Prognostic Index For T-cell Lymphoma Research Articles

A Retrospective Study on the Efficacy and Safety of Chidamide As a Maintenance Therapy for Peripheral T-Cell Lymphoma

Background: Peripheral T-cell lymphomas (PTCLs) are a set of rare and highly heterogeneous tumors of non-Hodgkin's lymphoma (NHL) with inferior outcomes. Chidamide is a novel benzamide class of histone deacetylase (HDAC) inhibitor (HDACi) that was approved by the Chinese Food and Drug Administration in 2014 for the treatment of relapsed or refractory (R/R) PTCL patients. This study aimed to assess the efficacy and safety of chidamide as a maintenance therapy after induction or salvage treatment in patients with PTCLs. Methods: The clinical data of 58 patients with different PTCL subtypes who received chidamide as a maintenance therapy after first-line or salvage treatment were collected. Progression-free survival (PFS), overall survival (OS), and safety were analyzed. Results: Fifty-eight patients enrolled in our study between January 2015 and July 2022, of whom 39 patients received chidamide as a maintenance therapy after first-line treatment and 19 patients after salvage treatment. All patients started chidamide maintenance after reaching at least partial response (PR). The median age was 66 (29-83) years. Patients with angioimmunoblastic T-cell lymphoma (AITL) represented the largest subgroup (34, 58.6%), followed by PTCL, not otherwise specified (PTCL-NOS) (10, 17.2%), anaplastic large cell lymphoma (ALCL) (8, 13.8%), NK/T cell lymphoma (NKTCL) (5, 8.6%) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) (1, 1.7%). Thirty-four (58.6%) patients were stage III-IV, and 38 (65.5%) patients had intermediate or high risk (prognostic index for T-cell lymphoma (PIT) 2-4). Among the 39 patients who underwent chidamide maintenance after first-line treatment, 30/39 (76.9%) patients began maintenance after reaching complete response (CR) and 9/39 (23.1%) after achieving PR. Notably, 8/9 (88.9%) patients achieved CR from PR during maintenance treatment, with a median time of 6 (3-12) months. A total of 11/39 (28.2%) patients experienced disease progression during the maintenance treatment, and their median duration of remission was 6 (3-13) months. Among them, 2 patients experienced disease progression 2 to 3 months after drug withdrawal due to COVID-19 infection. A total of 19 patients who received maintenance treatment after salvage therapy, 9 (47.4%) received maintenance therapy after CR and 10 (52.6%) received maintenance therapy after PR. Among them, 9/19 (47.4%)had disease progression and their median duration of remission was 16 (2-25) months. The remaining 10 patients (8 CR and 2 PR) were still undergoing maintenance treatment and follow-up. The median maintenance treatment time for all patients was 16 (1-72) months, and the median maintenance dose was 20 (15-30) mg twice weekly. The median follow-up time was 39 (2-79) months, the median PFS was 33 months, and the median OS had not been reached (Figure 1 a, b) for all patients. The median PFS and OS of the patients who received first-line maintenance therapy were not reached, which were significantly better compared to patients who received chidamide as salvage treatment maintenance (the median PFS and OS were 7 and 67 months, P < 0.001, P = 0.009, respectively) (Figure 1 c, d). There was no statistical difference in PFS and OS among the different pathological subtypes, but AITL seemed to achieve better PFS (Figure 1 e, f). The most common toxicities were hematologic toxicities, including neutropenia (42, 72.4%), anemia (23, 39.7%), and thrombocytopenia (29, 50.0%), followed by fatigue (35, 60.3%), anorexia (31, 53.4%), liver dysfunction (10, 17.2%), and pneumonia (4, 6.9%). Most adverse events were grade 1 or 2, and the grade 3‒4 adverse events were neutropenia (15/42), thrombocytopenia (7/29), fatigue (1/35), and pneumonia (2/4). Twelve (20.7%) patients underwent a dose reduction and three patients discontinued treatment (two patients with severe pulmonary infections, and one patient had intolerable fatigue) due to adverse events. One patient stopped maintenance treatment after taking chidamide for 10 months for financial reasons and he is still in follow-up. Conclusion: The findings of this study showed that patients with chidamide maintenance therapy had a better PFS and OS with a manageable safety profile, especially as the first-line maintenance therapy. We conclude that chidamide can be used as a maintenance treatment to improve the survival of patients with PTCLs.

Impact of Therapy Sequence on Survival Outcomes Among Patients with Relapsed or Refractory Mature T and NK Cell Neoplasms: A Global Retrospective Cohort Study

Despite evolution of therapeutic strategies, there is no universal standard of care for relapsed or refractory (RR) mature T and NK-cell neoplasms (TNKL). Most patients receive multiple lines of therapy and cycle through many available options. 1-3 There is no data to inform optimal therapy sequence, however emerging data suggest that exposure to epigenetic modifiers (EM) can sensitize tumors to other therapies. 4-6 Here we report results of comparative analyses assessing survival outcomes based on therapy sequence using a global RR TNKL patient cohort with data from 15 centers across 6 continents. We conducted a retrospective target-trial 7,8 cohort study using an updated global patient cohort. 9 Patients were excluded from analyses if they had anaplastic large cell lymphoma (as EM is infrequently used 10,11), did not receive first line cytotoxic chemotherapy (CC), or no documented second line (2L) start date. Cohort assignment was based on 2L therapy received: EM (e.g. histone deacetylase or DNA methyltransferase inhibitors), small molecule inhibitors (SI; broad or selective), or CC. Antibody-drug conjugates were included in CC. Outcomes were overall survival (OS; time from 2L start to death) and real-world progression-free-survival-2 (rwPFS2; time from 2L start to fourth line start or death 12 to assess if 2L modifies the effect of third line [3L]). Planned subgroups included histologic subtype and those who received allogeneic hematopoietic transplant (HSCT) after 2L. For sequence analyses, included patients must have received 3L. Outcomes were assessed between all prespecified 2L to 3L sequences using a single comparator, and pairwise. Kaplan Meier curves were used, and adjusted hazard ratios (aHR) were estimated using Cox regression with previously described a priori covariates. 9 Maximal, minimal, and no covariate Cox models were compared using likelihood ratio tests and Akaike's information criterion. Of the 925 RR patients in the global cohort, 472 were included who received EM (n=89), SI (n=46), or CC (n=337) at 2L. The most common SI included immunomodulatory imide drug (26.1%), PI3K inhibitor (21.7%), investigational pathway inhibitor (19.6%) and JAK inhibitor (17.4%). Within EM, SI, and CC, 42.7%, 37%, and 47.2% of patients were primary refractory to first line, respectively. The most common histologies were PTCL-NOS (51.7%, 41.3%, and 57.3%) and AITL (43.8%, 54.3%, and 26.4%) in EM, SI, and CC, respectively. Most patients had a Prognostic Index for T-cell Lymphoma (PIT) score at diagnosis of 1 (27%, 34.8%, and 27%) or 2 (28.1%, 26.1%, and 25.8%) in EM, SI, and CC, respectively. In EM, 34.8% received first-line autologous HSCT, versus 28.2% in SI, and 15.4% in CC. Following 2L, 12.4%, 17.4%, and 9.8% received allogeneic HSCT in EM, SI, and CC, respectively. The Cox model containing histology, PIT, and primary refractory status was used as the final model (vs maximal model: p=0.88). Compared to CC at 2L, EM did not affect OS (aHR 0.88, 95% CI 0.63-1.24; p=0.46) or rwPFS2 (aHR 0.84, 95% CI 0.61-1.16; p=0.28), however SI improved OS (aHR 0.61, 95% CI 0.37-0.97; p=0.038) and rwPFS2 (aHR 0.61, 95% CI 0.38-0.90; p=0.038). In the allogeneic HSCT subgroup, there was no difference in OS (EM vs CC: aHR 0.32, 95% CI 0.04-2.40; p=0.27; SI vs CC: aHR 0.51, 95% CI 0.06-4.69; p=0.55) or rwPFS2 (EM vs CC: aHR 0.30, 95% CI 0.05-1.96; p=0.21; SI vs CC: aHR 0.64, 95% CI 0.05-3.90; p=0.46). There were no differences in PTCL-NOS patients in OS (EM vs CC aHR 0.80, 95% CI 0.51-1.25; p=0.33; SI vs CC: aHR 1.00, 95% CI 0.54-1.84; p=0.99) or rwPFS2 (EM vs CC: aHR 0.91, 95% CI 0.61-1.38; p=0.66; SI vs CC: aHR 0.90, 95% CI 0.49-0.97; p=0.16). In AITL, SI improved OS (aHR 0.34, 95% CI 0.16-0.76; p=0.009) and rwPFS2 (aHR 0.36, 95% CI 0.17-0.77; p=0.008) versus CC, but EM showed no difference in OS (aHR 0.80, 95% CI 0.43-1.46; p=0.46) or rwPFS2 (aHR 0.56, 95% CI 0.31-1.02; p=0.059). There was no difference in rwPFS2 or OS across sequences overall (Figure 1) or between pairwise sequence comparisons (Figure 2). Compared to CC, SI at 2L improved OS and rwPFS2 in AITL patients. Therapy sequence did not affect OS or rwPFS2. Advanced approaches such as machine learning and dynamic treatment regimes have been initiated to fully elucidate the effect of therapy sequence. Our study highlights several equally effective therapy sequences to treat RR TNKL allowing therapy to be individualized based on patient and disease characteristics, and drug access at a given time.

25-Hydroxy vitamin D deficiency is an inferior predictor of peripheral T-cell lymphomas.

The aim of the study was to explore the significance and prognostic value of 25-hydroxy vitamin D (25-(OH) D) deficiency in peripheral T-cell lymphomas (PTCLs). One hundred fifty-six patients of newly diagnosed PTCLs were enrolled in the study. Univariate and multivariate regression analyses were performed to determine independent risk factors for progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic (ROC) curves were plotted, and corresponding areas under the curve (AUC) were calculated to estimate the accuracy of International Prognostic Index (IPI) plus 25-(OH) D deficiency and Prognostic Index for T-cell lymphoma (PIT) plus 25-(OH) D deficiency respectively in PTCL risk stratification. Our results showed that the 25-(OH) D deficiency was an independent inferior prognostic factor for both PFS (P = 0.0019) and OS (P = 0.005) for PTCLs, especially for AITL and PTCL-not otherwise specified (PTCL-NOS). Additionally, adding 25-(OH) D deficiency to PIT indeed has a superior prognostic significance than PIT alone for PFS (P = 0.043) and OS (P = 0.036). Multivariate COX regression analysis revealed that PIT 2‒4, albumin (ALB) ≤ 35g/L, and 25-(OH) D deficiency were regarded as independent risk factors of PFS and OS. Our results showed that 25-(OH) D deficiency was associated with inferior survival outcome of PTCLs, especially for AITL and PTCL-NOS. PIT plus 25-(OH) D deficiency could better indicate the prognosis for PFS and OS of PTCLs than PIT.

Prognostic Impact of Pre-Treatment Cell-Free DNA Concentration in Newly Diagnosed Peripheral T-Cell Lymphomas

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Although some risk factors associated with worse survival are known, there are no reliable predictive biomarkers of response. Considering the prognostic relevance of cell-free DNA (cfDNA) in B-cell lymphomas, in this work we aimed to explore its role in 75 patients (pts) enrolled in the PTCL13 prospective study (NCT02223208), including newly diagnosed Peripheral T-cell Lymphoma, Not Otherwise specified (PTCL-NOS, n=30), nodular T Follicular Helper Lymphoma (nTFHL, n=26) and Anaplastic Lymphoma Kinase negative Anaplastic Large Cell Lymphoma (ALK-ALCL, n=19). Cell-free DNA was extracted using the Maxwell® RSC LV ccfDNA Kit (Promega) from plasma samples. Pre-treatment cfDNA concentration had a median value of 19.1 ng/mL of plasma (range: 2.27-1082 ng/mL) and was significantly increased in the presence of high-risk clinical parameters, including disease-related risk factors (increased lactate dehydrogenase levels, p<0.0001; presence of extranodal disease p=0.04), prognostic scores used in PTCLs (International Prognostic Index >2, p<0.0001; Prognostic Index for T-cell lymphoma >1, p=0.0006), and patient condition (poor performance status, p=0.0003), compared with cfDNA concentration in low-risk categories. On the other hand, no association was detected between age, Ann Arbor stage, bone marrow involvement and cfDNA levels. In addition, higher baseline cfDNA concentration was found in pts who progressed compared with those who achieved a response at the end of 6 chemotherapy cycles (p= 0.0303). Importantly, pre-treatment cfDNA level had a negative impact on both progression-free survival (PFS, Univariate Cox linear model, p=0.0001) and overall survival (OS, Univariate Cox nonlinear model, p=0.0105). Multivariate analysis confirmed a significant influence of cfDNA on PFS [Multivariate Cox Model, HR 1.34, 95% Confidence Interval (CI) 1.14-1.58, p= 0.0004 and HR 1.28, 95% CI 1.11-1.48, p= 0.0006] greater than that of IPI and PIT scores, LDH, performance status, and extranodal disease. Furthermore, to identify a specific pre-treatment cfDNA concentration associated with a worse prognosis, an analysis by receiver operating characteristic (ROC) curve was performed by dividing the values according to the death event. In doing so, a cut-off of 42.78 ng/mL was identified (Youden's J statistics) above which PFS and OS are significantly reduced (log-rank test p= 0.0177 and < 0.0001, Figure 1 and 2 respectively). Among the 21 pts with cfDNA>42.78 ng/mL, 8 were PTCL-NOS, 4 nTFHL and 9 ALK- ALCL, with nTFHL being significantly less represented than ALK-ALCL (p=0.043). Multivariate analysis confirmed a significant effect on survival when cfDNA above or below 42.78 ng/mL were tested with IPI, LDH and ECOG (HR 2.76, 95% CI 1.24-6.16, p= 0.0128 for PFS; HR 9.45, 95% CI 3.10-28.81, p=0.0001 for OS). When tested together with PIT, ECOG and extranodal disease, both cfDNA and PIT score were associated with OS (HR 9.30, 95% CI 3.22-26.87, p<0.0001 and HR 0.34, 95% CI 0.12-0.94, p=0.037 respectively), while no significant correlations with PFS were found (cfDNA≥ vs <42.78 ng/mL, HR 1.83, 95% CI 0.86-3.91, p= 0.1178). Moreover, sequencing of cfDNA and diagnostic biopsy-extracted DNA was performed in an exploratory cohort of 25 pts using a target custom panel of 60 genes. We identified lymphoma mutations in 18 plasma samples (number of mutations in pts with at least a mutation: median=2, range 1-5) and in 20 biopsy samples (median=2, range 1-6). Mutations identified in biopsy were confirmed in coupled plasma samples in 74.4% cases. In conclusion, our data demonstrate that pre-treatment cfDNA concentration has a strong prognostic impact in PTCLs and represents a superior predictor of shorter survival, compared to canonical parameters. Despite the fact that sequencing is feasible as demonstrated in our preliminary analysis, and is crucial to identify molecular alterations, its applicability in routine clinical practice is limited. On the other hand, cfDNA concentration is an inexpensive biomarker that can quickly provide prognostic information in the real-world scenario. Its influence on survival in the context of a prospective study where PTCLs were homogeneously treated identifies cfDNA as an easily assessable biomarker that could become part of those to be measured in newly diagnosed PTCLs.

Low T3 syndrome as a predictor of poor prognosis in peripheral T-cell lymphomas.

The purpose of the study was to evaluate the prognostic value of low T3 syndrome in peripheral T-cell lymphomas (PTCLs). One hundred and seventy-four patients of newly diagnosed PTCLs were enrolled in the study. We performed statistical analysis based on the clinical data collected. Thirty-Six (20.69%) patients had low T3 syndrome at first admission. Results suggested that the patients with higher score of ECOG PS, International Prognostic Index (IPI) and Prognostic Index for T-cell lymphoma (PIT), bone marrow involvement and lower level of albumin tended to develop low T3 syndrome. The median progression-free survival (PFS) and overall survival (OS) were 10months and 36months, respectively, for all patients. Pre-existing low T3 syndrome was in correlation with worse PFS and OS. Patients with low T3 syndrome showed worse PFS (4months vs 13months, P = 0.0001) and OS (7months vs 83months, P < 0.0001) than patients without low T3 syndrome. IPI and PIT, respectively, combined with low T3 syndrome improved the ability to predict OS and PFS of PTCLs. The study indicated that low T3 syndrome may be a good candidate for predicting prognosis of peripheral T-cell lymphomas.

Prognostic value of 18F-FDG lesion dissemination features in patients with peripheral T-cell lymphoma (PTCL).

To explore the prognostic value of the distance between the two lesions that were farthest apart (Dmax) on baseline 18F-FDG PET/CT in peripheral T lymphoma (PTCL) and establish a new prognostic model for predicting the survival outcomes of patients with PTCL. In this study, a retrospective analysis of 95 patients with PTCL who underwent baseline 18F-FDG PET/CT was performed to assess the predictive value of Dmax. The total metabolic tumour volume (TMTV), total lesion glycolysis (TLG), standardized uptake value (SUV), and Dmax were calculated with LIFEx software. Progression-free survival (PFS) and overall survival (OS) were used as endpoints. The prognostic model was developed based on the results of the multivariate analysis. The time-dependent area under the ROC curve (tdAUC), calibration curves, Harrell C-index, and decision curve analysis (DCA) were used to assess the model. Patients were followed up for a median of 17.0months. Multivariate analysis showed that bone marrow biopsy (BMB) and Dmax were independent predictors of PFS (HR: 1.889, P = 0.039; HR: 1.965, P = 0.047) and OS (HR: 1.923, P = 0.031; HR: 1.982, P = 0.034). The model consisting of Dmax, TMTV, and BMB had substantial prognostic value for survival outcomes of PTCL and could successfully identify four groups of patients with significantly different prognoses (χ2 = 13.731, P = 0.003 for PFS; χ2 = 11.841, P = 0.008 for OS). The tdAUC, C-index, calibration curves, and DCA supported that the model was superior to the prognostic index for T-cell lymphoma (PIT) and International Prognostic Index (IPI) scores. BMB and Dmax were independent predictors of PTCL in our study. Moreover, a prognostic model based on the Dmax, TMTV, and BMB could be useful for predicting the survival outcomes of patients with PTCL.

Age, Albumin, and LDH Predict Outcome of Patients with Limited Stage Peripheral T Cell Lymphoma: A Prognostic Model Developed on 244 Cases Enrolled in the T Cell Project 1 By the International T Cell Project Network

Background: Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous disease group accounting for 10% of non-Hodgkin lymphoma. Approximately 25-30% of patients present with stage I or II disease. The natural history and outcomes of patients with limited stage PTCL is poorly defined. Considering the paucity of literature, the purpose of this study was to assess the outcome of patients with limited stage PTCL, to investigate the potential prognostic factors and build a prognostic model specific for limited stage PTCLs. Methods: The International T Cell Project database (TCP 1) is a prospective registry that collected clinical data and biological information in >1,500 cases with PTCLs at 75 institutions worldwide between 2006-2018. The TCP was searched for all patients aged >18 years diagnosed with PTCL NOS, AITL or ALK+ or ALK- ALCL with stage I or II disease. Survival was updated until database lock on 30 March 2019. The primary end point was overall survival (OS) at 5 years measured from the date of diagnosis until death from any cause or the date of last known contact for living patients. Cox models were used to investigate the association between survival outcomes and covariates with hazard ratios used as a summary measure. Covariates identified to have an independent prognostic effect on OS were used to create a novel prognostic model (Limited Stage Peripheral T Cell Lymphoma Prognostic Model)(SALENTO Model). An external validation cohort of patients with newly diagnosed PTCLs registered in the Australian Lymphoma and Related Diseases Registry (LaRDR) and the Brazilian T-Cell Lymphoma Registry (BrTCLR) was used to validate the predictive model. The performance of the Salento model was compared to published prognostic indices: Prognostic Index for T-cell lymphoma (PIT), Prognostic Index for T-cell lymphoma and platelets (IPTCLP) using Akaine information criterion (AIC) and concordance index (c-Harrell). High-risk disease was defined as Salento≥2; PIT≥2 or IPTCLP≥2 as previously reported. Statistical analyses were performed using Stata (version 14.2) and SPSS (version 20.0). Results: 244 patients registered in the TCP fulfilled the inclusion criteria: PTCL-NOS (n=129), AITL (n=28), ALCL ALK+ (n=33) and ALCL ALK- (n=54). The median age was 57 years (range 18-88). 199 pts (81%) received anthracycline-based regimens, 27 pts (11%) radiotherapy alone (RT), 8 pts (3%) chemotherapy+RT and 12 pts (5%) best supportive care. After a median follow-up of 52 months, the 5-year OS and progression-free survival (PFS) rates were 52% and 43%, respectively. Age >60y, elevated LDH and low serum albumin were independent prognostic factors. The resulting score identified three groups with low- (LR, 29% pts, score 0), intermediate- (IR, 39% pts, score 1), and high-risk (HR, 33% pts, score 2-3) with 5-yr OS of 83% [95% CI 31-100], 53% [95% CI 27-71], and 25% [95% CI 23-84], respectively (P<0·001)(Figure - left panel) and 5-yr PFS of 72% [95% CI 35-100], 44% [95% CI 9-68], and 17% [95% CI 9-35], respectively (P<0·001)(Figure - right panel). 110 patients registered in the LaRDR/BrTCLR fulfilled the inclusion criteria and represented an external validation cohort. The median follow-up of the validation cohort was 22 months (range 20-27 months), and 52 events (53% of patients) were recorded. The model was therefore tested in terms of 2-yr OS: 27 patients (23%) LR, 53 patients (49%) IR; and 30 patients (31%) HR. The distribution of the different risk groups was almost superimposable between the training and validation cohorts. The 2-year OS of the three groups was 95% [95% CI 82-ne], 81% [95% CI 74-88] and 52% [95% CI 23-812] for the LR, IR and HR, respectively (P<0,001, HR=3.55, 95% CI 1.7-7.2) in the validation cohort. In comparison to the PIT and IPTCLP, the Salento model demonstrated the greatest discriminant power with a lower AIC (512) and higher Harrell C-statistic (0.701) than the other prognostic indices (Harrell C- statistic 0.641 for PIT and 0.528 for IPTCLP). Conclusions: The Salento Model (Limited Stage Peripheral T Cell Lymphoma Prognostic Model) is an objective, simple and robust prognostic tool. It demonstrated greater discriminatory power than established prognostic indices and an analogous distribution and outcomes in the validation cohort. The model identifies a high-risk group with poor outcomes, comparable to advanced stage disease, that should be considered for innovative first-line approaches. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Long-Term Outcomes of Patients Aged 65 Years or Older with Peripheral T-Cell Lymphoma, Not Otherwise Specified (PTCL-NOS) and T-Follicular Helper T-Cell Lymphoma (TFHTCL) Treated with Curative Intent CHOP(like) Chemotherapy

Introduction CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the standard treatment for older adults with non-anaplastic large cell lymphoma (ALCL), nodal peripheral T-cell lymphomas (PTCLs). However, recent studies suggest that patients (pts) > 75 years (y) have similar outcomes with CHOP compared to those receiving palliative regimens (Ellin et al. Hematological Oncology 2017). In addition, with studies demonstrating sensitivity of PTCLs to epigenetic therapies, especially in the T-follicular helper (TFH) subtypes, there are emerging clinical trials evaluating these agents in newly diagnosed PTCL patients > 60 y (NCT02232516). We evaluated the long-term outcomes of pts aged 65 y or older with PTCLs, a group generally not transplant eligible, treated with systemic therapy with a focus on those treated with curative intent CHOP(like) chemotherapy. Methods The BC Cancer Lymphoid Cancer Database was reviewed and pts > 65 years with PTCL, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) as well as other T-Follicular Helper PTCL (collectively referred to as TFH T-cell lymphoma [TFHTCL]) diagnosed between 2000-2021 and who received front-line chemotherapy were included. Diagnoses were based on the World Health Organization (WHO) classifications of 2001, 2008, and 2017, depending on the era of diagnosis. Time to progression (TTP) was measured from the date of pathologic diagnosis to the date of relapse/progression, death due to treatment toxicity or lymphoma. Results 152 pts were initially identified, of which 5 were excluded: stage IA/IAE (n=3); CNS involvement only (n=2). Of the remaining 147 pts, 67 (46%) had PTCL-NOS and 80 (54%) had TFHTCL. The median age was 74 y (range 65-90) and the majority of pts had high risk features: International Prognostic Index (IPI) score of > 3 (n=113, 76%), stage III/IV disease (n=136, 93%) and PS of > 2 (n=85, 58%). Most pts (n=127, 86%) received multi-agent chemotherapy with curative intent. All pts received CHOP/CHOP-like chemotherapy (including five pts treated with CHP-brentuximab vedotin)Over half of these patients (n=66, 52%) received attenuated doses of chemotherapy starting from cycle 1, typically 50-75% dose intensity. Only two patients received consolidative autologous stem cell transplant. The remaining 20 patients received chemotherapy with palliative treatment intent, the majority (n=18, 90%) receiving cyclophosphamide alone or with the CVP (cyclophosphamide, vincristine, and prednisone) regimen. The median follow-up of all pts using the reverse Kaplan-Meier method was 9.2 y (range 0.9 to 12.5). The estimated 5-y TTP and overall survival (OS) for all patients were 21%, and 26%, respectively. Outcomes were similar in PTCL-NOS and TFHTCL (5-y TTP 17% vs 25%; p = 0.26). Curative intent chemotherapy was used more frequently in the 65-74 y vs > 75 y age group (70% vs 36%, p = 0.004). As expected, outcomes were superior in those treated with curative intent (Table 1): Median TTP of 11.3 months (m) vs 3.0 m; median OS of 24 m vs 4.5 m. Improvements in TTP and OS extended to those > 75 y (p < 0.001 for both). Considering the curative intent cohort, 91% of the relapse/progression events occurred within the first 3 y, and there was no significant difference in outcomes (5-y TTP/OS) with increasing age: 65-75 (19%/25%), >75 (34%/35%) (p = 0.08/0.6). Further, the outcomes of pts who received attenuated doses of CHOP-like chemotherapy were not inferior compared to full dose chemotherapy (5-y TTP/OS 32%/37% vs. 17%/21% p= 0.2/0.3). 5-y TTP/OS by the IPI ranged from 30%/52% for IPI of 1-2 to 12%/14% for IPI 4-5. The prognostic index for T-cell lymphoma (PIT) was more effective at identifying a lower risk group: 5-y TTP/ OS (PIT 1 40%/57%; PIT 2 21%/28%; PIT 3 21%/20% PIT 4 9%/10%, p = 0.002/0.001). Both models were prognostic in PTCL-NOS and TFHTCL. (Table 1) Conclusion With mature follow-up, ~ 30% of all older pts treated with curative intent CHOP-like chemotherapy remain progression-free and are alive at 5 y. Although results remain suboptimal, robust older patients can still be considered for curative intent CHOP chemotherapy with tailored doses to mitigate toxicity. Those with low risk IPI/PIT scores have a more favourable outcome with this approach, with a 5-y OS of > 50%, suggesting a benefit of subsequent therapies. In contrast, higher risk disease have poor outcomes and novel therapeutic approaches should be considered. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

TET-2 mutations predict poor outcomes and are associated with unfavorable clinical-biological features in PTCL, not otherwise specified and angioimmunoblastic T-cell lymphoma in Brazilian patients.

Nodal peripheral T-cell lymphomas [nPTCL] constitute a heterogeneous group of rare malignancies with aggressive biological behavior and poor prognosis. Epigenetic phenomena involving genes that control DNA-methylation and histone deacetylation play a central role in their pathogenesis. However, the mutational landscape involving epigenetic regulators has never been reported in Latin American patients and their prognostic impact remains controversial. From 2000 to 2019, 59-Brazilian patients with nPTCL were eligible for screening mutations in the IDH-1, IDH-2, RHOA, TET-2 and DNMT3A genes by Sanger sequencing at Formalin-Fixed Paraffin-Embedded samples [FFPE] of diagnosis. We reported the frequency, distribution and potential prognosis of these mutations. With a median follow-up of 3.70 years, estimate 2-year OS and PFS were 57.1% and 49.2%, respectively. Mutations in the IDH-1 gene were not found, mutations in the IDH-2 occurred in 3.4% (2/59), RHOA in 23.7% (14/59), TET-2 in 50.8% (30/59) and DNMT3A in 62.7% (37/59). RHOA gene mutations were more frequent in PTCL, NOS and AITL (p= 0.06). Almost half of the patients had more than one mutation in concomitance, particularly RHOA-mut and TET-2-mut. Mutations in RHOA (p= 0.030) and TET-2 (p= 0.046) were associated with high-tumor burden. In the non-ALCL subgroup (PTCL, NOS and AITL) TET-2 mutations were associated with decreased 2-year PFS [HR: 2.22, p= 0.048]. Likewise with lower overall response rate [ORR] (p= 0.048) and unfavorable clinical features, as bulky disease (p= 0.012), ECOG ⩾ 2 (p= 0.032), B-symptoms (p= 0.012), ⩾ 2 extranodal sites compromised (p= 0.022) and high-risk Prognostic Index for T-cell lymphoma (p= 0.005). Mutations in RHOA, TET-2 and DNMT3A were frequent in Brazilian patients with nPTCL. TET-2 mutations were associated with lower ORR for CHOP-like chemotherapy, decreased PFS and unfavorable clinical-biological characteristics in non-ALCL (PTCL, NOS and AITL). Further studies using a larger cohort may validate our findings.

Characteristics and clinical outcomes of patients with ALK-positive anaplastic large cell lymphoma: Report from the prospective international T-cell lymphoma project.

The T-cell Lymphoma Project is an international registry prospective study that enrolled patients with newly diagnosed peripheral T-cell and NK-cell lymphomas (PTCL). The main objective was to define the clinical features and outcomes, establishing a robust benchmark for future clinical trials. Seventy-four institutions from 14 countries in North America, South America, Europe, and Asia collected data on patients diagnosed and treated at their respective centers between September 2006 and February 2018. Among 1553 PTCL patients, 131 (8.4% of the total cohort) were confirmed to have anaplastic large cell lymphoma - kinase positive (ALCL, ALK+). The median age of the patients was 39years (18-84). Sixty-five patients (66%) had advanced-stage disease, although majority (45 patients, 54%) had a low-risk International Prognostic Index (IPI) score (0-1). Of 97 patients treated with chemotherapy, 97% received anthracycline-containing regimens. The overall response rate was 81%, with 69 patients (70%) achieving complete remission. Estimated OS and PFS at 3years were 77% (95% CI: 54%-99%) and 68% (95% CI: 46%-90%), respectively, and at 5years were very similar, 77% of OS (95% CI: 62%-92%) and 64% of PFS (95% CI: 34%-94%). Multivariate analysis for PFS showed advanced stage (hazard ratios [HR]: 4.72, 95% CI: 1.43-23.9, p=0.015), elevated lactate dehidrogenade (LDH)(HR 4.85; 95% CI: 1.73-13.60, p=0.001), and Eastern Cooperative Oncology Group Performance Status scale (ECOG-PS) ≥2 (HR: 5.25; 95% CI: 1.68-16.4, p=0.024). For OS, elevated LDH (HR: 3.77; 95% CI: 1.98-14.17, p=0.014) and ECOG-PS ≥2 (HR: 4.59; 95% CI: 1.46-14.39, p=0.004) were identified. In summary, although the outcome of ALK+ ALCL is superior to that of other PTCLs, it remains sufficiently favorable, given the young median age of the patients. Our results confirm the usefulness of both IPI and Prognostic Index for T-cell Lymphoma (PIT)in identifying groups of patients with different outcomes. Clinical Trials ID: NCT01142674.

Clinico-Epidemiological Features of Elderly Patients with Peripheral T-Cell Lymphoma Not Otherwise Specified: A Study from the Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL)

Introduction: Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is the most common PTCL subtype, accounting for approximately 25% of all PTCL cases. The median age at diagnosis is 60 years and is more prevalent among males. Currently, most epidemiological data on T- and NK-cell lymphomas come from developed countries. Thus, very few data are available regarding this condition in Latin American countries, especially in those aged 60 years and older. The Latin American Group of Lymphoproliferative Disorders (GELL) has previously reported on the impact of serum albumin level in survival outcomes in PTCL-NOS. Therefore, we aim to evaluate the clinical, demographic, and outcome patterns of elderly patients with PTCL-NOS.Methods: We conducted an observational, retrospective study of newly diagnosed PTCL-NOS between January 2000 and December 2020. Patient must be aged 60 years and older. All clinical data were retrieved from clinical records at the different participating institutions. The study outcomes were overall survival (OS) and progression-free survival (PFS). The International Prognostic Index (IPI), the Prognostic Index for T-cell lymphoma (PIT), and the NCCN IPI scores were used for risk stratification. Kaplan-Meier and log-rank test were used for survival analysis. Univariate and multivariate Cox regression analysis were used to estimate hazard ratios (HR) with a 95% confidence interval (CI). Outcomes with a p-value <0.05 were considered statistically significant.Results: A total of 107 patients were included; median age at diagnosis was 72 years (range 60-92), 61% were male, 46% had an ECOG ≥2, 70% had stage III-IV, and 15% had more than one extranodal site. The IPI, PIT and NCCN-IPI scores stratified 51%, 69%, and 74% of patients as high- / high-intermediate risk, respectively. Seventy-four (69%) patients received first-line systemic therapy. Most patients (53%) were managed with CHOP/CHOP-like regimen, followed by CHOEP (19%). The overall response (OR) rate to first-line therapy was 61% (complete response, CR 41%). Salvage therapy was given to only 9 patients; the OR rate was 44% (CR 11%). With a median follow-up of 29 months (95% CI 13-45 months), the 2-year OS was 46% (95% CI 36-59), with median survival time of 16 months (95% CI 10-NR). In the multivariate analysis, patients with serum albumin levels <3.5 g/dL had median survival of 7 months (95% CI 3-20) and 2-year OS rate of 24% (95% CI 13-46%), while patients with albumin ≥3.5 g/dL did not reach the median survival time and had a 2-yOS rate of 67% (95% CI 36-65%) (p<0.0001) (Table 1, Figure 1). Patients with a lymphocyte-to-monocyte ratio (LMR) >7.6 had a median OS of 8 months (95% CI 6-NR) and a 2-year OS of 10% (95% CI 2-65), while patients with a LMR ≤7.6 did not reach the median OS and had a 2-year OS of 57% (95% CI 45-72) (p = 0.0108) (Table 1, Figure 1).Conclusions: This large cohort of Latin American PTCL-NOS patients aged ≥60 years showed overall response rates comparable to previously published data. However, survival rates were shorter compared to those reported in developed countries. In this study, we again confirmed low serum albumin level (<3.5 g/dL) as an adverse prognostic factor for OS in PTCL-NOS, and independent from the IPI, PIT and NCCN-IP scores. Additionally, we describe for first time in a Latin American cohort the impact of the LMR on survival, demonstrating poor outcomes in those with LMR >7.6. We are currently validating our findings in a prospective cohort of Latin American PTCL patients and to improve clinical decision-making in those deemed at high-risk for early mortality. [Display omitted] DisclosuresOtero: Astra Zeneca: Current Employment. Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

A Simplified Novel Prognostic Score to Predict Early Mortality and Disease Progression in Patients with Aggressive Adult T-Cell Leukemia/Lymphoma

▪Background: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive mature peripheral T-cell neoplasm caused by HTLV-1 infection. Despite aggressive therapy, ATLL carries a very poor prognosis. Current prognostic models (i.e., the International Prognostic Index [IPI] and the Prognostic Index for T-cell lymphoma [PIT]) have shown to not completely predict survival in ATLL (Phillips, Cancer, 2010). Moreover, these models have not been validated in Latin American ATLL patients. Therefore, we aim to validate current prognostic systems (IPI, PIT) and to develop a novel model to predict early mortality in patients with ATLL.Methods: We conducted a retrospective cohort study by analyzing 12 demographic, clinical, and laboratory variables of 169 Latin American ATLL patients with acute and lymphomatous subtypes recruited by the “Grupo de Estudio Latinoamericano de Linfoproliferativos” (GELL). All patients received cancer-directed treatment. Conditional inference trees were used to construct a new prognostic model, the ATLL-GELL, by including serum lactate dehydrogenase (LDH) and the Eastern Cooperative Oncology Group (ECOG) performance status. Our primary outcome was overall survival (OS) at 15 months, while our secondary outcome was progression-free survival (PFS). The model identified a low-risk (LDH ≤2 times upper limit value [ULV] + ECOG score 0-1), and a high-risk (LDH >2 times ULV + ECOG score ≥2; or LDH >2 times ULV) group (Figure 1). The model was validated in an independent cohort of 95 North American ATLL patients with acute and lymphomatous subtypes from Miami, FL. We used the Kaplan-Meier method and the log-rank test to estimate the survival probabilities for the score. Cox regression was used to evaluate the risk of mortality and disease progression for each score. We used the C-index to determine the discriminatory power of each score.Results: Table 1 summarizes the demographic and clinical characteristics. The mean age was 57 (± 15.1) years with a male predominance (53%). Lymphomatous ATLL was the most common subtype (66%) in the training cohort, while acute ATLL (59%) in the testing cohort. Most patients had an Ann Arbor stage III-IV (88%) and received multiagent chemotherapy (76%) as first-line treatment (Table 1). With a median follow-up of 21 months, the 15-month OS and PFS rates of the training cohort were 29% and 27%, respectively. Patients with a high-risk ATLL-GELL score had a worse OS (16% vs. 61%, p<0.0001) and PFS (14% vs. 60%, p<0.0001) (Figure 2). Table 2 shows that the ATLL-GELL model had comparable prognostic discrimination than the IPI and PIT scores, according to the C-index. Similarly, the Cox regression analysis identified a better risk stratification of the new model for OS and PFS in the training and testing cohorts. In contrast, poor risk stratification for mortality and disease progression was found with the IPI and PIT scores in the training cohort. Table 2 shows that the risk for mortality and disease progression was higher in the high-intermediate (HR 7.91 and 8.07, respectively) than the high-risk (HR 7.12, and 7.85, respectively) group according to the IPI score. Moreover, the PIT score could not properly stratify patients' OS and PFS risk (Table 2). Figures 3 and 4 illustrate narrow and crossing survival curves between risk subgroups in both scores for OS and PFS estimates, respectively, suggesting poor visual discrimination of the IPI and PIT scores.Conclusion: ATLL carries a dismal prognosis, therefore we hypothesized that current prognostic systems might not yield an appropriate risk stratification since almost universally aggressive ATLL patients are at high risk for rapid disease progression and death. After considering different clinical-epidemiological and laboratory variables, our simplified prognostic model was able to predict early mortality and disease progression in patients with aggressive ATLL. Poor performance status, thus unfit for aggressive therapy, along with a high disease burden seems to reliably predict mortality in these patients. The ATLL-GELL model also showed better risk stratification and a more clear distinction of low- versus high-risk groups for aggressive ATLL than traditional models. We are currently validating our findings in a prospective cohort of Latin American ATLL patients and to improve clinical decision-making in those deemed at high risk for early mortality. [Display omitted] DisclosuresCastillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

Long Term Outcome Patterns and Risk Factors for Early Mortality and Disease Progression in ALK-Positive Anaplastic Large Cell Lymphoma

Long Term Outcome Patterns and Risk Factors for Early Mortality and Disease Progression in ALK-Positive Anaplastic Large Cell Lymphoma

Prognostic value of baseline total metabolic tumour volume of 18F-FDG PET/CT imaging in patients with angioimmunoblastic T-cell lymphoma

PurposeThe aim of this study was to explore the prognostic value of baseline metabolic parameters of 18F-FDG PET/CT imaging in patients with angioimmunoblastic T-cell lymphoma (AITL).Materials and methodsFifty-six AITL patients (average age 64.0 ± 1.3 years) diagnosed pathologically from August 2009 to August 2019 were enrolled in this retrospective study. The total metabolic tumour volume (TMTV), total lesion glycolysis (TLG), maximum standardized uptake value (SUVmax), and correlated clinical characteristics were collected and analysed. TMTV was computed with the 41% SUVmax threshold method. The chi-square test or Fisher’s exact probability method was used to compare clinical characteristics. Kaplan–Meier curves were used to describe progression-free survival (PFS) and overall survival (OS). The log-rank test was used to analyse the difference within groups. The statistically significant factors in the univariate regression analysis were incorporated into the Cox risk proportional regression model for multivariate survival analysis.ResultsThe TMTV cut-off value was 514.6 cm3 from the ROC curve analysis. Forty (71.4%) patients progressed and 31 (55.4%) patients died within a median follow-up time of 19.1 (interquartile range 7.8–34.6) months. The 1-year and 3-year PFS rates were 42.9% and 30.1%, and the 3-year and 5-year OS rates were 45.9% and 34.4%, respectively. Univariate survival analysis showed that high TMTV and TLG may be the factors contributing to poor PFS and OS. Multivariate analysis showed that TMTV and prognostic index for T-cell lymphoma (PIT) were independent parameters for PFS and OS in AITL patients. TMTV, combined with PIT, may have better risk stratification performance than TMTV alone.ConclusionsBaseline TMTV and PIT were independent prognostic predictors in AITL patients. The combination of TMTV and PIT can facilitate prognostic stratification and contribute to personalized therapy.

The Absolute Lymphocyte Count Is Associated with the Prognosis in Patients with Peripheral T-Cell Lymphoma, Not Otherwise Specified

IntroductionPeripheral T-cell lymphomas (PTCLs) are a heterogeneous group of tumors that belong to the category of aggressive lymphomas and are roughly subdivided into specified and not otherwise specified (NOS) types. Clinically, the International Prognostic Index (IPI) has been the effective prognostic model to discriminate the prognosis of patients with PTCL-NOS. Also, Prognostic Index for T-cell lymphoma (PIT) has been proposed, which further modified to the Bologna score (modified PIT, mPIT). However, no simple prognostic marker has been satisfactory in predicting treatment outcomes in patients with PTCL-NOS. In this study, we investigate the association between absolute lymphocyte count at diagnosis and the prognosis of patients with PTCL-NOS.MethodsAs a retrospective study, we searched the Lymphoma Registry of Asan Medical Center and Inje University Sanggye Paik Hospital. From April 2001 to Jun 2016, we identified 131 patients diagnosed with PTCL-NOS initially treated with CHOP or CHOP-like regimens. Patients diagnosed with PTCLs other than PTCL-NOS and primary cutaneous lymphoma were excluded. Event-free survival (EFS) was calculated from the date of diagnosis to the date of disease progression, treatment failure, relapse, or death from any cause. Overall survival (OS) was calculated from the date of diagnosis to the date of death from any cause. Lymphopenia was defined as absolute lymphocyte count < 1000 / μL. The association between clinical characteristics and response was analyzed by the Fisher's exact test. Survival curves were analyzed by the Kaplan-Meier method and compared with the log-rank test.ResultsAmong 131 patients, 42 (32.1%) patients showed lymphopenia, 58 (44.3%) patients showed B symptoms, and 46 (35.1%) patients showed bone marrow involvement. The median absolute lymphocyte count was 1392/μL (range, 61-10092/μL). According to the International Prognostic Index (IPI) scores, 33 (25.2%) patients belonged to the low risk group (L), 36 (27.5%) to the low-intermediate risk group (LI), 38 (29.0%) to the high-intermediate risk group (HI), and 24 (18.3%) to the high risk group (H).In univariate analysis, treatment outcomes including CR, EFS, and OS were associated with lymphopenia, B symptoms, performance status, lactate dehydrogenase, extranodal involvement, Ann Arbor stage, IPI risk group, and the Prognostic Index for T-cell lymphoma (PIT) risk groups. After multivariate analysis, lymphopenia was independently associated with CR (≥1000 vs. <1000, odd ratio [OR]: 2.899, 95% confidence interval [CI]: 1.229-6.841, P=0.015), EFS (≥1000 vs. <1000, hazard ratio [HR]: 0.523, 95% CI: 0.339-0.807, P=0.003), and OS (≥1000 vs. <1000, HR: 0.599, 95% CI: 0.375-0.955, P=0.031). IPI risk group was also associated with CR (L/LI vs. HI/H, P <0.001), EFS (P <0.001), and OS (P <0.001).ConclusionsAbsolute lymphocyte count is an independent prognostic factor for the patients with PTCL-NOS. Lymphopenia (<1000/μL) at diagnosis was associated with worse prognosis of patients with PTCL-NOS. Because the absolute lymphocyte count easily obtained from the initial complete blood count, it seems to be simple prognostic factors to estimate the prognosis of patients with PTCL-NOS. The larger scaled study is warranted to confirm our result. DisclosuresNo relevant conflicts of interest to declare.

Myeloablative Haploidentical Transplant as an Alternative to Matched Sibling Transplant for Peripheral T-Cell Lymphomas

The number of HLA-haploidentical allogeneic hematopoietic stem-cell transplantation (Haplo-HSCT) is increasing. Comparative studies about Haplo-HSCT versus allo-HSCT with HLA-matched sibling donors (MSD-HSCT) have been tried in leukemias and B-cell lymphomas. Few studies were reported in Peripheral T-cell lymphomas (PTCLs). We performed a multicenter retrospective study about 52 patients with PTCLs undergoing Haplo-HSCT (n = 20) or MSD-HSCT (n = 32). All Haplo-HSCT recipients received antithymocyte globulin (ATG) based graft versus host disease (GVHD) prophylaxis. The median follow-up for all survivors was 38 months. The 100-day cumulative incidence of grade II to IV acute GVHD was similar (19% in the MSD-HSCT group versus 28% in the Haplo-HSCT group, P = 0.52). The 2-year cumulative incidence of chronic GVHD (limited and extensive) after Haplo-HSCT (30%) was also similar with that in the MSD-HSCT group (50%, P = 0.15). The 3-year relapse rates (33% vs 27%, P = 0.84) and non-relapse mortality (21% vs 22%, P = 0.78) did not differ between these two groups. There were also no differences in 3-year overall survival (OS) (48% vs 50%, P = 0.78) and progression-free survival (47% vs 51%, P = 0.95) between these two groups. On multivariate analysis, prognostic index for T-cell lymphoma (PIT) score (higher than 1: hazard ratio [HR], 4.0; P = 0.003) and disease status (stable or progression disease before HSCT: HR, 2.8; P = 0.03) were independent variables associated with worse OS. We concluded that ATG-based haplo-HSCT platform could work as an alternative to MSD-HSCT for patients with PTCLs.

Comparison of prognostic scores in transplant-ineligible patients with peripheral T-cell lymphoma not otherwise specified and angioimmunoblastic T-cell lymphoma: a retrospective study from the national hospital organization in Japan

We retrospectively analyzed the risk factors for outcomes among patients with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS, n = 100) and angioimmunoblastic T-cell lymphoma (AITL, n = 128) who did not receive hematopoietic stem cell transplantation between 2008 and 2018. We designed a comparison of prognostic scores specifically for PTCL-NOS and AITL. The international prognostic index (IPI) was useful for investigating the risk factors associated with outcomes among transplant-ineligible patients with PTCL-NOS (Harrell’s c-statistic 0.715) and AITL (c-statistic 0.615). The prognostic index for T-cell lymphoma (PIT), modified PIT, and the International Peripheral T Cell Lymphoma Project for overall survival (OS) seemed to identify separate prognostic groups, based on visual assessment of Kaplan–Meier curves. However, better c-statistics (>0.7) were only found for the IPI score for OS in PTCL-NOS. Strategies that carefully select PTCL patients with higher IPI scores may help to identify individuals suitable for novel therapies.

Effects of stem cell transplantation in patients with peripheral T-cell lymphoma not otherwise specified and angioimmunoblastic T-cell lymphoma.

The effects of stem cell transplantation (SCT) in patients with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL) remain controversial. We analyzed the feasibility of SCT and risk factors associated with outcomes of PTCL-NOS and AITL patients to identify the potential clinical efficacy of SCT. We retrospectively analyzed the data of PTCL-NOS (n = 83) and AITL (n = 112) patients who received autologous (n = 10 and 16, respectively) or allogeneic (n = 12 and 4, respectively) SCT, or no SCT (n = 61 and 92, respectively) between 2008 and 2018. All PTCL-NOS and AITL diagnoses were reconfirmed by an experienced hematopathologist. Median age at PTCL-NOS and AITL diagnoses in the SCT group was younger than that in the no SCT group. Significant risk factors for lower overall survival were intermediate-high and high-risk international prognostic indexes in PTCL-NOS patients (P = 0.0052), and a > 2 modified prognostic index for T-cell lymphoma (P = 0.0079) and no SCT (P = 0.028) in AITL patients. Autologous or allogeneic SCT compared with no SCT in AITL patients resulted in 3-year overall survival of 68.6% and 100% vs. 57.2% (P = 0.018). Strategies should be developed to improve selection of PTCL-NOS and AITL patients suitable for SCT and/or additional novel therapies.

Ukraine Data on Prognostic Factors and Treatment Outcomes in Patients with Peripheral T-Cell Lymphomas.

Peripheral T-cell lymphomas (PTCLs) is a diverse group of lymphomas (10-15% of all non-Hodgkins lymphomas) with aggressive behavior. Despite the standard of 1st line anthracycline-containing regimens, clinical outcomes are poor compared to B-cell lymphomas. In addition, there are still debates about specific prognostic factors (PF) in PTCLs. Primary endpoints - event-free survival (EFS) and overall survival (OS). To evaluate the prognostic significance of five PTCLs scores (International Prognostic Index - IPI, International Peripheral T-cell lymphoma Project Score - IPTCL, Prognostic Index for T-cell lymphoma - PIT, modified Prognostic Index for T-cell lymphoma - mPIT and T-cell score). From 67 enrolled patients, only 50 were included: PTCL not otherwise specified (22, 44%), anaplastic large cell lymphoma ALK+ (anaplastic lymphoma kinase-positive) (10, 20%) and ALK (anaplastic lymphoma kinase-negative) (18, 36%). Patients received CHOP-like regimens (CHOP, CHOEP, EPOCH). The overall rate response was observed in 66% of cases (complete response 78%). There were 48% of relapses after the 1st line therapy during follow-up (median 11 months; range 1-85 months). Median age 57 (range 22-80) with male predominance 62%. In total, 40% of patients were &gt; 60 years old, 48% had stage III-IV. Majority of patients were assessed by five prognostic scores. IPI (45 patients): the 3-year EFS and OS were higher for IPI 1 vs. IPI &gt; 2 (80 vs. 18% and 87 vs. 27%, respectively; p = 0.0002). Receiver operating characteristic analysis confirmed poor clinical outcome to patients with PF &gt; 1 (Se = 88 %; Sp = 68 %; AUC = 0.7; p = 0.0081). IPTCLP (41 patients): the presence of PF = 1-2 showed EFS and OS reduction. A 3-year EFS rate for 1-2 PF was 25 vs. 70% for PF = 0 (p = 0.003). Thus, 3-year OS in patients with PF = 0 vs. PF = 1-2 was 100 vs. 20% (p = 0.0001). PIT (42 patients): better 3-year EFS and OS in patients with PF = 0 vs. PF = 1-3 (88 vs. 28% and 100 vs. 34%, respectively, p = 0.001). Patients with PF = 1-3 have a higher rate of relapses vs. PF = 0 (p = 0.0005 by Cox-test). mPIT (21 patients): no significant difference between PF and clinical outcomes. T-cell score (18 patients): higher survival rates with PF 2. More than 2 PF have an impact on EFS (p = 0.005). The 3-years OS in patients with PF 2 was 77 vs. 25% in cases with PF 3 (p = 0.001). IPI, PIT, IPTCLP are still very useful in defining risk stratification. As to mPIT and T-cell score, more patients to evaluate their prognostication possibility are needed.

Identifying a Simple Clinical Prognostic Model for Aggressive Adult T-Cell Leukemia/Lymphoma in Latin American Population and Its Validation: A Large International Study of the Latin America Working Group for Lymphomas (GELL)

Identifying a Simple Clinical Prognostic Model for Aggressive Adult T-Cell Leukemia/Lymphoma in Latin American Population and Its Validation: A Large International Study of the Latin America Working Group for Lymphomas (GELL)