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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 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.

Abstract Abstract 2634 The peripheral blood absolute lymphocyte/monocyte ratio (ALC/AMC) at diagnosis has been recently reported [Porrata et al, Hematologica 2012; 97(2):262-9] and confirmed [Koh et al, Oncologist 2012; 17(6):871-80] to be a predictor of clinical outcomes in classical Hodgkin lymphoma (HL). In addition, an inversed correlation has been reported between the ALC/AMC ratio and tumor associated macrophages in classical HL suggesting an association between the host biological response in the macro-environment and micro-environment. However, a limitation of the ALC/AMC ratio at diagnosis, the International Prognostic Score at diagnosis, the Positron-Emission Tomography (PET-scan) at diagnosis, or interim PET-scan during treatment is their inability to sequentially assess the host/tumor interaction during treatment. Therefore, we studied the ALC/AMC ratio recovery, as a surrogate marker of host immunity (i.e., ALC) and tumor micro-environment (i.e., AMC), at each treatment cycle phase to assess its predictive ability for clinical outcomes in classical HL. To participate in the study, patients were required to be diagnosed, treated, and followed at Mayo Clinic, Rochester, Minnesota and treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) with or without radiation therapy. An ALC/AMC ratio ≥ 1.1 cut-off was used in the study based on our previous publication [Porrata et al, Hematologica 2012; 97(2):262-9]. From 1990 until 2008, 190 classical HL patients qualified for the study. The cohort was evenly split with 50% males and 50% females. Fifty-eight percent of the patients had an interim PET-scan performed. The median age at diagnosis was 36 years (range: 18–83 years). Seventeen patients received 2 cycles; 5 patients 3 cycles; 51 patients 4 cycles; 5 patients 5 cycles and 112 patients 6 cycles. The median follow-up was 3.7 years (range: 0.2–20 years). The ALC/AMC ratio ≥ 1.1 at each treatment cycle phase of ABVD was a predictor for overall survival (OS), lymphoma-specific survival (LSS), progression-free survival (PFS) and time to progression (TTP). Patients were stratified based on how many cycles the ALC/AMC ratio did not reach the cut-off of 1.1. The more cycles with an ALC/AMC < 1.1 the worse survival was observed. The 23 patients who did not achieve an ALC/AMC ≥ 1.1 during the treatment cycles phase experienced the worst survival rates: 5 year OS of 33%; 5 year LSS of 43%; 5 year PFS of 16%; and 5 year TTP of 27%. Patients were then dichotomized into patients that did not achieve an ALC/AMC ratio ≥ 1.1 for all the cycles versus patients with an ALC/AMC ratio ≥ 1.1 in any cycle during treatment. Patients with an ALC/AMC ratio ≥ 1.1 in any cycle (N=167) experienced better survival compared with patients that in all cycles the ALC/AMC ratio was < 1.1 [ OS, the hazard ratio(HR) was 0.09, 95% CI (0.04–0.19), p < 0.0001; for LSS, HR =0.07, 95% CI (0.02–0.17), p <0.0001; for PFS, HR = 0.08, 95%CI (0.04–0.14), p < 0.0001; and for TTP, HR = 0.05, 95% CI (0.02–0.11), p < 0.0001]. In the multivariate analysis, an ALC/AMC ratio ≥ 1.1 in any cycle versus none was an independent predictor for clinical outcome when compared to ALC/AMC ratio at diagnsosis, PET-scan, International Prognostic Score, limited verus advanced stage, and radiation therapy [OS, HR = 0.14, 95% CI (0.04–0.40), p< 0.0002; for LSS, HR = 0.09, 95% CI (0.01–0.37), p <0.0006); for PFS, HR = 0.19, 95% CI (0.05–0.82), p < 0.03); and for TTP, HR = 0.15, 95% CI (0.02–0.89), p < 0.02]. In conclusion, the ALC/AMC ratio during ABVD treatment cycles in classical HL is a predictor for survival and provides an opportunity to develop therapeutic modalities to manipulate the ALC/AMC ratio during ABVD chemotherapy to improve clinical outcomes in classical HL. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 287 Purpose: Farnesyltransferases are key cellular enzymes involved in the prenylation of proteins. Prenylated proteins are important for malignant cell growth. The purpose of this phase II study (NCT00082888) was to assess tumor response and toxicity associated with the oral farnesyltransferase inhibitor tipifarnib (R115777, Johnson and Johnson) in patients with relapsed aggressive, indolent, or uncommon lymphoma. The uncommon group included low incidence lymphoma types such as Hodgkin lymphoma (HL) and T-cell non-Hodgkin lymphoma- cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL). Patients and Methods: Patients with relapsed or refractory non-Hodgkin (NHL) or Hodgkin (HL) were eligible if they had measurable disease, performance status ≤2, platelet count ≥75,000 × 10(6)/L, an absolute neutrophil count ≥1000 × 10(6)/L and a creatinine ≤2 × upper limit of normal. Patients initially received tipifarnib 300 mg twice daily, days 1–21 every 28 days. The trial was conducted by the University of Iowa/Mayo Clinic Lymphoma SPORE. Results: Ninety-three patients with lymphoma (42 aggressive, 15 indolent, and 36 uncommon) enrolled in the trial between March 2004 and November 2008. The median age was 62 years (range, 18–91). The median number of prior therapies was 5 (range, 1–17). The overall response rate (ORR) was 20% (19/93) with 6% (6/93) complete responses (CR) and 14% (13/93) partial responses (PR). The ORR was 17%, 7%, and 31% for the aggressive, indolent, and uncommon groups, respectively (Table). Among the 19 responders were 7 diffuse large B-cell lymphoma (DLBCL), 7 T-cell NHL, 1 follicular grade II, and 4 HL. The overall median response duration for the 19 responders was 7.5 months (mean, 12.8; range, 1.8 – 48.1 months). The median response duration was 11.3 months (mean, 10.1; range, 1.8 – 18.5 months), 2 months, and 7.5 months (mean, 15.5; range, 1.9 – 48.1 months) for the aggressive (7), indolent (1), and uncommon (11) groups, respectively. Five patients in the uncommon group are still receiving treatment with a range of treatment duration between 25 – 60+ months. Among the 5 still receiving treatment 4 responded and 1 is stable. The range of response duration is 15.4, 17.7, 43.1, and 48.1 months. These five patients (2 with HL, 1 anaplastic large cell cutaneous, and 2 PTCL) are currently receiving doses of 400 (1), 200 (2), and 100 (2) mg twice daily. The median time to progression for all patients was 3.6 months (95% CI: 2.1 – 4.5 months). The grade 3,4 toxicities observed were primarily fatigue (10%) and reversible myelosuppression with 11% anemia, 37% neutropenia, and 32% thrombocytopenia. Correlative studies demonstrated tipifarnib-induced upregulation of Bim, a marker of tipifarnib action in lymphoma cell lines, in 7 of 9 paired lymphoma biopsies. Conclusions: Tipifarnib has activity in lymphoma, with responses in patients with heavily pretreated DLBCL, HL and T-cell types, but little activity in follicular NHL. This agent has an excellent toxicity profile and targets a novel pathway. Further studies in combination with other agents are warranted for patients with DLBCL, HL or T-cell NHL. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 1268 Poster Board I-290 Purpose There are reports of an increased risk of skin cancers in patients with B-Chronic Lymphocytic Leukemia (CLL). These skin cancers include basal cell and squamous cell carcinoma. This analysis was performed to more completely define the prevalence of skin cancers in patients in the Mayo Clinic Rochester CLL database and to look for contributing factors. Methods The Mayo Clinic Rochester CLL Database includes all patients with a diagnosis of CLL since January 1995 seen in the Division of Hematology and who have signed institutional review board approved consents for research. For this study, 2240 patients were analyzed to compare differences in characteristics between CLL patients with and without skin cancer. Chi-square statistics were used to compare qualitative variables (age categories, gender, referral status, ALC categories, CD38, ZAP-70, IgVH gene mutation status, FISH categories, Rai stage), and t-tests were used for quantitative variables (age at diagnosis, ALC values). Overall survival (OS) and time to first treatment (TFT) analyses were performed with results being displayed using Kaplan-Meier curves and p-values calculated using a log-rank test. Prevalence of melanoma among CLL patients was compared to the age-adjusted prevalence of melanoma in individuals in the Iowa SEER registry. Results Median follow-up for the 2240 patients diagnosed between 1/1/1995 and 8/11/2009 was 4.6 years. In aggregate, 293 (13.1%) patients were found to have non-melanoma skin cancer (squamous cell carcinoma or basal cell carcinoma) cancer. The diagnosis of non-melanoma skin cancer occurred before the CLL diagnosis in 39% and at or after the diagnosis of CLL in 61%. There were 57 (2.5%) cases of melanoma in association with CLL. The diagnosis of melanoma occurred before the CLL diagnosis in 38% and at or after the diagnosis of CLL in 62%.The prevalence of non-melanoma skin cancer and melanoma skin cancer were both higher in non-referred (geographically regional) CLL patients than referred CLL patients (16.6% vs. 11.4%, p<0.001 for non melanoma; 2.0% vs. 3.6%, p=0.03 for melanoma). The prevalence of melanoma in CLL patients was higher than that of age-adjusted prevalence for individuals in the Iowa SEER registry (2.5% vs. 0.03%; p<0.001). We next evaluated the relationship between CLL patients with skin cancer and demographic characteristics, prognostic parameters, and CLL related treatment. The risk of non-melanoma skin cancer in CLL was found to be associated with age (median age at diagnosis with skin cancer 67.6 vs. without skin cancer 63.3, p<0.001) and with sex (males 15.1% vs females 8.9%, p <0.001). There was no statistical significant difference in frequency of non-melanoma skin cancer associated with absolute lymphocyte count (ALC), Rai stage, CD 38, Zap 70, IgVH gene mutation status, FISH, or treatment history. The risk of melanoma in CLL was found to be associated with age at diagnosis (median age with melanoma 69.9 vs. without melanoma 63.8, p=0.002) and CD38 (positive 1.3% vs negative 3.1%, p=0.03). There was no statistically significant difference associated with gender, ALC, Rai stage, Zap 70, IgVH gene mutation status, FISH, or treatment history. Since the presence of skin cancer could be a marker of immune dysregulation we hypothesized skin cancer may be associated with clinical outcome of CLL. Accordingly, we evaluated the relationship between non-melanoma skin cancer and melanoma skin cancer and TFT and OS. Contrary to our hypothesis, TFT (median 6.0 years vs. 4.9; p=0.04) and OS (median 10.8 years vs. 9.7; p=0.02) of patients with non-melanoma skin cancer were both longer than those without non-melanoma skin cancer. No differences in TFT (p=0.06) or OS (p=0.66) were observed among patients with melanoma compared to those without melanoma. Conclusions We find in our cohort of CLL patients a higher prevalence of melanoma than the general population. Risk of melanoma and non-melanoma skin cancer among patients with CLL does not appear to be related to CLL characteristics, with the exception of CD 38, or CLL outcome. The diagnosis of melanoma and non-melanoma skin cancer in patients with CLL does not appear to be a risk factor for either CLL specific outcomes (TFT) or shorter survival. Disclosures Kay: Biogenc-Idec, Celgene, Genentech, genmab: Membership on an entity's Board of Directors or advisory committees; Genentech, Celgene, Hospira, Polyphenon Pharma, Sanofi-Aventis: Research Funding. Zent:Genentech, Bayer, Genzyme, Novartis: Research Funding. Shanafelt:Genentech: Research Funding; Hospira: Membership on an entity's Board of Directors or advisory committees, Research Funding; Polyphenon E International: Research Funding; Celgene: Research Funding; Cephalon: Research Funding; Bayer Health Care Pharmaceuticals: Research Funding.

Abstract Background: Peripheral T-cell non-Hodgkin’s lymphomas (PTCL) account for approximately 10% of all non-Hodgkin’s lymphomas in the U.S. and Europe. PTCL, unspecified (PTCL-U), as classified by the WHO, is the most common subtype. The ability of high-dose therapy (HDT) and stem cell transplantation (SCT) to improve patient outcome was evaluated in the current study. Methods: All patients with PTCL-U evaluated at our institution who had tissue specimens available for review from January, 1994 to December, 2005 were identified and both clinical characteristics and treatment course obtained from the medical record. Results: 89 patients with PTCL-U were identified, with a median follow up of 13 months (range 1 month–12 years). The median age at diagnosis was 56 years (range 24–90). The IPI was low, intermediate or high in 34%, 44% and 22% of patients, respectively. On univariate analysis, age >60 (p<.0001), ECOG performance status >1 (p<.0001), LDH greater than normal (p=.004), Ann Arbor Stage III/IV (p=.01) and the presence of B symptoms (p=.0004) were associated with a poorer overall survival, as was an intermediate or high IPI (p<.0001). In contrast, on multivariate analysis only age >60 (p=.0006) and ECOG performance status >1 (p=.007) were independently associated with poorer overall survival. Fifty-seven percent of patients were treated initially with an anthracycline-based regimen, most commonly CHOP (53%). Patients with a low (0–1), intermediate (2–3) or high (4–5) IPI experienced a 61%, 29% and 18% 5-year overall survival, respectively. Fourteen patients (16%) received HDT and autologous (n=12) or allogeneic (n=2) SCT, either at the time of a first partial or complete response (n=11) or at the time of first relapse (n=3). The median survival in those patients treated initially with an anthracycline-based regimen alone was 11 months (95% CI 0.6–1.6 years). Improvement in both 5-year overall (75% vs 24%, HR=5.6, 95% CI 2.0–23.4, p=.0004) and disease-free (60% vs 26%, HR=3.2, 95% CI 1.3–9.3, p=.008) survival was observed in patients who received HDT/SCT, as compared to patients treated with anthracycline-based therapy alone. Furthermore, improvement in both 5-year overall (80% vs 26%, HR=5.8, 95% CI 1.7–35.7, p=.002) and disease free (72% vs 26%, HR=3.8, 95% CI 1.3–15.8, p=.009) survival was observed in patients who received HDT/SCT at the time of a first partial or complete response when compared to patients who received anthracycline-based therapy. When patients who failed to achieve a first partial or complete response were excluded from the analysis, improved 5-year overall (80% vs 57%, HR=0.5, 95% CI 0.1–2.1, p=.4) and disease-free (72% vs 53%, HR=0.7, 95% CI 0.1–2.3, p=.5) survival were observed in patients who received upfront HDT/SCT, although this failed to reach statistical significance. The improved overall and disease free survival observed in patients receiving HDT/SCT, either at the time of a first response or at the time of relapse, remained significant when accounting for differences in the IPI. In conclusion, selected patients with PTCL-U may benefit from treatment with HDT/SCT following a first response to conventional anthracycline-based chemotherapy.

Abstract Background: The prognosis of patients with T-cell large granular lymphocyte (LGL) leukemia is diverse, with some patients experiencing rapid progression of the disease while others surviving decades. Despite multiple case reports and a number of case series reported in literature, prognostic factors in this leukemia are unknown and no staging/prognostic system has been developed. Aim: To identify factors predicting the prognosis of patients with newly diagnosed T-cell LGL leukemia. Methods: We reviewed the presentation, laboratory data and the clinical course of patients with newly diagnosed T-cell LGL at seen at the Mayo Clinic, Rochester. T-cell LGL was diagnosed in patients with at least 2 of these criteria: morphological evidence of LGL leukemia on bone marrow biopsy or blood smear; LGL immunophenotype; evidence of clonal T-cell receptor gene rearrangements. Results: 286 patients seen at Mayo Clinic Rochester between 6/1986 and 5/2005 met diagnostic criteria (52% male, median age at presentation 64 years (range 27–88)). Lymphadenopathy, splenomegaly, and hepatomegaly were present in 9%, 4% and 1.5% of the patients respectively. Median hemoglobin was 11.7 g/dL (range 3.5 – 17.1). Median absolute neutrophil count (ANC) was 1.51 × 109/L (range 0.0 – 20 × 109/L) and median absolute lymphocyte count (ALC) was 2.2 × 109/L (range 0.1 – 24). Median LGL count on peripheral smear was 0.81 × 109/L (range 0.06–10.8 × 109/L). Cytogenetic studies were done for 122 patients, of which, only 9 were abnormal. 87 patients (29%) had associated autoimmune conditions: rheumatoid arthritis (n=29), Felty’s syndrome (n=11), other connective tissue disorders (n=9)). Pure red cell aplasia, aplastic anemia, idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia were seen in 17, 5, 8, 1 patients respectively. Median follow up was 50 months (range 1–229) and estimated median survival was 74.3 months. In multivariate analysis, the only independent risk factors were: anemia (hemoglobin<12 g/dl), hazard ratio (HR) 1.75, (95%CI 1.22–2.52, p= 0.0023), severe neutropenia (<0.1 × 109/L), HR 2.11 (95%CI 1.053–4.25) and lymphopenia (ALC< 1 × 109/L), HR 1.93 (95%CI 1.21–3.07). We developed a simple prognostic scoring system based on the above identified independent risk factors, stratifying patients in 3 groups: 0 - no risk factors present, 1 -one risk factor, 2 - two or more risk factors present. The median survival was 105, 55 and 5 months for score of 0, 1 and 2 respectively, p=0.004 (Figure). Conclusion: The prognosis of patients with newly diagnosed T-cell LGL is variable. The presence of anemia, severe neutropenia and lymphopenia are independent poor prognostic factors in T-cell LGL. Combining these factors allows the identification of patients at a high risk of death from the disease. Further studies are needed to prospectively validate these findings and establish if the high risk group would benefit from aggressive therapy. Figure Figure.

Abstract The peripheral blood absolute lymphocyte count (ALC) on day 15 after autologous stem cell transplantation (ASCT) has been shown to be an independent predictor for overall survival (OS) for many malignancies including acute myelogenous leukemia (AML), breast cancer, multiple myeloma (MM), primary systemic amyloidosis, and Hodgkin’s and non-Hodgkin’s lymphoma (NHL). However, due to the retrospective nature of previous studies, the peripheral blood lymphocyte subpopulations that predict survival are unknown. To prospectively correlate peripheral blood lymphocyte subpopulations after ASCT and progression free survival, peripheral blood lymphocytes collected from patients before and on day 15 after ASCT were analyzed by four color flow cytometry for CD3, CD4, CD8, CD16, CD 19, and CD56. Patients were then dichotomized into two groups: patients achieving normal numbers of lymphocyte subset (i.e. CD4, CD8, CD19, CD16/56) count versus those who did not. Progression free survival was then analyzed by the Kaplan-Mier method. In our cohort of 14 patients, 9 were male and 5 were female. Nine patients were diagnosed with diffuse large cell B cell lymphoma, two with mantle cell, two with follicular, and one with peripheral T cell lymphoma. On presentation, one patient had stage I, four patients had stage II, four had stage III, and five patients had stage IV disease. The median age at ASCT was 53 years (range: 26–70). The preliminary data from this ongoing prospective study of 14 patients shows that on day 15 after ASCT, 4/14 (29%) of patients achieved a normal CD3 count (median 321, range: 69–2069 cells/ml) 3/14 (21%) achieved a normal CD4 count (median 206, range: 31–1091 cells/ml), 6/14 (43%) achieved a normal CD 8 count (median 88.5, range: 13–813 cells/ml) 1/14 (7%) achieved a normal CD19 count (median 2, range:0–227 cells/ml), and 8/14 (57%) achieved a normal CD16/56 count (median 85.5, range: 10–744 cells/ml). The median follow-up was 12 months (range: 3–45 months). On univariate analysis, patients achieving an absolute NK cell count of ≥ 80 cells/μ on day 15 had significantly improved progression free survival compared to those who did not (not reached vs 3 months, p<0.006, respectively). Similar analysis evaluating the absolute CD3, CD4, CD8, and CD 19 count was not significant (p=0.1, p=0.258, p= 0.06, and p=0.55, respectively). To our knowledge, this is the first report detailing the critical role of NK cell immune reconstitution after ASCT in progression free survival. Figure Figure

Abstract Background: Absolute lymphocyte count (ALC) recovery is an independent prognostic factor for survival for different hematological malignancies treated with autologous stem cell transplantation. Recently, we reported superior overall survival (OS) in patients with follicular lymphomas that presented with a higher ALC (ALC ≥ 1 x 109/L) at diagnosis. The role of ALC at diagnosis on survival in T cell lymphomas is not known. Methods: All patients evaluated at the Mayo Clinic for T cell lymphomas from October 1984 until April 2005 were analyzed in the study. The primary objective of the study was to assess the role of ALC at diagnosis and survival in T cell lymphomas. ALC at diagnosis was obtained from the standard complete blood cell count (CBC). Results: 223 patients with T cell lymphomas were included in the study. The histology included: peripheral T-cell lymphoma-unspecified (40%), anaplastic large cell (13%), angioimmunoblastic (10%), angiocentric (4%), intestinal T-cell (2%), and other (31%). The median follow-up was 18.6 months (range: 1 month – 229 months [19 years]). The sample population included 60% male and 40% females with a median age of 60 years (15–90 years). The median ALC at diagnosis was 1.2 x 109/L (range: 0.04–6.7 x 109/L). ALC as a continuous variable was identified as predictor for OS in the univariate analysis (HR= 0.690, 95%CI: 0.542–0.862, p < 0.0006). ALC ≥ 1 x 109/L was selected as the dichotomized value because it yielded the maximum difference in survival by c2 analysis looking at different cut-point from 0.6 to 1.7 x 109/L that were included between the 25% and 75% quartiles. Univariately, ALC ≥ 1 x 109/L was also identified as a predictor for OS (HR = 0.682, 95%CL= 0.578–0.804, p < 0.0001). Patients (N = 122) with an ALC ≥ 1 x 109/L experienced superior survival compared to patients (N = 101) with an ALC < 1 x 109/L [median OS: 76.3 vs 10.6 months, respectively; and 5 years OS estimates of 53% vs 23%, respectively, p < 0.0001]. When ALC ≥ 1 x 109/L was compared to the international prognostic index (IPI), ALC ≥ 1 x 109/L remained an independent predictor for survival in the multivariate analysis (HR = 0.779, 95%CL: 0.655–0.925, p < 0.004). Conclusion: This study demonstrates ALC as an independent predictor for OS in T cell lymphomas, suggesting that the host immune system affects survival in this group of patients.

Abstract Abstract 1527 Interim Positron-Emission Tomography (PET-scan), as a functional imaging test for tumor activity, has been shown to be a predictor for progression-free survival (PFS) and time to progression (TTP) in classical Hodgkin lymphoma (HL). The peripheral blood absolute lymphocyte/monocyte ratio (ALC/AMC) at diagnosis, as a surrogate marker of host immunity (i.e., ALC) and tumor microenvironment (i.e., AMC), has been recently reported [Porrata et al, Hematologica 2012; 97(2): 262–9] and confirmed [Koh et al, Oncologist 2012; 17(6): 871–80] to be also a predictor for PFS and TTP in classical HL. Therefore, we evaluated the combination of ALC/AMC ratio at diagnosis and the interim PET-scan to further stratify the clinical outcomes of PFS and TTP in patients with classical HL. To participate in the studies, patients were required to be diagnosed, treated, and followed at Mayo Clinic, Rochester, Minnesota. The treatment consisted of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) with or without radiation therapy. Patients were required to have an interim PET-scan performed. An ALC/AMC ratio ≥1.1 cut-off was used in the study based on our previous publication [Porrata et al, Hematologica 2012; 97(2): 262–9]. From 2000 until 2008, 111 classical HL patients qualified for the study. The cohort included 54% males and 46% females. The median age at diagnosis was 37 years (range: 18–83 years). The median follow-up was 2.8 years (range: 0.3–10.4 years). Patients with a negative interim PET-scan (N=98) presented with a higher ALC/AMC ratio at diagnosis (median of 2.32, range: 0.26–37.5) compared with patients with a positive interim PET-scan (N = 13) (median of 0.9, range: 0.29–3.10), p < 0.004. By univariate analysis, the ALC/AMC ratio at diagnosis and the interim PET-scan were predictors for PFS [ ALC/AMC ratio, R =0.13, 95% CI (0.05–0.35), p < 0.0002; and interim PET-scan, HR = 0.13, 95% CI (0.05–0.37), p < 0.0003] and TTP [ALC/AMC ratio, R =0.07, 95% CI (0.02–0.24), p < 0.0001; and interim PET-scan, HR = 0.05, 95% CI (0.01–0.18), p < 0.0003]. By multivariate analysis, ALC/AMC ratio at diagnosis and the interim PET-scan were independent predictors for PFS [ ALC/AMC ratio, R =0.13, 95% CI (0.07–0.63), p < 0.006; and interim PET-scan, HR = 0.11, 95%CI (0.02–0.47), p < 0.003] and TTP [ALC/AMC ratio, R =0.11, 95% CI (0.02–0.71), p < 0.02; and interim PET-scan, HR = 0.10, 95% CI (0.02–0.46), p < 0.003] when compared to the International Prognostic Score, limited versus advanced stage, and radiation. Patients were stratified into four groups: group 1 included patients with a negative interim PET-scan and ALC/AMC ratio at diagnosis ≥1.1 (N = 88); group 2 included positive interim PET-scan and ALC/AMC ratio at diagnosis ≥1.1 (N = 5); group 3 included negative PET-scan and ALC/AMC ratio at diagnosis < 1.1 (N = 10); and group 4 included positive PET-scan and ALC/AMC ratio at diagnosis <1.1 (N = 8). The three year PFS rates for each group were for goup1 95% (Events = 6); group 2 40% (Events = 3); group 3 56% (Events = 4); and group 4 50% (events = 4), p < 0.0001. The three year TTP rates for each group were: for group1 was 100% (Events = 0); for group 2 of 40% (Events = 3); for group 3 of 65% (Events = 3); and group 4 of 50% (events = 4), p < 0.0001. In conclusion, the ALC/AMC ratio at diagnosis is independent of the interim PET-scan to predict PFS and TTP in classical HL. Further studies are warranted to confirm our findings and to assess if the combination of the ALC/AMC ratio at diagnosis and interim PET can be use for planning of risk-adapted treatment. Disclosures: Ansell: Seattle Genetics, Inc.: Research Funding.