Ristow, Kay M.

Abstract The International Prognostic Index at the time of relapse (IPI-R) has been reported to predict clinical outcome in patients with relapsed diffuse large B-cell lymphoma (DLBCL) undergoing autologous stem cell transplantation (ASCT) [Jabbour et al, Leukemia & Lymphoma2005;46(6):861–867; Lerner et al, Biology of Blood and Marrow Transplant2006;13:486–492; and Costa et al, Bone Marrow Transplant2008;41:715–720]. The absolute lymphocyte count (ALC) has been reported as a prognostic factor for survival at diagnosis, during standard chemotherapy and at day 15 post-ASCT for multiple hematological malignancies; however, no reports have addressed whether ALC at the time of relapse (ALC-R) predicts survival. Thus, we assessed the prognostic significance of ALC-R in patients with relapsed DLBCL. To be included in the study, patients were required to have been diagnosed with relapsed DLBCL, have ALC values available from the time of relapse, and to be followed at Mayo Clinic, Rochester. From Feb 2,1987 until March 6, 2006, 121 DLBCL patients qualified for the study. The overall survival (OS) was measured from the time of relapse to the date of death or last follow-up and progression-free survival (PFS) was defined as the time from relapse to the time of progression, relapse, death, or last follow-up. The median age at relapse was 68 years (range:25–88 years) and the median ALC-R was 1.21 x 109/L (range: 0.33–5.99 x 109/L). The value of ALC-R ≥ 1.0 x 109/L was used for the analysis based on previous publications. The groups (ALC-R ≥ 1 or < 1 x 109/L) were balanced for the IPI-R (p=0.1), as well as for undergoing ASCT (p=0.4). Superior OS was observed in patients with an ALC-R ≥ 1.0 x 109/L (N = 76) [median OS: 27.5 months, 3 years OS rates of 42%] compared with patient with an ALC-R < 1.0 x 109/L (N =45) [median OS: 9.4 months, 3 years OS rates of 13%] (p <0.0001). Superior PFS was also observed in patients with an ALC-R ≥ 1.0 x 109/L (N = 76) [median PFS: 14.8 months, 3 years PFS rates of 30%] compared with patient with an ALC-R < 1.0 x 109/L (N =45) [median PFS: 6.2 months, 3 years PFS rates of 11%] (p <0.001). ALC-R was an independent prognostic factor for OS [RR = 0.551, p < 0.009] and PFS [RR = 0.674, p < 0.02] in the multivariate analysis when compared with the IPI-R and whether patients underwent ASCT or not. Our study supports the hypothesis that ALC at relapse predicts clinical outcome in DLBCL and suggests that patient host immunity is an important variable predicting survival in relapsed DLBCL.

Abstract Background: Recent literature suggests that statins may have anticancer potential. This effect is thought to be mediated through 2 primary mechanisms - impairment of protein prenylation and interference with the formation of cholesterol-rich lipid microdomains, or “lipid rafts” within the cell membrane. Both of these processes are critical for signaling activity of numerous proteins important for lymphomagenesis and tumor survival. Recent data, however, suggest that statin use may directly inhibit rituximab binding to CD20 and therefore rituximab efficacy. These findings raised significant concerns about statin use during rituximab treatment. Here we report on statin use and clinical outcome in a cohort of FL and DLBCL treated patients, most of whom were treated with rituximab containing regimens. Methods: 293 newly diagnosed FL patients and 228 newly diagnosed DLBCL patients were prospectively enrolled in our Lymphoma SPORE registry from 9/2002 through 6/2007. Pathology was centrally reviewed. All patients were followed for retreatment, progression-free and overall survival. Statin use at the time of diagnosis and time of initial treatment was abstracted from the medical record. An event was defined by disease progression, retreatment, or death due to any cause. Results: 19% of FL patients and 22% of DLBCL patients were on statins at diagnosis; 16% and 19% were on statins during treatment, respectively. Initial therapy for the FL patients was observation (40%), R-CHOP (19%), R-CVP (12%), rituximab alone (8%), CVP (7%), RT (6%), and other (8%). All DLBCL patients received rituximab with CHOP or a CHOP-like regimen. At a median follow-up of 36 months (range 3–73), 109 (37%) and 65 (29%) of FL and DLBCL patients had an event; 19 (6%) and 46 (20%) of FL and DLBCL patients died, respectively. After adjusting for FLIPI, grade, and initial therapy type, statin use at diagnosis was associated with better event-free survival (HR = 0.57, 95% CI: 0.34–0.95, p=0.03) in FL patients. Statin use during treatment in FL patients was also associated with better event-free survival, though not statistically significant (HR = 0.67, 95% CI: 0.39–1.16, p=0.15). The improvement in EFS for FL patients was consistent across initial therapies, including observation. Statin use was not associated with IPI-adjusted overall survival or event-free survival in DLBCL (all p > 0.50). Conclusions: Statin therapy does not appear to be associated with inferior clinical outcome in DLBCL treated with rituximab and CHOP or CHOP-like therapy. Therefore direct inhibition of rituximab binding to CD20 may have limited clinical significance or/and may be overcome by inhibitory impact of statins on cell signaling. The latter possibility is supported by our observation that statin use is associated with improved event-free survival in follicular lymphoma. Figure Figure Figure Figure

Abstract Background: Inhibitors of HMG-CoA reductase (“statins”) are effective in reducing the risk of cardiovascular disease. Preclinical data from rodents suggested that they may increase the incidence of some cancers, including lymphoma. However, monitoring of randomized trials in humans have generally found decreased cancer risks, and these findings have been supported by a growing number of observational studies, including three recent reports of a protective association in NHL. The suggested anti-carcinogenic mechanisms for statins include their impact on inflammatory (including a shift from a Th1 to Th2 profile) and angiogenesis pathways, as well as the induction of apoptosis by modulation of signaling pathways, all of which are of biologic relevance in NHL. Methods: We evaluated the history of statin use and risk of NHL in a clinic-based study of 243 newly diagnosed NHL cases and 499 frequency matched controls enrolled at the Mayo Clinic from 2002-2005. Risk factor data were collected using self-administered questionnaires, and included history of use of cholesterol lowering drugs two or more years before diagnosis (for cases) or enrollment (for controls); specific drug names were not available. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI), adjusting for age, gender, and residence. NHL subtypes were centrally reviewed, and subtype-specific risks were estimated using polychotomous logistic regression. Results. The mean age at diagnosis was 59.5 years for cases and 55% were men; among controls, the mean age at enrollment was 61.8 years and 54% were men. Twenty-one percent of the cases reported ever using statins compared to 30% of the controls, supporting a lower risk of NHL for ever users (OR=0.69; 95% CI 0.47–1.00). The lowest risk was seen for the longest users; i.e., compared to never users, person who had 10 or more years of use had the greatest reduction in risk (OR=0.52; 95% CI 0.24–1.10). A history of high cholesterol was also inversely associated with risk of NHL (OR=0.72; 95% CI 0.55–0.93). However, the association for the type of treatment for cholesterol lowering varied. Those who were medically treated had inverse association with risk of NHL (OR=0.63; 95% CI 0.46–0.86), while the no treatment and dietary change only groups were found to have no association with risk. The reduction in NHL risk with medical treatment was specific to statin use, as the use of other cholesterol lowering drugs was not associated with risk (OR=1.13; 95% CI 0.50–2.57). These results were not confounded by education, family history of NHL, body mass index, cigarette smoking or alcohol use. In subtype analysis, the inverse association was seen for diffuse large B-cell lymphoma (OR=0.27; 95% CI 0.08–0.90), but not for CLL/SLL or follicular NHL. Conclusions. Statin use was associated with a lower risk of developing NHL, particular diffuse large B-Cell lymphoma.

Abstract Background: In Hodgkin’s Disease (HD), G-CSF has been used to maintain maximum dose intensity by avoiding neutropenia and treatment delays. Pre-clinical data and anecdotal reports have shown an association between G-CSF administration and bleomycin pulmonary toxicity (BPT). This complication may cause access morbidity and have a detrimental impact on survival in this otherwise good prognosis population. We embarked on a retrospective analysis to determine if G-CSF increased the incidence of this complication or had an impact on outcomes. Methods: We reviewed all patients managed for HD at Mayo Clinic, Rochester, from January 1986 to February 2003. BPT was defined by the presence of pulmonary symptoms, bilateral interstitial infiltrates, and no evidence for an infectious etiology. Patients who received G-CSF support with one or more of their bleomycin-containing chemotherapy cycles were considered as being treated with G-CSF. Results: A retrospective review identified 141 patients with HD treated with a bleomycin-containing regimen. The mean age of patients at diagnosis was 34 years. Fifty four percent were males. The histology was nodular sclerosing in 85%. The Hasenclever index was 0 in 15%, 1 in 35%, 2 in 24%, 3 in 16%, 4 in 9%, and ≥ 5 in 1%. The G-CSF and non G-CSF groups were balanced for poor prognosis risk factors including Hasenclever index. Frontline chemotherapy included ABVD in 57%, MOPP-ABV(D) in 33%, COPP-ABV in 8%, BEACOPP in 3%, and Stanford V in 2%. Forty one percent of patients received radiation. The 5-year overall survival (OS) and progression free survival (PFS) for all patients were 87% and 79% respectively. G-CSF was administered to 52% (74/141) of patients. BPT occurred in 18% of patients (25/141). A higher rate of BPT was observed in patients receiving G-CSF, 26% (19/74) versus 9% (6/67) in non G-CSF patients (p=0.0141). In this population, G-CSF administration was the only factor associated with an increased risk of BPT. There was no difference between the two groups for BPT associated risk factors including radiation, bleomycin dose, renal insufficiency, smoking history, and underlying lung disease. Additionally these risk factors showed no correlation with the development of BPT. The mortality from BPT was 4.2% (6/141) in all patients and 24% (6/25) in patients who developed the pulmonary syndrome. Of the 6 patients who died acutely, 83% (5/6) received G-CSF. CR rates were equal between the G-CSF and non G-CSF groups at 92% and 94% respectively. Five year OS and PFS were equal between the G-CSF and non G-CSF groups at 82% versus 89% (p=0.473) and 74% versus 84% (p=0.152) respectively. Conclusion: G-CSF administration increases the incidence of pulmonary toxicity in HD patients treated with bleomycin based chemotherapy. The major impact was on treatment related morbidity as 5-year OS and PFS were equal between the G-CSF and non G-CSF groups.

Abstract Background: Bleomycin-containing chemotherapy regimens have become the mainstay of treatment in Hodgkin’s Disease (HD). The risk of bleomycin pulmonary toxicity (BPT) ranges from 0–46% and mortality rates range from 0–27%. Although there is no excepted standard treatment for BPT, corticosteroid treatment, withholding bleomycin from subsequent chemotherapy, and proceeding with a non-bleomycin containing regimen is the most common approach. We reviewed our experience to better delineate outcome and appropriate treatment in these patients. Methods: We reviewed all patients managed for HD at Mayo Clinic, Rochester, from January 1986 to February 2003. BPT was defined by the presence of pulmonary symptoms, bilateral interstitial infiltrates, and no evidence for an infectious etiology. Results: A retrospective review identified 141 patients with HD treated with a bleomycin-containing regimen. The mean age of patients at diagnosis was 34 years. Fifty four percent were males. The histology was nodular sclerosing in 85%. The Hasenclever index was 0 in 15%, 1 in 35%, 2 in 24%, 3 in 16%, 4 in 9%, and >5 in 1%. Frontline chemotherapy included ABVD in 57%, MOPP-ABV(D) in 33%, COPP-ABV in 8%, BEACOPP in 3%, and Stanford V in 2%. Forty one percent of patients received radiation. The 5-year overall survival (OS) and progression free survival (PFS) for all patients were 87% and 79% respectively. BPT was observed in 18% of patients (25/141). There was a significant decrease in OS, 63% in patients with BPT versus 90% in non-BPT patients at 5 years (p=0.0013). The mortality from BPT was 4.2% (6/141) in all patients and 24% (6/25) in patients who developed the pulmonary syndrome. These 6 patients all died within 9 months of their HD diagnosis from BPT. The Hasenclever index was 3 or less in 5 of these 6 patients. CR rates were equal at 91% and 93% in BPT and non-BPT patients respectively (p=0.299). Twenty two percent (31/141) of patients, either symptomatic or asymptomatic, had bleomycin omitted at any time from their regimen with no difference in OS or PFS, 83% versus 88% (p=0.369) and 82% versus 78% (p=0.853) respectively. The mean bleomycin dose was 84 mg/m2 (range of 20–180 mg/m2). Bleomycin dose had no impact on OS or PFS. In BPT patients subsequent non-bleomycin therapy included AVD 44%, MOPP-AV 31%, or no further chemotherapy 25%. The five-year OS was equal between the AVD and MOPP-AV groups at 91%. However in patients who received no further chemotherapy 5-year OS was 30% (p=0.0001). Conclusion: Bleomycin pulmonary toxicity (BPT) results in a significant decrease in OS survival at 5 years in patients being treated for Hodgkin’s Disease. In patients who do not die acutely from pulmonary toxicity both OS and PFS appear equal despite the omission of bleomycin.

7554 Background: Predicting early clinical failure in patients with untreated FL is important but difficult. Lymphoma involvement of EN sites is better detected by FDG-PET/CT than CT alone, but PET parameters are not part of the usual predictive indices. We aimed to determine the incidence and patterns of spleen and EN disease using PET/CT, and learn if they are useful in predicting early clinical failure. Methods: PET/CT images from 613 cases of newly diagnosed FL between 2003 – 2016 were retrospectively reviewed. The location, pattern, and number of EN sites, as well as splenic involvement, were recorded. Associations with outcomes were assessed using event-free survival (EFS) and overall survival (OS). Results: 49% (301/613) of patients had PET/CT-detected EN involvement, and 28% (171/613) had spleen involvement. Presence of ≥2 EN sites, spleen, bone, or soft tissue involvement, as well as a multifocal on diffuse pattern of bone involvement by imaging, were univariate predictors of EFS; presence of ≥2 EN sites and bone involvement pattern were also predictive of OS. In a multivariate analysis with FLIPI-2 factors, spleen involvement, pattern of bone involvement, and soft tissue involvement independently predicted a lower EFS (Table). When the multivariate analysis was performed using PRIMA-PI factors, the presence of ≥2 EN sites was an adverse independent prognostic factor for OS (HR 2.28; 95% CI 1.01-5.18; p=0.05). Conclusions: Baseline PET/CT identifies EN and spleen sites of disease that can predict early clinical failure of FL. These results may be useful to better identify high-risk patients and guide appropriate therapy. [Table: see text]

8538 Background: Follicular lymphoma (FL) is a heterogeneous disease with a variable prognosis. Transformation to an aggressive lymphoma is associated with a poor prognosis. Previous studies have identified tumor microenvironment cells such as CD68+ macrophages, PD-1+ and FOXP3+ cells as prognostic in FL. However, results have been conflicting and infrequently address the risk of transformation. In this study we analyzed various components of the microenvironment and their association with transformation. Methods: Patients with FL that later transformed were identified through Mayo Clinic lymphoma database. Tissue specimens at diagnosis were stained with CD68, CD11c, CD21, CXCL13, FOXP3, PD-1 and CD14 and characterized by pattern of location and semi-quantitative cell content. Time to transformation (TTT) and overall survival (OS) were assessed by Kaplan-Meir analysis. Significant variables were further analyzed by cox proportional hazards model. Results: 58 patients were included with a median TTT of 4.7 years (range, 0.4-20). Presence of CD14+ cells vs absence and their location (follicular vs non-follicular) were associated with shorter TTT (4.5 vs 6.2 yrs., p=0.037 and 3.8 vs 5.9 yrs. p= 0.027, respectively). The quantity of PD-1+ cell content was not associated with TTT or OS. However, localization of PD-1 to the follicle compared to diffuse was associated with a longer TTT (6.1 vs 3.6 yrs. p=0.033) and superior OS (9.7 vs 4.6 yrs. p=0.009). On multivariate analysis, the pattern of CD14 and PD-1 staining remained significantly associated with shorter TTT (Table). Conclusions: In follicular lymphoma, a diffuse pattern of PD-1+ cells is associated with inferior TTT and OS. CD14+ cells localized to the follicle is associated with a shorter TTT. After accounting for FLIPI score, both these factors remained significant. These results identify two independent predictors of the rate of transformation in follicular lymphoma and suggest it is location rather than quantity of CD14+ or PD-1+ cells that influence outcomes. [Table: see text]

18505 Background: Besides radiation, the immunologic mechanisms of action of 90Y ibritumomab tiuxetan (Zevalin) radioimmunotherapy (RIT) have been attributed to complement mediated lysis and antibody-dependent cellular cytotoxicity (ADCC). We hypothesized that a stronger host immune system prior to Zevalin therapy for relapsed follicular (grade 1&2) lymphomas (FL) would result in an improved time to progression (TTP). As a surrogate marker of host immune status, we studied absolute lymphocyte count (ALC) prior to Zevalin therapy and its impact on TTP in relapsed FL patients. Methods: Between 1996 and 2006, 75 patients with relapsed FL were treated with single agent Zevalin (0.4 mCi/kg, maximum of 32 mCi) at the Mayo Clinic. ALC was obtained from the complete blood cell count prior to RIT. Results: The median age of the cohort was 60 years (range, 29–82 years). 36% (27/75) patients were rituximab refractory. The median TTP in all patients was 6.4 months (range, 1–99+ months). Univariately, ALC as a continuous (HR = 0.448, p < 0.006) or dichotomized [ALC = 1.0 x 109/l (HR = 0.684, p < 0.007)] variable was identified as a prognostic factor for TTP. Superior TTP was observed with an ALC = 1.0 x 109/l (N = 32) compared with an ALC < 1.0 x 109/l (N=43) (median: 12.4 months vs 6.5 months, respectively, p < 0.007). Both groups were balanced in regard to the Follicular Lymphoma International Prognostic Index (FLIPI). ALC, as a continuous (HR = 0.507, p < 0.02) or dichotomized [ALC = 1.0 x 109/l (HR = 0.697, p < 0.01)] variable was identified as an independent prognostic factor for TTP in the multivariate analysis when compared with FLIPI. In the ALC = 1.0 x 109/l group, 14/32 (44%) of FL patients achieved a TTP = 12 months compared to only 7/43 (16%) in the ALC < 1.0 x 109/l group, (p < 0.02). Conclusions: This study supports our hypothesis that a higher ALC, as a marker of immune status of the patient, predicts longer TTP following Zevalin therapy in relapsed FL. No significant financial relationships to disclose.

Background: Neurolymphomatosis (NL) is a highly rare disorder defined as infiltration of peripheral nervous system by a lymphoproliferative neoplasm, both presented as the first manifestation of the malignancy (primary NL) or as a site of disease progression or relapse (secondary NL). Due to rarity of this disorder data on clinical features, best approach and outcome are limited. Furthermore diagnosis of this disease is often uncertain and based on radiological images only. Methods: We retrospectively reviewed clinical records of all histologically confirmed-NL, diagnosed and treated at the Division of Hematology of Mayo Clinic in Rochester, MN between January 2002 and December 2018. Clinical features and outcome were analyzed. Responses to therapy were assessed by post-treatment radiological changes and clinical symptoms improvement. Survival analysis such as progression free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier curves with log-rank test. Comparison between subgroups was investigated using Fisher's exact test and Wilcoxon test for categorical and continuous variables, respectively. Results: Over a 16-year period 40 patients with biopsy-proven NL were included in study. Primary and secondary NL were 19 (48%) and 21 (52%) respectively, with a median age of 60.5 years (range 37-83) and male sex 24/40 (60%). The predominant histology was represented by B-cell lymphomas (39/40, 97%) with a vast majority large B-cell lymphoma (LBCL) 27/40 (67%) and only 1 case of T-cell lymphoma. The affected structures included brachial plexus (12/40, 35%), lumbosacral plexus (5/40, 12%), cauda equine and nerve roots (14/40, 35%), sciatic nerve (12/40, 30%), femoral nerve (4/40, 10%), cranial nerves (8/40, 20%), multiple nerves involved in 23/40 (57%). Four out of 40 cases had brain involvement and cerebrospinal fluid (CSF) was positive in 7/29 (24%). NL clinical manifestations included muscular weakness (33/4, 82%), sensory deficit (32/40, 80%), pain (28/40, 70%) and autonomic dysfunction (3/40, 7%). Magnetic resonance imaging (MRI) detected neural abnormalities in 35/36 cases (97%), CT imaging identified disease in 3/8 (37%) and FDG-PET scan was positive in 22/31 (71%); electromyography showed some grade of neuropathy in 28/29 (97%). Treatment included systemic chemotherapy in 38/40 (95%) cases, containing high dose methotrexate (HD-MTX) in 26/40 (65%) and rituximab in 20/40 (50%); 11/39 (28%) patients underwent consolidative autologous stem cell transplant (ASCT); 4/40 received consolidative radiotherapy (RT), 1/40 was treated with RT alone; intrathecal chemotherapy was infused in 1/40 cases; one patient with solely great auricular nerve NL involvement was cured with surgery only. Treatment efficacy evaluated by imaging and clinical improvement consisted with an overall response rate (ORR) of 73% (27/37) with a 24% (9/37) of complete remission (CR); No statistical difference in rate of response was observed by different systemic treatments. Of note, patients undergoing HDC-ASCT consolidation obtained 100% of ORR (n=10) versus 61.5% (n=16) achieved by others (P=0.03). With a median follow up of 45.1 months (range 0.5-186.7) a 36 months-OS of 77% (95% CI, 60-88) was observed for the whole cohort. A trend of longer survival rate for primary NL was observed, with a 36-month OS of 95% (95% CI, 72-99) vs. 55% (95% CI, 30-77) for secondary NL (p 0.134). A strong benefit in terms of outcome was observed for patients receiving rituximab-containing regimens with a 36 months-PFS of 72% (95% CI, 55-92) vs 28% (95% CI, 12-53) (P=0.001), and a 36 months-OS of 87% (CI 95%, 60-98) vs. 65% (95% CI , 41-84) (P=0.04) (figure 1); no survival difference was observed for patients treated with systemic therapy containing HD-MTX vs. others. ASCT consolidation was associated with a trend of improved survival with a 36 months-PFS of 69% (95% CI, 35-90) vs. 47% (95% CI, 29-66) for others (P=0.09). Conclusions: With the limit of a retrospective analysis, LBCL represent the predominant histologic subtype of NL; MRI and FGD-PET appeared to be the most accurate radiological tools to detect neural disease. Systemic treatments including rituximab should be preferred, HD-MTX seems to be not so effective while ASCT consolidation may be considered in selected patients. Due to the spare number of cases treated with RT its role cannot be clarified by our study. Disclosures Nowakowski: NanoString: Research Funding; MorphoSys: Consultancy, Research Funding; Genentech, Inc.: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Curis: Research Funding; Bayer: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Selvita: Membership on an entity's Board of Directors or advisory committees.

Background: Central nervous system (CNS) involvement by peripheral T cell lymphoma (PTCL) is a rare condition. Among primary CNS lymphomas, only 2% are secondary to PTCL, while the risk of CNS relapse in all cases of PTCL is estimated at 2% to 6%. Little is known about the presentation and outcomes of PTCL patients with CNS involvement given the rarity of this entity. In this study, we describe patient characteristics, histology, and clinical course of patients with CNS involvement by PTCL. Methods: The Mayo Clinic Lymphoma Database was used to identify PTCL patients with primary or secondary CNS involvement seen at our institution between 2000 and 2018. A total of 12 patients were identified and their medical records were reviewed for patient and disease characteristics, CNS-directed treatment modality, and outcomes. The Kaplan-Meier method was used for time-to-event analysis. Results: The median age at CNS diagnosis was 63 years (range 41 to 76) and 11 (93%) patients were male. The histological diagnoses were PTCL, NOS in 9 (75%) patients, enteropathy-associated T-cell lymphoma in 2 (17%) patients, and angioimmunoblastic T-cell lymphoma in 1 (8%) patient. Five patients presented with primary T-cell CNS lymphoma (all with a PTCL, NOS histology), while the remaining 7 (58%) patients also had systemic involvement. All patients presented with neurologic symptoms at the time of CNS involvement diagnosis including: focal motor deficits in 6 patients (unilateral upper extremity weakness, gait impairments, and hemiparesis), cognitive decline in 5 patients (memory impairments, reduced attention, and confusion), headache in 4 patients, and seizure in 3 patients. The CNS disease location included the brain parenchyma in 9 (75%) patients, leptomeninges in 1 (8%) patient, and lumbar plexus in 1 (8%) patient. One patient (8%) had positive CSF finding only without radiologic evidence of involvement. CSF analysis was performed in 11 patients. Elevated protein levels were noted in 3 (27%) patients, malignant cells in 2 (18%), and no clear abnormalities in the remaining 6 (55%) patients. Concomitant bone marrow involvement was seen in only 1 patient. Elevated LDH was seen in 2 patients. The a median LDH was 195 U/L (range 139 to 4,360) The most common CNS-directed therapies were: high-dose methotrexate (MTX)-based regimens in 8 (67%) patients, including high-dose MTX in combination with temozolomide (n=2), or cytarabine and thiotepa (n=2). Intrathecal MTX, temozolomide and dexamethasone, lenalidomide, high-dose steroids, and surgical resection were the treatment modality used for one patient each. At a median follow up of 18 months, eight (75%) out of 12 patients were not alive at the time of last follow up. The median overall survival (OS) from diagnosis was 16 months (95% CI: 2.8-173). The median progression free survival (PFS) from initiation of CNS-directed therapy was 9 months (95% CI: 1.6-33) (figure). Four patients had a PFS longer than 12 months. These 4 patients were treated with: temozolomide/dexamethasone, high-dose MTX, lenalidomide, and high-dose MTX followed by cytarabine/thiothepa. Conclusion: CNS involvement by T-cell lymphoma is a rare complication that carries a poor prognosis. Early onset of neurologic symptoms should trigger prompt investigation of CNS involvement. Despite the short OS and PFS, some patients may achieve a relatively longer disease free interval. Disclosures Bennani: Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Seattle Genetics: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Adicet Bio: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Kite Pharma: Other: Advisory board. Cerhan:Celgene: Research Funding; NanoString: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Nowakowski:Celgene: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Curis: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Genentech, Inc.: Research Funding; MorphoSys: Consultancy, Research Funding; NanoString: Research Funding; Selvita: Membership on an entity's Board of Directors or advisory committees. Ansell:Mayo Clinic Rochester: Employment; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding. Paludo:Celgene: Research Funding; Verily Life Sciences: Research Funding; Verily Life Sciences: Research Funding; Celgene: Research Funding.