Colgan, Joseph P.

Abstract Abstract 3642 Purpose: The reactive pathologic background in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) consists of lymphocytes and histocytes. Lymphopenia is a negative prognostic factor in NLPHL as it is also in Classical Hodgkin Lymphoma (cHL). In cHL, tumor-associated macrophages recruited from circulating monocytes are a negative prognostic factor for survival. Thus, we studied if the peripheral blood absolute lymphocyte count/absolute monocyte count ratio at diagnosis (ALC/AMC-DX), as a surrogate biomarker of the host response against the neoplastic lymphocytic and/or histiocytic (L&H) cells, affects survival in NLPHL. Patients and Methods: We performed a retrospective analysis of the association between ALC/AMC-DX and survival in 103 consecutive NLPHL patients that were followed at Mayo Clinic from 1974 to 2010. Receiver operating characteristic (ROC) and area under the curve (AUC) were used for ALC/AMC-DX cut-off value analysis and proportional-hazards models were used to compare survival based on the ALC/AMC-DX ratio. Results: The cohort included 67 (65%) males and 36 (35%) females. Eighty-three percent of patients presented with stage I/II and 17% with stage III/IV. Sixty-five (63%) patients were treated with radiation alone; 20 (20%) patients with chemotherapy alone; and 18 (17%) patients with chemotherapy and radiation. The median follow-up period was 8.9 years (range: 0.3–31 years). An ALC/AMC-DX ≥ 2.1 was the best cut-off value for survival with an empirical AUC of 0.82 (95% confidence interval [CI], 0.78 to 0.88), a sensitivity of 70% (95% CI, 61% to 76%) and specificity of 84% (95%CI, 59% to 82%). The cut-off value for ALC/AMC-DX ≥ 2.1 was validated by the k-fold cross validation method, showing a cross validation ROC with an AUC of 0.82 (95% CI, 0.72 to 0.93) for an ALC/AMC-DX ≥ 2.1. Using Kaplan-Meier analysis, we studied overall survival (OS), lymphoma-specific survival (LSS), progression-free survival (PFS), and time to progression (TTP) based on ALC/AMC-DX ≥ 2.1. Patients with an ALC/AMC-DX ≥ 2.1 experienced an superior OS, LSS, PFS, and TTP compared with patients with an ALC/AMC-DX < 2.1: [OS: median was 22.1 years vs 6.3 years, 10-years OS rates of 89% (95%CI, 80% to 98%) vs 44% (95%CI, 27% to 65%), p < 0.0001, respectively; LSS: median was not reached vs 7.3 years, 10-years LSS rates of 99% (95%CI, 90% to 100%) vs 45% (95%CI, 29% to 67%), p < 0.0001, respectively; PFS: median was 20.6 years vs 4.6 years, 10-years PFS rates of 84% (95%CI, 80% to 97%) vs 26% (95%CI, 18% to 55%), p < 0.0001, respectively; and TTP: median was not reached vs 5.5 years, 10-years TTP rates of 93% (95%CI, 85% to 99%) vs 29% (95%CI, 19% to 57%), p < 0.0001, respectively]. After adjusting for the International Prognostic Factors and the International Prognostic Score, ALC/AMC-DX remained an independent prognostic factor for OS {hazard ratio (HR), 0.42, 95%CI, 0.23 to 0.64, p< 0.004]; LSS [HR, 0.14; 95%CI, 0.04 to 0.23, p <0.0004]; PFS [HR, 0.14; 95%CI, 0.03 to 0.34, p < 0.001], and TTP [HR, 0.16, 95%CI, 0.04–0.34, p <0.002]. Conclusion: ALC/AMC-DX is an independent prognostic factor for survival and provides a single biomarker to predict clinical outcomes in NLPHL. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: Primary Mediastinal Large B-cell Lymphoma (PMLBCL) is a biologically and pathologically distinct subset of large B-cell lymphoma of thymic origin. The natural history of PMLBCL is not well defined. While earlier reports suggested that PMLBCL is an aggressive disease with a poorer prognosis when compared to other large cell B cell lymphomas, recent studies report more favorable results. Some of the outcome variability reported in previous studies may be related to the inclusion of other pathological lymphoma subtypes involving mediastinum. Thus, we reviewed the pathology and clinical course of patients with PMLBCL seen at our institution. Methods: We reviewed the biopsies on all patients diagnosed with mediastinal B-cell non-Hodgkin lymphoma (NHL) between 10/1983 and 10/2004. The pathological criteria for diagnosis of PMLBCL was a diffuse infiltrate of neoplastic CD20+ large B-cells within the mediastinum that frequently had "clear" cytoplasm and were often associated with fibrosis. We then reviewed the clinical data for patients with a pathological diagnosis of PMLBCL. Results: 121 patients were diagnosed with mediastinal B cell NHL and had tissue available for review. Of these, 88 fulfilled the pathological diagnostic criteria for PMLBCL. The median age at presentation was 37 years (range 18–83). The male to female ratio was 1.06. Age adjusted IPI was: 0, 1, 2, 3 in 18%, 56%, 18% and 8% of the patients respectively. The most commonly used treatments were: CHOP (70%), R-CHOP (22%) and ProMACE-CYTABOM (6%). 62% of the patients received adjuvant radiotherapy. 24% of the patients received high dose chemotherapy with autologous stem cell transplantation (2 patients in first remission). The median follow up was 66 months. The 2 and 5 year survival was 72% and 68% respectively. On univariate analysis, age >60 (p=0.012) and presence of B symptoms (p=0.0094) were associated with an adverse outcome. On multivariate analysis, only the presence of B symptoms (p=0.039) was an independent predictor of shortened overall survival. The 2 year survival of patients with age adjusted IPI of 0–1 or 2–3 was 86% and 68% respectively (p=0.023). Patients treated with adjuvant radiation therapy had a 5 year survival of 74% versus 53% in patients who did not receive adjuvant radiation (p=0.042). However, there was a higher percentage of Ann Arbor stage 3 and 4 disease patients found in the group who did not receive radiotherapy treatment (66% vs 17% respectively). Conclusions: The overall survival rates seen in patients with a confirmed pathological diagnosis of PMLBCL were superior to that reported in earlier studies and similar to that reported with the use of more intensive chemotherapy regimens. While many authors report a high proportion of female patients with PMLBCL, we did not observe any gender differences. While patients receiving adjuvant radiation therapy had a better outcome than those that did not, the retrospective nature of this study and differences in stage distribution preclude conclusions regarding the role of adjuvant radiation therapy. Randomized studies will be necessary to assess the optimal treatment for PMLBCL.

Abstract Abstract 3652 Purpose: Gene expression profiling has shown biologically distinct cell of origin categories for diffuse large B-cell lymphoma (DLBCL): germinal center B-cell like (GCB), and activated-B-cell like (ABC). GCB, DLBCL patients experienced better clinical outcomes compared with ABC, DLBCL patients. However, gene microarray technology is not broadly available in a non-research setting. Absolute lymphocyte count (ALC) at diagnosis is a prognostic factor for survival in DLBCL. Recently, gene-expression profiling and immunohistochemistry-based studies in non-Hosgkin's lymphoma demonstrate the important role of monocytes and their progeny, particularly lymphoma-associated macrophages, in promoting lymphomagenesis. thus, we studied if the peripheral blood absolute lymphocyte count/absolute monocyte count at diagnosis (ALC/AMC-DX), as a surrogate biomarker of the host response against the cell of origin in DLBCL, affects survival in DLBCL. Patients and Methods: We perfromed a retrospective analysis of the association between ALC/AMC-DX and survival in 131 consecutive DLBCL patients that were followed at Mayo Clinic from 2004 to 2010, with available tissue immunostaining for CD10, BCL6, MUM 1, and BCL 2 (Hans' algorithm) to identified GCB and ABC DLBCL patients. Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used for ALC/AMC-DX cut-off value determientaion and proportional-hazards models wee used to compare survival based on the ALC/AMC-DX. Results: The cohort included 91 (70%) GCb DLBCL patients and 40 (30%) ABC, DLBCL patients. All patients were treated with rituximab, cyclosphosphamide, adriamycin, vincristine, and prednisone (R-CHOP-21). The median follow-up period was 2.1 years (range 0.1–6.9 years). An ALC/AMC-DX >= 1.5 was the best cut-off value for survival with an empircal AUC of 0.83 (95% CI, 0.77 to 0.89), a sensitivity of 83% (95% CL, 72% to 92%) and specificity of 79% (95%CI, 72% to 85%). The cut-off value for ALC/AMC-DX >= 1.5 was validated by the k-fold cross validation method, showing a cross validation ROC with an AUC of 0.89 (95%CI, 0.80 to 0.95) for an ALC/AMC-DX >=1.5. Using Kaplan-Meier analysis, the overall survival (OS), defined as the time from diagnosis to last follow-up or death due to any cause; and progression-free survival (PFS), defined as the time from diagnosis to death of any cause, relapse, progression, or last follow-up, based on ALC/AMC-DX >= 1.5 were evaluated. patients with an ALC/AMC-DX >=1.5 experienced a superior OS and PFS compared with patients with an ALC/AMC-DX < 1.5: [OS: median was not reached vs 20.8 months, 5-years OS rates of 83% (95%CI, 70% to 95%) vs 36% (95%CI, 20% to 55%), p < 0.0001, respectively; and PFS: median was not reached vs 10.8 months, 5-years PFS rates of 70% (95%CI, 58% to 88%) vs 28% (95% CI, 17% to 46%), p < 0.0001, respectively]. Multivariate Cox stepwise regression analysis identified cell of origin, International Prognostic Index (IPI) and ALC/AMC-DX as the strongest predictors for OS and PFS, with ALC/AMC-DX out-performing cell of origin and IPI: OS [HR = 0.17, 95%CI, 0.07 to 0.36, p < 0.0001] and PFS [HR=0.21, 955CI, 0.11 to 0.39, p < 0.001]. conclusion: ALC/AMC-DX is independent of the cell of origin to predict survival and provides a single biomarker to predict clinical outcomes in DLBCL. Confirmatory studies are required. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: The PI3K/mTORC pathway is upregulated in DLBCL and can be targeted with mTORC1 inhibitors such as everolimus. Everolimus has demonstrated single agent activity in relapsed DLBCL (Leukemia. 2011; 25(2):341-7). These data provide the rationale to combine everolimus with standard RCHOP-21 to improve the effectiveness of upfront therapy for DLBCL. Methods: A phase I study was designed to determine the maximum tolerated dose of everolimus on days 1-10 or 1-14 in combination with RCHOP-21 along with a feasibility cohort to examine response in patients with newly diagnosed CD20+ DLBCL. Response assessment was evaluated using PET/CT and standard criteria. Results: We previously reported (J Clin Oncol 33, 2015 suppl; 8518) that in the phase I portion of trial N1085 that the dose of everolimus recommended for further study was everolimus 10 mg daily days 1-14; RCHOP day 1 and pegfilgrastim 6 mg day two for each of six 21-day cycles. The trial has now completed enrollment with a total of 26 patients. Two phase I patients were replaced during cycle 1 for personal, non-medical issues leaving 24 eligible patients for response assessment. The median age was 59.5 years (23 - 78); 42% were female; 18 (75%) stages III/IV; 12 (50%) had an elevated LDH; 29% had a high IPI score; and 4 (17%) had B-symptoms. Genotype was performed by immunohistochemistry using the Hans algorithm and 54% (13/24) were non-GCB; 13 (5 GCB, 8 non-GCB) had FISH for double hit and all were negative. Twenty-one (88%) patients received everolimus at 10 mg d1-14; the other three patients received 10 mg d1-10. Twenty-two (92%) patients received all 6 cycles. All patients have now completed therapy and the overall response rate was 96% (23/24) with 23 patients attaining functional CR by PET/CT. The remaining patient went off study for refusal in cycle 1, received further RCHOP-21 off study, and attained a CR off study. The median follow-up for the 24 patients is now 16.8 months (7.3 - 35.7) with 20 patients having ≥12 months of follow-up and 8 patients having ≥24 months of follow-up. To date, none of the 24 patients have died and none have experienced relapse with DLBCL. One patient relapsed 16 months from DLBCL diagnosis with a biopsy-proven follicular grade 1 NHL and received off-study Zevalin and achieved a second CR. The most common grade 3/4 toxicity was hematologic with 71% of patients having grade 4. Five (21%) patients had febrile neutropenia. Only 1 patient had grade 3 hyperglycemia and 3 patients had grade 3 hypertriglyceridemia. Reversible rash and pneumonitis were observed in 1 case each. Conclusions: The mTORC1 inhibitoreverolimus at 10 mg daily d1-14 of a standard RCHOP-21 cycle is tolerable with a 96% CR rate in both GCB and non-GCB DLBCL. With a median follow-up of 16.8 months and 8 patients out ≥24 months, the lack of DLBCL relapse is encouraging. Longer follow-up and a larger trial will be necessary to confirm the benefits of this novel combination. Clinical trial information: NCT01334502 Disclosures Off Label Use: Everolimus is an mTOR inhibitor which has activity in B cell lymphomas. It is being investigated in combination with SOC therapy for newly diagnosed DLBCL to examine potential toxicity as well as potential for enhanced disease response.. Ansell:Bristol-Myers Squibb: Research Funding; Celldex: Research Funding.

Abstract Abstract 1580 Background: Extranodal Marginal Zone Lymphomas of Mucosa Associated Lymphoid Tissue (MALT) account for approximately 5% of all non-Hodgkin Lymphoma cases. Specific MALT lymphomas are characterized by distinct clinical features, treatment strategies, and outcome, depending on site of the disease. While previous reports have described clinical course and treatment of gastric and pulmonary MALT lymphomas, a paucity of data exist describing primary parotid MALT lymphoma. This is a single institution experience. Methods: Patients with primary parotid MALT lymphoma were identified from the Mayo Clinic Lymphoma Database since 1986. This database includes all consenting patients with lymphoma seen at Mayo Clinic Rochester. Clinical characteristics, treatment, and outcomes were collected. Pathology was reviewed by a lymphoma pathologist; WHO criteria were used for diagnosis. PFS and OS were assessed using the Kaplan-Meier method and Cox proportional hazard model was used to asses the impact of variables on PFS and OS. Results: Seventy-six consecutive patients with primary parotid MALT lymphoma were evaluated and treated at Mayo Clinic from 1986 to 2010. The median age at diagnosis was 60 years (18–90). 58 (76%) were female. 42 (55.3%) patients had a history of Sjögren's Disease and 51 (67.1%) had a history of autoimmune disorders. 52 (68.4%), 4 (5.3%), and18 (23.7%) had stage I, II, and IV disease, respectively. 2 cases did not have complete staging information. 6 (7.8%) and 2 (2.6 %) had bone marrow and lung involvement, respectively. No patients had GI tract, liver, or CNS involvement. Median estimated OS (overall survival) was 18.3 years and median PFS (progression free survival) was 7.9 years. ALC<0.96 (p=0.0162) were associated with shorter survival. Age, ECOG performance score, stage, LDH, and history of Sjögren's disease were not prognostic for overall survival. The treatment approach and PFS are outlined in the table. For stage I disease, outcomes were excellent with local therapy. The median estimated PFS was 7.9 years with 72% of patients undergoing surgery surviving at 8 years. Patients receiving radiotherapy had an estimated median PFS of 15.7 years and median OS of 18.3 years. In contrast, patients being observed had a median PFS of 5.5 years. The use of systemic therapy with chemotherapy, immunotherapy or in combination was associated with a median PFS of 7.4 years. Summary: Primary parotid MALT lymphoma is strongly associated with Sjögren's disease. This lymphoma is usually limited to the parotid and associated with a favorable prognosis. For limited disease, local treatment with radiation or surgery appears to be an effective treatment options. For extensive disease, both immunotherapy and chemotherapy are efficacious treatments. Further prospective studies and long-term follow up are needed to determine the optimal treatment approaches and efficacy of chemotherapy/immunotherapy regimens. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 4136 Background: The serum free light chain (FLC) assay quantitates free kappa and free lambda immunoglobulin light chains. This assay has prognostic value in MGUS, multiple myeloma (MM), solitary plasmacytoma, and amyloid light chain (AL) amyloidosis, and has been incorporated in response criteria for both MM and AL amyloidosis. We previously showed elevated FLC was associated with poor outcome in diffuse large B-cell lymphoma (DLBCL) patients from a phase II cooperative group clinical trial (Blood (ASH Annual Meeting Abstracts) 2009 November 20, 2009; 114(22): 136). Here we replicate those findings in a large clinic based epidemiology cohort, as well as examine FLC abnormalities in other lymphoma subtypes. Methods: Newly diagnosed lymphoma patients were prospectively enrolled in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER). Serum FLC was quantitated from enrollment research serum draws within 9 months of diagnosis using the Freelite FLC assay (The Binding Site, Ltd., Birmingham, UK). Elevated FLC was defined as either kappa or lambda above the published reference range. Monoclonal elevated FLC was defined as elevated FLC with an abnormal FLC ratio; polyclonal elevated FLC was defined as elevated FLC with an FLC ratio in the normal reference range. Clinical data was abstracted using a standard protocol for the MER and patients were followed systematically for event-free (progression, retreatment, or death due to any cause) and overall survival (EFS and OS, respectively). Cox proportional hazards models were used to evaluate the unadjusted association between FLC and outcome. Results: 1118 lymphoma patients diagnosed between September 2002 and February 2008 with available serum were assayed. At a medium follow-up of 49 months (range 1–94), 484 patients (43%) had an event and 249 patients died (22%). Elevated FLC was present in 27% of lymphomas, with prevalence ranging from 13% in follicular lymphoma (FL) to 64% for mantle cell lymphoma (MCL) and 77% for lymphoplasmacytic lymphoma. Elevated FLC was present in 27% of DLBCL and associated with poor EFS (monoclonal hazard ratio (HR)=2.56, polyclonal HR=1.99, all p<0.001) and OS (monoclonal HR=3.22, polyclonal HR=2.91, all p<0.0001), replicating our previous findings. Elevated FLC was generally polyclonal (FLC ratio normal) across lymphoma subtypes, though monoclonal elevated FLC (FLC ratio abnormal) was common in MCL and the post-follicular lymphomas. Elevated FLC was associated with inferior EFS in all lymphomas combined (monoclonal HR=1.92, 95% CI:1.44-5.55, polyclonal HR=1.38, 95% CI:1.09-1.74); this association remained consistent in most subtypes (see table). In addition, elevated FLC was associated with poor EFS in MCL (monoclonal) and Hodgkin lymphoma (HL; polyclonal). Elevated FLC was also significantly associated with OS in HL (polyclonal HR=6.24, 95% CI 2.44–15.9), FL (polyclonal HR=5.85, 95% CI 2.62–13.0), post follicular lymphomas (polyclonal HR=4.16, 95% CI 1.17–14.8), as well as for all lymphomas combined (monoclonal HR=2.24, 95% CI 1.52–3.29, polyclonal HR=2.33, 95% CI 1.74–3.11). Conclusions: A significant percentage of lymphoma patients have elevated FLC. Our previous discovery of elevated FLC predicting poor outcome in DLBCL was confirmed in a large, independent dataset. Prevalence and type of elevated FLC (monoclonal vs. polyclonal) varies by lymphoma subtype. Elevated monoclonal and polyclonal FLC is associated with poor outcome broadly in lymphoma, as well as specifically for a number of lymphoma subtypes, supporting FLC as a potentially useful prognostic biomarker in many lymphoma subtypes. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 1926 Background: Follicular lymphoma (FL) is the second most common non Hodgkin lymphoma in the United States, comprising up to 30% of all non Hodgkin lymphomas. Typically an indolent disease, relapses are common. High dose therapy followed by autologous stem cell transplant is an option that has shown to produce prolonged progression-free and relapse-free survival in patients who relapse. Adequate bone marrow reserve for peripheral stem cell mobilization has been shown to be adversely effected by prior regimens such as fludarabine and radioimmunotherapy. Concerns regarding stem cell mobilization at the point of relapse have led some to collect stem cells early in the course of disease to allow for potential subsequent transplant after relapse. Recent advances in stem cell mobilization have resulted in a 3% collection failure rate for lymphoma patients at the point of planned transplant at our institution versus a historical rate of up to 30%. We studied the utilization of stem cells collected for potential future use in FL patients in remission or prior to therapy at the point of relapse or progression in order to determine the utility of this approach. Methods: Record review of patients diagnosed with FL through the Mayo Clinic Tumor Registry and the Mayo Clinic Lymphoma Data Base who had cryopreserved stem cells for potential future transplant at relapse. Cost of stem cell storage at our institution was reviewed as was the subsequent use of the collected cells. Results: 73 patients with FL had stem cells collected and stored. 37 (51%) were collected prior to a double dose yttrium-90 (90Y) ibritumomab tiuxetan trial for relapsed lymphoma as required by the study. The median age at collection of this group was 56 years (range 28–70). Stem cells remain in storage for a median of 44 months (range 8–119). The median cost of cryopreservation and storage is $4,094 based on the median storage time of 44 months (range $3,628 to 5,065) with a collection cost of $3,524.20 and an annual storage fee of $155.39. This does not include the cost of filgrastim for mobilization, nor line placement. At 5 years, 60% of the cells were not utilized, and at 10 years, 56% of the cells were not utilized. 36 (49%) of the total number of patients were not part of the double dose 90Y ibritumomab tiuxetan trial, but were collected in remission for possible future use or in the setting of relapsed, progressed or transformed disease for potential future transplant. Five of these patients required the use of plerixafor for adequate mobilization. The median age at collection of this group was 47 years (range 24–76). Stem cells remain in storage for a median of 39 months (range 2–128). The median cost of cryopreservation and storage is $4,029 based on the median storage time of 39 months (range $3,550 to 5,182) with a collection cost of $3,524.20 and an annual storage fee of $155.39. This does not include the cost of filgrastim or plerixafor for mobilization, nor line placement. At 5 years, 89% of these cells were not used, and at 10 years, 71% of cells were not used. Conclusion: The utilization of stem cells collected early in the course of FL patients is low, with the majority of cells not being utilized at 10 years. Given improved mobilization techniques resulting in 97% efficacy of stem cell collection at relapse, routine collection and storage of stem cells early in the course FL is not recommended. Disclosures: Micallef: Genzyme: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Abstract Abstract 4168 Background: Primary Pulmonary MALT lymphoma represents 15–20% of Extranodal Marginal Zone Lymphomas of Mucosa Associated Lymphoid Tissue (MALT). In contrast to the more common gastric MALT lymphoma, natural history, prognosis and treatment outcomes for primary pulmonary MALT lymphoma are not well defined. Herein, we report a single institution experience. Methods: Consecutive patients with primary pulmonary MALT lymphoma registered in the Mayo Clinic Lymphoma Database, which includes all consenting patients with lymphoma seen at Mayo Clinic Rochester, were reviewed for clinical features, treatment outcome progression free survival (PFS) and overall survival (OS). The pathology for all patients was centrally reviewed by hematopathologist and the diagnoses were based on WHO lymphoma classification criteria. PFS and OS were assessed using the Kaplan–Meier method and the Cox proportional hazard model was used to assess the impact of variables on PFS and OS. Results: Between December 1986 and June of 2009, ninety-seven patients with primary pulmonary MALT lymphoma were enrolled. The median age at diagnosis was 63 years (range 31–87). There were 43 (44%) males. The initial presentation was a unilateral pulmonary lesion (n=47, 48%), bilateral pulmonary lesions (n=41, 42%), and pulmonary lesion with intrathoracic lymphadenopathy (n= 4, 4%). Bone marrow involvement and presence of B symptoms were 4, 4% and 5, 5%, respectively. International Prognostic Index (IPI) was 0–1, 2–3 and 4–5 in 69, 25 and 1 patient(s) respectively. The median follow-up was 10.4 years. The estimated median OS was 13. 6 years and the median PFS was 5.5 years (Figure). In a multivariate analysis, age >60 (p=0.02) and ECOG PS>2 (p=0.01) were associated with shortened survival. The IPI and age adjusted IPI were not predictive of overall survival. The treatment outcomes for the most common treatment modalities are summarized in the Table below. The median PFS of the 38% of patients who had a complete surgical resection was excellent at 11.2 years; whereas for observed patients with residual disease after biopsy was 3.2 years. Only 8 patients received single agent rituximan with relatively low response rate. Summary: The prognosis of primary pulmonary MALT lymphoma is favorable, with a median survival of over 13 years. In patients with resectable disease, surgery alone is associated with excellent disease control. Further prospective studies are needed to define the optimal treatment of primary pulmonary MALT lymphoma. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 2692 Background: Massive splenomegaly is occasionally encountered in patients with Non-Hodgkin's Lymphoma (NHL) and can be associated with abdominal symptoms, anemia and thrombocytopenia. The spleen may also be a primary focus of the disease itself. Splenectomy offers the benefit of localized treatment of the disease as well as relief of symptoms from splenomegaly and associated cytopenias. The safety and long term clinical outcomes of splenectomy for massive splenomegaly (>1500 gm) in patients with various histologies of NHL was analyzed. Methods: Data was obtained from clinical records of 90 patients with a diagnosis of NHL who underwent a splenectomy at Mayo Clinic Rochester from January 1998 to December 2007. Demographics, previous treatments, histology, post- surgical complications were collected and analyzed for the entire cohort. Additionally, median overall survival, improvement in symptoms, anemia and thrombocytopenia were analyzed by NHL type. Results: Median age at splenectomy was 67 years (range 42–84 yrs.) and 56 (62%) of patients were male. Average time from diagnosis to splenectomy was 3 months (range 0–217 months). Splenectomy was the first treatment in 56 (62%) patients; the other 34 patients were treated with chemotherapy with an average of two previous regimens. Most patients had involvement outside of the spleen, 65 (72%) with concurrent bone marrow involvement and 35 (50%) with lymph node involvement. Various different NHL histologies were represented: marginal zone (MZ) (34%), mantle cell (MC) (26%), diffuse large B-cell lymphoma (DLBCL) (10%), follicular (FL) (11%), lymphoplasmacytic (LP) (6%) and T cell NOS (4%). With a median follow-up time of 25 months, the median overall survival differed by histology type of NHL (Table 1). Indolent lymphomas such as FL, LP and MZ had more favorable survival compared with more aggressive lymphomas such as DLBCL and T cell NOS. Splenectomy was safe and well tolerated with only one treatment related death. There were no reported post-splenectomy septic events. Two patients did develop a portal vein thrombosis. 95% of patients had relief in pressure and abdominal symptoms post-splenectomy. With the exception of patients with DLBCL and T-cell NHL, a majority of patients had improvement in anemia and thrombocytopenia related to splenomegaly (Table 2). Conclusions: This represents the largest reported series of patients with lymphoma treated with splenectomy. Our results indicate that median overall survival after splenectomy is determined by the underlying type of NHL. Patients with LP, FL, MZ and MCL have a favorable outcomes following splenectomy. Splenectomy remains a safe and effective treatment option for massive splenomegaly in selected patients during the course of their disease management. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 3088 Background: Despite the use of modern immunochemotherapy (R-CHOP) regimens, almost 50% of patients with diffuse large-B-cell lymphoma (DLBCL) will relapse. Current prognostic models, most notably the International Prognostic Index, are comprised of patient and tumor characteristics and are unable to identify patients with less than a 50% chance of long-term survival. However, recent observations demonstrate that factors related to host adaptive immunity and the tumor microenvironment are powerful prognostic variables in non-Hodgkin lymphoma Methods: We retrospectively examined the absolute neutrophil count (ANC), monocyte count (AMC) and lymphocyte count (ALC), obtained from an automated complete blood count with differential, as prognostic variables in a cohort of 255 consecutive DLBCL patients that were uniformly treated with R-CHOP between 2000 and 2007 at a single institution. The primary study objective was to assess if ANC, AMC, and ALC at diagnosis were predictors of overall survival (OS) in DLBCL. Results: At diagnosis, the median ANC was 4720/uL (range 1190–17690), the median AMC was 610/uL (range 30–4040), and the median ALC was 1220/uL (range 140–5410). The median follow-up for these patients was 48 months. In the univariate analysis, each of these variables predicted OS as continuous variables. As dichotomized variables, an elevated ANC (≥5500/μL; hazard ratio 1.75, 95% confidence interval 1.14–2.60, p=0.01) and AMC (≥610/μL; hazard ratio 3.36, 95% confidence interval 2.10–5.59, p<0.0001) were each associated with inferior OS. In contrast, the presence of lymphopenia, defined as an ALC ≤1000/uL, was associated with inferior OS (hazard ratio 2.21, 95% confidence interval 1.43–3.39, p=0.0004). When components of the IPI were included on multivariate analysis only the AMC and ALC were independently significant prognostic factors for OS, with hazard ratios of 3.37 (95% confidence interval 2.05–5.74, p<0.0001) and 2.19 (95% confidence interval 1.38–3.44, p=0.0009), respectively. The dichotomized AMC and ALC generated the AMC/ALC prognostic index (PI) and stratified patients into 3 risk groups: very good (AMC <610/uL and ALC >1000/uL), good (AMC ≥610/uL or ALC ≤1000/uL), and poor-risk (AMC ≥610/uL and ALC ≤1000/uL) populations. For both the very good (n=79) and good-risk (n=134) groups median OS has not been reached with estimated 5-year overall survival of 88% and 69%, respectively. Median OS for poor-risk (n=42) patients was 1.7 years (95% confidence interval 1.1–2.7 years) with an estimated 5-year overall survival of 28% (p<0.0001). By comparison, the R-IPI was unable to identify a group of patients with a median survival less than 8 years. The estimated 5-year OS was 93%, 71% and 53% for very good, good and poor-risk patients, respectively. We sought to determine whether the AMC/ALC PI may provide additional prognostic information when combined with the R-IPI. To test this possibility, the 171 very good/good risk and 84 poor risk patients identified by the R-IPI were subsequently risk stratified using the AMC/ALC PI. Among R-IPI very good/good risk patients a subset of poor risk patients (n=21) with a median OS of 2.2 years (95% confidence interval 1.1–6.6 years) and 35% 5-year OS could be identified with the AMC/ALC PI. In contrast, 5-year OS ranged from 75%-88% among very good and good risk patients. Similarly, stratification of R-IPI poor risk patients by the AMC/ALC PI identified subsets of very good (n=19) and good risk (n=44) patients with median OS that had not been reached and 86% and 55% 5-year OS, respectively. High risk (n=21) patients had a median OS of 1.4 years (95% confidence interval 0.9–2.2 years) and an estimated 5-year OS of less than 25%. Conclusions: Measurement of AMC and ALC at diagnosis is widely applicable, cost effective, predicts OS, and identifies high-risk patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.