scholarly journals Derivation and Validation of the POD-IPI Score for Progression of T Cell Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4546-4546
Author(s):  
Linquan Zhan ◽  
Xiangxiang Zhou ◽  
Shunfeng Hu ◽  
Yiqing Cai ◽  
Tiange Lu ◽  
...  
Keyword(s):  
Regression Analysis ◽  
T Cell ◽  
Logistic Regression Model ◽  
Validation Cohort ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
T Cell Lymphoma ◽  
Training Cohort ◽  
Clinical Models ◽  
Validation Set

Abstract Background: Late years have witnessed that novel targeted treatment modalities are corroborated successful clinical applications in T cell lymphoma (TCL). Yet, there are a considerable proportion of patients suffering from relapse or progression of disease (POD). Early POD (ie, POD within 24 months) has been validated as a novel prognostic indicator in various pathological types of lymphoma. At present, the clinical function of early POD in TCL has not been explored with influencing factors unknown. Herein, we developed a novel risk stratification model for predicting early POD by integrating International Prognostic Index (IPI) score and serum total protein (TP) level. Methods: We retrospectively identified patients diagnosed with TCL in Shandong Provincial Hospital from Mar 2011 to Jan 2021. Patients aged≥18 years with confirmed tissue diagnosis of TCL were included and were divided into a training cohort and a validation cohort. The prognostic role of early POD was evaluated using Cox proportional hazards model. Univariate analysis was applied to identify covariates for a logistic regression model predicting early POD. A clinical point score was generated according to multivariate analysis. The predicting performance was assessed by validation cohort and compared to clinical models. Results: A total of 141 potentially eligible patients were identified. Overfitting was prevented by splitting the data into training (70%) and validation (30%) set. Median follow-up was 32 months. In the training cohort, the median age at diagnosis was 52.2 years (range 18-81), and 70 (67.3%) were under 60 years old. While in validation set, the median age was 55 years (range 21-77), among whom 73% were under 60. In both group combined, there was a male predominance (66.3% vs 73.0%). The most frequently had lymphoma that was NK/T-cell lymphoma (NKTCL) (31.7% vs 35.1%) with peripheral T-cell lymphoma (PTCL) (25.0% vs 24.3%) next. More than half of patients (51.0% vs 59.5%) suffered from early POD. In univariate and multivariate cox regression analysis, early POD was the most independent prognostic factor (p <0.001) with an adjusted HR for PFS of 310.708 (95% CI:27.625-3494.686) and for OS an adjusted HR of 23.416 (95% CI:8.178-67.05). K-M curve indicated a significant difference in both OS and PFS between early-POD and non-POD groups (Figure A). To ask whether early POD prediction could be made by analyzing clinical risk factors at diagnosis, univariate analysis in the training cohort identified variables significantly associated with early POD and were included into the multivariable logistic regression model that were 10-fold cross-validated. We found that IPI score, serum TP level were independent predictors for early POD (AUC 0.775, 95% CI, 0.683-0.866; p<0.001), and the Hosmer-Lemeshow test confirmed good calibration (p=0.635). In the validation set, the model remained strong predictive performance. Figures B, C showed the calibration curves and nomograms of early POD predicted by the model on training and validation cohorts, respectively. Cut-off points of TP level were determined by ROC analysis to simplify the risk model. Selected cut-off points were adjusted to the nearest whole integer to maximize ease of use. Eventually, two independent predictors (IPI score and serum TP≤64 g/L) of early POD were retained through multivariable regression analysis, and the risk score was then calculated for each factor according to the regression coefficient. This resulting algorithm was named as POD-IPI score. Afterwards, patients were stratified into 3 groups: low-risk (0 score, n=13, 12.5%), intermediate-risk (1-3 score, n=49, 47.1%), and high-risk (>3 score, n=42, 40.4%) groups. Compared to IPI score and NCCN-IPI score, the discriminative ability of the proposed score was good in the ROC, thereby outperforming existing clinical models in two cohorts (AUC=0.784, 95% CI: 0.695-0.873, AUC=0.809, 95% CI: 0.667-0.952, respectively). The outcomes of early POD by the stratification of POD-IPI score in training group were represented in Figure D. The curves were well separated, indicating the good discriminatory ability of this novel model. Conclusions: POD-IPI achieved a specific prediction of early POD in TCL patients, which was validated to allow for simplified stratification and comparison of risk distribution. Its use, together with clinical judgment, may provide guidelines on treatment decisions in TCL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Development and External Validation of a Prognostic Nomogram for Angioimmunoblastic T-Cell Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1440-1440
Author(s):  
Hua Wang ◽  
Bibo Fu ◽  
Guanjun Chen
Keyword(s):  
T Cell ◽  
Validation Cohort ◽  
Cell Lymphoma ◽  
External Validation ◽  
Prognostic Index ◽  
Curve Analysis ◽  
T Cell Lymphoma ◽  
Survival Prediction ◽  
Decision Curve Analysis ◽  
Training Cohort

Abstract Introduction: Heterogeneity exists in prognosis of Angioimmunoblastic T-cell lymphoma (AITL) patients. Thus, a personalized prognostic model is crucial for survival prediction for each AITL patient. Nomogram is a powerful mathematical tool to predict survival. In this study, we aimed to develop a prognostic nomogram for AITL based on data from a large clinical database and validate it in an independent external cohort. In addition, we compared the accuracy of the nomogram with previous prognostic models used in AITL including International Prognostic Index (IPI) and Prognostic Index of T-cell lymphoma (PIT) model. Methods: Totally, 1071 patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database as the training cohort; 156 patients diagnosed from 2009-2021 in Sun Yat-Sen University Cancer Center or The First Affiliated Hospital of Guangzhou Medical University were recruited as the external validation cohort. 105 patients with IPI information in the training cohort were used to compare the nomogram and IPI. 156 patients in the external cohort were used to compare the nomogram and IPI or PIT. The Prognostic risk factors in the nomogram were identified by cox proportional hazards model. Concordance index (C-index) and calibration curves were used for internal and external validation. C-index and decision curve analysis (DCA) curves were used to compare the models. Results: Age, sex, systematic symptoms, Ann Arbor stage and chemotherapy were risk factors finally included to develop the nomogram. C-indexes of the nomogram were 0.676 and 0.652 in the training cohort and the validation cohort. Favorable agreement of nomogram-predicted and actual probability of overall survival (OS) was detected by calibration curves in both training and validation cohorts. In the cohort of 105 patients, C-indexes of the nomogram and IPI were 0.696 vs 0.616 (P<0.05); in the cohort of 156 patients, C-indexes were 0.652 vs 0.597 (P=0.08) of the nomogram and IPI while 0.652 vs 0.616 (P=0.176) of the nomogram and PIT. Decision curve analysis (DCA) showed superiority of the nomogram as compared with the IPI or the PIT model in both 105 and 156 patients' cohorts. A web calculator was published for convenient clinical application. Based on the prognostic scores calculated by the nomogram, three cut points were identified by X-tile program to establish a classification system that could significantly distinguish patients in four risk groups. Conclusion: We establish a nomogram for survival prediction of AITL, which may assist in treatment strategy making and survival consultation. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

NK/T Cell Versus Peripheral T Cell Lymphoma: Significant Differences in Clinical Characteristics and Survival.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4600-4600
Author(s):  
Soon-Thye Lim ◽  
Fei Gao ◽  
Lay-Cheng Lim ◽  
Richard Quek ◽  
Daryl Lim ◽  
...  
Keyword(s):  
T Cell ◽  
Who Classification ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Advanced Stage ◽  
Peripheral T Cell Lymphoma ◽  
Nk T Cell

Abstract Background: To compare the clinico-pathologic characteristics and prognosis of Natural Killer/T cell lymphoma (NK/TL) with peripheral T cell lymphoma (PTCL). Methods: A total of 556 resident patients (pts) with lymphoma were treated in the departments of medical oncology and hematology in an Asian institution from 2000 to 2005. Of these pts, 71 (12.8%) had NK/TL or PTCL and were included in this analysis. Pathology was centrally reviewed and classified according to the WHO classification. Results: NK/TL and PTCL comprised of 4.7% (26/556) and 7.9% (45/556) of all cases. Of the PTCL cases, histology was PTCL-NOS in 21, anaplastic large cell in 12 (5 were ALK-1 positive) and angioimmunoblastic T cell in 8 pts. Subcutaneous panniculitis T cell and γ/δ T cell lymphoma accounted for one case each. There were no significant differences between the two groups of pts in terms of sex, performance status, extranodal involvement and LDH level at presentation. However, more patients with NK/TL presented with stage I/II disease (65% vs. 31%, p=0.003). Among pts with NK/TL, 17 (65%) received CHOP-based chemotherapy, 4 received radiation alone and 5 received palliative chemotherapy. In the PTCL group, 39 (87%) received CHOP-based chemotherapy, 2 received radiation alone and 3 received palliative treatment only. Compared to PTCL, NK/TL was associated with a significantly inferior rate of complete remission (27% vs. 58%, p=0.01) and inferior overall survival (5 vs. 28.4 mos, p=0.001). Although age > 60, ECOG ≥ 2, elevated LDH, advanced stage, IPI ≥ 2 and NK/T cell histology were each associated with decreased survival on univariate analysis, only NK/T cell histology and advanced stage were independently associated with decreased survival (see table 1). Conclusions: Contrary to expectation, the incidence of PTCL based on WHO classification in this Asian series is not higher than that reported in Western series. Compared to PTCL, the NK/T subtype is associated with a paricularly inferior prognosis and overrides the prognostic significance of IPI. These data suggest that NK/TL should be considered as a seperate entity and should not be considered together with other subtypes of T cell lymphoma in clinical trials. Table 1. NK/TL vs. PTCL: Univariate and Multivariate Analyses Univariate Analysis Multivariate Analysis Median (yr) P Hazard Ratio 95% CI P Male vs. Female 1.03 vs. Not reached 0.06 0.62 0.28 to 1.40 0.25 Age<60 vs. ≥ 60 2.37 vs. 0.51 0.01 1.41 0.70 to 2.83 0.33 ECOG 0/1 vs. ≥ 2 1.99 vs. 0.36 0.002 1.52 0.63 to 3.65 0.354 LDH normal vs. High Not reached vs. 0.75 0.03 1.29 0.53 to 3.13 0.57 Stage I/II vs. III/IV 1.99 vs. 1.41 0.16 2.91 1.17 to 7.2 0.02 IPI 0/1 vs. ≥ 2 Not Reached vs. 0.42 0.002 2.22 0.82 to 5.99 0.12 PTCL vs. NK/TL 2.37 vs. 0.42 0.001 5.8 2.36 to 14.24 <0.001

Clinical, Pathological, and Prognostic Characteristics Of Mature Nodal Or Extranodal T-Cell and NK-Cell Non-Hodgkin´s Lymphoma (NHL) In a Single Mexican Institution

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1763-1763
Author(s):  
Gladys P Agreda-Vásquez ◽  
Erick Crespo-Solis ◽  
Gustavo J Ramos-Blas ◽  
Cesar Lara-Torres ◽  
Carmen Lome-Maldonado ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
T Cell ◽  
High Risk ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Prognostic Index ◽  
T Cell Lymphoma ◽  
Number Of Patients ◽  
Who 2008

Abstract Background Mature nodal or extranodal T-cell and NK-cell NHL are a rare and heterogeneous group of NHL with aggressive behavior and poor clinical outcome. Their incidence varies according to geographical region and racial characteristics. Mexico is included in those countries known to have a high incidence of extranodal T/NK-cell lymphoma, type nasal (NKTCL). Objective To evaluate the outcome and prognosis of patients with mature nodal or extranodal T-cell or NK-cell NHL in a single institution in Mexico City. Methods Clinicopathological characteristic, treatment, outcome, and prognosis of patients admitted to our institution between August, 1991 and December 2009 were analyzed. Prognostic Index T-cell (PIT) was used in all subtypes of lymphomas except in NKTCL subtype. All tissue biopsies and immunophenotypic markers were reviewed by an expert hematopathologist and reclassified according to the WHO 2008 classification. Univariate analysis using log-rank test was used to determine the correlation between clinical features and overall survival (OS). Multivariate analysis using Cox proportional hazard models were performed. A p value < 0.05 was considered significant. Results A total of 67 patients were analyzed. Median age was 37 years. B symptoms were presented in 83.6%, 74.6% had at least one site with extranodal disease, 73.1% advanced clinic stage, 32.8% high risk by International Prognostic Index (IPI) and 47.5% high risk by PIT. According to WHO 2008 classification the most common subtype was peripheral T-cell lymphoma not otherwise (PTCL NOS) specified in 38 patients (56.7 %), angioimmunoblastic T-cell lymphoma (AITL) and NKTCL were the second most common subtypes with 8 cases in each group (11.9 %), anaplastic large cell lymphoma (ALCL) kinase-positive (ALK-positive) was identified in 3 patients (4.5 %), ALCL ALK-negative in 2 cases (3.0 %), lymphoblastic lymphoma and subcutaneous panniculitis-like T-cell lymphoma (SPTCL) with 3 patients in each group (4.5 %), hepatosplenic T-cell lymphoma (HSTL) and aggressive NK-cell leukemia with one case in each group (1.5 %). CHOP-like therapy was used in 71.6 % of patients. Nine percent of patients did not receive treatment. The response was evaluated in 53 patients in whom overall response was 71.7 % with 44.8 % achieving complete remission (CR). Median OS was 2760 days (CI 95 % 1153.145-4366.855). Histopathology subtype did not predict OS. Both prognostic scores, IPI and PIT, were able to identify 4 groups of patients with different outcomes. The analysis failed to demonstrate any advantage of adding etoposide to the chemotherapy schedule. Multivariate analysis showed that, IPI, PIT, and CR were predictive for OS (Table 1). Conclusion Previous publications in Mexican population, with larger number of patients included, were particularly focus on clinical characteristics and prognosis of NKTCL. Our series provides data of mature nodal or extranodal T-cell and NK-cell NHL in Mexico. The current study confirms the poor prognosis of aggressive forms of mature nodal or extranodal T-cell and NK-cell NHL regardless of the chemotherapy schedule employed. Disclosures: No relevant conflicts of interest to declare.

Prognostic value of different B symptoms in upper aerodigestive tract NK/T-cell lymphoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19544-e19544
Author(s):  
J. Xiao ◽  
C. Guo ◽  
L. Zhai ◽  
H. Li ◽  
X. Fu ◽  
...  
Keyword(s):  
Weight Loss ◽  
T Cell ◽  
Prognostic Value ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Night Sweat ◽  
Aerodigestive Tract ◽  
T Cell Lymphoma ◽  
Upper Aerodigestive Tract ◽  
Ann Arbor

e19544 Background: Extranodal NK/T-cell lymphoma (ENKL) is a rare disease originated from NK or toxic T cells. ENKL arising from the upper aerodigestive tract (UNKTL) is a newly recognized subtype and commonly presents with B symptoms. This study is to investigate the prognostic value of different B symptoms in UNKTL. Methods: UNKTL cases with detailed clinical, pathological and prognostic data in our center since 2001 to 2007 were retrospectively analyzed with the major study endpoint of overall survival (OS). Central pathological review was performed. Survival curves were estimated by Kaplan-Meier method and tested by Log Rank method. Statistically significant factors in univariate analysis were then included in multivariate analysis. B symptoms were defined as fever, night sweat and weight loss according to the Ann Arbor Cotswolds meeting. The predictive values of survival for each type of B symptoms were studied independently. Results: 172 cases of UNKTL with a median follow-up duration of 27.4 months were included. 45 ladies and 127 gentlemen had a median age of 43 years. 98 cases were Ann Arbor stage I, 54 were stage II and the remaining 20 cases were stage III or IV. About half of the patients present B symptoms: 82 had fever, 5 had night sweat and 6 present weight loss. Totally 18 patients had ECOG PS larger than 1. The 5-year OS rate of the whole group is 41.8%. Patients with persistent fever before treatment indicated a poor outcome in the univariate analysis (p=.033) and its prognostic value was also confirmed by the Cox regression (p=.030) whereas those of night sweat and weight loss were not (p= .960 and .824 respectively). Conclusions: B symptoms were common in UNKTL patients. Our data suggested that only fever among the three types of B symptoms was independent prognostic factor for UNKTL but it still needs further confirmation. No significant financial relationships to disclose.

scholarly journals Baseline and interim functional imaging with PET effectively risk stratifies patients with peripheral T-cell lymphoma

2019 ◽  
Vol 3 (2) ◽  
pp. 187-197 ◽  
Author(s):  
Neha Mehta-Shah ◽  
Kimiteru Ito ◽  
Kurt Bantilan ◽  
Alison J. Moskowitz ◽  
Craig Sauter ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
T Cell ◽  
Confidence Interval ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Standardized Uptake Value ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma

Abstract The prognosis of peripheral T-cell lymphoma (PTCL) is heterogenous. Baseline or interim imaging characteristics may inform risk-adapted treatment paradigms. We identified 112 patients with PTCL who were consecutively treated with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)/CHOP-like regimens with the intent to consolidate with an autologous transplant. Baseline (n = 93) and interim (after 4 cycles, n = 99) positron emission tomography (PET) images were reevaluated, and we calculated baseline total metabolic tumor volume (TMTV). Interim PET (iPET) responses were graded visually by 5-point score (i5PS) and by percentage change of standardized uptake value. By univariate analysis, predictors of event-free survival (EFS) included Prognostic Index for Peripheral TCL (PIT) higher than 1 (hazard ratio [HR], 1.83; P = .021), International Prognostic Index (IPI) higher than 3 (HR, 2.01; P = .021), high TMTV (&gt;125 cm3; HR, 3.92; P = .003), and positive iPET (HR, 3.57; P &lt; .001). By multivariate analysis, high baseline TMTV predicted worse overall survival (OS; HR, 6.025; P = .022) and EFS (HR, 3.861; P = .005). Patients with i5PS of 1 to 3 had a longer median OS and EFS (104 months, 64 months) than those with i5PS of 4 to 5 (19 months, 11 months; P &lt; .001). Four-year OS and EFS for patients with i5PS of 1 to 3 and PIT of 1 or less were 85% and 62%, respectively. However, 4-year OS and EFS for those with i5PS of 4 to 5 and PIT higher than 1 were both 0% (P &lt; .001). In multivariate analysis, after controlling for IPI and PIT, i5PS was independently prognostic for EFS (HR, 3.400 95% confidence interval, 1.750-6.750; P &lt; .001) and OS (HR, 10.243; 95% confidence interval, 4.052-25.891; P &lt; .001). In conjunction with clinical parameters, iPET helps risk stratify patients with PTCL and could inform risk-adapted treatment strategies. Prospective studies are needed to confirm these findings.

AMG 319, a Novel Inhibitor of Phosphoinositide-3 Kinase Delta (PI3Kd), Demonstrates Activity in Lymphoma Pre-Clinical Models

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3718-3718 ◽  
Author(s):  
Amanda Herko ◽  
Cory Mavis ◽  
Myron S. Czuczman ◽  
Francisco Hernandez
Keyword(s):  
T Cell ◽  
B Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Primary Tumor ◽  
Cell Lymphoma ◽  
Single Agent ◽  
T Cell Lymphoma ◽  
Clinical Models

Abstract Abstract 3718 The PI3k/AKT/mTOR signaling pathway has been found to be deregulated in patients with various subtypes of B-cell lymphoma including mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL). Targeting this particular pathway has been evaluated in multiple pre-clinical models and clinical trials using pharmacological inhibitors with variable degrees of success. More selective and potent PI3K inhibitors, such as AMG 319 are being developed and need proper evaluation in currently relevant pre-clinical models (i.e. rituximab resistant models). To this end, we evaluated the activity of AMG 319 as a single agent or in combination with monoclonal antibodies, targeted agents and chemotherapy drugs in a panel of rituximab-sensitive (RSCL), rituximab-resistant cell lines (RRCL) and primary lymphoma cells isolated from patients with treatment naïve or relapsed/refractory (rel/ref) B- and T-cell lymphoma. Furthermore, we attempted to characterize the cell death pathways executed following in vitro exposure to AMG 319. RSCL, RRCL, T-cell lymphoma, Hodgkin's lymphoma (HL) and MCL cell lines were exposed to escalating doses of AMG 319 (0.1 to 100μM). Isolated primary lymphoma cells were exposed to lower doses of AMG 319 (1 and 10μM) as a single agent and in combination with bortezomib (BTZ) (5–10nM). Cell viability was determined utilizing presto blue and cell titer glo assays. 51Cr release studies were conducted to assess the effect of AMG 319 in rituximab or ofatumumab immunological activity. Lymphoma cell lines were exposed to AMG 319 (10μM) or DMSO (0.1%) for 48 hours. Subsequently cells were labeled with 51Cr and exposed to rituximab, ofatumumab or isotype control with human serum (25%) or effector cells isolated from healthy donors (effector/target ratio 40/1). Finally, to characterize the contribution of the intrinsic apoptotic pathway to AMG 319 activity, primary tumor cells isolated from lymphoma patients were exposed to AMG 319 with or without a pan-caspase inhibitor (Q-VD-Oph, 5μM) and changes in cell viability were detected. AMG 319 exhibited dose-dependant activity as a single agent against various cell lines including RSCL, RRCL, MCL and T-cell lymphoma cell lines. In addition, AMG 319 induced cell death in primary tumor cells (N=5) at lower doses than in cell lines. Preliminary experiments suggest a synergistic activity when AMG 319 is combined with BTZ in vitro, although further analysis is required with a larger number of primary tumor cell samples. Pre-exposure of one RRCL and one RSCL to AMG 319 enhanced the biological activity of rituximab and ofatumumab in terms of antibody dependent cellular cytotoxicity (ADCC) or complement mediated cytotoxicity (CMC), and further investigations with additional cell lines are ongoing. Finally, caspase inhibition diminished AMG 319 activity in primary tumor cells in vitro, suggesting that induction of apoptosis via the mitochondrial pathway plays a role in its anti-tumor activity. Our data suggests that AMG 319 as a single agent is active against NHL cells and potentiate the anti-tumor activity of BTZ and to a lesser degree monoclonal antibodies targeting CD20 antigen. Ongoing studies are aimed to evaluate AMG 319 in combination with chemotherapy agents in order to better optimize the activity of this novel PI3 kinase delta inhibitor in B-cell and T-cell lymphomas. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Atypical Immunophenotype Predicts Worse Prognosis in Adult T-Cell Lymphoma/Leukemia: A Retrospective Study of 63 Caribbean Patients at a New York City Tertiary Center

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2906-2906 ◽  
Author(s):  
Bachar Samra ◽  
Edwin Chiu ◽  
Bo Lin ◽  
Eric Tam ◽  
Babak Baseri ◽  
...  
Keyword(s):  
New York ◽  
Bone Marrow ◽  
T Cell ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Aggressive Disease ◽  
Tertiary Center ◽  
The Caribbean

Abstract Background: Adult T-Cell Lymphoma/Leukemia (ATLL) is a rare and aggressive HTLV-1 related peripheral T-cell lymphoma that occurs predominantly in Japan and the Caribbean basin. Acute (A) and lymphomatous (L) subtypes are the most aggressive forms with a median overall survival (OS) of 6-12 months despite chemotherapy. Typical immunophenotype (IP) of ATLL is CD4+/CD8- with strong co-expression of CD25. Atypical IP has been reported in ~10-20% of cases, and has been linked to a more aggressive disease in rare Japanese case reports. However, little literature exists on the Caribbean population. Kings County Hospital (KCH) and University Hospital of Brooklyn (UHB) serve a big Caribbean community in Brooklyn, New York. Our primary objective is to describe the clinicopathologic characteristics and treatment outcomes of our Caribbean patients. We also aim to evaluate the effect of IP on prognosis. Methods: We conducted a retrospective analysis of all patients diagnosed with HLTV1+ ATLL at KCH and UHB between 2005 and 2017. Diagnosis of ATLL was established based on clinical history, pathological findings and HTLV1 serum positivity. We included patients with A and L subtypes only. IP was based on flow cytometry from peripheral blood and/or immunostaining from lymph node biopsy. For the univariate analysis, outcomes were calculated using the log-rank test, and survival curves were estimated by Kaplan-Meier method. Results: We identified 63 patients with A and L subtypes. The median age was 54 with female predominance (65%). A and L subtypes were noted in 55% and 45% of patients respectively, and 95% had Ann Arbor stage III/IV. Two patients transformed to A subtype from chronic disease, and one patient transformed to L subtype from smoldering disease. Organ involvement at presentation was as follows: lymphadenopathy (80%), bone marrow (63%), hepatomegaly (25%), skin lesions (24%), bone lesions (23%), splenomegaly (21%), pleural effusions (14%), lung (11%), and CNS (8%). Hypercalcemia was noted in 47%, and only 4 patients had normal LDH. Out of 26 patients with a reported karyotype, 8 patients had abnormal cytogenetics (31%). Most patients received upfront EPOCH (78%) or CHOP chemotherapy (14%). The objective response rate (ORR) was 47% (complete response [CR] 16%, partial response [PR] 31%) and stable disease (SD) was achieved in 14%. None of the patients received antiviral therapy or consolidative stem cell transplant. The median duration of response was 2.1 months. The median OS was 5.8 months and median progression-free survival (PFS) was 4 months. Strikingly, 4 patients survived beyond 3 years including two who remain alive at 5+ years without further therapy. Of patients with relapsed/refractory (R/R) disease (85%), 35 patients (66%) received 2nd line treatment (mostly ICE chemotherapy: 27%). ORR was 21% (1 CR and 6 PR) and another patient had SD. For R/R patients, the median OS was 2.2 months and median PFS was 2 months. Univariate analysis showed that the following factors were associated with shorter OS and PFS: LDH > twice the upper limit of normal (p=0.002 and <0.001, respectively), bone marrow involvement (p<0.001), hypercalcemia >13 mg/dl (p<0.001), and absence of response to first line chemotherapy (p<0.001). Abnormal cytogenetics correlated with shorter PFS (p=0.04) but not OS (p=0.13). 14 patients had atypical IP (32%) with the following distribution: CD4- (3 patients), CD4+/CD8+ (3 patients), CD4-/CD8- (2 patients), CD25 dim (5 patients) and CD25- (1 patient). Among those who received chemotherapy, atypical IP was associated with shorter OS (p=0.04) and PFS (p=0.04) (Figure 1). Normal LDH correlated with OS beyond 1 year. Conclusion: Our large cohort of Caribbean patients with acute and lymphomatous subtypes of ATLL suggests a chemo-refractory and more aggressive disease compared with Japanese population, highlighting the need for novel therapies. In our patient population, incidence of atypical immunophenotype was higher than previously reported and was associated with worse PFS and OS. Disclosures: No relevant conflicts of interests to declare. Disclosures No relevant conflicts of interest to declare.

International Prognostic Index, Serum IgA Level, and Monocytes Count Are Independently Associated with Overall Survival in Patients with HTLV-I-Negative Nodal Peripheral T-Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1577-1577
Author(s):  
Aiko Kato ◽  
Yukihiro Imai ◽  
June Takeda ◽  
Nobuhiko Yamauchi ◽  
Yuki Funayama ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Prognostic Score ◽  
Univariate Analysis ◽  
Bone Marrow Involvement ◽  
Prognostic Index ◽  
T Cell Lymphoma ◽  
Poor Survival ◽  
Risk Of Death ◽  
Serum Iga

Abstract Abstract 1577 Introduction: Except for minor subtypes of disease with prolonged clinical courses, peripheral T cell lymphoma (PTCL) is clinically aggressive and associated with poor survival. Although the International Prognostic Index (IPI) and the PTCL prognostic index (PIT) are used for prognostic stratification, their predictive utility is in need of improvement. PTCL can be subdivided into two types, nodal and extra-nodal, the latter of which is composed of diseases with characteristic clinical presentations. The nodal group includes PTCL not otherwise specified (NOS), angioimmunoblastic T cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), and adult T cell leukemia (ATL). While ATL is a distinct disease caused by HTLV-I, the remaining three diseases have several characteristics in common, and their differential diagnosis is sometimes difficult. Patients and Methods: Patients who were newly diagnosed with biopsy-proven, HTLV-I-negative nodal PTCL and referred to our institution between May 1994 and February 2012 were retrospectively analyzed. Patients treated with regimens not intended to induce remission, as well as those with insufficient clinical data, were excluded. This study was Institutional Review Board-approved and complied with the Declaration of Helsinki. The diagnoses were primarily based on histopathology, and in select instances, molecular and immunological analysis was used to support the diagnosis. The overall survival rate (OS) and progression-free survival rate (PFS) were calculated using the Kaplan-Meier method and significance was determined by log-rank test. Univariate and multivariate analyses were performed with the Cox proportional hazards regression model. Results: A total of 77 patients, including 50 PTCL-NOS, 17 AITL, and 10 ALCL patients, 5 of whom were ALK-positive, were identified. The median follow-up time for survivors was 49 months. The median age was 65 years (range, 23–83), and there was a male predominance (male/female ratio: 1.95). 61 had advanced stage (stage III/IV), 20 had more than 1 site of extranodal involvement, and 20 had documented bone marrow involvement. 35 had ECOG performance status of greater than 1. Laboratory data showed elevated serum LDH level in 55. The IPI score was greater than 2 in 47, and the PIT score was greater than 1 in 50. All but one were treated with anthracycline-containing combination chemotherapies. In addition, 16 received high-dose chemotherapy with autologous stem cell rescue. The 5 year OS for the entire population was 42%, and histological diagnosis did not significantly affect OS (the OS for PTCL-NOS, ALCL, and AITL was 35%, 67%, and 47%, respectively). To explore prognostic factors further, univariate analysis was performed using various pretreatment characteristics. Variables significantly associated with poor survival were advanced stage, extranodal involvement > 1 site, bone marrow involvement, anemia, monocyte ≥800 /μL, soluble interleukin-2 receptor > 3,000 U/mL, serum IgG ≥1700 mg/dL, and serum IgA ≥410 mg/dL. The IPI classification was highly correlated with prognosis in this cohort: the relative risk of death was 2.78, 3.99, and 5.61 times higher for pts with IPI of LI, HI, and H, respectively, when compared with IPI L pts (log-rank test; P = 0.0213). By contrast, the PIT classification did not have prognostic value. Then, by using variables associated with poor survival by univariate analysis and not included into IPI, prognostic variables independent of IPI were identified on multivariate analysis. Monocytosis and elevated serum IgA levels were significantly associated with poor survival independently of IPI. The dichotomized monocyte and IgA were combined to generate an IgA/monocytosis prognostic score and pts were stratified into three risk groups: low (IgA < 410 mg/dL and monocyte < 800 /μL), int. (IgA ≥410 or monocyte ≥800), and high-risk (IgA ≥410 and monocyte ≥800) populations. The relative risk of death was 8.56 and 2.83 times higher for pts in the high and int. risk groups, respectively, when compared to the low-risk population (P < 0.0001). Clearly, the new prognostic score was able to stratify pts by risk in a manner comparable to the IPI. Conclusions: Monocytosis and high IgA levels were a novel prognostic factor independent of IPI in the limited number of HTLV-I-negative nodal PTCL patients included in this retrospective study. Further analysis is warranted in a greater number of patients. Disclosures: No relevant conflicts of interest to declare.

The Integration of PD1 blockade with epigenetic therapy is highly active and safe in heavily treated patients with T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8049-8049
Author(s):  
Enrica Marchi ◽  
Helen Ma ◽  
Francesca Montanari ◽  
Ahmed Sawas ◽  
Jennifer K Lue ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Patient Characteristics ◽  
T Cell Lymphoma ◽  
Epigenetic Therapy ◽  
Highly Active ◽  
Progression Of Disease ◽  
Clinical Models ◽  
Grade 3 ◽  
Pd1 Blockade

8049 Background: Our group has demonstrated that combinations of epigenetic modifiers produce potent synergy in pre-clinical models of PTCL and induce the expression of cancer testis antigen, suggesting a role in the addition of the immune-checkpoint inhibitor, pembrolizumab. Methods: This is a phase 1b study of pembrolizumab combined with pralatrexate alone (Arm A), with pralatrexate + decitabine (Arm B), or decitabine alone (Arm C) in patients with relapsed and refractory PTCL and CTCL. A standard 3+3 dose-escalation is applied in the triplet Arm (Arm B) while in the doublet Arms (A and C) de-escalation is applied in case of toxicity. Pharmacokinetic and pharmacodynamic studies are ongoing. Results: We treated a total of 12 patients with 4 patients in each Arm. All patients that received at least one dose of drug were evaluable for toxicity. There was a dose limiting toxicity (DLT) in each arm including prolonged grade 3 thrombocytopenia (Arm A), febrile neutropenia (Arm B), grade 3 hyponatremia, and rash (Arm C). There were no treatment-related deaths. Six patients out of 12 were evaluable for response at the time of this analysis. One patient achieved a complete remission, 2 had partial remission, 1 had stable disease, and 2 experienced progression of disease. Interestingly, all of the responses were seen in the triple combination of pralatrexate, decitabine, and pembrolizumab. Table summarizes the patient characteristics, toxicities, and response rates. Conclusions: These preliminary clinical data suggest that the integration of pembrolizumab on an epigenetic backbone is safe and demonstrates encouraging responses in patient with PTCL and CTCL. Clinical trial information: 03240211 . [Table: see text]

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