Search tips
Search criteria

Results 1-25 (1840796)

Clipboard (0)

Related Articles

1.  Prognostic Markers in Peripheral T-Cell Lymphoma 
Based on their own experience and knowledge of the literature, the authors review the pathobiological characteristics of peripheral T-cell lymphomas (PTCLs), focusing on the available prognostic indicators. The International Prognostic Index (IPI), which is based on age, performance status, lactate dehydrogenase [LDH], stage, and extranodal involvement, appears to be efficient as a prognostic index for PTCLs, at least in part and especially for certain PTCL subtypes. However, it is not so satisfactory for the two commonest PTCLs, PTCL not otherwise specified (PTCL/NOS) and angioimmunoblastic T-cell lymphoma (AITL), for which novel scores, possibly based on the biologic features of the tumors, have been explored. An Italian cooperative group proposed a revision of the IPI for PTCL unspecified (PTCL-U), the Prognostic Index for PTCL-U (PIT), which includes age, performance status, LDH, and bone marrow involvement. The PIT apparently offered some advantages, but they were not confirmed in subsequent studies. A clinical-biological score (the Bologna score) was then proposed, including tumor proliferation and clinical features (age, LDH, and performance status). This score appears promising and offers the intriguing advantage of integrating biological and clinical elements, but independent validation on a large series is still warranted. More recently, gene expression profiling has been used to identify novel molecular prognostic factors. In particular, inactivation of the NFκB pathway, high expression of proliferation-associated genes, and cytotoxic molecular phenotype seem to be associated with a worse outcome. So far, however, none of these indicators has been validated in an independent series. Finally, various reports have dealt specifically with the prognostication of NK-derived tumors, including nasal and nasal-type lymphomas. Both the IPI and dedicated models have turned out to be of prognostic relevance for these tumors. In conclusion, although the IPI is somewhat effective for PTCL prognostication, novel scores that are more refined and possibly disease-specific are warranted. The validation process for several models, including clinical-pathological and molecular models, is now ongoing.
PMCID: PMC2948168  PMID: 20690003
Peripheral T-cell lymphoma; PTCL; Prognostication; Gene expression profile; International prognostic index; Bologna score
2.  Significance of clinical factors as prognostic indicators for patients with peripheral T-cell non-Hodgkin lymphoma: A retrospective analysis of 252 cases 
Molecular and Clinical Oncology  2013;1(5):911-917.
The aim of this study was to retrospectively analyze the significance of different clinical factors for predicting the prognosis of patients with peripheral T-cell non-Hodgkin lymphoma (PTCL) with a median follow-up of 23 months. A total of 252 PTCL patients admitted to the First Affiliated Hospital of the School of Medicine of Zhejiang University between 2005 and 2011 were retrospectively reviewed. At a median follow-up of 23 months, the overall survival (OS) rate was 23.8%. Our results revealed that the presence of B symptoms (P<0.001), Eastern Cooperative Oncology Group (ECOG) score ≥2 (P<0.001), bone marrow involvement (BMI) (P<0.001), elevated lactate dehydrogenase (LDH) levels (P<0.001), elevated β2-MG levels (P<0.001), Ann Arbor stages III/IV (P=0.007) and International Prognostic Index (IPI) ≥3 (P=0.001) were poor prognostic factors for OS and intensive chemotherapy achieved a better OS outcome compared to the CHOP treatment. In conclusion, elevated LDH and β2-MG levels, B symptoms, Ann Arbor stages III/IV, BMI, high IPIs and high ECOG scores predict an unfavorable prognosis for PTCL patients. Compared to the conventional CHOP regimen, the intensive chemotherapy treatment may improve the prognosis of PTCL patients.
PMCID: PMC3915658  PMID: 24649270
β2-microglobulin; bone marrow involvement; international prognostic index; lactate dehydrogenase; peripheral T-cell non-Hodgkin lymphoma
3.  A TNM Staging System for Nasal NK/T-Cell Lymphoma 
PLoS ONE  2015;10(6):e0130984.
Ann Arbor stage has limited utility in the prognostication and treatment decision making in patients with NK/T-cell lymphoma (NKTCL), as NKTCL is almost exclusively extranodal and the majority is localized at presentation for which radiotherapy is the most important treatment and local invasiveness is the most important prognostic factor. In this study, we attempted to establish a TNM (Tumor-Node-Metastasis) staging system for nasal NKTCL (N-NKTCL). The staging rules of other head and neck cancers were used as reference along with the data of our 271 eligible patients. The primary tumor was classified into T1 to T4, and cervical lymph node metastasis was classified into N0 to N2 according to the extent of involvement. Any lesions outside the head and neck were classified as M1. N-NKTCL thereby was classified into four stages: stage I comprised T1-2N0M0; stage II comprised T1-2N1M0 and T3N0M0; stage III comprised T3N1M0, T1-3N2M0, and T4N0-2M0; and stage IV comprised TanyNanyM1. This staging system showed excellent performance in prognosticating survival. In the current series, the 5-year survival rates of patients with stages I, II, III, and IV N-NKTCL were 92%, 64%, 23%, and 0, respectively. Moreover, the predictive value of several currently used factors was abrogated in the presence of the TNM stage. The TNM staging system is highly effective in stratifying tumor burden and survival risk, which may have significant implications in the treatment decision making for patients with N-NKTCL.
PMCID: PMC4476596  PMID: 26098892
4.  PD-L1 is upregulated by EBV-driven LMP1 through NF-κB pathway and correlates with poor prognosis in natural killer/T-cell lymphoma 
Natural killer/T-cell lymphoma (NKTCL) is an Epstein–Barr virus (EBV)-associated, highly aggressive lymphoma. Treatment outcome remains sub-optimal, especially for advanced-stage or relapsed diseases. Programmed cell death receptor 1 (PD-1) and PD ligand 1 (PD-L1) have become promising therapeutic targets for various malignancies, but their role in the pathogenesis and their interactions with EBV in NKTCL remains to be investigated.
Expression of PD-L1 was measured in NK-92 (EBV-negative) and SNK-6 (EBV-positive) cells by western blot, quantitative real-time PCR and enzyme-linked immunosorbent assay, and flow cytometry, respectively. Latent membrane protein 1 (LMP1)-harboring lentiviral vectors were transfected into NK-92 cells to examine the correlation between LMP1 and PD-L1 expression. Proteins in the downstream pathways of LMP1 signaling were measured in NK-92 cells transfected with LMP1-harboring or negative control vectors as well as in SNK-6 cells. PD-L1 expression on tumor specimens and serum concentration of soluble PD-L1 were collected in a retrospective cohort of patients with Ann Arbor stage I~II NKTCL, and their prognostic significance were analyzed.
Expression of PD-L1 was significantly higher in SNK-6 cells than in NK-92 cells, at both protein and mRNA levels. Expression of PD-L1 was remarkably upregulated in NK-92 cells transfected with LMP1-harboring lentiviral vectors compared with those transfected with negative control vectors. Proteins in the MAPK/NF-κB pathway were upregulated in LMP1-expressing NK-92 cells compared with the negative control. Selective inhibitors of those proteins induced significant downregulation of PD-L1 expression in LMP1-expressing NK-92 cells as well as in SNK-6 cells. Patients with a high concentration of serum soluble PD-L1 (≥3.4 ng/ml) or with a high percentage of PD-L1 expression in tumor specimens (≥38 %) exhibited significantly lower response rate to treatment and remarkably worse survival, compared with their counterparts. A high concentration of serum soluble PD-L1 and a high percentage of PD-L1 expression in tumor specimens were independent adverse prognostic factors among patients with stage I~II NKTCL.
PD-L1 expression positively correlated LMP1 expression in NKTCL, which was probably mediated by the MAPK/NF-κB pathway. PD-L1 expression in serum and tumor tissues has significant prognostic value for early-stage NKTCL.
Electronic supplementary material
The online version of this article (doi:10.1186/s13045-016-0341-7) contains supplementary material, which is available to authorized users.
PMCID: PMC5064887  PMID: 27737703
Natural killer/T-cell lymphoma; Latent membrane protein 1; Epstein–Barr virus; Programmed cell death receptor 1
5.  Lymphopenia is an important prognostic factor in peripheral T-cell lymphoma (NOS) treated with anthracycline-containing chemotherapy 
Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of aggressive T-cell lymphomas with poor treatment outcomes. The aim of this study was to evaluate whether lymphopenia at diagnosis would have an adverse effect on survival in patients with PTCL-NOS treated with anthracycline-containing chemotherapy.
A total of 118 patients with PTCL-NOS treated with anthracycline-containing chemotherapy from 4 Korean institutions were included.
Thirty-six patients (30.5%) had a low absolute lymphocyte count (ALC, < 1.0 × 109/L) at diagnosis. Patients with lymphopenia had shorter overall survival (OS) and progression-free survival (PFS) rates compared with patients with high ALCs (P = 0.003, P = 0.012, respectively). In multivariate analysis, high-intermediate/high-risk International Prognostic Index (IPI) scores and lymphopenia were both associated with shorter OS and PFS. Treatment-related mortality was 25.0% in the low ALC group and 4.8% in the high ALC group (P = 0.003). In patients considered high-intermediate/high-risk based on IPI scores, lymphopenia was also associated with shorter OS and PFS (P = 0.002, P = 0.001, respectively).
This study suggests that lymphopenia could be an independent prognostic marker to predict unfavorable OS and PFS in patients with PTCL-NOS treated with anthracycline-containing chemotherapy and can be used to further stratify high-risk patients using IPI scores.
PMCID: PMC3170642  PMID: 21843362
peripheral T-cell lymphoma; not otherwise specified; lymphopenia; international prognostic index; prognostic factor
6.  18F-fluorodeoxyglucose positron emission tomography in the staging and prognosis of T cell lymphoma 
Leukemia & lymphoma  2013;54(10):2163-2167.
We previously reported that 18F-fluorodeoxyglucose positron emission tomography scan (FDG-PET) is almost universally positive in patients with T cell lymphoma. In the present analysis we examined the impact of FDG-PET on the initial staging of peripheral T cell lymphomas (PTCLs), and the prognostic value of interim FDG-PET. This retrospective analysis identified patients with mature T or natural killer (NK) lymphomas who had PET scans as part of initial staging or staging at relapse [(n = 95) (staging cohort)] in the PTCL database at Memorial Sloan-Kettering Cancer Center. A subset of these patients had repeat PET for interim restaging during initial therapy with curative intent [(n = 50) (interim restaging cohort)]. The frequency of specific T cell histologies included in this analysis were: PTCL not otherwise specified (NOS) (n = 35); angioimmunoblastic T cell lymphoma (AITL) (n = 17); anaplastic large cell lymphoma (ALCL), ALK-1+ (n = 11) and ALK-1− (n = 12); adult T cell lymphoma/leukemia (ATLL) (n = 7); NK/T cell lymphoma (NKTCL) (n = 10); and enteropathy-associated T cell lymphoma (EATL) (n = 3). In the staging cohort, 77 patients were newly diagnosed, and 18 had relapsed disease. Pretreatment FDG-PET was positive in 96% of patients. PET identified additional disease sites in 47/95 patients (50%) when added to conventional staging. Most frequently identified additional sites were: other nodal (n = 24); bone (n = 10); skin (n = 8); nasopharynx (n = 4); spleen (n = 3); and lung (n = 2). However, FDG-PET modified computed tomography (CT)-based staging in only 5/95 patients (5.2%): two patients were upstaged and three patients were downstaged. FDG-PET-based staging did not alter planned treatment for any patient. Interim restaging with PET was performed after a median of 4 cycles of chemotherapy. In this cohort, treatment regimens included cyclophosphamide, doxorubicin, vincristine and prednisone CHOP (n = 19); CHOP/ifosfamide, carboplatin and etoposide (ICE) (n = 26); and other (n = 7). Subsequently, 29 patients were consolidated with either autologous (n = 22) or allogeneic (n = 7) stem cell transplant. After a median follow-up of 3.4 years for surviving patients, those with negative interim PET had superior progression-free survival (PFS) compared to patients with positive interim PET (p = 0.03). There were no differences in overall survival (OS). In PTCL, FDG-PET commonly identifies additional sites of disease but infrequently impacts CT-based staging and does not influence therapy. Interim FDG-PET may predict for PFS. FDG-PET should be integrated into prospective trials to confirm these findings.
PMCID: PMC3915724  PMID: 23369041
Lymphoma and Hodgkin disease; FDG-PET; T cell lymphoma; prognosis; staging
7.  Comorbidity as an independent prognostic factor in elderly patients with peripheral T-cell lymphoma 
OncoTargets and therapy  2016;9:1795-1799.
The aim of the present study was to investigate the role of comorbidities in the outcomes of patients with peripheral T-cell lymphoma (PTCL) in a Chinese population. Fifty-six newly diagnosed PTCL patients aged >60 years were enrolled in our institution between April 2008 and August 2014. Medical record details including clinical parameters, pathological status, and treatment were reviewed. Prognostic factors were assessed using univariate and multivariate analyses. Forty-one (73.2%) patients with PTCL, not otherwise specified (PTCL-NOS), nine (16.1%) with angioimmunoblastic T-cell lymphoma, and six (10.7%) with anaplastic large cell lymphoma were recruited in this study. Twenty-eight (50%) had at least one comorbidity. Univariate analysis showed that an Eastern Cooperative Oncology Group score of 2–4, the presence of B symptoms, an International Prognostic Index (IPI) score of 3–5, and a Charlson Comorbidity Index (CCI) score ≥2 were significantly associated with shortened overall survival (OS), whereas the presence of B symptoms, an IPI of 3–5, and a CCI ≥2 were associated with worsened progression-free survival (PFS). Multivariate analysis indicated that a high CCI (≥2) and a high IPI (3–5) were poor independent prognostic factors for OS and PFS in the elderly patients with PTCL. Comorbidity was identified as a new independent poor prognostic factor for elderly patients with PTCL.
PMCID: PMC4818048  PMID: 27069369
comorbidity; peripheral T-cell lymphoma; OS; PFS; prognostic factor
8.  The pretreatment albumin to globulin ratio predicts survival in patients with natural killer/T-cell lymphoma 
PeerJ  2016;4:e1742.
Background. The pretreatment albumin to globulin ratio (AGR) has been reported to be a predictor of survival in several types of cancer. The aim of this study was to evaluate the prognostic impact of AGR in patients with natural killer/T-cell lymphoma (NKTCL).
Methods. We retrospectively reviewed the available serum biochemistry results for 331 NKTCL patients before treatment. AGR was calculated as albumin/(total protein—albumin), and a cut-off value of 1.3 was used to define AGR as low or high. Survival analysis was used to assess the prognostic value of AGR.
Results. A low AGR (<1.3) was associated with significantly more adverse clinical features, including old age, poor performance status, advanced stage, elevated lactate dehydrogenase, B symptoms, and high International Prognostic Index (IPI) and natural killer/T-cell lymphoma prognostic index (NKPI) scores. Patients with a low AGR had a significantly lower 5-year overall survival (44.5 vs. 65.2%, P < 0.001) and progression-free survival (33.1 vs. 57.4%, P < 0.001). In the multivariate analysis, a low AGR remained an independent predictor of poorer survival. Additionally, AGR distinguished patients with different outcomes in the IPI low-risk group and in the NKPI high-risk group.
Discussion. Pretreatment AGR may serve as a simple and effective predictor of prognosis in patients with NKTCL.
PMCID: PMC4782740  PMID: 26966671
Albumin to globulin ratio; Extranodal natural killer/T-cell lymphoma; Prognosis; International prognostic index; Natural killer/T-cell lymphoma prognostic index
9.  High Pretreatment D-Dimer Levels Correlate with Adverse Clinical Features and Predict Poor Survival in Patients with Natural Killer/T-Cell Lymphoma 
PLoS ONE  2016;11(3):e0152842.
Pretreatment plasma D-dimer levels have been reported to predict survival in several types of malignancies. The aim of this study was to evaluate the prognostic value of D-dimer levels in patients with newly diagnosed natural killer/T-cell lymphoma (NKTCL). The cut-off value of D-dimer to predict survival was set as 1.2 μg/mL based on the receiver operating curve analysis. Patients with a D-dimer level ≥ 1.2 μg/mL had significantly more adverse clinical features, including poor performance status, advanced stage diseases, B symptoms, elevated serum lactic dehydrogenase levels, involvement of regional lymph nodes, more extranodal diseases, and higher International Prognostic Index and natural killer/T-cell lymphoma prognostic index scores. A D-dimer level ≥ 1.2 μg/mL was significantly associated with inferior 3-year overall survival (OS, 13.0 vs. 68.5%, P < 0.001). In the multivariate analysis, a D-dimer level ≥ 1.2 μg/mL remained an independent predictor for worse OS (HR: 3.13, 95% CI: 1.47–6.68, P = 0.003) after adjusting for other confounding prognostic factors. Among patients with Ann Arbor stage I-II diseases, those with a D-dimer level ≥ 1.2 μg/mL had a significantly worse survival than those with a D-dimer level < 1.2 μg/mL (3 year-OS: 76.2 vs. 22.2%, P < 0.001). Survival of early-stage patients with a high D-dimer level was similar to that of the advanced-stage patients. In conclusion, pretreatment plasma D-dimer level may serve as a simple but effective predictor of prognosis in patients with NKTCL.
PMCID: PMC4816543  PMID: 27032016
10.  Angioimmunoblastic T-cell lymphoma in Taiwan shows a frequent gain of ITK gene 
Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma (PTCL) of follicular helper T-cell origin and is rare in Taiwan. There are overlapping features of AITL and peripheral T-cell lymphoma with a follicular growth pattern (PTCL-F). Around one fifth of PTCL-F exhibits t(5;9)(q33;q22)/ITK-SYK chromosomal translocation, which is essentially absent in AITL. We retrospectively investigated 35 cases of AITL from Taiwan with histopathology review, immunohistochemistry, in situ hybridization for Epstein-Barr virus (EBV) and fluorescence in situ hybridization (FISH) for t(5;9)(q33;q22)/ITK-SYK and correlated the results with overall survival. Twenty-six cases of not otherwise specified PTCL (PTCL-NOS) were also examined by FISH for comparison. Most AITL patients were male (69%) and elderly (median age at 67 years) with frequent bone marrow involvement (53%), high Ann Arbor stages (77%), and elevated serum lactate dehydrogenase (68%). Most cases (80%) showed a typical CD4+/CD8- phenotype and in 90% cases there were scattered EBV-positive B-cells (less than 10% cells). None of these cases showed t(5;9)(q33;q22)/ITK-SYK translocation by FISH. Gain of ITK and SYK gene was identified in 38% and 14% tumors, respectively, but both were not associated with overall survival. Performance status < 2 was associated with a better outcome but not the other clinicopathological factors. All PTCL-NOS cases were negative for ITK-SYK translocation with similar rates (38% and 12%, respectively) of gains at ITK and SYK loci as that of AITL. In this so far the largest series of AITL from Taiwan, we reported the clinicopathological features and FISH findings on ITK and SYK genes. We confirmed the absence of t(5;9)(q33;q22)/ITK-SYK translocation, which may serve as an additional differential diagnostic tool from PTCL-F when present. PTCL-NOS shared a similar pattern of ITK and SYK gains with AITL. More studies are warranted to elucidate the roles of SYK and ITK and other genes in the lymphomagenesis of AITL in Taiwan.
PMCID: PMC4203228  PMID: 25337257
Angioimmunoblastic T-cell lymphoma; follicular helper T-cell; follicular T-cell lymphoma; ITK; peripheral T-cell lymphoma; SYK; Taiwan
11.  Role of frontline autologous stem cell transplantation in young, high-risk diffuse large B-cell lymphoma patients 
Several studies have demonstrated the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) as a salvage treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL). However, the role of auto-HSCT as a frontline treatment has not been fully investigated in the rituximab era. We validated the age-adjusted International Prognostic Index (aaIPI) score for high-risk DLBCL patients and identified a possible role for frontline auto-HSCT.
We recommended frontline auto-HSCT for high-risk DLBCL patients who satisfied the criteria of both a higher Ann-Arbor stage (III to IV) and an elevated lactate dehydrogenase (LDH) level at diagnosis with an aaIPI score ≥ 2. From 2006 to 2011, among the 150 DLBCL patients aged ≤ 60 years who were treated with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), 23 high-risk patients with a complete response (CR) were treated with auto-HSCT. For comparison, we selected 35 well-matched high-risk patients with CR who completed R-CHOP treatment alone. In addition, there were 81 low-risk patients and 11 refractory patients.
DLBCL patients with an aaIPI score ≥ 2 showed inferior overall survival (OS; p = 0.040) and progression-free survival (PFS; p = 0.007) compared to the aaIPI score 0 to 1. Between the two treatment arms among the high-risk DLBCL patients, the clinical parameters were not different. The high-risk group treated with frontline auto-HSCT showed similar OS (p = 0.392) and PFS (p = 0.670) to those in the low-risk group. Thus, frontline auto-HSCT showed superior PFS (p = 0.004), but only a trend towards favorable OS (p = 0.091) compared to R-CHOP alone.
We identified the possible role of frontline auto-HSCT for high-risk DLBCL with a higher stage (III to IV) and elevated LDH level.
PMCID: PMC4438291  PMID: 25995667
Lymphoma; Lymphoma, large B-cell, diffuse; Autologous hematopoietic cell transplantation
12.  Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy 
Annals of Oncology  2014;25(11):2211-2217.
Peripheral T-cell lymphomas remain clinically challenging in the modern era with 3-year progression-free and overall survivals of 32% and 52% in this multicenter analysis. Favorable prognostic factors were stage I-II disease and complete response to upfront therapy. Consolidation with stem-cell transplant offered no clear benefit in first remission. Novel treatment approaches are needed.
Optimal frontline therapy for peripheral T-cell lymphoma (PTCL) in the modern era remains unclear.
Patients and methods
We examined patient characteristics, treatment, and outcomes among 341 newly diagnosed PTCL patients from 2000 to 2011. Outcome was compared with a matched cohort of diffuse large B-cell lymphoma (DLBCL) patients, and prognostic factors were assessed using univariate and multivariate analyses.
PTCL subtypes included PTCL, not otherwise specified (PTCL-NOS) (31%), anaplastic large T-cell lymphoma (ALCL) (26%), angioimmunoblastic T-cell lymphoma (23%), NK/T-cell lymphoma (7%), acute T-cell leukemia/lymphoma (6%), and other (7%). Median age was 62 years (range 18-95 years), and 74% had stage III-IV disease. Twenty-three (7%) patients received only palliative care whereas 318 received chemotherapy: CHOP-like regimens (70%), hyperCVAD/MA (6%), or other (18%). Thirty-three patients (10%) underwent stem-cell transplantation (SCT) in first remission. The overall response rate was 73% (61% complete); 24% had primary refractory disease. With 39-month median follow-up, 3-year progression-free survival (PFS) and overall survival (OS) were 32% and 52%. PFS and OS for PTCL patients were significantly inferior to matched patients with DLBCL. On multivariate analysis, stage I–II disease was the only significant pretreatment prognostic factor [PFS: hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.34–0.85, P = 0.007; OS: HR 0.42, 95% CI 0.22–0.78, P = 0.006]. ALK positivity in ALCL was prognostic on univariate analysis, but lost significance on multivariate analysis. The most dominant prognostic factor was response to initial therapy (complete response versus other), including adjustment for stage and SCT [PFS: HR 0.19, 95% CI 0.14–0.28, P < 0.0001; OS: HR 0.26, 95% CI 0.17–0.40, P < 0.0001]. No overall survival difference was observed based on choice of upfront regimen or SCT in first remission.
This analysis identifies early-stage disease and initial treatment response as dominant prognostic factors in PTCL. No clear benefit was observed for patients undergoing consolidative SCT. Novel therapeutic approaches for PTCL are critically needed.
PMCID: PMC4481543  PMID: 25193992
peripheral T-cell lymphoma; PTCL; anaplastic large-cell lymphoma; angioimmunoblastic T-cell lymphoma; stem-cell transplantation
13.  Clinical analysis and prognostic significance of L-asparaginase containing multidrug chemotherapy regimen in incipient peripheral T-cell lymphoma 
Objective: To observe the clinical effects and adverse reactions, and analyze the clinical significance of L-asparaginase (L-ASP) containing multidrug chemotherapy regimen in incipient peripheral T-cell lymphoma (PTCL). Methods: A retrospective analysis was conducted of 102 patients with incipient PTCL who received L-ASP containing multidrug chemotherapy regimens or not in our hospital from January 2010 to December 2013. Complete remission (CR) rate, partial remission (PR) rate, overall remission (OR) rate, progression free survival (PFS), overall survival (OS) and adverse reactions were compared. Results: Patients who received L-ASP containing multidrug chemotherapy (L-ASP group) had higher OR rate than those who received L-ASP-free ones (non L-ASP group) (83.3% vs 61.7%, P=0.016), particularly those at phase III/IV (82.4% vs 54.0%, P=0.007) and with an international prognostic index (IPI) score of ≥2 (82.1% vs 50.0%, P=0.006). The median survival time (OS) was 10.5 months (range, 1-47months) in L-ASP group, while 13 months (range, 0.3-68 months) in non L-ASP group, and they had no statistically significance (P=0.754). Similarly, the progression free survival time(PFS)was 10 months (range, 1-47 months) in L-ASP group,while 11 months (range, 0.3-68 months) in non L-ASP group, also had no statistically significance (P=0.414). The 3-year OS rate of L-ASP group and non L-ASP group were 48.9% and 65.0% , respectively (P=0.974) and the 3-year PFS rate of L-ASP group and non L-ASP group were 40.8% and 61.0%, respectively (P=0.479). They all had no statistically significance. The L-ASP group had more adverse reactions than the non L-ASP group, though most of them were mild and could be improved by symptomatic and supportive care. Conclusion: L-ASP containing multidrug chemotherapy regimen in incipient PTCL showed a better short-term effect and controllable adverse reactions. A large prospective clinical trial of use L-ASP in first-line treatment of PTCL is worthy of further research and investigation.
PMCID: PMC4537992  PMID: 26309599
Lymphoma; peripheral t-cell; l-asparaginase; effect; adverse reaction; safety
14.  Nasal Type Extranodal Natural Killer/T (NK/T) Cell Lymphoma Presenting as Periorbital Cellulitis: A Case Report 
Patient: Male, 25
Final Diagnosis: Nasal type • extra nodal NK/T-cell lymphoma
Symptoms: Left periorbital swelling • redness • pain for 25 days • yellowish eye discharge associated • headache • fever
Medication: —
Clinical Procedure: —
Specialty: Otolaryngology
Unusual clinical course
Extranodal lymphoma of the paranasal sinuses is a rare clinical entity seen in only 5–8% of extranodal lymphomas of the head and neck. Nasal natural killer/T cell lymphoma (Nasal NKTCL), which is a subtype of peripheral T cell lymphoma, constitutes about 1.4% of all lymphomas. NKTCL is usually diagnosed at a late stage because it presents with nonspecific symptoms in the early stages.
Case Report:
We report the case of a 25-year-old male patient who presented with periorbital swelling treated as fungal sinusitis but proven to have NKTCL. We review the literature and discuss the clinical manifestations of the disease, its relation to EBV virus, the histological and radiological characteristics, the prognostic indicators, and treatment options. This case report shows physicians that NKTCL lymphoma can present as periorbital cellulitis, although few similar cases are found in the literature.
NKTCL is a destructive midline tumor that should be kept in mind as a differential diagnosis of paranasal sinus lesions to help in early diagnosis, which can improve the prognosis.
PMCID: PMC5153321  PMID: 27932776
Granuloma, Lethal Midline; Nose Neoplasms; Orbital Cellulitis; Sinusitis
15.  Reassessment of the prognostic value of the International Prognostic Index and the revised International Prognostic Index in patients with diffuse large B-cell lymphoma: A multicentre study 
The International Prognostic Index (IPI) is a widely accepted model that is used to predict the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) who are treated using chemotherapy. However, the prognostic value of the IPI has been a focal point of debate in the immunochemotherapy era. The aim of this study was to reassess the value of the IPI and revised IPI (R-IPI) in a Chinese population. A multicentre retrospective analysis of DLBCL patients who were treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like chemotherapy alone or chemotherapy plus rituximab (R-CHOP-like) was performed. The prognostic values of IPI and R-IPI at the time of diagnosis with respect to overall survival (OS) and progression-free survival (PFS) were evaluated. Among the 438 patients in the study, 241 received a CHOP-like regimen and 197 patients received an R-CHOP-like regimen. Although the IPI remained predictive for the CHOP-like group, it failed to distinguish between the various prognostic categories in the R-CHOP-like group. Notably, redistribution of the IPI factors into R-IPI factors identified three discrete prognostic groups with significantly different outcomes in both the CHOP-like and R-CHOP-like groups. In the R-CHOP-like group, these three risk groups, very good, good and poor, had distinctly different 3-year PFS rates of 96, 84.3 and 67.5% (P=0.001), and 3-year OS rates of 96, 87.6 and 71.1% (P=0.003), respectively. Our study demonstrates the power of the R-IPI as a simplified and more clinically relevant predictor of disease outcome than the standard IPI in DLBCL populations in the rituximab era. Therefore, the R-IPI merits further study in a larger population-based prospective study.
PMCID: PMC3503699  PMID: 23181121
International Prognostic Index; diffuse large B-cell lymphoma; rituximab
16.  Predictors of survival of natural killer/T-cell lymphoma, nasal type, in a non-Asian population: a single cancer centre experience 
ecancermedicalscience  2016;10:688.
Natural killer/T-cell lymphoma (NKTCL), part of T-cell and NK-cell neoplasms in the World Health Organisation (WHO) classification, is an aggressive lymphoma with poor prognosis more predominantly seen in Asian and South American countries. This study evaluates the factors associated with survival among patients with newly diagnosed NKTCL in Peru.
Information was abstracted from medical records (MR) for all NKTCL patients >13 years of age at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 2002 and 2011. The estimate of the survival curves was performed by the Kaplan-Meier method, and the difference was computed by the log-rank test.
Around 226 MR were reviewed, 153 met the selection criteria, the median age was 40 years (14–84). The median progression-free survival (PFS) was 20 months, five year PFS was 42.6%, univariable analysis (UA) showed statistical significance (p < 0.05) for male sex, non-nasal primary site, advanced clinical stages, B symptoms, poor performance status, regional nodal involvement (RNI). In the multivariate analysis the only poor prognostic factors was primary non-nasal (Hazard ratio (HR) = 2.40, 95% confidence interval (CI) = 1.43– 4.02, P = 0.01). The median overall survival (OS) was 49 months, five year OS was 48.9%, UA showed statistical significance for non-nasal primary site, advanced clinical stages, B symptoms, lactate dehydrogenase (LDH) > normal, RNI and local tumour invasion. In the multivariate analysis, primary non-nasal was the only poor prognostic factor with HR = 2.57, 95% CI = 1.37–4.83, P = 0.03.
In Peru, OS of NKTCL is similar to other countries. This result suggests that non-nasal NKTCL is the only poor prognostic factor of OS and PFS.
PMCID: PMC5130333  PMID: 27994644
survival; predictors; natural killer/T-cell lymphoma; chemotherapy
17.  Treatment of Peripheral T-cell Lymphoma: Are We Data Driven or Driving the Data? 
Opinion Statement
Peripheral T-cell lymphomas (PTCL) are a group of uncommon and heterogeneous malignancies arising from a post-thymic or mature T-lymphocyte. The treatment of PTCL remains a challenging endeavor. Compared to the more common aggressive B-cell lymphomas, more patients with PTCL will be refractory to initial therapy and those who achieve responses will often have shorter progression free survival. Despite retrospective data suggesting that anthracycline based multi-agent chemotherapy regimens may not provide a benefit compared to non-anthracycline regimens, non-anthracycline based regimens, with the notable exception of L-asparaginase regimens for extranodal NK/T-cell lymphoma, have been disappointing so far. Based on phase II evidence and subset analyses available, we believe that the addition of etoposide to standard regimens and consolidation of first remissions with autologous stem cell transplantation (autoSCT) provides the best outcome in patients with PTCL and currently use CHOEP followed by ASCT for eligible patients with the common PTCL subtype: PTCL-NOS, AITL, and ALK negative ALCL. For those with ALK positive ALCL standard CHOP or CHOEP is appropriate with consideration of ASCT only for those with high-risk disease. Other strategies to incorporate additional agents such as with dose adjusted-EPOCH or sequential CHOP-ICE regimens are logical options; however, they lack the supporting literature of CHOEP. While the above recommendation is our current off-protocol approach, with the possible exception of low risk ALK positive ALCL, none of these choices is supported by strong enough data to supplant a well-conceived clinical trial as the truly preferred strategy in PTCL.
The novel agents, romidepsin, pralatrexate and brentuximab vedotin, are currently approved in the relapsed/refractory setting. These agents are being studied as additions or substitutions for other agents in up-front multi-agent chemotherapy regimens. In the relapsed/refractory setting both pralatrexate and romidepsin remain well-studied choices with some patients achieving a response with durability. Clinical trials of new agents in PTCL continue to be a valuable option and an important part of routine patient management as progressive disease is often seen. Lastly, we believe patients with relapsed/refractory PTCL should be considered for allogeneic stem cell transplantation if a suitable response is demonstrated and a willing donor is available.
PMCID: PMC3938283  PMID: 23568456
Peripheral; non-cutaneous; T-cell lymphoma; transplantation; autologous; relapsed; refractory
18.  Localized primary gastrointestinal diffuse large B cell lymphoma received a surgical approach: an analysis of prognostic factors and comparison of staging systems in 101 patients from a single institution 
Diffuse large B cell lymphoma (DLBCL) represents the most common histological subtype of primary gastrointestinal lymphoma and is a heterogeneous group of disease. Prognostic characterization of individual patients is an essential prerequisite for a proper risk-based therapeutic choice.
Clinical and pathological prognostic factors were identified, and predictive value of four previously described prognostic systems were assessed in 101 primary gastrointestinal DLBCL (PG-DLBCL) patients with localized disease, including Ann Arbor staging with Musshoff modification, International Prognostic Index (IPI), Lugano classification, and Paris staging system.
Univariate factors correlated with inferior survival time were clinical parameters [age >60 years old, multiple extranodal/gastrointestinal involvement, elevated serum lactate dehydrogenase and β2-microglobulin, and decreased serum albumin], as well as pathological parameters (invasion depth beyond serosa, involvement of regional lymph node or adjacent tissue, Ki-67 index, and Bcl-2 expression). Major independent variables of adverse outcome indicated by multivariate analysis were multiple gastrointestinal involvement. In patients unfit for Rituximab but received surgery, radical surgery significantly prolonged the survival time, comparing with alleviative surgery. Addition of Rituximab could overcome the negative prognostic effect of alleviative surgery. Among the four prognostic systems, IPI and Lugano classification clearly separated patients into different risk groups. IPI was able to further stratify the early-stage patients of Lugano classification into groups with distinct prognosis.
Radical surgery might be proposed for the patients unfit for Rituximab treatment, and a combination of clinical and pathological staging systems was more helpful to predict the disease outcome of PG-DLBCL patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s12957-015-0668-5) contains supplementary material, which is available to authorized users.
PMCID: PMC4536702  PMID: 26271948
Primary gastrointestinal lymphoma; DLBCL; Prognosis; Surgical approach; Prognostic staging system
19.  Impact of dexamethasone, etoposide, ifosfamide and carboplatin as concurrent chemoradiotherapy agents for nasal natural killer/T-cell lymphoma 
Molecular and Clinical Oncology  2013;1(4):680-684.
The nasal type of extranodal natural killer (NK)/T-cell lymphoma (NKTCL) is a rare aggressive lymphoma with poor prognosis. The reported 5-year overall survival for patients with localized nasal NKTCL treated with cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP) is <50%. Dexamethasone, etoposide, ifosfamide and carboplatin (DeVIC) chemotherapy was designed as a salvage chemotherapeutic regimen for aggressive lymphoma, comprising multidrug resistance (MDR) non-related agents and etoposide, which is considered to be effective against nasal NKTCL. An experimental chemoradiotherapy (CRT) is currently being designed using DeVIC as the concurrent chemotherapeutic regimen for nasal NKTCL. The aim of this study was to examine the initial outcome of this treatment and evaluate its effectiveness and feasibility. Six patients (age range, 29–82 years; median age, 68 years) were treated with CRT using DeVIC between April, 2004 and February, 2010. The median follow-up was 56 months (range, 11–80 months). All patients were administered 3–6 cycles of full-dose DeVIC regimen. The chemotherapy was administered concurrently with radiotherapy (RT) and was repeated every 3 weeks. RT was performed using 4-MV X-ray and the prescription dose was 46–50 Gy/23–25 fx (median, 50 Gy). After treatment, all patients were followed up at our hospital. A complete remission was achieved in 5 patients (83%) at 1 month after treatment. The 5-year overall survival and disease-free survival rates were 100%. No severe adverse effect (grade ≥3) was reported. In conclusion, the initial results of the experimental CRT with DeVIC for this type of aggressive lymphoma were very encouraging. Further investigation is required on concurrent CRT with 50 Gy/25 fx and 3 cycles of DeVIC comprising non-MDR agents and etoposide for nasal NKTCL.
PMCID: PMC3916130  PMID: 24649228
carboplatin; chemoradiotherapy; dexamethasone; etoposide; extranodal natural killer/T-cell lymphoma; ifosfamide
20.  Expression of HAT1 and HDAC1, 2, 3 in Diffuse Large B-Cell Lymphomas, Peripheral T-Cell Lymphomas, and NK/T-Cell Lymphomas 
Korean Journal of Pathology  2012;46(2):142-150.
It has generally been proven that histone acetylation and deacetylation are involved in the malignant transformation. To date, however, this has rarely been studied in cases of malignant lymphoma.
We studied nine cases of reactive lymphoid hyperplasia, 78 cases of diffuse large B-cell lymphoma (DLBCL), 13 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), and 13 cases of extranodal NK/T-cell lymphoma, nasal type (NKTCL). Thus, we attempted to elucidate the associations of the degree of the expression of histone acetyltransferase 1 (HAT1), histone deacetylase (HDAC) 1, HDAC2, and HDAC3 with the clinical behaviors of above malignant lymphomas using the immunohistochemistry and a western blot analysis.
The degree of the expression of HAT1 was higher in cases of DLBCL, PTCL-NOS or NKTCL as compared with reactive lymphoid hyperplasia (p<0.05). The degree of the expression of HAT1 was correlated with that of HDAC1 in cases of DLBCL or NKTCL (p<0.05). The degree of the expression of HAT1 and HDAC1 was correlated with a poor survival in cases of DLBCL or PTCL-NOS (p>0.05).
HAT1, HDAC1, and HDAC2 play a critical role in the development of malignant lymphomas. Both HAT1 and HDAC1 might be indicators for a poor prognosis in cases of DLBCL as cooperating factors.
PMCID: PMC3479788  PMID: 23109994
Acetylation; Deacetylation; Histone deacetylase inhibitors; Lymphoma
21.  Romidepsin for the Treatment of Peripheral T-Cell Lymphoma 
The Oncologist  2015;20(9):1084-1091.
Knowledge of approved agents is key for optimizing therapeutic approaches to peripheral T-cell lymphoma (PTCL), particularly in a community setting. This review provides an overview of PTCL and an in-depth examination of romidepsin, a histone deacetylase inhibitor approved for the treatment of relapsed or refractory PTCL, and highlights difficulties of diagnosis and optimization of treatment modalities for patients with PTCL.
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas associated with poor prognosis in most subtypes. Diagnosis of this rare disease by expert hematopathologists improves accuracy of subtyping, and referral to academic or specialty centers is recommended. Many patients, however, will receive treatment in the community, and knowledge of approved agents is key to optimizing therapeutic approaches for all patients. There is no current standard of care for patients with PTCL and no approved therapies for first-line treatment. Although many patients initially respond to induction chemotherapy, responses are often brief, and many patients relapse or become treatment refractory. For patients with relapsed or refractory PTCL, achievement of durable responses is challenging, and there are few treatment options. Romidepsin is a histone deacetylase inhibitor approved by the U.S. Food and Drug Administration for the treatment of patients with cutaneous T-cell lymphoma who have received one prior systemic therapy or more and patients with PTCL who have received one prior therapy or more. Approval of romidepsin for PTCL was based on a pivotal phase II study of patients with relapsed or refractory PTCL (n = 131) that demonstrated an objective response rate of 25% including 15% with complete response; responses lasted a median of >2 years. Long-term responses to romidepsin were achieved in patients regardless of baseline characteristics, including subtype, heavy pretreatment, response to prior therapy, or advanced disease. Common adverse events included hematologic abnormalities, gastrointestinal or asthenic conditions, and infections; romidepsin was not correlated with clinically meaningful QT prolongation or electrocardiogram abnormalities.
Implications for Practice:
Due to the rarity, severity, and heterogeneous nature of peripheral T-cell lymphoma (PTCL), diagnosis by expert hematopathologists is preferred, and referral to specialty centers is recommended. Many patients, however, will receive treatment in the community, and community oncologists play a key role in the recognition and treatment of PTCL. Knowledge of approved agents is key for optimizing therapeutic approaches. This review provides an overview of PTCL and an in-depth examination of romidepsin, a histone deacetylase inhibitor approved for the treatment of relapsed or refractory PTCL, and highlights difficulties of diagnosis and optimization of treatment modalities for patients with PTCL.
PMCID: PMC4571813  PMID: 26099743
Lymphoma; T cell, peripheral; Romidepsin
22.  Primary gastric mucosa associated lymphoid tissue lymphoma: Clinical data predicted treatment outcome 
AIM: To determine clinical characteristics and treatment outcome of gastric lymphoma after chemotherapy and immuno-chemotherapy.
METHODS: Thirty four patients with primary gastric mucosa associated lymphoid tissue (MALT) lymphoma (Ann Arbor stages I to IV) were enrolled. All had upper gastric endoscopy, abdominal ultrasonography, CT and H pylori status assessment (histology and serology). After anti-H pylori treatment and initial chemotherapy, patients were re-examined every 4 mo.
RESULTS: Histological regression of the lymphoma was complete in 22/34 (64.7%) and partial in 9 (26.5%) patients. Median follow up time for these 31 responders was 60 mo (range 48-120). No regression was noted in 3 patients. Among the 25 (73.5%) H pylori positive patients, the eradication rate was 100%.
CONCLUSION: Using univariate analysis, predictive factors for overall survival were international prognostic index (IPI) score, hemoglobin level, erythrocyte sedimentation rate (ESR), and platelet numbers (P < 0.005). In addition to this, Cox proportion hazard model differentiate IPI score, ESR, and platelets as predictors of survival.
PMCID: PMC2705095  PMID: 18416467
MALT lymphoma; Prognostic factors; Clinical features; Treatment
23.  Clinicopathologic Characteristics of T-cell Non-Hodgkin's Lymphoma: A Single Institution Experience 
Although the incidence of T-cell non-Hodgkin's lymphoma (NHL) is higher in Far East Asia than in Western countries, its incidence and clinical course in Korea are not well-defined. Therefore, we assessed the relative frequency and clinical features of T-cell NHL in Korea.
We performed a retrospetcive analysis of 586 patients with NHL.
101 (17.2%) had T-cell NHL. The most frequent subtypes of T-cell NHL were extranodal NK/T-cell lymphoma, nasal type (NASAL), peripheral T-cell lymphoma, unspecified type (PTCL-U), and anaplastic large cell lymphoma, T/null cell, primary systemic type (ALCL). The seven pathological subtypes could be classified into three prognostic subgroups. When patients with the three most frequent subtypes were grouped together, their survival was reflected in the International Prognostic Index (IPI) scores. Univariate analysis of IPI elements and other clinical features showed that clinical stage and extranodal sites were significant predictors of survival. Cox multivariate analysis showed that the number of extranodal sites was the only independent prognostic indicator.
The relative frequency of T-cell NHL seems to be decreasing in Korea, although NASAL remains frequent. Korean patients with ALCL appear to have an unfavorable prognosis. Large-scale studies are warranted for Korean patients with T-cell NHL.
PMCID: PMC2698621  PMID: 19543491
Lymphoma; T-cell; Peripheral
24.  FilGAP, a Rac-specific Rho GTPase-activating protein, is a novel prognostic factor for follicular lymphoma 
Cancer Medicine  2015;4(6):808-818.
FilGAP, a Rho GTPase-activating protein (GAP), acts as a mediator of Rho/ROCK (Rho-associated protein kinase)-dependent amoeboid movement, and its knockdown results in Rac-driven mesenchymal morphology. Herein, we focus on the possible roles of FilGAP expression in normal and malignant lymphocytes. Eighty-three cases of follicular lymphoma (FL), 84 of diffuse large B-cell lymphoma (DLBCL), and 25 of peripheral T-cell lymphoma (PTCL), as well as 10 of normal lymph nodes, were immunohistochemically investigated. In normal lymph nodes, FilGAP immunoreactivity was significantly higher in lymphocytes in the mantle zone as compared to those in the germinal center and paracortical areas. In contrast, the expression levels of both cytoplasmic and perinuclear Rac1 were significantly lower in the germinal center as compared to paracortical regions, suggesting that changes in the FilGAP/Rac axis may occur in B-cell lineages. In malignant lymphomas, FilGAP expression was significantly higher in B-cell lymphomas than PTCL, and the immunohistochemical scores were positively correlated with cytoplasmic Rac1 scores in FL and DLBCL, but not in PTCL. Patients with FL and germinal center B-cell-like (GCB)-type DLBCL showing high FilGAP scores had poor overall survival rates as compared to the low-score patients. Moreover, multivariate Cox regression analysis showed that a high FilGAP score was a significant and independent unfavorable prognostic factor in FL, but not in DLBCL. In conclusion, FilGAP may contribute to change in cell motility of B-lymphocytes. In addition, its expression appears to be useful for predicting the behavior of B-cell lymphoma, in particular FL.
PMCID: PMC4472203  PMID: 25641953
B-lymphocyte; FilGAP; follicular lymphoma; prognosis; Rac
25.  Clinical characteristics and treatment of 69 patients with extranodal natural killer T-cell lymphoma 
Molecular and Clinical Oncology  2016;5(6):750-756.
This study was conducted to retrospectively analyze the clinical characteristics and survival of patients with extranodal natural killer-T cell lymphoma (ENKL) and compare different treatment regimens. The univariate analysis demonstrated that survival was worse for patients with extranasal primary tumors, Eastern Cooperative Oncology Group performance status (ECOG PS) scores of ≥2, International Prognostic Index (IPI) scores of 3–5, Ann Arbor stage III and IV disease, B symptoms, lymph node involvement and absence of radiotherapy. The Cox analysis demonstrated that ECOG PS score, stage, IPI, presence of B symptoms and radiotherapy were independent prognostic factors for overall survival (OS). The effect of diverse therapies on survival was then analyzed, and it was found that the 5-year survival rate of patients receiving chemoradiotherapy differed significantly from that of patients who received chemotherapy alone [hazard ratio (HR)=0.347, P=0.0203], but did not differ significantly from the survival of patients treated with radiotherapy alone (HR=1.534, P=0.6371). A subgroup analysis revealed a difference between the radiotherapy and non-radiotherapy groups for patients with extranasal-type stage III/IV disease. It was concluded that ECOG score, stage, IPI, presence of B symptoms and radiotherapy were independent prognostic factors for OS in patients with ENKL. The addition of radiotherapy achieved better outcomes compared with chemotherapy alone, but no difference was observed between chemoradiotherapy and radiotherapy. Patients with advanced-stage disease may also benefit from radiotherapy.
PMCID: PMC5228303
extranodal natural killer T-cell; lymphoma; clinical characteristics; prognosis; treatment

Results 1-25 (1840796)