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Gandhi, Sangeetha

A5020191332 | I1330342723

Mayo Clinic

Mayo Clinic

Citations 17

Association of lymphocyte to monocyte ratio with clinical response and survival in patients with relapsed, aggressive non-Hodgkin lymphoma treated with axicabtagene ciloleucel CAR-T.

Journal of Clinical Oncology | May 25, 2020 | Volume: 38 | Issue: 15_suppl | Pages: 3028-3028

10.1200/jco.2020.38.15_suppl.3028

3028 Background: Chimeric antigen receptor T-cell (CAR-T) therapy induces complete remission (CR) in 30-40% of patients with non-Hodgkin lymphoma (NHL). However, for patients who do not achieve CR as their first response, predictors for achieving CR as best response can guide management between careful observation or early intervention. Increased absolute lymphocyte count to absolute monocyte count ratio (ALC/AMC) predicts better response rates and survival in NHL patients receiving chemotherapy and/or autologous stem cell transplant. We evaluated the prognostic impact of ALC/AMC in CAR-T therapy for NHL. Methods: This was a retrospective review of patients who received CAR-T for NHL from June 2016-August 2019. ALC/AMC was assessed at the start of lymphodepletion (LD) chemotherapy. The receiver operator curve (ROC) was used to determine the best cutoff for ALC/AMC in predicting CR at 3 months. Event-free survival (EFS) was defined from time of CAR-T infusion to relapse or death, whichever occurred first. Overall survival (OS) was defined from time of infusion to death of any cause. Results: Forty-seven patients received axicabtagene ciloleucel, with a median follow-up of 14 months. By ROC, ALC/AMC > 0.8 before LD chemotherapy was predictive of achieving CR at 3 months. Baseline characteristics were similar between the high (n = 30) and low (n = 17) ALC/AMC groups. Patients with an ALC/AMC > 0.8 at the time of LD chemotherapy were more likely to achieve CR at 3 months (46% vs. 12%, p = 0.01), 6 months (52% vs. 0%, p < 0.0005), and 12 months (42% vs. 0%, p = 0.01). Correspondingly, the EFS and OS were significantly shorter in patients with ALC/AMC≤0.8 vs. those > 0.8 (median EFS: 2 vs. 13 months, P < 0.0001) and (median OS: 15 months vs. not reached, P = 0.03), respectively. Association between ALC/AMC ratio and EFS and OS remained consistent in multivariate Cox models after adjusting for other prognostic variables, including abnormal lactate dehydrogenase and increased ferritin level at infusion day. Conclusions: ALC/AMC > 0.8 before lymphodepletion chemotherapy is a strong predictor for complete remission as well as improved event-free and overall survival for axicabtagene ciloleucel in NHL.
Elevated serum lactate in lymphoma: Not always infection.

Journal of Clinical Oncology | March 12, 2020 | Volume: 37 | Issue: 15_suppl | Pages: e19039-e19039

10.1200/jco.2019.37.15_suppl.e19039

e19039 Background: In patients with lymphoma, lactate dehydrogenase (LDH) is an important prognostic marker. Serum lactate can also be elevated due to hypermetabolism from aggressive lymphoma. We have observed critically ill lymphoma patients with elevated serum lactate who had a delay in the diagnosis and treatment of their underlying lymphoma because the cause of the elevated lactate was presumed to be infection. This clinical observation led us to perform a study to evaluate the relationship between serum lactate and LDH levels in lymphoma patients. Methods: We used the Mayo Clinic Lymphoma Database to search for patients with lymphoma and elevated lactate during a recent two year time period, January 2014 through December 2015. Fifty patients met these initial criteria and underwent medical chart review. The patients were divided into two groups – those with documented infection (SepsisLA group) and those without infection (all cultures negative) where the elevated lactate was due to lymphoma hypermetabolism (LymLA group). The Wilcoxon/Kruskal-Wallis test was used to compare the SepsisLA and LymLA groups. Kaplan-Meier analysis was used to estimate survival. Results: The mean age of the 66 patients was 65 ± 14.8 years and 60% were male. At the time of presentation, the mean lactate and LDH values were 4.5 ± 2.81mmol/L (UNL < 2 mmol/L) and 835.1 ± 1741.4 U/L (UNL < 222 U/L), respectively. 64% (32/50) of patients had elevated LDH values. After review, 32 (64%) patients were in the SepsisLA group; 18 (36%) were in the LymLA group. DLBCL was the most common disease type in both the SepsisLA (50%; 16/32) and LymLA (88%; 16/18). The sepsisLA and LymLA groups were not significantly different in terms of age, sex, lactate levels, or maxSUV on PET scan (N = 13). However, patients in the LymLA group did have higher LDH values (p = 0.02) compared to those with SepsisLA. Patients with LymLA had a reduced overall survival (OS) (1.45 median months) compared to those with SepsisLA (7.83 median months) p = 0.02. Conclusions: This study demonstrates that the level of lactate elevation is not helpful indiscriminating SepsisLA vs LymLA; however an elevated LDH with elevated lactate is more likely LymLA. Lymphoma pts with LymLA had an inferior survival compared to SepsisLA. We are unable to define the true incidence and prognostic value of elevated serum lactate in lymphoma; this will require a prospective study with fresh samples. In summary, lymphoma activity can masquerade as infection with elevated lactate. Once sepsis is ruled out, treatment for the lymphoma should not be delayed as this presentation portends poor prognosis.
Baseline Hypoalbuminemia Does Not Appear to be an Adverse Prognostic Factor in Patients with Relapse/Refractory B-Cell Lymphomas Treated with Axicabtagene Ciloleucel (axi-cel)

Blood | November 14, 2019 | Volume: 134 | Issue: Supplement_1 | Pages: 5343-5343

10.1182/blood-2019-126594

BACKGROUND: Axi-cel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for treatment of relapsed/refractory (R/R) large B-cell lymphoma and is associated with high response rates and durable remissions. Recent data show that axi-cel is effective across various adverse prognostic features, namely cell of origin, disease bulkiness, and extranodal disease, among others. Hypoalbuminemia is a known adverse prognostic factor in lymphomas. It is unknown if axi-cel overcomes the adverse prognostic feature of hypoalbuminemia in R/R large B-cell or transformed follicular lymphoma. METHODS: We conducted a retrospective analysis of patients treated with axi-cel across three Mayo Clinic campuses (Rochester, Jacksonville, and Phoenix) from 06/01/2018 until 04/01/2019. The primary objective of this analysis was to assess the impact of hypoalbuminemia (defined at day 0, prior to infusion) on outcome after axi-cel therapy. RESULTS: A total of 50 (male=37, 74%) patients (pts), median age of 53 (26-67) years received axi-cel. The median number of prior lines of therapy was 3 (2-8) (Table 1). Two pts had no available serum albumin levels at time of axi-cel infusion. Seven (15%) of 48 pts had serum albumin levels lower than 3.5 g/dL (median= 3.3 g/dL (range 2.6-3.4)) and the median follow up of survivors was 7.6 (1.9-14.3) months. The best overall response rate (ORR) and complete remission (CR) rates in these pts were 57% and 57%, respectively. One (14%) patient had stable disease and 2 (29%) had disease progression. The median overall survival (OS) for pts with hypoalbuminemia was not reached. On the other hand, 41 (85%) pts had a normal serum albumin level (median=4.0 (range 3.5-5.1) g/dL) and the median follow up for survivors was 6.3 months. The best objective response rate (ORR) and complete remission (CR) rates in these pts were 82% and 44%, respectively. The median OS for pts with normal serum albumin was 14 (95%CI=6.3-29.6) months. There was no significant difference at 6-months and 1-year OS between pts with hypoalbuminemia vs. those with normal baseline serum albumin levels [6-month=100% vs. 79%(95%CI=64-93%); 1-year (100% vs. 54% (95%CI=26-82%), p=0.17] (Figure 1). All grades cytokine release syndrome (CRS) was diagnosed in all 7 pts with hypoalbuminemia (100%) and in 38 of 41 (92%) pts without hypoalbuminemia. There was no difference in the median duration of CRS between pts with or without hypoalbuminemia [6 (range 1-11) days vs 5 (range 1-19) days, p=0.89]. Neurotoxicity (all grades) was observed in 5 (71%) pts with hypoalbuminemia compared 26 (63%) with normal albumin levels. There was no statistically significant difference in median duration of neurotoxicity between pts with hypoalbuminemia and those with normal baseline albumin levels [9 (range 1-10) days vs. 3 (range 0-25) days, p= 0.72]. CONCLUSIONS: Hypoalbuminemia does not have a significant impact on the outcomes of axi-cel therapy, including the incidence of CRS or neurotoxicity. These results need to be validated in a large collaborative multicenter study. Further investigation is needed to assess the prognostic impact of severe hypoalbuminemia (<3g/dL) on axi-cel therapy. Disclosures Ansell: Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Affimed: Research Funding. Bennani:Seattle Genetics: Other: Advisory board; Kite Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board. Paludo:Verily Life Sciences: Research Funding; Celgene: Research Funding; Verily Life Sciences: Research Funding; Celgene: Research Funding. Tun:DTRM Biopharma: Research Funding; Mundi-pharma: Research Funding; BMS: Research Funding; Celgene: Research Funding; Curis: Research Funding; TG Therapeutics: Research Funding. Foran:Agios: Honoraria, Research Funding. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy.
Central Nervous System Involvement in Peripheral T-Cell Lymphoma

Blood | November 14, 2019 | Volume: 134 | Issue: Supplement_1 | Pages: 5293-5293

10.1182/blood-2019-131965

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.
Peak Lymphocyte Count after CAR T Infusion Is a Clinically Accessible Test That Correlates with Clinical Response in Axicabtagene Ciloleucel Therapy for Lymphoma

Blood | November 14, 2019 | Volume: 134 | Issue: Supplement_1 | Pages: 4106-4106

10.1182/blood-2019-127094

Background: Two-year follow-up from ZUMA-1 trial for axicabtagene ciloleucel (axi-cel) CD19 chimeric antigen receptor T-cell (CART) in aggressive non-Hodgkin lymphoma (NHL) demonstrated that patients (pts) achieving complete remission (CR) as their best response have the longest progression free survival (PFS), while PFS remained poor for others. Majority of the best response are achieved by month 3 post-infusion. Moreover, a subset of pts who do not achieve CR by month 1 may still achieve CR while others will progress within months. Having a clinically available test to predict for durable response can assist clinicians in selecting pts who can be observed for continued response vs. those who may need intervention earlier. Peak CAR-T expansion has been correlated with best clinical response to axi-cel. However there is no clinically available test to quantify CART cells post treatment. Given the prolonged lymphotoxic effect of the lymphodepletion (LD) chemotherapy administered before CART infusion, we hypothesize that the peak expansion of absolute lymphocyte count (ALC, ALCpeak) after infusion likely corresponds to CART expansion. We examined for correlation between ALCpeak and clinical response at month 3 post-infusion for pts who received axi-cel. Methods: Data was collected from pts who received axi-cel between June 2016 and March 2019 at Mayo Clinic Rochester (NCT02348216, NCT03153462, and standard of care). All infused pts were included in the intention to treat analysis for response and event-free survival (EFS). Lugano 2014 criteria were used for clinical response. EFS was defined as the date of infusion until progression or death due to any cause and evaluated 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. Statistical analysis performed using JMP Pro 14.1. Results: Of the thirty-six NHL pts treated with axi-cel, the median age was 56 yrs (range 26-65); 78% (28) were male; 44% (16) had DLBCL; the median number of prior therapies was 3 (2-6), 47% (17) had stem cell transplant. Nineteen (53%) pts received bridging therapy after leukapheresis. All pts received fludarabine and cyclophosphamide for LD chemotherapy and achieved ALC nadir by the day of CART infusion (median 0.03 x 10^9/L, range 0.01-0.11). As CART expansion were found to peak within the first two weeks in ZUMA-1 trial, we examined ALC trend over 15 days post infusion and found that ALCpeak generally happened within the same timeframe (median ALCpeak day: 9, range 6-15). At 3 months post infusion, 33.3% (12/36) of pts achieved CR, 8.3% (3/36) pts were in partial remission (PR). No correlation was found between CR response and clinical characteristics: age >60 years, stage III/IV, B symptoms, elevated LDH, IPI score 3-4, number of previous treatments, use of bridging therapy, peak CRP and ferritin. However, the ALCpeak was significantly different between CR and non-CR pts (median, range: 1.09, 0.35-2.55; 0.67, 0.15-1.03; p=0.04). Using receiver operator curve (ROC)-derived area under the curve (AUC) estimates, ALCpeak 1.08 x 10^9/L was identified as the best threshold to discriminate patients at different likelihood to achieve CR at month 3. Pts achieving ALCpeak ≥ 1.08 showed a strong increased likelihood of achieving CR at month 3 (OR 2.8; 95% CI, 1.12-6.99; P=0.02). There was no statistical difference between the ALCpeak high and low groups in terms of use of bridging therapy, occurrence of any grade or higher grade cytokine release syndrome or neurotoxicity, or the use of tocilizumab or steroid. Interestingly, for pts who had changes in clinical response from month 1 to month 3, all 3 pts who converted to CR by month 3 had ALCpeak≥1.08, while the 13 of the 15 pts who had progressed by month 3 had ALCpeak<1.08. In addition, EFS was significantly different between pts who had ALCpeak above and below 1.08 (6 months EFS rate 75% vs. 25%, respectively, Figure 1). Conclusions: We found that the ALC expansion occurred in the first 15 days post axi-cel infusion, consistent with the known time frame for CART expansion. Higher ALCpeak level in this timeframe correlated with higher likelihood of achieving CR, and is associated with conversion to CR. This study is limited by the small sample size and limited follow-up, but the results are promising for further prospective investigation in a larger cohort of patients. Disclosures Paludo: Verily Life Sciences: Research Funding; Verily Life Sciences: Research Funding; Celgene: Research Funding; Celgene: Research Funding. Ansell:Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding. Bennani:Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Adicet Bio: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Adicet Bio: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Karyopharm: Research Funding; Rigel: Consultancy. Kapoor:Celgene: Honoraria; Janssen: Research Funding; Cellectar: Consultancy; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Glaxo Smith Kline: Research Funding. Kenderian:Novartis: Patents & Royalties, Research Funding; Tolero: Research Funding; Humanigen: Other: Scientific advisory board , Patents & Royalties, Research Funding; Lentigen: Research Funding; Morphosys: Research Funding; Kite/Gilead: Research Funding. Kumar:Takeda: Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.
Non-Diffuse Large B-Cell Primary Central Nervous System Lymphoma

Blood | October 14, 2019 | Volume: 132 | Issue: Supplement 1 | Pages: 4208-4208

10.1182/blood-2018-99-119741

Abstract Background: The majority of subjects with a diagnosis of primary central nervous system lymphoma (PCSNL) have diffuse large B-cell lymphoma (DLBCL) as their histology. However, there are a sub-set of PCSNL patients who present with other histologies. This retrospective study was conducted to evaluate histological morphology, risk factors and clinical course in subjects with non-diffuse large B-cell primary CNS lymphoma. Methods: We used the Mayo Clinic Lymphoma Database to search for patients with PCSNL during the time period from January 1995 to June 2018. One hundred and fifty nine patients met the criteria and underwent record review. One hundred and nine patients were excluded as they had PCSNL with DLBCL histology (N=47, 43%), secondary central nervous system lymphoma (N=56, 51%) and post-transplant lymphoproliferative disorders (PTLD) with DLBCL morphology (N=6, 5%). We identified fifty patients with PCSNL Non-DLBCL histology, by evaluating the biopsy reports. We abstracted clinical data and outcomes for these groups through medical chart review. Kaplan-Meier analysis was used to estimate survival. Results: The mean age of the study population was 70 ± 11.3 years and 66% were male. Of the 50 patients, the most common histology was low grade CNS lymphoma (N=14, 28%) while Hodgkin's lymphoma (N= 1, 2%), Burkitt's lymphoma (N= 1, 2%) and histiocytic lymphoma (N= 1, 2%) were the least common. The frequencies of other PCSNL Non-DLBCL histology are demonstrated in Table1. Most patients showed good ECOG performance status of 0-2 and four patients had ECOG performance status of grade 3 (N=4, 8%). Six of the patients were immunocompromised (N=6, 12%), PPD positive tuberculosis; corticosteroids and PTLD with DLBCL histology were the causes for the immunocompromised state. The location of the CNS lymphoma included brain (N=24, 50%); spinal cord (N=9, 18%); orbits (N=5, 10%); deep structures which included brainstem, cerebellum, cerebellopontine angle and cauda equina (N=5, 10%); leptomeninges (N=4, 8%) and neural involvement which included sciatic, peroneal and facial nerve (N=3, 6%). CSF examination revealed increased protein levels (N=10, 20%), malignant cells (N=11, 22%), negative cytology (N=14, 28%) and unknown or not done (N=15, 30%). Most patients presented with neurological symptoms such as seizures, peripheral neuropathy (numbness/weakness/tingling), headache, confusion & cognitive disturbances (memory changes), gait disturbances (difficulty with balance/ataxia), visual disturbances (blurry vision) and paraplegia, but none of them presented with B-cell symptoms such as fever, night sweats and weight loss. Treatment modalities included chemotherapy, radiation and surgery. Fourteen patients underwent radiation therapy (N=14, 28%); three of the patients had undergone surgery of which the patient with peripheral T-cell lymphoma had undergone a complete excision, the patient with marginal zone lymphoma had undergone debulking with subtotal craniotomy and the patient with MALT lymphoma had undergone resection with gamma knife. Table 2 demonstrates the various chemotherapy drugs used and the distribution of frequency of biopsy, radiation and surgical treatment in the different pathology of PCSNL Non-DLBCL. The median overall survival period using Kaplan-Meier analysis showed that Burkitt's Lymphoma had the least median time survival of less than a month and PTLD had the highest median survival of 146.25 months (p=0.0017). Table 3 shows the median survival time for all the different pathology's of PCSNL Non-DLBCL. Conclusion: This retrospective study reinforces the critical need for a histologic diagnosis when a patient is diagnosed with PCNSL. PCSNL is considered to be DLBCL but there are other histology's that could potentially be PCSNL and the treatment should be tailored to the individual patient's histology. Disclosures No relevant conflicts of interest to declare.
Anorectal pressures measured with high‐resolution manometry in healthy people—Normal values and asymptomatic pelvic floor dysfunction

Neurogastroenterology & Motility | April 8, 2019 | Volume: 31 | Issue: 7 | Pages: No page available

10.1111/nmo.13597 | PMID 30957382

AbstractBackgroundHigh‐resolution manometry (HRM) is used to measure rectoanal pressures in defecatory disorders and fecal incontinence. This study sought to define normal values for rectoanal HRM, ascertain the effects of age and BMI on rectoanal pressures, and compare pressures in asymptomatic women with normal and prolonged balloon expulsion time (BET).MethodsHigh‐resolution manometry pressures and BET were measured in 163 asymptomatic healthy participants. Women (96) and men (47) with normal BET were used to estimate normal values and the effects of age/BMI on pressures using a Medtronic 4.2‐mm‐diameter rectoanal catheter.Key ResultsAge is associated with lower resting pressure, higher rectal pressure during evacuation, and a higher rectoanal gradient during evacuation in women and men. In women, the BET is also inversely correlated with age while the BMI is correlated with a higher threshold volume for discomfort and a longer BET. The anal squeeze pressure increment, squeeze duration, and HPZ length are higher in men than women. The rectoanal gradient during evacuation is also lower (ie, more negative) in asymptomatic women with an abnormal than a normal BET.Conclusions & InferencesThese findings provide an expanded database of normal values for anorectal HRM in men and women. Age and sex affect anal resting and squeeze pressures, respectively; rectal pressure during evacuation is also higher in older people. Less than 15% of asymptomatic people have BET >60 seconds, which is associated with manometry features of impaired evacuation.