Prognostic Index For Peripheral T-cell Lymphoma Research Articles

Retrospective Study of Allogeneic Hematopoietic Stem Cell Transplantation for Relapse or Refractory Peripheral T-Cell Lymphoma at Toranomon Hospital and Toranomon Hospital Kajigaya

[Background] Relapsed or refractory peripheral T-cell lymphoma (R/R PTCL) is known to have a poor prognosis. Although new medications have been introduced in recent years, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment for R/R PTCL. We review the results of allo-HSCT for PTCL at our institution. [Methods] We performed a retrospective analysis of R/R PTCL patients who underwent first allo-HSCT at our hospital from February 2011 and April 2023. The primary endpoint was OS, which was defined as the time from allo-HSCT to death from any cause or the last follow-up. The secondary endpoints included progression-free survival (PFS), relapse/progression incidence (RI) and non- relapse mortality (NRM). PFS was defined as the time from allo-HSCT to relapse/progression, death, or the last follow-up. OS and PFS were estimated by the Kaplan-Meier method and multivariate Cox proportional hazard models. The cumulative incidence of relapse and NRM were investigated with a competing risk analysis using Gray's test and multivariable Fine and Gray competing risk regression. [Results] During the study period, a total of 44 patients received first allo-HSCT for PTCL (ALK positive ALCL: 2, ALK negative ALCL: 2, AITL: 10, PTCL-NOS: 21, CTCL: 7, HSTL: 2). The median follow-up months of survivors was 51.6 (range, 2.6-141.6). The median age of patients at transplantation was 50 years (range, 17-70). Clinical stage I/II at diagnosis was 10 cases, and clinical stage III/IV was 34 cases. Prognostic Index for PTCL(PIT) was score 1 in 20 cases, score 2 in 20 cases and score 3 in 3 cases. Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) ≧ 2 was 21 cases. Performance Status (PS) 0-1 was 32 cases and PS 2-4 was 12 cases. Primary induction failure (PIF) was 28 cases and relapse after first remission (REL) was 16 cases, including 5 cases of relapse after autologous stem cell transplantation. Median number of chemotherapy regimens received before allo-HSCT was 3 (range, 1-8). Clinical stage at transplantation was CR/PR in 23 patients and SD/PD in 21 patients.The majority, thirty-two had received unrelated cord blood transplantation (CBT), six did unrelated bone marrow transplantation (uBMT), and 6 did related peripheral blood stem cell transplantation (rPBSCT). Thirty-two patients received myeloablative conditioning (MAC), eighteen of which included total body irradiation (TBI) and 15 of which included busulfan (BU). Twelve patients received reduced-intensity conditioning (RIC) . Regarding the primary endpoint, the 4-year OS after allo-HSCT was 53.3%. The 4-year PFS, RI and NRM were 50.4%, 20.7% and 28.8%, respectively. The 4-year OS of CBT, uBMT and rPBSCT patients was 55.2%, 66.7% and 33.3%, respectively. The 4-year OS of REL and PIF patients was 79.1% and 39.5%, respectively (p<0.01). The 4-year OS of MAC and RIC was 49.5% and 64.3%, respectively (p=0.58). The 4-year OS of patients with TBI was superior to patients without TBI (71.1% vs 40.3%, p=0.05). The 4-year OS of CR/PR patients at transplant was superior to SD/PD patients (67.1% vs. 42.9%, p=0.05). In the univariate analysis, PS 0-1, HCT-CI 0-1, REL, CR/PR patients at transplant, patients with TBI and patients without BU were favorable prognostic factors. In the multivariable analysis, REL was associated with better OS (p=0.01, HR 0.16; 95% CI: 0.04-0.65). Except for 3 patients who died from transplant complications before engraftment, 41 patients achieved neutrophil engraftment, with a median engraftment date of 19 days (range, 11-31 days) after transplantation. Twenty-seven patients had acute GVHD (Grade I: 3, Grade II: 13, Grade III: 8, Grade IV: 3), and 11 patients had chronic GVHD. Eleven patients relapsed after transplant, and the median time from transplant to relapse was 26.3 months (range, 0.6-87.1 months). Three patients survived at the last follow up, and the median follow-up time of survivors from relapse was 430 days (range, 12-1301). [Conclusion] Our data indicated good results of allo-HSCT for R/R PTCL, and significantly better in relapse after first remission patients.

Validation of Angioimmunoblastic T-Cell Lymphoma (AITL) Score in Korean AITL Patients

Background: Angioimmunoblastic T cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma (PTCL), accounting for approximately 2% of all non-Hodgkin lymphoma and 20% of PTCLs. AITL generally displays aggressive clinical course and prognosis is poor with 5-year OS (Overall survival) rate of approximately 40%. The International Prognostic Index (IPI), Prognostic Index for PTCL (PIT), and Prognostic Index for AITL (PIAI) have been widely used for the prognostication of AITL patients. Recently, the international T-cell lymphoma project proposed a novel prognostic score, AITL score based on age, ECOG performance status (ECOG PS), serum CRP level and serum B2-microglobulin (B2-M) level. AITL score demonstrated better discriminant power compared with the IPI, PIT, and PIAI. However, the prognostic significance of AITL score has not been validated. In this study, we aim to validate the prognostic significance of AITL score in Korean AITL patients. Methods: Between March 2001 and August 2021, 98 patients who were newly diagnosed with AITL were identified in the database of the Asan lymphoma Registry, Asan Medical Center, Seoul, South Korea. After excluding patients with no baseline serum β2-microglobulin level (n=13) and CRP (n=4), 81 patients were included in this retrospective analysis. Key baseline characteristics including age, performance status, stage, serum CRP level, serum B2-M level were collected. The upper limit of normal (ULN) of serum CRP level and serum B2-M level are 6 mcg/mL and 2.4 mcg/mL, respectively. Overall survival (OS) was defined as time from diagnosis to any cause of death. Survival curves were estimated by Kaplan-Meier method and compared using log-rank test. In the multivariate analysis, variables exhibiting a potential association with survival (p < 0.5) in the univariate analysis were included. Results: The median age was 61 years (range, 28-83), 47 patients (58.0%) were male, 79 (97.5%) had advanced disease at diagnosis, and 77 (95.1%) had elevated B2-M levels. In addition, two patients (2.5%) had ECOG PS > 2, 31 (38.3%) had extranodal involvement > 1. With a median follow-up duration of 2.0 years, the median OS was 3.6 years. A total 81 patients were found to be evaluable for the prognostic model. There was no significant difference in OS of patients stratified according to the AITL score, with 2-year OS of 44.4%, 59.2%, and 58.4% for patient with low-risk (0-1 risk factor, n=6, 7.4%), intermediate-risk (2 risk factors, n=43, 53.1%) and high-risk (3-4 risk factors, n=32, 39.5%) groups, respectively (p=0.7). The lack of prognostic significance of the AITL score was mainly due to the fact that most of the patients had elevated B2-M (n=77, 95.1%), and serum B2-M had no significant association with OS in the univariate analysis (HR: 2.44, 95% CI: 0.33-17.79, p=0.379). Thus, we reevaluated the prognostic significance of B2-M by using 2 times of the ULN (2 x ULN, 4.8 mcg/mL). Serum B2-M of > 2 x ULN was significantly associated with poor OS in the univariate analysis (HR: 3.38, 95% CI: 1.75-6.50, p<0.001), and its prognostic significance remained in the multivariate analysis (HR: 2.66, 95% CI:1.09-6.49, p=0.031). Thus, we modified the AITL score using 2 x ULN as a cut-off value for B2-M instead of 1 x ULN (modified AITL score). There was a significance difference in OS of patients according to the modified AITL score with 2-year OS rate of 73.5%, 57.2%, and 40.3% for patient with low-risk (0-1 risk factor, n=31, 38.3%), intermediate-risk (2 risk factors, n=24, 29.6%) and high-risk (3-4 risk factors, n=26, 32.1%) groups, respectively (p=0.004). Conclusion: The AITL score failed to be validated in Korean AITL patients due to the fact that most patients had B2-M of > 1 x ULN. Modified AITL score, which adjusted the B2-M cut-off to 2 x ULN provided significant risk stratification of the patients. The optimal cut-off value for B2-M in AITL patients should be validated in future studies.

Clinicopathologic characteristics, outcomes, and prognostic factors of angioimmunoblastic T-cell lymphoma in China.

This study aimed to better characterize the clinicopathologic characteristics, outcomes, and prognostic factors of AITL in China. We retrospectively analyzed 312 patients with AITL enrolled between January 2011 and December 2020 from five institutions in China. The median age was 65 years, with 92.6% advanced stage, 59.7% elevated LDH, 46.1% anemia, and 44.0% hypergammaglobulinemia. The majority of patients (84.9%) received anthracycline-based regimens with or without etoposide, and only 6.1% underwent autologous stem cell transplantation following first remission. The 5-year OS and PFS estimates were 43.4% and 25.0% with no significant improvement of survival between patients treated during 2011-2015 and 2016-2020, respectively. Both the International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT), were predictive for OS. In multivariate analysis, age >70 years, elevated LDH, and albumin level <35 g/L were independent prognostic factors for OS. Combining these three factors, a novel prognostic model (the Chinese AITL score) was constructed, which stratified patients into low-, intermediate-, and high-risk groups, with 5-year OS rates of 69.0%, 41.5%, and 23.7%, respectively. This new model was successfully validated in an independent cohort. Patients with AITL were mainly treated with anthracycline-based regimens, and the outcomes were still unsatisfactory in China. Our novel prognostic model may improve our ability to identify patients at different risks for alternative therapies.

Low serum cholesterol levels predict inferior prognosis and improve prognostic index scoring for peripheral T-cell lymphoma, unspecified

Peripheral T-cell lymphomas, unspecified (PTCL−U) is a heterogeneous group of non-Hodgkin lymphomas, arising from the transformation of mature, post-thymic T-cells. Prognostic index for PTCL−U (PIT) is based on Europeans and may not be applicable for Chinese PTCL-U patients. Besides, low circulating cholesterol concentration is associated with elevated cancer incidence and mortality. The purpose of our study was to assess the prognostic value of serum lipid levels in PTCL−U and improve PIT. We screened the prognostic factors associated with progression−free survival (PFS) and overall survival (OS) by multivariate Cox regression analysis in ninety−one enrolled patients. The results showed that low-level high−density lipoprotein cholesterol (HDL−C) and low-density lipoprotein cholesterol (LDL−C) were associated with unfavorable OS. Furthermore, we developed a new risk model, PITC, based on low-level HDL−C, LDL−C and PIT. In Chinese PTCL−U, PITC was superior to PIT in PFS and OS. In conclusion, serum cholesterol levels may be good candidates for predicting prognosis in PTCL−U.

55例血管免疫母细胞性T细胞淋巴瘤的临床特征和预后模型

Angioimmunoblastic T-cell lymphoma (AITL) is a distinct subtype of peripheral T-cell lymphoma with unique clinical and pathological features. This study aim to analyze the characteristics of AITL and to design a prognostic model specifically for AITL, providing risk stratification in affected patients. We retrospectively analyzed 55 newly diagnosed AITL patients at the Affiliated Tumor Hospital of Guangxi Medical University from January 2007 to June 2016 and was permitted by the Ethics Committee of the Affiliated Tumor Hospital of Guangxi Medical University. Among these patients, the median age at diagnosis was 61 (27-85) and 54.55% (30/55) of the patients were older than 60 years. 43 patients were male, accounting for 78.18% of the whole. Among these, 92.73% (51/55) of the diagnoses were estimated at advanced stage. A total of 20 (36.36%) patients were scored &amp;gt;1 by the ECOG performance status. Systemic B symptoms were described in 16 (29.09%) patients. In nearly half of the patients (27/55; 49.09%) had extranodal involved sites. The most common extranodal site involved was BM (11/55; 20.00%). 38.18% (21/55) and 27.27% (15/55) patients had fever with body temperature ≥37.4℃ and pneumonia, respectively. 40% (22/55) patients had cavity effusion or edema. Laboratory investigations showed the presence of anemia (hemoglobin &amp;lt;120 g/L) in 60% (33/55), thrombocytopenia (platelet counts &amp;lt;150×109/L) in 29.09% (16/55), and elevated serum LDH level in 85.45% (47/55) of patients. Serum C-reactive protein and β2-microglobulin levels were found to be elevated in 60.98% (25/41) and 75.00% (36/48)of the patients, respectively. All patients had complete information for stratification into 4 risk subgroups by IPI score, in which scores of 0-1 point were low risk (9/55;16.36%), two points were low-intermediate risk (17/55; 30.92%), three points were high-intermediate risk (20/55; 36.36%), and four to five points were high risk (9/55; 16.36%). 55 patients were stratified by PIT score with 7.27% (4/55) of patients classified as low risk, 32.73% (18/55) as low-intermediate risk, 34.55% (19/55) as high-intermediate risk, and 25.45% (14/55) as high risk depending on the numbers of adverse prognostic factors.The estimated two-year and five-year overall survival (OS) rate for all patients were 50.50% and 21.70%. Univariate analysis suggested that ECOG PS (p= 0.000), Systemic B symptoms (p= 0.006), fever with body temperature ≥ 37.4℃ (p= 0.000), pneumonia (p= 0.001), cavity effusion or edema (p= 0.000), anemia (p= 0.013), and serum LDH (p= 0.007) might be prognostic factors (p&amp;lt; 0.05) for OS. Multivariate analysis found prognostic factors for OS were ECOG PS (p= 0.026), pneumonia (p= 0.045), and cavity effusion or edema(p= 0.003). We categorized three risk groups: low-risk group, no adverse factor; intermediate-risk group, one factor; and high-risk group, two or three factors. Five-year OS was 41.8% for low-risk group, 15.2% for intermediate-risk group, and 0.0% for high-risk group (p&amp;lt; 0.000). Patients with AITL had a poor outcome. This novel prognostic model balanced the distribution of patients into different risk groups with better predictive discrimination as compared to the International Prognostic Index and Prognostic Index for PTCL. Disclosures No relevant conflicts of interest to declare.

Baseline total lesion glycolysis combined with interim positron emission tomography-computed tomography is a robust predictor of outcome in patients with peripheral T-cell lymphoma.

BackgroundPeripheral T‐cell lymphoma (PTCL) represents a heterogeneous and rare subgroup of aggressive lymphomas that generally demonstrate poor clinical outcomes with conventional treatment. Since the prognosis of PTCL is heterogeneous, more accurate risk assessment, and risk‐adapted treatment strategies are required. In this study, we examined whether interim positron emission tomography (iPET)‐computed tomography (PET/CT) results can be combined with baseline volume‐based metabolic assessments including total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) for risk stratification in PTCL.MethodsThe data of 63 patients with nodal PTCL, who had analyzable baseline PET/CT and iPET, were retrospectively reviewed. We calculated the baseline TMTV and TLG values. All iPET responses were analyzed using the Deauville 5‐point scale.ResultsOn univariate analysis, a prognostic index for PTCL (PIT) higher than 2 (hazard ratio [HR], 2.03; P = .026), high TMTV (>389 cm3; HR, 2.24; P = .01), high TLG (>875; HR, 3.77; P = .0005), and positive iPET (HR, 2.18; P = .009) were significantly associated with poorer progression‐free survival (PFS). On multivariate analysis, only high TLG and positive iPET independently predicted both poorer overall survival (OS) and PFS. A model combining TLG and iPET showed that patients with low TLG and negative iPET had superior outcomes, with a 5‐year PFS and OS of 72% and 90%, respectively. Conversely, both 5‐year PFS and OS for those with high TLG and positive iPET were 0%.ConclusionsIn summary, TLG combined with iPET predicted survival in PTCL more accurately. This information may help in the development of risk‐adapted treatment strategies for PTCL.

Development of a Novel Clinical Prognostic Model for Patients With Angioimmunoblastic T-Cell Lymphoma.

In this study we aimed to identify a set of prognostic factors for angioimmunoblastic T-cell lymphoma (AITL) and establish a novel prognostic model. The clinical data of 64 AITL patients enrolled to the Fourth Hospital of Hebei Medical University (from 2012 Jan to 2017 May) were retrospectively analyzed. The estimated 5-year overall survival and progression-free survival of this cohort of patients were 45.8% and 30.8%, respectively. Univariate analysis showed that age > 60 years, performance status ≥2, Ann Arbor stage III/IV, lactate dehydrogenase > 250 U/L, serum albumin (ALB) < 30 g/l, Coombs test positive, and Ki-67 rate ≥ 70% were significantly associated with poor prognosis. Multivariate analysis demonstrated that age > 60 years, ALB < 30 g/l, Ki-67 rate ≥ 70%, and Coombs test positive were independent prognosis factors for AITL. Here a new prognostic model, named as AITLI, was constructed using the top 5 significant prognostic factors for AITL prognostic prediction. The AITL patients were stratified into 3 risk groups: low, intermediate, and high risk groups. The new prognostic model AITLI showed better performance in predicting prognosis than the International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT) that were wisely used to predict the outcome for patients with other subtypes of lymphoma.

Prognostic Value of Platelet Count in Patients with Peripheral T Cell Lymphoma

Background: Peripheral T cell lymphoma (PTCL) is a heterogeneous entity with poor survival. We evaluated the neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and platelet count as new prognostic factors for PTCL. Patients and Methods: We retrospectively analyzed 77 patients with PTCL initially treated with anthracycline-based chemotherapy. Survival curves were compared between groups with different initial NLR (iNLR), end-point NLR (eNLR), initial ALC, and platelet counts. Cox regression was used to analyze the risk factor for survival. Results: Patients with a higher eNLR (≥3), lymphopenia (< 1,000/μL), and thrombocytopenia (< 150 K/μL) had an inferior progression-free survival (PFS) and overall survival (OS) compared to their counterparts, while a higher iNLR (≥3) was predictive of a shorter OS but not PFS. Among these, thrombocytopenia was an independent poor prognostic factor for both PFS and OS, with a hazard ratio of 2.42 (p = 0.012) for PFS and 4.21 (p = 0.006) for OS. The presence of thrombocytopenia further stratified patients with a worse prognosis within overlapping risk-groups by the prognostic index for PTCL. Conclusions: Our study showed that thrombocytopenia at diagnosis was an independent prognostic factor for survival in patients with PTCL.

Reappraisal of nodal Epstein-Barr Virus-negative cytotoxic T-cell lymphoma: Identification of indolent CD5+ diseases.

Nodal cytotoxic molecule (CM)‐positive peripheral T‐cell lymphoma (CTL) has recently been recognized as a clinicopathologically distinct disease. To further characterize this disease, here we compared 58 patients with Epstein‐Barr virus (EBV)‐negative CTL to 48 patients with EBV‐positive CTL. The two groups did not differ in histopathology, T‐cell receptor (TCR) expression or rearrangement incidences, or survival curves. However, patients with EBV‐negative CTL less frequently showed hepatic involvement (P = .007), B symptoms (P = .020), hemophagocytosis (P = .024), and detectable CD4 (P = .002) and CD5 (P = .009). Univariate and multivariate analyses identified three factors that independently predicted favorable survival, onset age <60 years (P = .002), CD5 expression (P = .002), and mixed morphology (P = .013), TCRαβ was not an independent predictor (P = .30), but was strongly linked with long survivorship among patients younger than 60 years old. A prognostic model incorporating these factors worked well for prognostic delineation, independently of the International Prognostic Index (P = .007 vs P = .082) and Prognostic Index for PTCL (P = .020 vs P = .15). Moreover, this constellation of findings indicated two nodal indolent diseases: CD5+ TCRαβ (n = 13), and CD5+ NK‐cell type lacking TCR expression or clonal TCRγ rearrangement (n = 4). The survival curves for these two groups were significantly superior to others (n = 29, P < .001). These diseases appear to be unique in their indolent clinical behavior, and should be managed differently from other diseases.

Clinicopathological analysis of 12 patients with Epstein-Barr virus-positive primary intestinal T/natural killer-cell lymphoma (EBV+ ITNKL).

Epstein-Barr virus-positive (EBV+ ) intestinal T/natural killer (NK) cell lymphoma (ITNKL) is an uncommon tumour with an extremely aggressive clinical behaviour. However, the clinicopathological characteristics of this tumour, including T cell receptor (TCR) phenotype and the patient's background, remain unknown. The aim of this study was to elucidate the detailed clinicopathological profile of EBV+ ITNKL. We enrolled 12 patients with EBV+ ITNKL without nasal involvement into the study. All patients were characterized by involvement of the small intestine with concurrent lesions of the large intestine in two patients. Seven patients (58%) had Lugano stages IIE/IV disease and eight (67%) were categorized as high-intermediate/high-risk according to the Prognostic Index for PTCL (PIT). Three patients (25%) with an age of onset of less than 50 years had chronic active EBV infection (CAEBV). Five CD56-positive patients (42%) had a poorer prognosis than those without CD56 expression (P = 0.008). NK cell-type lymphoma defined by the absence of any TCR expression or clonal TCR-γ rearrangement was found in six patients (50%). Interestingly, EBV+ intra-epithelial lymphocytosis was observed in one case with a background of CAEBV. This study is the first to shed light on the significant heterogeneity of EBV+ ITNKL and its relationship with CAEBV, especially in patients younger than 50 years of age. These observations will provide a guide for diagnostic and therapeutic approaches in routine practice.

Long Term Curative Effects and Prognostic Analysis of Stem Cell Transplantation for Treating Patients with Peripheral T Cell Lymphoma

To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation in the treatment of patients with peripheral T cell lymphoma (PTCL). The clinical records of 53 patients with PTCL were collected and analyzed retrospectively. The prognostic value of prognostic index PIT were evaluated. Among 53 cases of PTCL, 31 patients underwent hematopoietic autologous stem cell transplantation (auto-HSCT), 22 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), their median follow-up time was 62 (1-174) months, from them 1 patients was not engrafted in each group, 4 patients underwent allo-HSCT died within 1 month after transplantation. The 3-year overall survival rates in auto- and allo-HSCT groups were 42.3% (95% CI 24.1-60.5%) and 42.9% (95% CI 21.7-64.1%) respectively, 11 and 3 patients died of relapse after auto-HSCT and allo-HSCT, respectively, the treatment-related mortality (TRM) was 22.6% (95% CI 6.1%-39.0%) and 48.7% (95% CI 26.8%-70.7%), respectively. Univariate analysis showed that bone marrow involvement at diagnosis was associated with poor prognosis. In allo-HSCT group, PIT showed statistically significant difference in both OS and PFS between the patients without or with one risk factor and the patients with 3-4 risk factors. The relapse rate of relapse/refractory patients is high after auto-HSCT. The TRM is high after allo-HSCT, but long term survival is promising. The prognostic index for PTCL can reliably assess the prognosis of PTCL.

Interim Positron Emission Tomography Scan Predicts Early Outcomes Of Patients With Peripheral T-Cell Lymphoma

IntroductionInterim positron emission tomography (PET) scan has shown to be useful for evaluating response in Hodgkin lymphoma. And, there has been increasing interests in using interim PET for predicting outcomes in diffuse large B-cell lymphoma. However, few data are available regarding prognostic value of interim PET in patients with peripheral T cell lymphoma (PTCL). Recently, in an attempt to standardize reporting criteria for interim PET, Deauville five-point scale (5-PS), which visually assess the uptake of lesions in comparison with background mediastinal and liver uptakes, were proposed, but this was not investigated in PTCL. Therefore, the aim of this study was to determine the prognostic role of interim PET, assessed by Deauville 5-PS, in patients with PTCL treated with systemic chemotherapy. Patients and MethodsWe consecutively enrolled newly diagnosed PTCL patients, treated with systemic chemotherapy (CHOP/CHOP-like or non-anthracycline-based) and had the baseline PET data with ³1 evaluable hypermetabolic lesion between 2006 and 2012 in two Korean institutions. Patients treated with upfront chemoradiotherapy before interim PET scan were excluded. Interim PET scan was performed after 3 cycles of chemotherapy, before 1 week of the next cycle. Interim PET response was visually assessed by 5-PS and four point or higher was regarded as positive. All PET assessment was performed by 2 nuclear medicine specialists at each institution, and the discrepancy of assessment was resolved by the agreement through discussion. ResultsA total of 35 patients was included in this analysis. The median age was 60 years (range, 31-79) and 26 (74%) were male. Histologic subtypes included were PTCL, not otherwise specified in 10 (29%), extranodal NK/T cell lymphoma in 8 (23%), angioimmunoblastic T cell lymphoma in 7 (20%), anaplastic large cell lymphoma, ALK negative in 4 (11%), and others in 6 (18%). 22 patients (63%) were presented as advanced stage disease and 9 (26%) had B symptoms. ECOG performance status was ≥ 2 in 7 (20%), serum LDH level was elevated in 16 (46%), and bone marrow was involved in 5 (14%). Thus, 14 patients (40%) were classified as high risk (≥ 2 factors) by the prognostic index for PTCL (PIT). 31 patients (89%) completed planned systemic chemotherapy ± involved-field radiotherapy and 25 (71%) achieved complete response by systemic chemotherapy. 10 patients (29%) underwent consolidative autologous stem cell transplantation (ASCT).Using 5-PS, interim PET scan was visually scored as follows; 1 point in 10 patients (29%), 2 in 6 (17%), 3 in 8 (23%), 4 in 7 (20%), and 5 in 4 (11%). Among these, 11 patients (31%) had 4 point or above were considered positive for interim PET scan. With a median follow-up of 43.4 (range, 4.3-89.8) months, progression-free survival (PFS; median, 5.2 vs 38.0 months, respectively; P=0.001) and overall survival (median, 12.6 months vs not reached, respectively; P=0.004) was significantly worse in patients with positive interim PET than those with negative results. In multivariate analysis for PFS, high risk of PIT (HR, 3.67; 95% CI, 1.13-11.99) and positive interim PET (HR, 4.02; 95% CI, 1.32-12.23) were independently associated with faster disease progression, whereas consolidation with ASCT was independent prognostic factor for better PFS (HR, 0.23; 95% CI, 0.06-0.84). ConclusionVisual assessment of interim PET scan using Deauville 5-PS appears to predict early outcomes of patients with PTCL. Patients with positive interim PET shows highly predictive of extremely poor outcomes. Therefore, our findings suggest further studies regarding early stratification based on interim PET results as a response-adapted treatment strategies in patients with PTCL are needed to improve outcomes. Disclosures:No relevant conflicts of interest to declare.

Autologous Stem Cell Transplantation as the First-Line Treatment for Peripheral T Cell Lymphoma: Results of a Comprehensive Meta-Analysis

Objective: In view of the poor prognosis of most peripheral T cell lymphoma (PTCL) subtypes treated with conventional chemotherapy such as CHOP/CHOP-like regimens, high-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) seems a reasonable option in eligible patients. Nevertheless, owing to the small size of the study and the heterogeneity of most published series, a consensus on the role of ASCT as the first-line consolidation therapy for high-risk PTCL patients has not been reached so far. Study Design: We searched MEDLINE, EMBASE, EBSCO, Web of Science, clinicaltrials.gov and the Cochrane Library. Hazard ratio (HR) and 95% confidence intervals (CIs) were calculated by a fixed/random effect model. Results: Twenty-one studies were eligible. Although no statistical significance was observed in these studies, there was a trend toward survival advantage for the HDT/ASCT group as compared to the historical control group (HR 0.81, 95% CI 0.31-2.13). Statistical differences were confirmed in terms of overall survival (OS) between complete remission (CR) and non-CR patients (HR 3.17, 95% CI 0.92-5.42), patients with good and poor risk according to the International Prognostic Index (IPI; HR 0.36, 95% CI 0.22-0.60, I² 49%) and Prognostic Index for PTCL (PIT; HR 0.31, 95% CI 0.17-0.58; HR 0.31, 95% CI 0.18-0.54). Conclusion: The clear and convincing proof of the effects of up-front HDT/ASCT still depends on sufficient large PTCL-restricted randomized trials in the future. Patients who failed to attain CR before transplant exhibited a worse prognosis; patients with good risk of IPI or PIT had a substantially better OS after ASCT.

Loss of TCR-beta F1 and/or EZRIN expression is associated with unfavorable prognosis in nodal peripheral T-cell lymphomas

Nodal peripheral T-cell lymphoma (nodal PTCL) has an unfavorable prognosis, and specific pathogenic alterations have not been fully identified. The biological and clinical relevance of the expression of CD30/T-cell receptor (TCR) genes is a topic under active investigation. One-hundred and ninety-three consecutive nodal PTCLs (89 angioimmunoblastic T-cell lymphomas (AITL) and 104 PTCL-unspecified (PTCL-not otherwise specified (NOS)) cases) were analyzed for the immunohistochemical expression of 19 molecules, involving TCR/CD30 pathways and the associations with standard prognostic indices. Mutually exclusive expression was found between CD3 and TCR-beta F1 with CD30 expression. Taking all PTCL cases together, logistic regression identified a biological score (BS) including TCR molecules (TCR-beta F1 and EZRIN) that separates two subgroups of patients with a median survival of 34.57 and 5.20 months (P<0.001). Multivariate analysis identified BS and the prognostic index for PTCL (PIT) score as independent prognostic factors. This BS maintained its significance in multivariate analysis only for the PTCL-NOS subgroup of tumors. In AITL cases, only a high level of ki67 expression was related to prognosis. A BS including molecules involved in the TCR signaling pathway proved to be an independent prognostic factor of poor outcome in a multivariate analysis, specifically in PTCL-NOS patients. Nevertheless, validation in an independent series of homogeneously treated PTCL patients is required to confirm these data.

Autologous stem cell transplantation as consolidation therapy for patients with peripheral T cell lymphoma in first remission: long-term outcome and risk factors analysis

This report is a retrospective analysis of 65 patients with peripheral T cell lymphoma (PTCL), who underwent high-dose therapy and autologous hematopoietic stem cell transplantation (autoHCT) as a consolidation of first response achieved with either induction or salvage chemotherapy. We intended to determine the prognostic factors that influenced outcome after autoHCT and to define the predictive value of the scoring systems most often applied for transplant outcomes. Nineteen patients in either complete or partial remission underwent autoHCT after induction chemotherapy. Forty-six patients received second-line chemotherapy as a consolidation of partial response after induction chemotherapy (n = 34) or as a salvage therapy after primary induction failure (n = 12), and thereafter proceeded to autoHCT. Finally, the 36 patients were in complete remission, and 29 in partial remission at autoHCT. The median follow-up of survivors was 53 months (range 7–157 months). The 5-year overall survival and progression-free survival for all patients were 61.5 % (95 % CI 47.0–74.2 %) and 59.4 % (95 % CI 46.1–71.5 %), respectively. In multivariate analysis, bone marrow involvement at diagnosis and less than partial remission after induction chemotherapy were factors independently predictive for overall survival and progression-free survival. The prognostic index for PTCL could reliably stratify the prognosis of PTCL in this analysis.

Nodal cytotoxic molecule (CM)‐positive Epstein–Barr virus (EBV)‐associated peripheral T cell lymphoma (PTCL): a clinicopathological study of 26 cases

The clinicopathological distinctiveness of nodal cytotoxic molecule (CM)-positive Epstein-Barr virus (EBV)-associated peripheral T cell lymphoma (PTCL) remains to be clarified. We investigated 26 patients with this lymphoma compared to nodal CM(+) EBV(-) PTCL (n = 39) and extranasal natural killer/T cell lymphoma of nasal type (ENKTL, n = 44). Nodal CM(+) EBV(+) PTCL patients were more likely to have B symptoms (P = 0.019) and hepatic involvement (P = 0.026) than nodal CM(+) EBV(-) PTCL patients. The former also had more Stage III/IV disease (P = 0.025) but much less cutaneous involvement (P < 0.001) than ENKTL patients at diagnosis. This nodal EBV(+) lymphoma possessed a distinctive immunophenotype of high CD8(+), CD56(-) pattern with an aggressive clinical course (median, 6.6 months). Thrombocytopenia was present in 11 (50%) patients and found to be the strongest prognostic indicator (P = 0.001) in this nodal EBV(+) group. For all nodal CM(+) PTCL cases CD5 negativity, but not EBV positivity, was the significant adverse prognostic factor (P < 0.002) in a multivariate analysis, independent of prognostic index for PTCL (PIT) or International Prognostic Index (IPI) scores. Nodal CM(+) EBV(+) PTCL constitutes a unique group of lymphomas distinct from ENKTL. The data provide support for our assertion that nodal CM(+) PTCL should be distinguished in the 2008 WHO category of PTCL, not otherwise specified.

Retrospective analysis of prognostic factors for angioimmunoblastic T-cell lymphoma: a multicenter cooperative study in Japan

AbstractAngioimmunoblastic T-cell lymphoma (AITL) is a major type of peripheral T-cell lymphoma (PTCL). To elucidate the clinicopathologic characteristics and prognosis of AITL in Japan, we retrospectively analyzed 207 patients with AITL. The median patient age was 67 years (range, 34-91 years), with 73% of patients older than 60 years. With a median follow-up of 42 months in surviving patients, 3-year overall survival (OS) was 54% and progression-free survival (PFS) was 38%. The International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT) were predictive for OS in this analysis. Multivariate analysis found that age older than 60 years, elevated white blood cell (WBC) and IgA levels, the presence of anemia and thrombocytopenia, and extranodal involvement at > 1 site were significant prognostic factors for OS, and IgA, anemia, and mediastinal lymphadenopathy were significant prognostic factors for PFS. A novel prognostic model consisting of the prognostic factors for OS was successfully constructed. In conclusion, IPI and PIT were still useful for prognostication of AITL, and other factors, including those not used in IPI, such as IgA, anemia, WBC count, thrombocytopenia, and mediastinal lymphadenopathy, also significantly affected prognosis. Future investigations for IgA as a unique prognostic factor are warranted.

Frontline Autologous Stem Cell Transplantation As Intensive Consolidation in Patients with Peripheral T Cell Lymphomas: Multicenter Phase II Trial in Korea

Abstract 4477Peripheral T cell lymphomas (PTCLs) are an aggressive subtype of non-Hodgkins lymphoma and they have shown the shorter survival compared with B cell lymphoma. High-dose chemotherapy (HDT) followed by autologous stem cell transplantation (HDT/ASCT) for PTCLs has a potential meaning of consolidating remission for PTCLs. However, the effectiveness of ASCT on distinct conditioning regimens, the optimal transplant timing in the frontline or relapsed are still unclear.We investigated the clinical outcomes of HDT/ASCT as frontline intensification in 46 patients with newly diagnosed PTCLs except ALK(+) anaplastic large cell lymphoma. Patients underwent ASCT with a uniform conditioning regimen (busulfex, cyclophosphamide and etoposide). The median age was 47 years (17–65). The histological subtypes were 47.9% PTCL-NOS (n=23), 18.8% anaplastic large cell lymphoma (n=9), 4.2% angioimmunoblastic T cell lymphoma (n=2), 25% extranodal NK/T cell, nasal type (n=12), 2.1% hepatosplenic T cell lymphoma (n=1) and 2.1% enteropathy-associated T cell lymphoma. Thirty patients (62.6%) presented with advanced stage disease (III/IV) and 16 (33.3%) had B symptoms. At diagnosis, 21 patients (43.8%) were classified as high-intermediate/high risk by the age-adjusted IPI (aaIPI) and 10 (20.9%) were classified as high-risk (more than 2 factors) by the prognostic index for PTCL (PIT). Thirty-one patients (67%) could undergo HDT/HSCT and disease status at pretransplant consisted of 23 patients (50 %) with CR and 8 patients (17.4%) with PR. 6 out of 8 patients with PR at pretransplantation improved the response to CR after HDT/ASCT. There was no significant difference of the response rate between CHOP alone or CHOP-like chemotherapy and non-anthracycline-based chemotherapeutic regimen. At a median follow-up of 32.9 months, 23 patients (50%) are alive. The 5-year probability of overall and progression-free survival (PFS) was 48.2 ± 8.1 % and 47.4 ± 8.1%, respectively. However, the 5-year OS and PFS rate in transplanted patients was 57.3± 10.2 % and 55.3 ± 11.3 %, respectively. Conclusion:Frontline HDT/ASCT in patients with PTCL could be performed with a high response rates and a substantial impact on improving outcome for PFS. Our findings also indicate that busulfex, cyclophosphamide and etoposide is a feasible conditioning regimen in ASCT for PTCLs. Disclosures:No relevant conflicts of interest to declare.

Multicentre phase II study of the CyclOBEAP regimen for patients with peripheral T-cell lymphoma with analysis of biomarkers

Peripheral T-cell lymphoma (PTCL) has a poorer prognosis than diffuse large B-cell lymphoma (DLBCL). We administered the CyclOBEAP regimen (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) to patients with DLBCL, and reported its safety and efficacy. Here, we report the results of a multicentre phase II study of the CyclOBEAP regimen in patients with PTCL. In addition, NME1 remained a prognostic factor for survival, as shown in patients who were treated with CyclOBEAP. There were 84 eligible patients and the median age was 54 years. The 5-year overall survival (OS) rate was 72% and progression-free survival (PFS) rate was 61%. The 5-year OS was 93% among the anaplastic large-cell lymphoma cases, 74% among the angioimmunoblastic T-cell lymphoma cases, and 63% among the cases of PTCL-not otherwise specified. When the patients were divided according to the International Prognostic Index or Prognostic Index for PTCL, the 5-year OS and PFS rates did not significantly differ among the risk groups. Positivity for NME1 was found to be a significant independent prognostic factor. Grade 4 neutropenia was observed in 80 patients and thrombocytopenia in nine patients. Our results suggest that the CyclOBEAP therapy is safe and effective for PTCLs. Furthermore, the NME1 protein may be an important prognostic factor in PTCL.

Clinical Usefulness and Prognostic Value of Interim PET/CT for the Treatment of Peripheral T Cell Lymphomas.

AbstractAbstract 2808Although interim 18F-fluoro-2-dexoy-D-glucose-positron emission tomography (FDG-PET)/computerized tomography (CT) scan has emerged as a powerful prognostic tool in predicting treatment outcome in Hodgkin's lymphoma (HL) and diffuse large B cell lymphoma (DLBCL), the positive predictive value (PPV) of interim PET/CT scanning has not been determined in patients with peripheral T cell lymphoma (PTCL). The sequential interim PET/CT was prospectively investigated to determine whether it provided additional prognostic information and could be a positive predictable value for the treatment of PTCL. Patients and Methods:Fifty-five newly diagnosed patients with PTCL were enrolled from Sep. 2005 to July 2009 at a single institution. The PET/CT analysis was performed at the time of diagnosis and mid-treatment of CHOP/CHOP-like or other chemotherapy (EPOCH and IMEP). The clinical stage and response of the patients were assessed according to revised response criteria for aggressive lymphomas (Cheson, J Clin Oncol, 2007). The positivity of interim PET/CT was determined based on the semi-quantitative assessment of the maximal standardized uptake value (Cut-off SUVmax value of 3.0). Results:Median age was 55 years (range: 23–77). 31 patients (56.4%) presented in advanced stages and 13 (23.6%) had bone marrow involvements. The histological subtypes were 40.0% PTCL-unspecified (n=22), 5.1% angioimmunoblastic T cell (n=5), 38.2% nodal or extranodal NK/T cell (n=21), and others. At diagnosis, 24 patients (43.6%) were classified as high-risk by the international prognostic index (IPI) and 22 (40%) were classified as high-risk (more than 2 factors) by the prognostic index for PTCL (PIT). 47 patients could be assessed the interim response and 24 patients (43.6%) remained positive metabolic uptakes in interim PET/CT. The patients with positive interim PET/CT showed a significantly higher relapse rate (75.0%) than those with negative interim PET/CT (43.5%) (P =0.028). After following median 12.7 months, positivity of interim PET/CT was the prognostic factor for both OS and PFS, with a hazard ratio of 4.11 (1.30 – 13.01) and 3.26 (1.19 – 8.96), respectively. Six patients (10.9%) who determined to have positive interim PET/CT were revealed false-positive uptakes after locoregional biopsy (PPV of 0.75). [Display omitted] Conclusions:Interim PET/CT has a significant predictive value for disease progression and survival of PTCL. The patients with positive interim PET/CT response should be considered an intensive therapeutic plan for overcoming their poor clinical outcome. Disclosures:No relevant conflicts of interest to declare.