, Other=19) received chemotherapy and total body irradiation as part of a myeloablative conditioning (MAC) or reduced intensity conditioning (RIC) with or without thymoglobulin (ATG) followed by a DUCBT (MAC=14, RIC=23, RIC+ATG=17). Median age was 52 (range 22-69) years. Seven pts demonstrated persistent mixed chimerism in the myeloid and/or lymphoid cell lines beyond day 100. A total of 20 pts with available chimerism data received at least one CB unit matched to the recipient at HLA-C, with one patient excluded due to persistent mixed chimerism. Six pts received both CB units matched at HLA-C, but of the 13 pts receiving one matched and one mismatched unit, the HLA-C matched unit was the engrafting unit 69% (9/13) of the time. Comparing similar HLA mispairings, a matched unit engrafted over a mis-matched unit at HLA-A 50% (5/10) of the time, at HLA-B 38% (5/13) of the time, and at HLA-DRB1 50% (3/6) of the time. TNC dose (larger vs smaller with a required difference of at least 0.03 x 107 TNC/kg), order of infusion (first vs second unit), and overall CB unit HLA matching (4/8-8/8), were assessed as potential predictors for engraftment. Of evaluable patients, the CB unit with the larger TNC engrafted 44% (16/36) of the time, and the first unit infused was the engrafting unit 54% (21/39) of the time. In patients with an unequal overall match grade between the CB units, the better HLA-matched CB unit engrafted 64% (14/22) of the time. Survival analysis of all pts revealed that those who received at least one CB unit antigen matched at HLA-C (n=20) had a 100 day and 1 year overall survival (OS) of 85% (95% Confidence Interval(CI): 67–97%) and 55% (95% CI: 33–75), respectively, whereas pts receiving two HLA-C mismatched CB units (n=34), 100 day OS was 62% (95% CI: 45–77) with 1 year OS 44% (95% CI: 28–61) (Fig 1). Conclusion: HLA-C antigen matching appears to help predict the winning unit in settings of HLA-match disparity and DUCBT. Confirmation in a larger population of DUCBT recipients is necessary. To date, the effects of HLA matching and other variables influencing engraftment have been predominately evaluated in recipients of single unit transplants and studies in DUCBT have been limited. Further investigation assessing HLA matching as well as donor-donor interactions is best served through a multicenter data resource. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Gastro-intestinal GVHD (GI GVHD) is a common and severe complication of allogeneic hematopoietic cell transplantation (HCT). Systemic glucocorticoids remain the standard of care for GI GVHD, despite their incomplete efficacy and toxicity. Steroid-sparing activity and improved survival were reported with oral administration of poorly absorbed beclomethasone dipropionate (BDP) in combination with systemic glucocorticoids for upper GI GVHD, and promising results were described with the adjunct of budesonide (BUD) for lower GI GVHD. No data have been reported on BDP or BUD without systemic glucocorticoids. Our team has adopted the practice of administering BDP/BUD without systemic glucocorticoids as fist-line therapy. Here we assess safety and efficacy of our practice in the treatment of isolated GI GVHD. Methods: We analyzed retrospective data from 297 consecutive patients (pts) with isolated GI GVHD after hematopoietic peripheral blood stem cell transplantation performed at the Moffitt Cancer Center between July 2004 and June 2013. At discretion of the treating physician, patients with upper with or without lower GI GVHD were treated with BDP (5 mg BID or TID orally), BDP plus prednisone (PRED 0.5-2 mg/kg or equivalent glucocorticoid dose), BDP+BUD (3 mg BID or TID orally) or BDP+BUD+PRED. The primary study endpoint was response of GI GVHD after 28 days, defined as complete resolution of all GI symptoms without addition of other immune suppressive (IS) agent(s) or partial reduction of GI symptoms, without resolution and without addition of other IS agent(s). Secondary endpoints were response to treatment after 200 days, chronic GVHD (CGVHD), CMV infection, relapse free survival (RFS), and overall survival (OS). All endpoints were analyzed according to treatment arm (Figure 1). A multivariable model was used to test the association between response after 28 days and treatment arm, after adjusting for primary diagnosis, conditioning regimen, disease status at HCT, pts/donor characteristics, GI GVHD overall grade, GI GVHD site, and albumin level. Results: BDP vs. BDP+PRED. Baseline characteristics were well balanced among the BDP (n=90) and BDP+PRED (n=24) groups, including treatment for isolated upper GI GVHD (84% vs. 67%, p=0.08), with the remainder affected by both upper and lower GI GVHD. BDP+PRED showed a significantly higher response of GI GVHD after 28 days compared to BDP (88% vs. 56%, multivariate OR 23, 95% CI 3-161, p=0.002); however there was no significant difference in response after 200 days (50% vs. 33%, univariate p=0.5). There were no significant differences in terms of treatment duration, requirement of additional IS agents, CMV reactivation, CGVHD development, RFS and OS between the two treatment cohorts. BDP+BUD vs. BDP+BUD+PRED. BDP+BUD+PRED pts (n=53) had more rapid onset of GI GVHD (median 20 vs. 26 days after HCT, p=0.001), higher incidence of lower GI involvement (61% vs. 38%, p=0.008) and higher incidence lower GI stage II-III GVHD (p=0.0004) compared to BDP+BUD pts (n=130). Despite adjusting for these higher risk features by multivariable analyses, BDP+BUD+PRED was associated with a significantly higher response after 28 (90% vs. 75%, multivariate OR 15, 95% CI 3-62, p=0.0003) and 200 days (70% vs. 45%, univariate p=0.0003). There were no significant differences in treatment duration, CMV reactivation, CGVHD development, RFS and OS between the two treatment cohorts. Conclusions: This retrospective analysis suggests that the addition of systemic PRED to topical BDP/BUD therapy for isolated GI GVHD was associated with a better response after 28 days of treatment. Despite the inferiority in GI GVHD response, there were no differences in secondary endpoints including treatment duration, CMV reactivation, RFS and OS. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Background: Patients undergoing stem cell transplant (SCT) are at risk of bloodstream infections (BSI). BSI led to prolonged hospitalization, intensive care admissions, prolonged antibiotic treatment and increased mortality. Recently, the Centers for Disease Control and Prevention developed a modification of the Central line associated bloodstream infection (CLABSI) definition, termed "mucosal barrier injury laboratory-confirmed bloodstream infection" (MBI-LCBI) to differentiate BSI likely related to mucosal barrier injury. BSI are identified as an MBI-LCBI if: (1) it resulted from 1 or more of a group of selected organisms known to be commensals of the oral cavity or gastrointestinal tract and (2) occurred in a patient with signs or symptoms compatible with the presence of mucosal barrier injury such as gastrointestinal graft-versus-host disease and/or neutropenia. We utilized the CIBMTR database to determine the incidence and timing of MBI-LCBI, risk factors for development of MBI-LCBI, and compare transplant outcomes by 1 year after SCT. Methods: We identified 16,875 pediatric and adult patients receiving first allogeneic transplant from 2009-2016. Patients were classified into 4 categories based on the occurrence of BSI in first 100 days: MBI-LCBI (n=1434; 8.5%), MBI-LCBI +other BSI (n=700; 4.1%), BSI only (n=3016; 17.8%), and control (n=11725; 69.5%) (Figure 1). Demographics and outcomes, including overall survival (OS), chronic GVHD, and transplant-related mortality (TRM, for malignant disease patients only), were compared between groups. Results: The cumulative incidence of MBI-LCBI was 13% (99% CI: 12-13%) by day 100 whereas the probability for another BSI not meeting MBI-LCBI criteria was 22% (99% CI: 21-23%) by day 100. The median time from transplant to first MBI-LCBI was 8 days (

Description: Graft-versus-host disease (GVHD) remains the principal obstacle to successful outcomes in allogeneic hematopoietic stem cell transplant (HCT). Glucocorticoids are the current standard initial treatment for acute GVHD with variable complete responses rates (30% to 60%). New immunosuppressive strategies are required to improve survival and to decrease immunosuppressive toxicities. Vorinostast, a histone deacetylase inhibitor (HDACi), have shown efficacy for acute GVHD prevention in MRD HCT. Panobinostat is a potent inhibitor of deacetylases and HSP90 belonging to a structurally novel class of the cinnamic hydroxamic acid class and is one of most potent pan-HDACi. This protocol tested the safety and efficacy of Panobinostat (LBH589) as initial adjunct treatment for acute GVHD, administered within 72 hours of the first high dose glucocorticoid (methylprednisolone 0.8 mg/Kg/day IV or equivalent PO for 14 days and then taper per MD discretion). We have enrolled 19 subjects, median age 53 years (range, 34-76), male (n=12)/female (n=7), white(n=14)/hispanic(n=5); with diagnosis of CLL (n=2), MDS (n=2), Myeloma (n=1), Follicular NHL (n=1), CML(n=1), Myelofibrois (n=3), AML (n=5), MDS/CMML (n=3) or ALL(n=1). Conditioning regimens included Busulfan(BU)/fludarabine(FLU) AUC 5300 (n=10) or AUC 3500 (n=3), FLU/Melphalan (n=4) or Pentostatin/BU (n=2); and GVHD prophylaxis for MUD 8/8 (n=11) or MRD (n=5) HCT with TAC/MTX (n=6), TAC/rapamycin(n=7), TAC/MMF(n=3) and for mismatched transplants with either TAC/RAPA/ATG (n=2) or TAC/MTX/ATG (n=1). Median day of acute GVHD (n=16) onset was day + 37 post HCT (26 -109 days) with overall grade GVHD II (n=13) or III (n=6); and median day of acute symptoms in overlap GVHD patients (n=3) was day + 712 (528-981). All Patients were treated with voriconazole (n=15) or micafungin (n=4) for fungal prophylaxis. For the first four patients Panobinostat was administered intravenously (IV) weekly x 4 at 2.5MG/M2 (n=3) or 5MG/M2 IV (n=1) with all 4 achieving either CR (n=3) or PR (n=1) GVHD responses by day +15 of Panobinostat. Due to manufacturer discontinuation of IV formulation, the protocol was amended to use PO Panobinostat. Using 10mg PO TIW 3 doses q week x 4 weeks, we treated 2 subjects which were both discontinued from study drug due to presumed GHVD progression within 7 days of Panobinostat (after 3-4 doses). First subject had grade II GVHD (skin stage 3, gut stage 1 and liver stage 0) that progress in gut and skin; second subject with grade II GVHD (skin stage 3, gut stage 1, liver stage 1) with LFTs worsening ultimately evolving into VOD. Due to safety concerns next subjects were treated with 5 mg PO TIW 3 doses q week x 4 weeks, dose that was determined to be the maximal tolerated dose (MTD) after 6 patients completed therapy in phase I. Currently we are enrolling in phase II portion (n=7). GVHD response rate among MTD treated was complete in 85% (n=11), partial in 7.6% (n=1) or progressive in 7.6% (n=1) by day +36 after Panobinostat with majority achieving responses by day +21. Chronic GVHD at day +365 in evaluable patients (n=6) was none (n=3) or mild (n=3) and steroid was discontinued at a median of 3 months (3-6). Hematological toxicities in evaluable patients (n=13) were mild with worsening of prior thrombocytopenia (n=7/10), anemia (n=3/10) and leukopenia (n=3/10) and returned to baseline within 1-2 weeks; LFTs deterioration (n=1) within 1 week of Panobinostat in a GVHD stages 3 liver/3 skin patient; pericarditis/cardiogenic shock CTCAE 5 of unclear etiology (n=1); worsening thyroid function (n=1) and hypercholesterolemia (n=1). Preliminary correlative studies in MTD treated patients showed that CD4 and CD8 numbers remained stable during treatment. T regulatory cells numbers decreased at day +8 after Panobinostat and recovered by days +15 and +29 of treatment. Level of T regs inducing cytokines (TGFB and IL-10) increased, possibly contributing to an immune-modulatory environment. There is evidence of an increased in acetylation of histone 3 in CD4, CD8 and monocytes subsets over time. We are encouraged with tolerability of level -1 Panobinostat dose and the high GVHD response rate of 85% which may compare favorably to the historical GVHD response rate. These results suggest a potential role for Panobinostat as a tool to improve success of glucocorticoids for acute GVHD treatment. Disclosures No relevant conflicts of interest to declare.

Description: Key Points Cytomegalovirus after bone marrow transplantation remains associated with lower survival but not prevention of leukemia relapse.

Description: Tacrolimus exhibits high inter-patient pharmacokinetics (PK) variability, as well as a narrow therapeutic index, and therefore requires therapeutic drug monitoring. Germline mutations in cytochrome P450 isoforms 4 and 5 genes (CYP3A4/5) and the ATP-binding cassette B1 gene (ABCB1) may contribute to interindividual tacrolimus PK variability, which may impact clinical outcomes among allogeneic hematopoietic stem cell transplantation (HSCT) patients. In this study, 252 adult patients who received tacrolimus for acute graft versus host disease (aGVHD) prophylaxis after allogeneic HSCT were genotyped to evaluate if germline genetic variants associated with tacrolimus PK and pharmacodynamic (PD) variability. Significant associations were detected between germline variants in CYP3A4/5 and ABCB1 and PK endpoints (e.g., median steady-state tacrolimus concentrations and time to goal tacrolimus concentration). However, significant associations were not observed between CYP3A4/5 or ABCB1 germline variants and PD endpoints (e.g., aGVHD and treatment-emergent nephrotoxicity). Decreased age and CYP3A5*1/*1 genotype were independently associated with subtherapeutic tacrolimus trough concentrations while CYP3A5*1*3 or CYP3A5*3/*3 genotypes, myeloablative allogeneic HSCT conditioning regimen (MAC) and increased weight were independently associated with supratherapeutic tacrolimus trough concentrations. Future lines of prospective research inquiry are warranted to use both germline genetic and clinical data to develop precision dosing tools that will optimize both tacrolimus dosing and clinical outcomes among adult HSCT patients.

Description: Allogeneic HCT has been shown to induce long term remissions in FL pts who have chemosensitive relapsed disease. The BMT CTN (sponsored by the NHLBI and NCI) conducted a multicenter phase 2 trial to examine the efficacy of rituximab (RTX)-containing RIC alloHCT (BMT CTN 0701: NCT 00912223). The primary objective was 2 year progression-free survival (PFS). Conditioning regimen consisted of fludarabine, cyclophosphamide and high-dose RTX (FCR) in which three* of the 4 doses of RTX were given IV at a dose of 1000 mg/m2 on days -13, -6*, + 1* and +8*. Graft vs host disease (GvHD) prophylaxis consisted of tacrolimus and mini-methotrexate. Sixty five patients who demonstrated chemosensitivity to the most recent salvage regimen were enrolled from 2009 to 2012 and 62 were evaluable. Median age was 55 years (range, 29-74). Matched related (47%) and unrelated (53%) donors provided mobilized blood allografts. This group was heavily pre-treated as 77% of pts received ≥ 3 prior regimens with 32% having received ≥ 5 prior regimens. No graft failures occurred and the overall response rate after HCT was 94% with 90% achieving a complete remission (CR), including 24 patients not in CR before alloHCT. With a median follow-up of 24 months (range, 12-31), the 2 year PFS and overall survival were 75% (95% confidence interval: 61%, 84%) and 83% (95% confidence interval: 70%, 90%) respectively. The 2 year cumulative incidence of relapse/progression and non-relapse mortality was 10% and 15%, respectively. The 2 year cumulative incidences of grade 2-4 and grade 3-4 acute GvHD were 27% and 10%, respectively, with a 55% incidence of extensive chronic GvHD. Of the 10 reported deaths, 1 was from relapse/progression, 6 were related to GvHD, 2 were related to infections and 1 unexpected death. Serum RTX concentrations were examined at 4 time points up to 1 year. Serum RTX levels peaked at day +28 and remained detectable as late as 1 year in 23 pts with available 1-year RTX level results (n=39). Blood absolute T lymphocytes including CD4 and CD8 subsets remained within normal range up to 1 year post-HCT; however, B-cell lymphocytes were significantly reduced or not detectable up to 1 year post-HCT. In conclusion, RIC allogeneic HCT with the FCR conditioning regimen confers high CR rates, a low incidence of relapse/progression and notable survival incidences in heavily pretreated FL patients. Serum RTX levels were detected in a majority of the patients for up to 1 yr post-HCT which may have contributed to the low incidence of relapse/progression. Figure 1 Figure 1. Disclosures Laport: Genentech: Research Funding. Off Label Use: fludarabine, cyclophosphamide, rituxiamb. Lazarus:Actinium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Celgene Pharmaceuticals: Speakers Bureau.

Description: Prospective data regarding donation related toxicities and time to recovery in related donors (RDs) of bone marrow (BM) and peripheral blood stem cells (PBSC) are limited, in contrast to significant data available regarding unrelated donor experiences. To address this lack of data in RDs, the NHLBI-funded Related Donor Safety Study (RDSafe; NCT00948636) prospectively enrolled RDs of all ages between 2010 and 2013 at 54 transplant centers in the United States. RDs were assessed for pre-donation comorbidities and health status, and then followed for 1 year after donation, collecting detailed information on adverse events, pain levels and 10 collection-related NCI-CTC symptoms. This report describes baseline, peri-donation, and through 1 year post pain/symptoms for RDs aged 18-60: 124 BM (38 centers, med age 33, 48% female) and 919 PBSC (42 centers, med age 49, 44% female). Results: About 20% of RDs reported pain and NCI-CTC symptoms at baseline, mostly grade 1, with females reporting pain/symptoms more often than males (see figures). Pain occurred in approximately 80% of donors surrounding collection with other symptoms occurring in 50-70% of donors. Pain and symptoms persisted in 10-20% of RDs at 1, 6, and 12 months; pain/symptoms returned to baseline in only a few categories assessed, but mostly remained elevated from baseline at 1 year. In addition, for both males and females, at 1 year grade 2-4 pain or symptoms were 2-3 times baseline rates. Multivariate analysis was performed on PBSC donors, where numbers were sufficient to look at key risk factors (see table). Females had more grade 3-4 pain at collection, and grade 2-4 pain and symptoms at 1 year. Age differences were noted, with RDs age 30-39 experiencing the highest amount of pain and symptoms and RDs age 50-60 experiencing less pain compared to donors aged 18-29. Pain or symptoms at baseline were important predictors of higher levels of reported pain/symptoms, respectively, during the collection and also higher risk of grade 2-4 pain at 1 year. Conclusions: One in 5 RDs have mild/moderate pain and/or symptoms at baseline, and the presence of pain/symptoms at baseline increases risk for experiencing higher levels of pain/symptoms during collection. Although the majority of RDs return to baseline status within a month of donation, 〉10-20% of RDs have lingering pain/symptoms 6-12 months after donation, and rates of grades 2-4 pain and symptoms at 1 year are more than double baseline. Females have higher grades of pain with collection and more grade 2-4 pain and symptoms at 1 year compared to males. RDs should be informed of the risk of mild/moderate pain/symptoms lingering through the first year after donation. Ongoing efforts to correlate baseline comorbidities of RDs with outcomes should allow RDs to be better informed of risk and potentially identify clinical risk profiles where RDs should be deferred. *Pain = max grade 2-4 or 3-4 2 days post-donation of BM or day+5 of PBSC collection (collection day 1). **Symptoms = fever, fatigue, rash, local site reactions, nausea, vomiting, anorexia, insomnia, dizziness, and syncope Table 1. MV Analysis of PBSC RDs for pain and donation-related symptoms: Odds Ratio (p-value). Pain* Symptoms** day+5 Grd 2-4 day+5 Grd 3-4 1yr Grd 2-4 day+5 Grd 2-4 1yr Grd 2-4 Female 1.667 (0.010) 1.667 (0.016) 1.887 (0.041) Age (0.001) (0.008) (

Description: Introduction: Since the early days of allogeneic hematopoietic cell transplantation (HCT), positive serology for cytomegalovirus (CMV) in either the recipient or the donor, and CMV reactivation have been associated with poorer outcomes. In the 90’s, development of effective monitoring and potent antiviral drugs minimized and occasionally abrogated this negative impact. Recently, some studies have reported an unexpected association between early CMV reactivation and decreased incidence of relapse in AML. The Center for International Blood and Marrow Research (CIBMTR) sought to conduct a retrospective large scale study to reassess the impact of CMV serology and CMV reactivation in the current era. Methods: The analysis includes comprehensive data of 11,153 patients undergoing first allogeneic HCT between 2003 and 2010 reported to the CIBMTR. Separate analyses were conducted for each of the 6 patient categories: AML transplanted with bone marrow (BM) or peripheral blood stem cell (PBSC) (n=5310), AML transplanted with cord blood (CB) (n= 925), ALL with BM/PBSC (n=1883), ALL with CB (n= 759), CML with BM/PBSC (n=1079) and MDS with BM/PBSC (n=1197). CMV serology from the donor (D) or recipient (R), and reactivation of CMV (as a time-dependent co-variate) within the first year after HCT were analyzed as risk factors for outcomes. The median duration of follow up was 56 months (1 – 127 months). Results: The median time to CMV reactivation was 40 days (1 – 362 days) after HCT and 98% of reactivations occurred before day 100 (D+/R+ 32%, D+/R- 11%, D-/R+ 34%, D-/R- 4%). In multivariable analysis, throughout the 6 groups, a positive serology (D+/R+, D+/R-, D-/R+) vs a negative serology (D-/R-),had no effect on the risk of GVHD (acute or chronic) or the risk of relapse, except for an increased risk of chronic GVHD for BM/PBSC recipients with ALL. CMV positive serology was associated with a higher transplant related mortality (TRM) and a poorer overall survival (OS). For a R+ patient, a D- compared to a D+, had no negative impact except for ALL with BM/PBSC where a D- was associated with a poorer OS. After PBSC/BM transplantation, CMV reactivation was associated with a higher TRM for MDS (RR=1.61, p=0.0002), CML (RR=1.86, p=0.0004), AML (RR=1.68; p

Description: Background: A Phase I study revealed that vaccination of cancer patients with irradiated autologous tumor cells and GM.CD40L bystander cells (engineered to secrete GM-CSF and express CD40L) is safe, recruits/activates dendritic cells, and elicits tumor-specific T cell responses. We report final results using this vaccine strategy in patients with MCL, an aggressive and incurable B-cell malignancy. Methods: After lymph node resection for autologous tumor harvest, 4-6 cycles of chemotherapy, and restaging (CT, endoscopy, bone marrow biopsy), patients with usable vaccine who achieved a PR or CR lasting 1 month were vaccinated x4 at 28-day intervals with IL-2 (0.5 x 106 U SC BID x 14 d/cycle). Patients were monitored for toxicity, tumor response, tumor-specific immune responses, and median EFS/OS. Results: 43 were enrolled, including 21 with relapsed MCL, 20 with int/high MIPI, and 6 with blastoid MCL. Twenty never received vaccine: 2 withdrew, 1 progressed prior to nodal harvest, 7 had insufficient or contaminated specimens, and 10 progressed/died during chemotherapy. The unvaccinated were older (68.4y vs 62.8y; p=.026) but otherwise did not differ significantly by stage, LDH, MIPI, de novo status, or number of prior treatments. Among 23 treated, 10 had relapsed disease (median of 3 prior therapies), 10 had an int/high MIPI, and 2 had blastoid MCL. Pre-vaccination response following chemotherapy included 7 CR, 15 PR, and 1 SD. At 6 months after vaccination, 2 pts in PR had resolution of MRD within the bone marrow, 10 progressed (including 3 who progressed after 1-2 vaccines), and 11 had no change. Grade 3 toxicities were observed in three patients, and consisted of leukocytosis, neutropenia, and cough, none of which were attributed to vaccination. One patient remains in CR at 84 mo. A second who relapsed at 64mo remains without need for salvage therapy at 82 mo, suggestive of more indolent relapse post vaccination. Median EFS and OS are calculated from receipt of first vaccine. Median EFS is 9 mo, and median OS is 101 mo (median follow-up 81 mo). DTH was not observed. Biopsy of vaccine sites revealed lymphocytic response in 62%, however, this was not correlated with EFS or OS. Increased IFN gamma post vaccination was observed in 76%, and accompanied by an increase in EFS (p=.06). Increased GMCSF post vaccination was observed in 89%, with a trend for improved survival among those with higher peak levels. Conclusions: Extended follow up continues to show a sustained benefit in regards to overall survival for patients with de novo (85% alive at 81 months) and relapsed MCL (median OS 25 months), and support therefore the need for further studies of vaccination strategies in the context of new immunotherapeutic agents that are improving the outcomes of MCL patients. Figure 1 Figure 1. Disclosures Shah: Seattle Genetics, Inc.: Research Funding; NCCN: Consultancy; Celgene: Consultancy, Speakers Bureau; SWOG: Consultancy; Pharmacyclics: Consultancy; Janssen: Consultancy. Off Label Use: SGN-CD19A is an investigational agent being studied in patients with B-cell malignancies. SGN-CD19A is not approved for use. .