ALBERT

Description: Introduction: High standardized uptake value (SUV) on FDG PET scan in follicular lymphoma (FL) suggests aggressive disease and possible transformation to diffuse large B-cell lymphoma. Schoder et al, J Clin Oncol, 2005, reported that SUV 〉10 predicted aggressive lymphoma with 〉80% certainty and SUV 〉13 with 〉90% certainty. However, it is unknown whether the maximum SUV (SUVmax) on FDG PET scan at baseline, suggesting the possibility of focal aggressive or transformed disease, has prognostic value in FL. Here, we determined the prognostic value of SUVmax on baseline FDG PET scan in patients with advanced stage FL treated uniformly with R-CHOP chemoimmunotherapy at initial diagnosis. Methods: We reviewed medical records of all patients with stage III or IV FL who had FDG PET scan at initial diagnosis and were treated with R-CHOP chemoimmunotherapy at MD Anderson Cancer Center between January 2001 and December 2012. Patients with histological diagnosis of concurrent diffuse large B-cell lymphoma were excluded. Results: For the 225 patients studied, the median age was 57 years (range, 20-82). 83 (37%) patients were 〉= age 60, 137 (61%) had grade 1 or 2 FL, and 88 (39%) had grade 3A (n=57, 25%) or 3B (n=31, 14%). The Ki-67 score was 40% for 56 (40%) patients. FLIPI risk groups were 54 patients (24%) low, 74 (33%) intermediate, and 97 (43%) high. GELF criteria were met in 133 (59%) patients. Tumor bulk of 〉= 6 cm was seen in 97 (43%) patients. The absolute lymphocyte count (ALC) was normal or high in 155 (69%) patients and low in 70 (31%). Sixty-nine (31%) patients received rituximab maintenance. There was no correlation between baseline SUVmax on FDG PET scan and Ki-67 score (Pearson correlation co-efficient of 0.168). The overall and complete response rates were 96% and 87%, respectively. The median follow-up time was 66 months. At 5 years, progression-free survival (PFS) was 85% and overall survival (OS) was 90%. Male gender, stage IV, high risk FLIPI, presence of GELF criteria, high beta-2 microglobulin, and low ALC were associated with significantly inferior PFS and OS (p= 60 was associated with inferior OS but not PFS. Rituximab maintenance was associated with improved PFS but not OS. On baseline FDG PET scan, median SUVmax was 13.7 and the SUVmax range was 1.5-42.1. 105 (47%) patients had SUVmax 13. Patient characteristics including age, gender, histological grade, Ki-67 score, and FLIPI risk groups were not significantly different between the two SUVmax populations (p〉0.05). The overall response rates were 94% and 96% for the SUVmax 13 groups, respectively. The complete response rate was 87% in both groups. At 5 years, the PFS and OS were not significantly different between the low and high SUVmax groups (61% vs 63% for PFS, p=0.98 and 90% vs 89% for OS, p=0.63). PFS and OS were not significantly different even when the patients were grouped into SUVmax 10 (p=0.9 and 0.61, respectively) or when other cut-offs were used. SUVmax was also not predictive of PFS and OS when only the patients meeting GELF criteria were analyzed. Conclusions: In this large cohort of advanced stage FL patients treated uniformly with R-CHOP chemoimmunotherapy, SUVmax on baseline FDG PET scan was not predictive of clinical outcome or correlated with other features. It is possible that the doxorubicin-based chemotherapy regimen may have benefited patients with high SUVmax who may have underlying aggressive or undiagnosed transformed disease. It remains to be determined whether SUVmax is predictive of clinical outcome in FL patients treated with other commonly used therapies such as rituximab monotherapy, rituximab and bendamustine, or R-CVP. Figure 1 Figure 1. Disclosures Wang: Pharmacyclics, Janssen: Honoraria, Research Funding. Westin:Novartis: Research Funding.

Description: Purpose: We assessed the survival outcome of patients with anaplastic large cell lymphoma (ALCL) who experienced disease progression or relapse after first line and subsequent therapy. We sought to evaluate the impact of brentuximab vedotin (BV), and survival outcome of patients with ALCL who experienced progression after BV. Patients and Methods: A total of 176 patients (74 ALK+, 102 ALK-) initially diagnosed between 1999 and 2014 were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) after the progression/relapse following first-line chemotherapy (PFS1 and OS1), after first salvage therapy (PFS2 and OS2) and after second salvage therapy (PFS3 and OS3) were calculated. Outcome was separately analyzed according to the ALK status focusing on the use of BV. Results: The median age of the patients was 50 (range: 18-89). With a median follow up of 64 months, 111 patients (38 ALK+, 73 ALK-) experienced progression/relapse after the first-line therapy, of which 4 ALK- patients were post upfront stem cell transplant (SCT). Thirty and 15 patients eventually underwent autologous and allogeneic SCT after salvage chemotherapy, respectively. The median PFS1 and OS1 in patients with ALK+ALCL and ALK-ALCL were 8.4 and 28.5 months, and 13.1 and 47.7 months, respectively. In patients with ALK+ALCL, the median PFS1, PFS2 and PFS3 were 53.6, 5.2 and 2.3 months, respectively. The median OS1, OS2 and OS3 were not reached, 47.3 and 6.1 months, respectively. In patients with ALK-ALCL, the median PFS1, PFS2 and PFS3 were 12.9, 3.0 and 2.0 months, respectively. The median OS1, OS2 and OS3 were 54.3, 10.8 and 5.8 months, respectively. Interestingly, there were no significant difference in PFS2 between ALK+ALCL and ALK-ALCL. However, OS2 was significantly longer in patients with ALK+ALCL, suggesting possibly continued chemosensitivity of recurrent ALK+ALCL. A total of 30 patients received BV in 1st salvage (15 patients) and after 2nd salvage (15 patients).The use of BV at 1st salvage was associated with significantly longer PFS2 and OS2 both in patients with ALK-ALCL but not with ALK+ALCL likely due to small number of cases. Mutivariate analysis adjusting baseline PIT risk factors and the duration of the response to first line therapy revealed that use of BV (at any point in the salvage setting) is significantly associated with longer OS2 (HR: 0.43, 95%CI: 0.23-0.80). Overall, 12 patients experienced relapse/progression after BV treatment. The median OS after BV failure was 1.4 months (95%CI: 0.5-9.5 months) (Figure). Summary: Survival outcome for relapsed/refractory patients with ALK+ and ALK- patients is improved with BV. However, survival outcome after BV failure is very poor. A new treatment strategies to consolidate or maintain the response after BV and to develop more safe and better therapeutic options are needed. Figure 1. Figure 1. Disclosures Fanale: Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Research Funding; Infinity: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Research Funding; Genentech: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Molecular Templates: Research Funding; ADC Therapeutics: Research Funding; Onyx: Research Funding; Gilead: Research Funding. Westin:Spectrum: Research Funding. Nastoupil:Celgene: Honoraria; Genentech: Honoraria; AbbVie: Research Funding; Janssen: Research Funding; TG Therapeutics: Research Funding. Wang:Celgene: Research Funding.

Description: Introduction Plasmablastic lymphoma (PBL) is a rare, aggressive subtype of non-Hodgkin lymphoma. Published data are predominantly in the form of case reports and small retrospective case series. Initial reports of PBL were described in HIV positive patients (pts) with disease in the oral cavity, and in pts after organ transplantation on immunosuppressive therapy. The natural history may have evolved recently, with case reports of PBL in immunocompetent patients. There is no established standard of care therapy, though HIV positive pts benefit from initiation of anti-retroviral therapy, tend to respond to chemotherapy, have historically been associated with CD20 expression, and have increased overall survival rates compared with HIV negative pts with PBL. We now describe our experience in pts with PBL who received treatment at the University of Texas MD Anderson Cancer Center (UTMDACC). Methods We conducted a retrospective analysis of pts diagnosed with PBL between August 2000 and August 2012. We evaluated the baseline demographics, stage, therapy, response rate, progression-free survival (PFS) and overall survival (OS). Results 28 pts (males n=23) with PBL were identified, with a median age of 51 (range 26-81). 10 patients had a diagnosis of HIV, and 15 were EBV positive. 7 pts had stage I disease, 2 had stage II, 1 had stage III and 18 had stage IV disease. The primary site of disease in the 7 pts with stage I disease was: 2 in the maxillary sinus, 2 in the nasal cavity, and 1 each in the colon, testicle, and lower jaw. 2 pts with stage II disease had primary sites in bowel and tonsils. 7/17 (41%) of HIV negative pts and 2/10 (20%) of HIV positive pts had stage I/II disease. The median LDH was 492 IU/L (313-618), median Ki-67 proliferation index was 85%, and all pathological samples were CD20 negative. Median follow up was 16 months (1-120). 27 pts received systemic therapy (1 pt elected hospice care). PBL was an initial cancer diagnosis for 25 pts who received the following as first line therapy: Hyper-CVAD (cyclophosphamide, vincristine, Adriamycin, dexamethasone alternating with methotrexate and cytarabine) (n=10), CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone) (n=7), modified CVAD, 2 with EPOCH (etoposide, vincristine, cyclophosphamide, Adriamycin, prednisone) (n=4), bortezomib/dexamethasone (n=1), and the DeAngelis protocol (methotrexate, vincristine, procarbazine, with intrathecal methotrexate) (n=1) for CNS involvement. 2 pts had prior therapy for diagnosis of diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL) prior to diagnosis of PBL. The first pt with DLBCL was treated with Rituximab-hyper-CVAD 6 years earlier, and gemcitabine/oxaliplatin for the diagnosis of PBL. The second pt had CLL which underwent Richter's transformation to PBL, and was treated with hyper-CVXD (cyclophosphamide, vincristine, liposomal daunorubicin and dexamethasone). 1 pt underwent auto-stem cell transplant, while 8 pts received localized radiation (5 for consolidation and 3 for palliative therapy); 5/7 pts with stage I disease received consolidation with involved field radiation. After first line therapy, 20/27 patients (74%) achieved complete response, 5/27 (19%) partial response, and 2/27 (7%) stable disease. Median PFS and OS were 24.1 and 28.8 months, respectively. 5 year PFS and OS were 40% and 38%, respectively. Early stage disease (stage I or II) and younger age at diagnosis (less than 40 years old) were associated with improved survival. 5 year PFS for stage I/II pts was 90%. Conclusion 41% of HIV negative pts had stage I/II disease. Early stage PBL pts who received combined chemotherapy followed by radiotherapy achieved a good PFS of 90% at 5 years. PBL consistently lacked CD20 expression irrespective of HIV status. PBL can be seen in both HIV+ and HIV– patients with overall 40% long term survival. Disclosures: Qazilbash: Otsuka Pharmaceuticals: Research Funding. Fanale:Seattle Genetics, Inc.: Advisory/scientific board membership and travel expenses Other, Consultancy, Honoraria, Research Funding. Orlowski:Bristol-Myers Squibb: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene Corporation: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Millenium Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Onyx Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Resverlogix: Research Funding; Genentech: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Array Biopharma: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Merck: Membership on an entity’s Board of Directors or advisory committees.

Description: INTRODUCTION More active high-dose regimens are needed for non-Hodgkin’s (NHL) and Hodgkin’s lymphomas (HL), where standard BEAM offers poor results in refractory or poor-risk relapsed tumors. We previously developed a regimen of infusional gemcitabine with busulfan and melphalan (Gem/Bu/Mel), exploiting the synergy between gemcitabine and alkylators based on inhibition of DNA damage repair. Gem/Bu/Mel was safe and highly active against refractory lymphomas (Nieto, BBMT 2012). To further increase its activity we combined it in preclinical experiments with SAHA, which induces relaxation of the chromatin and renders DNA more accessible to DNA-targeting agents. Concurrent exposure to SAHA and Gem/Bu/Mel resulted in markedly increased apoptosis and cytotoxicity in refractory B- and T-NHL lines, with increased PARP1 cleavage and γ-H2AX reflecting increased DNA damage (Valdez, Exp Hematol 2012). SAHA has a dose-response effect in refractory lymphoma lines up to clinically achievable levels with doses of 1,000 mg, higher than its usual dose. We wished to clinically study the concurrent combination of SAHA and Gem/Bu/Mel in refractory NHL and HL. Methods Patients ages 12-65 with refractory lymphomas and adequate end-organ function were eligible for this dose-finding study of SAHA combined with Gem/Bu/Mel. SAHA was given on days -8 to -3 at 200-1,000 mg PO daily (levels 1-11), preceding all chemotherapy. Gemcitabine was given as a loading dose of 75 mg/m2 followed by infusion at a fixed dose rate of 10 mg/m2/min over 3.5 (levels 1-5), 4 (level 6) or 4.5 hours (levels 7-11) on days -8 and -3. Each gemcitabine dose was immediately followed by the corresponding dose of busulfan or melphalan. After a test dose on day -10, busulfan was given from days-8 to -5 targeting a daily AUC of 4,000. Melphalan was infused at 60 mg/m2/day on days -3 and -2. ASCT was on day 0. Patients with CD20+ tumors received rituximab (375 mg/m2) on days +1 and +8. Dose limiting toxicities (DLT) were defined as any G4-5 nonhematological organ toxicity, or as G3 skin or G3 mucositis lasting 〉3 days at peak severity. Dose escalation followed a Bayesian design targeting a maximal DLT probability of 20%. Results Between 10/11 and 6/13, 66 patients were enrolled with DLCL, HL and T-NHL (Table 1). SAHA was escalated up to 1,000 mg PO daily, combined with full doses of Gem/Bu/Mel without encountering DLTs. There were no treatment-related deaths. The toxicity profile was manageable, including mucositis (48% G2, 31% G3), skin (11% G2, 3% G3), self-limited transaminase elevation (30% G2, 6% G3), and self-limited elevation of bilirubin not associated to VOD (22% G2, 16% G3). There were no cardiac, pulmonary, renal or CNS toxicities. There was no QT prolongation detected after SAHA. Neutrophils and platelets engrafted promptly at median days +10 (range, 8-13) and +12 (range, 8-55), respectively. This toxicity profile is undistinguishable from the one we previously described with Gem/Bu/Mel. Activity and patient outcomes at median follow-up of 8 months (1-23) are shown on Table 2 and Figures: Conclusions Concurrent administration of SAHA with high-dose GemBuMel is feasible up to a daily dose of SAHA of 1,000 mg, with no increased toxicities compared to Gem/Bu/Mel alone. Early results indicate that SAHA/Gem/Bu/Mel is highly active in refractory or poor-risk relapsed HL and DLCL and warrants further study in earlier disease stages. Longer follow-up is needed to confirm these findings. Disclosures: Nieto: Otsuka Pharmaceuticals: Research Funding. Off Label Use: Vorinostat not approved for DLCL or Hodgkin's lymphoma. Qazilbash:Otsuka Pharmaceuticals: Research Funding. Andersson:Otsuka Pharmaceuticals: Research Funding.

Description: Background: The management of MCL is a significant therapeutic challenge, especially in patients with relapsed or refractory disease, who are generally refractory to salvage chemotherapy. Although recent studies have shown the clinical utility of radioimmunotherapy (RIT) in relapsed and transformed indolent B-cell lymphoma, the clinical efficacy of this treatment modality in patients with MCL is unknown. We report the results of an ongoing phase II clinical trial of yttrium 90 ibritumomab tiuxetan (Zevalin®) in patients with relapsed and refractory MCL. Patients and Methods: Patients with relapsed or refractory MCL with measurable disease, age 〉18 years, and performance status 1,500/mm3, platelets 〉100,000/mm3), liver, and kidneys. Patients were excluded if they had prior stem cell transplantation, RIT, CNS lymphoma, HIV infection, pleural effusion, HAMA reactivity, or circulating lymphoma cell count 〉5000/mm3. Patients with pretreatment platelet counts 〉150,000/mm3 received a dose of Zevalin at 0.4 mCi 90Y/kg (maximum dose 32 mCi), whereas those with platelet counts

Description: Emergence of rituximab (R) has significantly changed the clinical outcome of patients with B-cell lymphoma, which necessitates investigators to reassess the roles of previously determined prognostic factors. We performed a retrospective study to clarify the prognostic significance of serum sIL2R levels among other factors in patients with DLBCL. Study group consisted of 208 consecutive untreated patients with DLBCL who had serum sIL2R levels examined prior to treatment, and were treated in our institution between January 1999 and December 2006. Patients were treated with CHOP based chemotherapy without (R-, n=112) or with (R+, n=96) rituximab. Median follow up duration of each group was 55 and 19 months, respectively. Age (18–92), performance status (PS, ≥2 or

Description: Hemorrhage and infection carry significant morbidity and mortality in pts with leukemia. ICH can be a major clinical problem despite the current advances in supportive care. To analyze the incidence, outcome of ICH, and to identify potential risk indicators, we have conducted a retrospective analysis of pts with leukemia at M.D. Anderson Cancer Center (MDACC). We first reviewed all brain CTs of pts newly referred to MDACC from 1/2003 to 11/2003 with diagnosis of leukemia, myelodysplastic syndrome, or myeloproliferative disorder. Among 1185 pts (275 AML, 78 ALL, 163 CML, 296 CLL, 206 MDS, 47 MPD, 111 Other), 13 (1%) had ICH (8 AML, 3 APL, and 2 CML-myeloid blastic crisis). Based on this preliminary analysis, we limited this analysis to pts with newly diagnosed AML who received induction chemotherapy between 1/1998 and 11/2003. Among 993 such pts, 28 (3%) had ICH (parenchymal bleed in 12, subarachnoid hemorrhage in 4, subdural hematoma in 6, hemorrhagic infarct in 4, subarachnoid hemorrhage + subdural hematoma in 1, subarachnoid hemorrhage + subdural hemorrhage + parenchymal hemorrhage in 1) during the induction period (within 6 months after induction chemotherapy). Pt characteristics are shown in the table. Median time from induction therapy to ICH was 27 (0–122) days. In 16 (57%) pts death occurred before response to therapy could be determined (0–37 days). Thirteen out of 16 (81%) pts died of ICH as an immediate cause of death, and three of 16 (19%) died in the setting of multi-organ failure. Of 12 remaining pts whose disease status was assessed, 8 pts (66%) achieved complete remission (CR). Univariate analysis including age, gender, APL vs non-APL, cytogenetics, performance status, protective environment treatment, presence of antecedent hematologic disorder (AHD) and/or MDS, WBC〈 hemoglobin, platelet, PT, PTT, b2MG, bilirubin, creatinine, LDH, % of bone marrow blasts, % of peripheral blood blasts, and CR vs non-CR, indicated that APL, cytogenetics, thrombocytopenia, PT, bilirubin, and non-CR were associated with ICH. Differences in PT and bilirubin between the two groups, however, were clinically not significant. In a multivariate logistic regression analysis, APL remained as the only major predictive factor (odds ratio 3.35). In conclusion, ICH is limited to pts with myeloid malignancies, with an incidence of 3% in AML pts receiving induction therapy, with APL pts (13%) at greatest risk. ICH is associated with poor prognosis related to immediate mortality. Characteristics Age Male APL Platelet (x109/L) CR rate Median Survival ICH (n=28) 56 (36–84) 50% 29% 33(4–166) 29% 5 weeks No-ICH (n=965) 58 (17–89) 41% 6% 47(4–635) 54% 42 weeks

Description: Many patients with NHL suffer from refractory or relapsed disease, and platinum-based combination therapy is widely used for salvage therapy. Oxaliplatin, a novel platinum derivative, is a more potent cytotoxic agent than cisplatin, demonstrating greater efficacy against many tumor cell lines, including lymphoma cell lines. Clinical studies of oxaliplatin for other malignancies have shown a favorable toxicity profile. The objective of this phase II trial was to investigate the activity of oxaliplatin in patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL). Patients with measurable NHL who had experienced failure of one or more prior chemotherapy regimens were considered eligible. They were required to have an ECOG performance status £ 2 and adequate organ function. Patients were excluded if they had HIV infection, CNS lymphoma, or had chemotherapy or radiotherapy within 4 weeks prior to entering the study. All patients gave their written informed consent to participate. Oxaliplatin was administered at 130 mg/m2 every 21 days for up to six cycles in the absence of progression. Thirty-one patients (23 with aggressive NHL, 8 with indolent NHL) were enrolled on this trial. Thirty eligible patients received oxaliplatin, who were all assessable for toxicity. Response and survival were also analyzed in all 30 patients based on intention to treat analysis. The median patient age was 62 years, and most of the patients had an ECOG performance status of 0 or 1. The most common toxic effect was sensory neuropathy (87%). Grade 3 and 4 toxic effects included sensory neuropathy (10%), neutropenia (17%), and thrombocytopenia (20%). Objective responses occurred in 8 (27%) of the patients: 7 with aggressive NHL, 1 with indolent NHL. The median failure-free survival duration in the entire group, aggressive NHL group and indolent NHL group was 3.0, 2.1 and 4.0 months, respectively. It is noteworthy that three of the five patients with MCL (60%) had a significant response to oxaliplatin, including two CRus, with a median FFS duration of 5 months. When patient group is divided by IPI score (0/1 and 2 /3), the median FFS duration was 3.4 months and 2.6 months, respectively. Median response duration for entire group was 3.0 months. In summary, oxaliplatin has modest activity in patients with previously treated NHL, especially those with aggressive disease. The favorable toxicity profile of oxaliplatin warrants further investigation of it either in combination chemotherapy or with targeted biologic therapy.

Description: Abstract 2666 Background: In patients with diffuse large B-cell lymphoma (DLBCL), circulating lymphoma cells in the bloodstream are rarely detected by conventional morphology or flow cytometry evaluation. We developed a high-throughput sequencing based platform, LymphoSIGHT, to detect evidence of lymphoid malignancies in peripheral blood samples, as this could potentially be used for detection of minimal residual disease after treatment. This sequencing method has a sensitivity to detect one lymphoma cell per million leukocytes in peripheral blood. We herein report the results of our pilot study assessing the ability of this method to detect the lymphoma clone in peripheral blood samples from 5 DLBCL patients at the time of diagnosis. Methods: This study has been approved by IRB and consent has been obtained from patients. Using universal primer sets, we amplified immunoglobulin heavy chain (IgH@) variable, diversity, and joining gene segments from genomic DNA in tumor biopsy and peripheral blood samples (plasma and peripheral blood mononuclear cell (PBMC) compartments) collected at initial diagnosis. Amplified products were sequenced to obtain 〉1 million reads (〉10× sequencing coverage per IgH molecule), and were analyzed using standardized algorithms for clonotype determination. Tumor-specific clonotypes were identified for each patient based on their high-frequency within the B-cell repertoire in the lymph node biopsy sample. The presence of the tumor-specific clonotype was then quantitated in cell-free and PBMC compartments from the diagnostic blood sample. A quantitative and standardized measure of clone level among all leukocytes in the diagnostic sample was determined using internal reference DNA. Results: We detected a high-frequency IgH clonal rearrangement in all 5 lymph node biopsy samples. The lymphoma clonotype that was identified in the tumor biopsy was also detected in the plasma and/or PBMC compartment in all 5 patients at diagnosis. Specifically, the lymphoma clonotype was detected in the plasma compartment in 4 patients, while 3 patients demonstrated the presence of the lymphoma clonotype in the PBMC compartment (Table 1). We hypothesize that the positive lymphoma clone in the plasma is due to rapid proliferation and necrosis of the primary tumor, releasing the degraded component of lymphoma into the blood stream. However, in this small sample size, we did not observe an obvious correlation between the level of detection (PBMC or plasma) and clinical parameters (LDH, stage, size of tumor, tumor Ki67, cell-of-origin). All patients achieved complete response after initial treatment and four are being followed. We plan to analyze blood specimens while they are in remission. Conclusions: IgH clonal rearrangements were detected by sequencing in all tumor biopsy samples. Importantly, all peripheral blood samples showed signs of circulating lymphoma material in either the plasma or PBMC compartment at diagnosis. Analysis of diagnostic and post-therapy samples from additional DLBCL patients is ongoing. These data will determine whether the sequencing assay is a strong indicator for response to therapy and relapse monitoring. Disclosures: Faham: Sequenta, Inc.: Employment, Equity Ownership, Research Funding. Carlton:Sequenta, Inc.: Employment, Equity Ownership, Research Funding.

Description: Abstract 4154 Introduction: CNS relapse is a challenging complication in patients with DLBCL. Identification of high risk population is therefore critical, in whom prophylactic intrathecal (IT) chemotherapy may play a significant role. To calculate the cumulative incidence of CNS relapse, Kaplan-Meyer method tends to overestimate the incidence because a censored individual by death is still assumed to have a chance to fail from CNS relapse. To overcome this methodological conflict, we evaluated the risk factors for CNS relapse in patients with DLBCL using CRR analysis. Methods: Medical records of patients with DLBCL newly diagnosed and treated with CHOP or R-CHOP at Aichi Cancer Center Hospital between 1995 and 2008 were reviewed. Patients were excluded if they had evidences of CNS involvement at initial diagnosis. Results: A total of 386 patients who met the criteria for the study were analyzed. The median age of patients was 62 (range 18–95). All patients received CHOP based systemic chemotherapy with (n=203) or without (n=183) rituximab. Prophylactic IT chemotherapy was provided to 6 patients with testicular involvement. At a median follow up duration of 52.9 months, 24 patients experienced CNS relapse. Nine patients presented with brain parenchymal mass, 12 patients presented with leptomeningeal disease, and 3 patients presented with both. The median time from initial diagnosis to CNS relapse was 20.5 months (range 5.3–91.8 months). Five-year cumulative incidence of CNS relapse was 6.7% (95%CI: 4.2–9.8). Five-year cumulative incidence of CNS relapse in patients treated with and without rituximab was 5.9% and 7.3%, respectively (p=0.42). Multivariate analysis for the risk factors of CNS relapse using CRR identified three independent risk factors for CNS relapse; bulky disease (SHR 3.34 [1.45-7.66], p=0.004), lymphocyte count