PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (1301859)

Clipboard (0)
None

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.
doi:10.1007/s11899-010-0062-x
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.
doi:10.3892/mco.2013.146
PMCID: PMC3915658  PMID: 24649270
β2-microglobulin; bone marrow involvement; international prognostic index; lactate dehydrogenase; peripheral T-cell non-Hodgkin lymphoma
3.  Lymphopenia is an important prognostic factor in peripheral T-cell lymphoma (NOS) treated with anthracycline-containing chemotherapy 
Background
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.
Methods
A total of 118 patients with PTCL-NOS treated with anthracycline-containing chemotherapy from 4 Korean institutions were included.
Results
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).
Conclusion
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.
doi:10.1186/1756-8722-4-34
PMCID: PMC3170642  PMID: 21843362
peripheral T-cell lymphoma; not otherwise specified; lymphopenia; international prognostic index; prognostic factor
4.  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.
doi:10.3109/10428194.2013.767901
PMCID: PMC3915724  PMID: 23369041
Lymphoma and Hodgkin disease; FDG-PET; T cell lymphoma; prognosis; staging
5.  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
6.  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.
doi:10.3892/etm.2012.607
PMCID: PMC3503699  PMID: 23181121
International Prognostic Index; diffuse large B-cell lymphoma; rituximab
7.  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.
doi:10.3892/mco.2013.123
PMCID: PMC3916130  PMID: 24649228
carboplatin; chemoradiotherapy; dexamethasone; etoposide; extranodal natural killer/T-cell lymphoma; ifosfamide
8.  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.
doi:10.1007/s11864-013-0232-x
PMCID: PMC3938283  PMID: 23568456
Peripheral; non-cutaneous; T-cell lymphoma; transplantation; autologous; relapsed; refractory
9.  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.
Background
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.4132/KoreanJPathol.2012.46.2.142
PMCID: PMC3479788  PMID: 23109994
Acetylation; Deacetylation; Histone deacetylase inhibitors; Lymphoma
10.  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.
doi:10.3748/wjg.14.2388
PMCID: PMC2705095  PMID: 18416467
MALT lymphoma; Prognostic factors; Clinical features; Treatment
11.  Clinicopathologic Characteristics of T-cell Non-Hodgkin's Lymphoma: A Single Institution Experience 
Background/Aims
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.
Methods
We performed a retrospetcive analysis of 586 patients with NHL.
Results
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.
Conclusions
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.
doi:10.3904/kjim.2009.24.2.128
PMCID: PMC2698621  PMID: 19543491
Lymphoma; T-cell; Peripheral
12.  Comparison of Conventional Prognostic Indices in Patients Older than 60 Years with Diffuse Large B-Cell Lymphoma Treated with R-CHOP in the US Intergroup Study (ECOG 4494, CALGB 9793): Consideration of Age Greater than 70 Years in an Elderly Prognostic Index (E-IPI) 
British journal of haematology  2010;151(2):143-151.
Summary
To assess if immunochemotherapy influenced the prognostic value of IPI in elderly diffuse large B-cell lymphoma (DLBCL) patients, we evaluated the performance of the standard International Prognostic Index (IPI) and following modifications: age adjusted (AA)-IPI, revised (R)-IPI, and an elderly IPI with age cut-off 70 years (E-IPI) in patients >60 years treated with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). In 267 patients, by IPI/AA-IPI 60% were high-intermediate, 53% high and 12% low risk. With R-IPI, 60% were poor risk and none very good risk. Using E-IPI, 45% were high-intermediate/high risk and 27% low risk. No differences in outcome were seen in the low/low-intermediate groups with IPI/AA-IPI. For E-IPI, failure-free survival (FFS) and overall survival (OS) were significantly different for low/low-intermediate groups. No differences were detected in the four indices with model fit/discrimination measures; however, E-IPI ranked highest. For elderly R-CHOP treated patients, distribution of IPI/AA-IPI skewed toward high/high-intermediate risk with no differences in FFS/OS between low/low-intermediate risk. In contrast, with E-IPI, more are classified as low risk with significant differences in FFS/OS for low-intermediate compared to low risk. The R-IPI does not identify a very good risk group, thus minimizing its utility in this population. The prognostic discrimination provided by the E-IPI for low and low-intermediate elderly DLBCL patients needs validation by other datasets.
doi:10.1111/j.1365-2141.2010.08331.x
PMCID: PMC3615251  PMID: 20735398
immunochemotherapy; prognostic; elderly; NHL; CHOP
13.  High Dose Therapy and Autologous Hematopoietic Cell Transplantation in Peripheral T-Cell Lymphoma (PTCL): Analysis of Prognostic Factors 
SUMMARY
Patients with PTCL have a poor prognosis with current treatment approaches. We examined the outcomes of high-dose therapy (HDT) and autologous hematopoietic cell transplant (AHCT) on the treatment of PTCL and the impact of patient/disease features on long-term outcome. Sixty-seven patients with PTCL-not otherwise specified (n=30), anaplastic large cell lymphoma (n=30) and angioimmunoblastic T-cell lymphoma (n=7) underwent HDT/AHCT at City of Hope. The median age was 48 years (range: 5-78). Twelve were transplanted in 1CR/PR and 55 with relapsed or induction failure disease (RL/IF). With a median follow-up for surviving patients of 65.8 months (range: 24.5-216.0) the 5-year overall survival (OS) and progression-free survival (PFS) were 54% and 40% respectively. The 5-year PFS was 75% for 1CR/PR compared to 32% for RL/IF patients (p=0.01). When the Prognostic Index for PTCL unspecified (PIT) was applied at the time of transplant, patients in the PIT 3-4 group had 5-year PFS of only 8%. These results show that HDT/AHCT can improve long-term disease control in relapsed/refractory PTCL and that HDT/AHCT should ideally be applied either during 1CR/PR, or as part of upfront treatment. More effective and novel therapies are needed for patients with high-risk disease (PIT 3-4 factors) and allogeneic HCT should be explored in these patients.
doi:10.1016/j.bbmt.2011.02.008
PMCID: PMC3570567  PMID: 21338704
peripheral T-cell lymphoma; autologous stem cell transplantation
14.  Autologous stem cell transplantation as consolidation therapy for patients with peripheral T cell lymphoma in first remission: long-term outcome and risk factors analysis 
Annals of Hematology  2013;92(7):925-933.
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.
doi:10.1007/s00277-013-1716-2
PMCID: PMC3674342  PMID: 23471671
Peripheral T cell lymphoma; Autologous hematopoietic stem cell transplantation; Prognostic factors; Clinical outcomes; Scoring systems
15.  Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type 
Blood  2009;115(6):1226-1237.
Biopsies and cell lines of NK/T-cell lymphoma, nasal-type (NKTCL) were subject to combined gene expression profiling and array-based comparative genomic hybridization analyses. Compared to PTCL, NOS, NKTCL had higher transcript levels for NK-cell markers and cytotoxic molecules, especially granzyme H, a novel sensitive biomarker of NKTCL. Compared to normal NK cells, tumors were closer to activated than resting cells and overexpressed several genes related to vascular biology, EBV-induced genes and PDGFRA. Notably, PDGFRα and its phosphorylated form were confirmed at the protein level, and in vitro the MEC04 NKTCL-cell line was sensitive to imatinib. Deregulation of the AKT, JAK-STAT and NF-κB pathways suggested by bioinformatical analysis, was corroborated by nuclear expression of phosphorylated AKT, STAT3 and RelA in NKTCL, and several deregulated genes in these pathways mapped to regions of recurrent copy number aberrations (AKT3 (1q44), IL6R (1q21.3), CCL2 (17q12), TNFRSF21 (6p12.3)). Several features of NKTCL uncovered by this analysis (overexpression of VEGFA and its receptor KDR by the tumor cells, overexpression of MET-HGF) suggest perturbation of angiogenic pathways. Integrative analysis also evidenced deregulation of the tumor suppressor HACE1 in the frequently deleted 6q21 region. This study highlights emerging oncogenic pathways in NKTCL and identifies novel diagnostic and therapeutic targets.
doi:10.1182/blood-2009-05-221275
PMCID: PMC2826234  PMID: 19965620
16.  A poor prognostic case of peripheral T-cell lymphoma in the base of tongue with chemotherapy followed by radiation therapy 
SpringerPlus  2014;3:731.
A 59-year old male had odynophagia and globus sensation for 10 days prior to his visit. Endoscopically, a fungating mass was observed in the right side of the tongue base (BOT). The peripheral T-cell lymphoma (PTCL) was confirmed by a punch biopsy. The patient was classified as stage IIA according to the Ann Arbor staging classification. Radiation therapy (RT) using volumetric modulated arc therapy (VAMT) began after 8 cycles of CHOP chemotherapy. Although the patient achieved a complete remission without RT relating morbidity during the follow-up period, recurrence occurred in the right orbit at 3 months after treatment. The patient received RT with high energy electron on the right orbit. The salvage chemotherapy was followed by RT. The patient died of aggravation of PTCL at 17 months after VMAT. We report a poor prognostic case of PTCL in BOT with chemotherapy followed by RT.
doi:10.1186/2193-1801-3-731
PMCID: PMC4320182
Base of tongue; Peripheral T cell lymphoma; Radiation Therapy
17.  Fasting blood glucose is a novel prognostic indicator for extranodal natural killer/T-cell lymphoma, nasal type 
Cai, Q | Luo, X | Liang, Y | Rao, H | Fang, X | Jiang, W | Lin, T | Lin, T | Huang, H
British Journal of Cancer  2013;108(2):380-386.
Background:
Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL) is an aggressive disease with poor prognosis, requiring risk stratification. However, the prognosis of ENKTL is not fully defined and needs supplementation. We hypothesised that fasting blood glucose (FBG) may be a new prognostic factor for ENKTL.
Methods:
We retrospectively analysed 130 patients newly diagnosed with ENKTL.
Results:
Both univariate analysis and multivariate analysis revealed that FBG >100 mg dl−1 was associated with a poor outcome. Patients with FBG >100 mg dl−1 at diagnosis had more adverse clinical features, achieved lower complete remission rates (P=0.003) and had worse overall survival (P<0.001) and progression-free survival (P<0.001) compared with low-FBG patients. Measurement of FBG was helpful in differentiating between low-risk patients using the International Prognostic Index (IPI) and Prognosis Index for peripheral T-cell lymphoma (PIT) scoring and patients in a different category using the Korean Prognostic Index (KPI) scores with different survival outcomes (P<0.05).
Conclusion:
Our data suggest that measuring FBG levels at diagnosis is a novel, independent predictor of prognosis in ENKTL and helps to distinguish low-risk patients with poor survival, and this holds true in patients considered low-risk by IPI, PIT and KPI.
doi:10.1038/bjc.2012.566
PMCID: PMC3566812  PMID: 23299534
fasting blood glucose; extranodal NK/T-cell lymphoma; prognosis
18.  Primary Systemic Anaplastic Large Cell Lymphoma in Korean Adults: 11 Years' Experience at Asan Medical Center 
Yonsei Medical Journal  2008;49(4):601-609.
Purpose
Anaplastic large cell lymphoma (ALCL), a CD30+ T-cell non-Hodgkin's lymphoma, represents only 2 - 8% of lymphoma overall. Information on the clinical findings of primary systemic ALCL in Korea is limited. Our aims were to report the clinical features and outcomes of primary systemic ALCL.
Patients and Methods
We retrospectively reviewed the medical records of 36 adult patients diagnosed with primary systemic ALCL at Asan Medical Center from February 1995 through June 2006.
Results
Of 36 patients, 29 were male. The median age was 39 years (range, 17 - 67 years), and 26 (72%) presented with Ann Arbor stages III and IV. The most commonly involved extranodal sites were bone (n = 7) and soft tissue (n = 6). Thirty-two of all patients (89%) were treated with an anthracycline-based regimen including cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) as induction chemotherapy; 16 (50%) achieved complete remission (CR), and 13 (41%) achieved partial remission (PR). Median overall survival (OS) and event-free survival (EFS) were 49 and 17 months, respectively. Univariate analysis showed that performance status (p = 0.035), international prognostic index (IPI) (p = 0.025), and age-adjusted IPI (p = 0.034) were significant prognostic factors for OS, whereas anaplastic lymphoma kinase (ALK) expression did not affect OS (p = 0.483).
Conclusion
Our retrospective analysis of Korean primary systemic ALCL patients showed that median OS was 49 months and overall response to CHOP was 91%. Performance, IPI, and age-adjusted IPI were predictors of OS, whereas ALK expression did not have prognostic significance.
doi:10.3349/ymj.2008.49.4.601
PMCID: PMC2615286  PMID: 18729302
Anaplastic large cell lymphoma; anaplastic lymphoma kinase; CD 30; prognosis; International Prognostic Index
19.  c-FLIP is involved in tumor progression of peripheral T-cell lymphoma and targeted by histone deacetylase inhibitors 
Background
Peripheral T-cell lymphomas (PTCLs) are often aggressive tumors and resistant to conventional chemotherapy. Dysregulation of extrinsic apoptosis plays an important role on tumor cell sensitivity to chemotherapeutic agents. Cellular FLICE inhibitory protein (c-FLIP) is a key regulator of extrinsic apoptotic pathway.
Methods
c-FLIP expression was assessed by real-time PCR and compared according to clinical parameters in patients with PTCLs. The relation of c-FLIP to tumor cell apoptosis mediated by histone deacetylases inhibitors (HDACIs) and the possible mechanism were examined in T-lymphoma cell lines and in a murine xenograft model.
Results
c-FLIP was overexpressed and associated with decreased tumor TRAIL/DR5 expression, elevated serum lactate dehydrogenase level and high-risk International Prognostic Index of the patients. In vitro, molecular silencing of c-FLIP by specific small-interfering RNA increased TRAIL/DR5 expression, enhanced T-lymphoma cell apoptosis and sensitized cells to chemotherapeutic agents. However, HDACIs valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) could downregulate c-FLIP expression and triggered extrinsic apoptosis of T-lymphoma cells, through inhibiting NF-κB signaling and interrupting P50 interaction with c-FLIP promoter. As Class I HDACIs, both VPA and SAHA inhibited HDAC1, resulting in P50 inactivation and c-FLIP downregulation. In vivo, oral VPA treatment significantly retarded tumor growth and induced in situ apoptosis, consistent with inhibition of HDAC1/P50/c-FLIP axis and increase of TRAIL/DR5 expression.
Conclusions
c-FLIP overexpression in PTCLs protected tumor cells from extrinsic apoptosis and contributed to tumor progression. Although linking to chemoresistance, c-FLIP indicated tumor cell sensitivity to HDACIs, providing a potential biomarker of targeting apoptosis in treating PTCLs.
Electronic supplementary material
The online version of this article (doi:10.1186/s13045-014-0088-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s13045-014-0088-y
PMCID: PMC4261569  PMID: 25477070
Peripheral T-cell lymphoma; Apoptosis; c-FLIP; Histone deacetylase inhibitor; NF-κB
20.  Routine use of ancillary investigations in staging diffuse large B-cell lymphoma improves the International Prognostic Index (IPI) 
Background
The International Prognostic Index (IPI) is used to determine prognosis in diffuse large B-cell lymphoma (DLBCL). One of the determinants of IPI is the stage of disease with bone marrow involvement being classified as stage IV. For the IPI, involvement on bone marrow is traditionally defined on the basis of histology with ancillary investigations used only in difficult cases to aid histological diagnosis. This study aimed to determine the effect of the routine use of flow cytometry, immunohistochemistry and molecular studies in bone marrow staging upon the IPI.
Results
Bone marrow trephines of 156 histologically proven DLBCL cases at initial diagnosis were assessed on routine histology, and immunohistochemistry using two T-cell markers (CD45RO and CD3), two B-cell markers (CD20 and CD79a) and kappa and lambda light chains. Raw flow cytometry data on all samples were reanalysed and reinterpreted blindly. DNA extracted from archived paraffin-embedded trephine biopsy samples was used for immunoglobulin heavy chain and light chain gene rearrangement analysis. Using immunophenotyping (flow cytometry and immunohistochemistry), 30 (19.2%) cases were upstaged to stage IV. A further 8 (5.1%) cases were upstaged using molecular studies. A change in IPI was noted in 18 cases (11.5%) on immunophenotyping alone, and 22 (14.1%) cases on immunophenotyping and molecular testing. Comparison of two revised IPI models, 1) using immunophenotyping alone, and 2) using immunophenotyping with molecular studies, was performed with baseline IPI using a Cox regression model. It showed that the revised IPI model using immunophenotyping provides the best differentiation between the IPI categories.
Conclusion
Improved bone marrow staging using flow cytometry and immunohistochemistry improves the predictive value of the IPI in patients with DLBCL and should be performed routinely in all cases.
doi:10.1186/1756-8722-2-49
PMCID: PMC2786909  PMID: 19930611
21.  Serum C-Reactive Protein (CRP) as a Simple and Independent Prognostic Factor in Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type 
PLoS ONE  2013;8(5):e64158.
Background
C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL).
Methods
We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model.
Results
Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P<0.001), inferior progression-free survival (PFS, P = 0.001), and inferior overall survival (OS, P<0.001). Multivariate analysis demonstrated that elevated serum CRP levels, age >60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (P<0.001). The novel prognostic model was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups.
Conclusions
Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI.
doi:10.1371/journal.pone.0064158
PMCID: PMC3665788  PMID: 23724031
22.  Identification and Characterization of Peripheral T-Cell Lymphoma-Associated SEREX Antigens 
PLoS ONE  2011;6(8):e23916.
Peripheral T-cell lymphomas (PTCL) are generally less common and pursue a more aggressive clinical course than B-cell lymphomas, with the T-cell phenotype itself being a poor prognostic factor in adult non-Hodgkin lymphoma (NHL). With notable exceptions such as ALK+ anaplastic large cell lymphoma (ALCL, ALK+), the molecular abnormalities in PTCL remain poorly characterised. We had previously identified circulating antibodies to ALK in patients with ALCL, ALK+. Thus, as a strategy to identify potential antigens associated with the pathogenesis of PTCL, not otherwise specified (PTCL, NOS), we screened a testis cDNA library with sera from four PTCL, NOS patients using the SEREX (serological analysis of recombinant cDNA expression libraries) technique. We identified nine PTCL, NOS-associated antigens whose immunological reactivity was further investigated using sera from 52 B- and T-cell lymphoma patients and 17 normal controls. The centrosomal protein CEP250 was specifically recognised by patients sera and showed increased protein expression in cell lines derived from T-cell versus B-cell malignancies. TCEB3, BECN1, and two previously uncharacterised proteins, c14orf93 and ZBTB44, were preferentially recognised by patients' sera. Transcripts for all nine genes were identified in 39 cancer cell lines and the five genes encoding preferentially lymphoma-recognised antigens were widely expressed in normal tissues and mononuclear cell subsets. In summary, this study identifies novel molecules that are immunologically recognised in vivo by patients with PTCL, NOS. Future studies are needed to determine whether these tumor antigens play a role in the pathogenesis of PTCL.
doi:10.1371/journal.pone.0023916
PMCID: PMC3161784  PMID: 21887344
23.  A Systematic Review and Meta-Analysis of Front-line Anthracycline-Based Chemotherapy Regimens for Peripheral T-Cell Lymphoma 
ISRN Hematology  2011;2011:623924.
Anthracycline-based chemotherapy remains standard treatment for peripheral T-cell lymphoma (PTCL) although its benefits have been questioned. We performed systematic literature review and meta-analyses examining the complete response (CR) and overall survival (OS) rates for patients with PTCL. The CR rate for PTCL patients ranged from 35.9% (95% CI 23.4–50.7%) for enteropathy-type T-cell lymphoma (ETTL) to 65.8% (95% CI 54.0–75.9%) for anaplastic large cell lymphoma (ALCL). The 5-year OS was 38.5% (95% CI 35.5–41.6%) for all PTCL patients and ranged from 20.3% (95% CI 12.5–31.2%) for ETTL to 56.5% (95% CI 42.8–69.2%) for ALCL. These data suggest that there is marked heterogeneity across PTCL subtypes in the benefits of anthracycline-based chemotherapy. While anthracyclines produce CR in half of PTCL patients, this yields reasonable 5-year OS for patients with ALCL but not for those with PTCL-NOS or ETTL. Novel agents and regimens are needed to improve outcomes for these patients.
doi:10.5402/2011/623924
PMCID: PMC3197255  PMID: 22084700
24.  B-cell Lymphomas with Concurrent IGH-BCL2 and MYC Rearrangements Are Aggressive Neoplasms with Clinical and Pathologic Features Distinct from Burkitt Lymphoma and Diffuse Large B-cell Lymphoma 
B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements, also known as “double-hit” lymphomas (DHL), are rare neoplasms characterized by highly aggressive clinical behavior, complex karyotypes, and a spectrum of pathological features overlapping with Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and B-lymphoblastic lymphoma/leukemia (B-LBL). The clinical and pathological spectrum of this rare entity, including comparison to other high-grade B-cell neoplasms, has not been well defined. We conducted a retrospective analysis of clinical and pathologic features of 20 cases of DHL seen at our institution during a 5-year period. In addition, we performed case-control comparisons of DHL with BL and International Prognostic Index (IPI)-matched DLBCL. The 11 men and 9 women had a median age of 63.5 years (range 32-91). Six patients had a history of grade 1-2 follicular lymphoma (FL); review of the prior biopsy specimens in 2 of 5 cases revealed blastoid morphology. Eighteen patients had Ann Arbor stage 3 or 4 disease and all had elevated serum lactate dehydrogenase (LDH) levels at presentation. Extranodal disease was present in 17/20 (85%), bone marrow involvement in 10/17 (59%) and central nervous system (CNS) disease in 5/11 (45%). Nineteen patients were treated with combination chemotherapy, of whom 18 received rituximab and 14 received CNS-directed therapy. Fourteen patients (70%) died within 8 months of diagnosis. Median overall survival in the DHL group (4.5 months) was inferior to both BL (p=0.002) and IPI-matched DLBCL (p=0.04) control patients. Twelve DHL cases (60%) were classified as B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL, 7 cases (35%) as DLBCL, not otherwise specified, and 1 case as B-LBL. Distinguishing features from BL included expression of Bcl2 (p<0.0001), Mum1/IRF4 (p=0.006), Ki-67 <95% (p<0.0001), and absence of EBV-EBER (p=0.006). DHL commonly contained the t(8;22) rather than the t(8;14) seen in most BL controls (p=0.001), and exhibited a higher number of chromosomal aberrations (p=0.0009). DHL is a high-grade B-cell neoplasm with a poor prognosis, resistance to multi-agent chemotherapy, and clinical and pathological features distinct from other high-grade B-cell neoplasms. Familiarity with the morphologic and immunophenotypic spectrum of DHL is important in directing testing to detect concurrent IGH-BCL2 and MYC rearrangements when a karyotype is unavailable. The aggressive clinical behavior and combination of genetic abnormalities seen in these cases may warrant categorization as a separate entity in future classifications and call for novel therapeutic approaches.
doi:10.1097/PAS.0b013e3181cd3aeb
PMCID: PMC3152212  PMID: 20118770
MYC; BCL2; diffuse large B-cell lymphoma; Burkitt lymphoma; cytogenetics; high-grade B-cell lymphoma
25.  A large single-center experience with allogeneic stem-cell transplantation for peripheral T-cell non-Hodgkin lymphoma and advanced mycosis fungoides/Sezary syndrome 
Annals of Oncology  2011;22(7):1608-1613.
Background: The prognosis for patients with most forms of T-cell lymphoma is poor. Allogeneic hematopoietic stem-cell transplantation (HSCT) may improve the outcome.
Patients and methods: This study examines the outcome of 52 patients who underwent ablative or nonablative allogeneic HSCT for peripheral T-cell lymphoma (PTCL) or advanced mycosis fungoides/Sezary syndrome over a 12-year period at a single institution. We divided the patients into those with predominantly nodal histologies: peripheral T-cell not otherwise specified (PTCL NOS), angioimmunoblastic (AITL), or anaplastic large cell lymphoma, T/null type (systemic) (ALCL), and predominantly extranodal histologies: natural killer (NK)/T cell, enteropathy type, hepatosplenic, subcutaneous panniculitic, mycosis fungoides, or T cell or NK cell other.
Results: Median follow-up of survivors is 49 months. Non-relapse mortality and relapse at 3 years was 27% and 43%, respectively. The incidence of grade II–IV acute graft-versus-host disease (GVHD) was 21%. The incidence of extensive chronic GVHD at 2 years was 27%. The 3-year progression-free survival was 30%: 45% in patients with predominantly nodal histologies (PTCL NOS, AITL, and ALCL) and 6% in patients with predominantly extranodal histologies (P = 0.016). Overall survival at 3 years was 41% for all patients.
Conclusion: Allogeneic HSCT can produce long-term remissions in relapsed/refractory T-cell lymphoma, especially those with nodal histologies.
doi:10.1093/annonc/mdq698
PMCID: PMC3121969  PMID: 21252059
allogeneic transplant; CTCL; GVHD; mycosis fungoides; NK lymphoma; T-cell lymphoma

Results 1-25 (1301859)