A Clinical Prognostic Index for Angioimmunoblastic T Cell Lymphoma in an Asian Multi-Centre Study

Abstract Background and aims: Angioimmunoblastic T cell Lymphoma (AITL) is a subtype of peripheral T cell lymphoma that is generally felt to be aggressive and of poor prognosis. It is characterized as a lymphoma associated with inflammatory and immune conditions, typically seen in the older population and presenting at more advanced stages. The International T-Cell Lymphoma project recently reported a novel AITL score comprising of age, ECOG performance status, serum CRP level and serum B2-microglobulin level; the latter 2 variables suggesting a pro-inflammatory state. They also found that progression of disease within 24 months (POD24) to be strongly prognostic. In our Asian multicenter study, we aim to investigate the clinical prognostic factors affecting the outcomes of our AITL patients and attempt to identify a prognostic index that would be relevant to our Asian population. Methods: Patients who were consecutively diagnosed with AITL and seen at National Cancer Centre Singapore and Singapore General Hospital between June 1999 and Dec 2019 were retrospectively analyzed. Relevant demographical and clinical characteristics were collected. Median duration of follow up was 19.7 months. Outcomes of interest were that of 5-year overall survival (OS) and 5-year progression free survival (PFS). POD24 as defined by progression of disease within 24 months was also analyzed for its prognostic significance. Kaplan meier curves were plotted to estimate survival for each individual clinical parameter. Parameters found to be significant on univariate analysis were subsequently used in generation of multivariate cox regression models. Results: A total of 166 patients were included. The median age was 62.1 years. The majority of our patients (92.8%) had good performance status of ECOG 0-1 and 77.7% presented at advanced stages (Ann Arbor stage 3-4). The median PFS and OS was 1.5 years and 5.5 years respectively. The estimated 5-year PFS and OS was 40% and 53% respectively. Univariate analyses of various parameters were significant for age >60 years, presence of B symptoms, ECOG >1, Ann Arbor stage 3-4, bone marrow involvement, elevated serum lactate dehydrogenase > upper limit normal, elevated total white cell count > 12 x 10 9/L and low platelet count < 150,000/mm 3. In the multivariate analyses, age >60 years, bone marrow involvement, elevated total white cell count and low platelet count were associated with poorer PFS and OS. This allowed for a prognostic index (AITL-PI) differentiating patients into low (0-1 factors, n=62), moderate (2 factors, n=54) and high (3-4 factors, n=48) risk subgroups with 5-year OS of 83%, 41% and 26% respectively. The corresponding 5-year PFS of the low, moderate and high risk subgroups are 69%, 29% and 14%. Likewise, POD24 proved to be strongly prognostic in our cohort as patients with POD24 had a 5-year OS of 24%, whereas those without POD24 had a 5-year OS of 90% (p<0.0001). Conclusion: We validated POD24 as a strong prognostic factor. Our AITL-PI was able to identify 3 different subgroups of patients with disparate outcomes based on their presenting clinical parameters. Further work can be done to elucidate if there are unique pathological or molecular characteristics in these individual risk groups that can further guide treatment choices. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Serum Ferritin Level As a Prognostic Marker For Peripheral T-Cell Lymphoma.

Blood ◽

10.1182/blood.v122.21.4326.4326 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4326-4326

Author(s):

Satoshi Koyama ◽

Naoto Tomita ◽

Reina Watanabe ◽

Megumi Itabashi ◽

Daisuke Ishibashi ◽

...

Keyword(s):

T Cell ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Cell Lymphoma ◽

Ferritin Level ◽

Performance Status ◽

Prognostic Index ◽

T Cell Lymphoma ◽

Ann Arbor ◽

Group 3

Abstract Background Peripheral T-cell lymphoma (PTCL) is known to have an aggressive clinical course and be associated with poor survival. The International Prognostic Index (IPI) score and the Prognostic Index for T-cell lymphoma (PIT) have been suggested as methods to predict the prognosis of PTCL. Ferritin, the iron storage protein, is associated with chronic inflammation. Although higher levels of serum ferritin are detected in many cancer patients, the significance of elevated serum ferritin as a prognostic factor for lymphoma has yet to be established. Thus, our retrospective study aimed to examine the prognostic value of serum ferritin levels in PTCL. Patients and Methods Serum ferritin levels were evaluated in 78 patients with PTCL, who were treated with anthracycline-containing regimens in 8 institutions affiliated to the Yokohama City University Hematology Group between 1998 and 2011. Fourteen patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); 44 receivedpirarubicin, cyclophosphamide, vincristine, and prednisone (THP-COP); 3 received THP-COP followed by radiotherapy; 3 received up-front autologous peripheral blood stem cell transplantation; and 14 received THP-COP at 2-week intervals in a clinical trial. Results The study population comprised 50 male and 28 female patients with a median age of 64 years at the time of diagnosis (range, 16–83 years). With regard to the PTCL subtype, 39 patients had PTCL, not otherwise specified, and 39 had angioimmunoblastic T-cell lymphoma. Twelve patients had localized disease and 66 patients had advanced Ann Arbor stage lymphoma. Twenty-three patients had a poor Eastern Cooperative Oncology Group performance status (PS) of 2–4. B symptoms were present in 34 patients. Risk stratification according to the IPI was as follows: low risk, 9 patients; low–intermediate risk, 20 patients; high–intermediate (HI) risk, 30 patients; and high (H) risk, 19 patients. According to the PIT, 4 patients were categorized into group 1, 25 into, group 2 , 28 into, group 3, 21 into, as group 4. The median observation period for the surviving patients was 50 months. The median serum ferritin level was 183 ng/ml (range, 5–14,622 ng/ml). Factors associated with a poor overall survival (OS) in univariate analysis were HI and H risk status with regard to IPI (P = 0.024), assignment to group 3 or 4 with regard to PIT (P = 0.017), poor performance status (P< 0.001), and ferritin levels ≥ 300 ng/ml (P< 0.001). The 4-year OS rate of all 78 patients was 54%. The 4-year OS rate was poorer in patients with serum ferritin levels ≥300 ng/ml (n = 21) than in those with serum ferritin levels< 300ng/ml (n = 57; 22% vs. 65%; P< 0.001) (Figure). Multivariate analysis including each factor comprising the IPI (age, lactate dehydrogenase level, PS, Ann Arbor stage, and number of extranodal lesions), gender, bone marrow involvement, and serum ferritin level showed that poor PS (P = 0.002, relative risk [RR] 3.6) and a serum ferritin level ≥300 ng/ml (P = 0.014, RR 2.7) were independent risk factors for poor OS. Conclusion The serum ferritin level is a useful prognostic marker for PTCL. Disclosures: No relevant conflicts of interest to declare.

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The Prognostic Value of the Neutrophil to Lymphocyte Ratio in 209 Patients with Peripheral T-Cell Lymphoma

Blood ◽

10.1182/blood.v124.21.1675.1675 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1675-1675

Author(s):

Brady E Beltran ◽

Denisse Castro ◽

Julio C Chavez ◽

Eduardo M. Sotomayor ◽

Jorge J. Castillo

Keyword(s):

Bone Marrow ◽

T Cell ◽

Prognostic Value ◽

Cell Lymphoma ◽

Performance Status ◽

Bone Marrow Involvement ◽

T Cell Lymphoma ◽

Neutrophil To Lymphocyte Ratio ◽

Advanced Stage ◽

Lymphocyte Ratio

Abstract Introduction: Peripheral T-cell lymphomas (PTCL) are rare hematologic malignancies with a poor prognosis when treated with current standard therapies. Several factors have been developed to prognosticate survival in PTCL patients; however, more refined, easy to use and reliable prognostic tools are needed. The neutrophil to lymphocyte ratio (NLR) has been reported prognostic in patients with diffuse large B-cell lymphoma (Troppan et al. BJC 2014). We have investigated the prognostic value of the NLR in the overall survival (OS) of patients with untreated PTCL. Methods: We included patients with a pathological diagnosis of PTCL who were diagnosed and treated at our institution between 2001-2013. We excluded cases with primary cutaneous PTCL, CNS involvement, and patients with >50% incomplete data. IRB approval was obtained prior to research. Pathological samples were reviewed by expert hematopathologists to confirm a diagnosis of PTCL. Pertinent clinicopathological data such as age, sex, performance status, LDH levels, stage, bone marrow involvement, extranodal sites of disease, PTCL subtype, and absolute neutrophil and lymphocyte countswere collected through chart review, and are presented using descriptive statistics. The NLR was calculated by dividing the absolute neutrophil by the lymphocyte count, and dichotomized in NLR>=4 and NLR<4. The Prognostic Index for PTCL (PIT) was estimated using the clinical data above. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analyses were performed using Cox proportional-hazard regression models. Results: A total of 209 patients were included in our analysis from which 93 (44.5%) were PTCL, not otherwise specified (NOS), 83 (40%) were adult T-cell leukemia/lymphoma (ATLL), 22 (10.5%) were anaplastic large cell lymphoma (ALCL), 7 (3%) were extranodal NK/T-cell lymphoma (NKTCL), and 4 (2%) angioimmunoblastic T-cell lymphoma (AITL). The median age was 57 years (range 3-87 years) with equal distribution among men (52%) and women (48%). Poor performance status (ECOG >1) was seen in 85 (49%), elevated LDH levels in 116 (64%), >1 extranodal site in 31 (19%), bone marrow involvement in 64 (31%), and advanced stage (stage 3 and 4) in 151 (74%) of patients. Based on the NLR, 91 patients (59%) had NLR<4 and 62 (n=41%) had NLR>=4. Patients with NLR >=4 were more likely men (67% vs. 44%, p=0.005), and tended to present with elevated LDH (73% vs. 47%, p=0.002), advanced stage (87% vs. 61%, p=0.001) but lower bone marrow involvement (19% vs. 37%, p=0.02). There were no differences in age, performance status and number of extranodal sites. NLR>=4 was associated with a worse OS (HR 2.27, 95% CI 1.40-3.69; p=0.001). Specifically, NLR>=4 was associated with a worse OS in patients with non-ATLL PTCL (HR 2.99, 95% CI 1.67-5.37; p<0.001) but not in patients with ATLL (HR 1.16, 0.48-2.81; p=0.75). In the multivariate analysis, NLR>=4 was independently associated with worse OS when adjusting for the PIT score in non-ATLL PTCL patients (HR 2.12, 95% CI 1.06-4.26; p=0.03). Conclusion: The NLR appears as a novel and easy to use prognostic factor for OS in patients with untreated non-ATLL PTCL, independent of the PIT score. The NLR did not seem to be prognostic in ATLL patients. Our findings support the need for validation of the NLR in larger retrospective or prospective studies in patients with PTCL. Disclosures No relevant conflicts of interest to declare.

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International T-Cell Lymphoma Classification Project: Angioimmunoblastic T-Cell Lymphoma.

Blood ◽

10.1182/blood.v108.11.2052.2052 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2052-2052

Author(s):

Thomas Ruediger ◽

Bertrand Coiffier ◽

Dennis D. Weisenburger ◽

Massimo Federico

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

Performance Status ◽

Prognostic Index ◽

T Cell Lymphoma ◽

T Cell Lymphomas ◽

Stage Disease ◽

Classification Project ◽

And Performance ◽

Generalized Lymphadenopathy

Abstract Peripheral T-cell lymphomas are rare diseases: therefore, the International T-cell Lymphoma Project was undertaken to compare lymphomas at different sites throughout North America, Asia and Europe. Within this project, 243 angioimmunoblastic T-cell lymphomas (AILTs) were diagnosed which made up 21% of all peripheral T-cell lymphoma (PTCL). At presentation, generalized lymphadenopathy was noted in 76% of the patients. Interestingly, three patients presented with extranodal disease only. Among the skin symptoms, erythroderma was the most frequent (21% of patients). Hemolytic anemia was seen in 13% and dysproteinemia occurred in 50%, and among these monoclonal serum immunoglobulin was seen in 8% of the patients. Anemia, hypergammaglobulinemia and elevated LDH were significantly more frequent in AILT than in PTCL-unspecified. Similarly, patients with AILT had a significantly higher frequency of high stage disease (89% of the patients were stage 3 or 4), as well as worse prognostic indices. Despite this, their 5-year overall (33%) and failure-free survivals (18%) were similar to patients with PTCL-unspecified. Treatment was usually administered in combination with anthracycline. A few factors at presentation were prognostic for outcome, including the PIT (prognostic index for T-cell lymphoma; Gallamini et al.: Blood. 2004 Apr 1;103(7):2474–9), age, B-symptoms and performance status. The IPI, however, was not prognostic. Controlling for the PIT, a platelet count <150.000 μl was prognostic for overall survival whereas B-symptoms were prognostic for failure-free survival. In conclusion, AILT is an aggressive disease for which the optimum treatment has not yet been developed.

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Clinicopathologic Characteristics of HIV-Associated Peripheral T-Cell Lymphoma.

Blood ◽

10.1182/blood.v114.22.3924.3924 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3924-3924

Author(s):

Jorge Castillo ◽

Brady Beltran ◽

Jaime Collins ◽

Jose L Diez-Martin ◽

Francisco Hernandez-Ilizaliturri ◽

...

Keyword(s):

Bone Marrow ◽

T Cell ◽

Median Survival ◽

Cell Lymphoma ◽

Performance Status ◽

Bone Marrow Involvement ◽

The United States ◽

Response To Therapy ◽

T Cell Lymphoma ◽

Cd4 Count

Abstract Abstract 3924 Poster Board III-860 Introduction The incidence of lymphomas is increased in HIV-infected individuals. Most of the cases are B-cell subtypes of non-Hodgkin lymphoma. Although the incidence of mature or peripheral T-cell lymphomas (PTCL) seems to be increased in HIV-positive cases, clinicopathological data is lacking. The objective of this study is to describe the characteristics of non-cutaneous PTCL in HIV-infected individuals and identify potential prognostic factors. Methods Institutions within and outside of the United States were invited to submit original data on cases of HIV-associated PTCL. Data on each case included country of origin, age, sex, ethnicity, CD4 count, use of highly active antiretroviral therapy (HAART), B symptoms, lymphoma subtype according to the WHO classification of lymphoid neoplasms, expression of ALK, EBV and Ki-67, T-cell gene rearrangement, number of extranodal sites, bone marrow involvement, clinical stage, performance status, lactate dehydrogenase (LDH) levels, frontline therapy, response, use of stem cell transplantation (HSCT), final outcome, survival in months and cause of death; these will be presented using descriptive statistics. Univariate analyses were performed using Kaplan-Meier survival estimates compared using the log-rank test. Cox proportional-hazard regression test was used for the multivariate analysis. P-values of less than 0.05 were considered significant. Results Thus far, data on 24 cases have been obtained from 7 institutions. From these cases, 13 (54%) are from South America, 5 (21%) from Europe, 3 (12.5%) from North America and 3 (12.5%) from Asia. Thirteen cases (54%) are Hispanic, 5 (21%) are Caucasian, 3 (12.5%) are Black and 3 (12.5%) are Asian. Median age is 39 years (range 26 to 58 years) and the male-to-female ratio is 7:1. Sixteen cases (70%) presented with B symptoms. Median CD4 count is 129 cells/mm3 (range 4 to 305 cells/mm3). Twelve cases (63%) reported use of HAART. Fourteen cases (58%) are PTCL, unspecified (PTCLU), 4 cases (17%) anaplastic large cell lymphoma (ALCL), 4 cases (17%) of NK/T-cell lymphoma (NKTCL) and 2 cases (8%) angioimmunoblastic lymphoma (AITL). All ALCL cases were ALK-negative; EBV was expressed in 50% of NKTCL cases but in none of the AITL cases. Four of 15 cases (27%) had involvement of more than 2 extranodal sites, 3 of 11 cases (27%) had bone marrow involvement, 19 of 24 cases (79%) presented with advanced stage, 5 of 12 cases (42%) had an elevated LDH level and 8 of 24 cases (33%) had a performance status higher than 2. Thirteen of 24 cases (54%) were treated with chemotherapy alone from which 8 cases (62%) received CHOP therapy; six of 24 cases (25%) did not receive any therapy. Nine of 14 cases (65%) responded to therapy (29% CR and 36% PR); 35% of cases did not respond to therapy. Five cases of 14 (36%) underwent HSCT; 4 cases (29%) in the frontline and 1 case (7%) in the salvage setting. At the time of this report, 63% of cases have died; 53% due to infectious complications and 40% due to lymphoma progression. The median survival for the group was 10 months. The median survival for treated (n=19) and untreated cases (n=5) were 10.5 and 1 month, respectively (p=0.005). Conclusions HIV-associated PTCL tends to affect younger men with CD4 counts of less than 200 cells/mm3. PTCLU is the most common subtype reported in HIV-infected individuals. HIV-associated ALCL cases do not appear to express ALK. The survival of treated HIV-associated PTCL cases is short at 10.5 months despite a 65% initial response to therapy. Accumulation of data continues. Disclosures: No relevant conflicts of interest to declare.

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Local tumor invasiveness is more predictive of survival than International Prognostic Index in stage IE/IIE extranodal NK/T-cell lymphoma, nasal type

Blood ◽

10.1182/blood-2005-05-2056 ◽

2005 ◽

Vol 106 (12) ◽

pp. 3785-3790 ◽

Cited By ~ 125

Author(s):

Tae Min Kim ◽

Yeon Hee Park ◽

Sang-Yoon Lee ◽

Ji-Hoon Kim ◽

Dong-Wan Kim ◽

...

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

T Cell Lymphoma ◽

Local Tumor ◽

Nasal Type ◽

Tumor Invasiveness ◽

Ann Arbor ◽

Low Probability

This study was launched to determine the prognostic significance of local tumor invasiveness (LTI) in 114 patients diagnosed with stage IE/IIE extranodal natural killer (NK)/T-cell lymphoma, nasal type (NTCL). LTI was defined as bony invasion or destruction or tumor invasion of the skin. Complete remission (CR), overall survival (OS), and disease-free survival (DFS) were compared between each group according to LTI, Ann Arbor stage, and International Prognostic Index (IPI). LTI was observed in 23 patients. Using multivariate analysis, factors associated with low probability of CR were the presence of LTI (P < .001), the presence of B symptoms (P = .003), and single-modality chemotherapy (P = .045). The presence of LTI (relative risk [RR] = 8.4, 95% confidence interval [CI] 3.9-17.9; P < .001) and high IPI score (RR = 2.8, 95% CI 1.2-6.8; P = .019) were also predictive of OS. The presence of LTI (RR = 7.3, 95% CI 3.2-16.5; P < .001) was an independently significant factor for reduced DFS. Ann Arbor staging system did not predict CR, OS, or DFS but IPI did have predictive power with regard to survival outcome. LTI is the most important prognostic factor in predicting low probability of CR and reduced OS and DFS in nasal stage IE/IIE NTCL.

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Intensive Induction Chemotherapy Followed by Early High-Dose Therapy and Hematopoietic Stem Cell Transplantation Results in Improved Outcome for Patients with Hepatosplenic T-Cell Lymphoma: A Single Institution Experience.

Blood ◽

10.1182/blood.v110.11.3454.3454 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3454-3454

Author(s):

Martin Voss ◽

Andrew Zelenetz ◽

Esperanza B. Papadopoulos ◽

Hanna Weissbrot ◽

Steven M. Horwitz

Keyword(s):

Bone Marrow ◽

T Cell ◽

Cell Lymphoma ◽

Bone Marrow Involvement ◽

Prognostic Index ◽

T Cell Lymphoma ◽

High Dose ◽

Single Institution ◽

High Dose Therapy ◽

Hepatosplenic T Cell Lymphoma

Abstract Introduction: Hepatosplenic T-cell lymphoma (HSTCL) is a rare form of non-Hodgkin lymphoma with unique features including presentation primarily in young men, lymphomatous infiltration of the liver and spleen, frequent bone marrow involvement, B symptoms, infrequent lymphadenopathy and poor prognosis. First described by Farcet and Gaulard1, there are two larger published series in whom only 6/66 of patients (pts) were alive at the time of the reports. 2,3 4/6 surviving pts in these reports had undergone high dose therapy and autologous or allogeneic stem cell transplantation (HDT-SCT). There are no prospective studies of treatment of HSTCL but a recent review of published case reports of HSTCL treated with allogeneic SCT suggests a better outcome for that approach.4 Methods: We reviewed our T-cell lymphoma and bone marrow transplantation databases to examine our results in pts with HSTCL. We identified 9 consecutive pts with this diagnosis. This report summarizes our single center experience. Results: All pts were male with a median age of 37y (12–59). All pts had stage IV disease with hepatomegaly and/or splenomegaly. 5/9 had documented bone marrow involvement, 7 had elevated LDH, and all 9 had B symptoms. Thrombocytopenia was present at diagnosis in 5 pts, anemia in 4 pts, and leukopenia in 4 pts. Transaminases and/or alkaline phosphatase were elevated in 6 pts. 4/9 had previous autoimmune disease: 2 with ulcerative colitis and 2 with rheumatoid arthritis. Responses to induction regimens were: CHOP (PR-2, POD-1) ICE/IVAC (CR-2, PR-2), pentostatin/2-CDA (POD-2). 2/4 pt achieved a CR to ICE as second line therapy. 8/9 pts achieved at least a PR and proceeded to HDT-SCT. 6 pts received an allogeneic SCT (one after relapse from autologous SCT), and 3 pts an autologous SCT. At the time of this report, 4/9 patients are alive in remission, 20–158 mos from diagnosis; the 4 surviving patients all underwent HDT/SCT. Following autologous-SCT 2/3 pts relapsed at 5 and 35 mos. Following Allogeneic-SCT 2/6 pts relapsed at 3 and 6 mos, 1 of whom was effectively treated with donor lymphocytes and remains in remission at 20 mos. 2/6 pts undergoing allo-SCT died of treatment related toxicities without documented recurrent disease. Complete information to determine the age-adjusted international prognostic index (aaIPI) was available for 8/9 pts; the aaIPI appeared to correlate with outcome: 4/5 pts with an aaIPI of low intermediate to high intermediate risk (1–2 factors) were alive compared to 0/3 aaIPI high risk disease (3 factors). The prognostic index for PTCL (PIT) consisting of age, performance status, LDH, and bone marrow involvement was also assessed. All 8 pts had at least one risk factor; 4/6 pts with a PIT of 1–2 were alive vs 0/2 pts for PIT of ≥3. Four pts received ICE or IVAC as their initial therapy and 3/4 were alive compared to only 1/5 for those who received other initial regimens. Conclusions: In this single institution experience, use of non-CHOP induction chemotherapy regimens such as ICE or IVAC and early use of HDT-SCT consolidation appear to improve the outcome for pts with HSTCL compared to reported results with CHOP or CHOP-like regimens.

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Clinicopathologic Analysis of Primary Gastrointestinal T-Cell Lymphoma with a Special Reference to Intestinal and Gastric Type in Japan.

Blood ◽

10.1182/blood.v112.11.1782.1782 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1782-1782

Author(s):

Hideko Yamamoto ◽

Keitaro Matsuo ◽

Hidemi Goto ◽

Shigeo Nakamura

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

Performance Status ◽

Prognostic Index ◽

T Cell Lymphoma ◽

Cell Leukemia ◽

Clinical Factors ◽

Intestinal Lymphoma ◽

Total Protein Level ◽

T Cell Lymphomas

Abstract Primary gastrointestinal T-cell lymphomas (PGITL) are very rare and heterogeneous diseases with poor prognosis. Their incidence and pathogenesis may vary with geographical locations. In this study, we aimed to define clinicopathologic and prognostic features of PGITL in Japan, non endemic area for celiac disease, with compared to those in Western countries. 79 patients with PGITL (41 gastric and 38 intestinal lymphoma cases) were enrolled. Epstein-Barr virus associated NK-/T-cell lymphoma and human T-cell leukemia virus type 1 associated adult T-cell leukemia/lymphoma cases were excluded from this study. Our intestinal cases (63%) were histopathologically characterized by monomorphic small-to medium-sized tumor cells, which appeared to be contrasted with higher incidence of pleomorphic appearance among Western patients, and by frequent expression of CD8, CD56, and cytotoxic molecules (CM) of those cells, which is consistent with immunohistochemical features of Western cases. Our gastric cases were unique in showing a wide range of histologic and immunophenotypical characteristics with a significantly higher inclusion of non-cytotoxic lymphoma than intestinal cases (33% vs. 9%, P=.0299). Approximately 62% of patients also showed pleomorphic appearance most frequently with CD4+CD8− and CD4–CD8-phenotype. In comparison with gastric patients, intestinal ones were significantly associated with several clinical factors to indicate poor prognosis such as poorer performance status (P=.0232), lower total protein level (P=.0018), and lower serum albumin level (P=.0303). Overall survival of intestinal cases were significantly inferior to that of gastric patients (P = 0.026), while no statistically significant differences were found in survival between CM-positive PGITL cases and –negative ones (P = 0.6). In univariate analysis, the factors that turned out to correlate significantly with survival were total protein level (<6.0g/dL) (HR, 3.696; 95% CI, 1.671 to 8.171; P=.0012), platelet level (<10.0 /μl) (HR, 10.706; 95% CI, 2.713 to 42.244; P=.0007), a higher than normal serum lactate dehydrogenase (LDH) level (HR, 2.574; 95% CI, 1.266 to5.231; P=.009), direct invasion or gastrointestinal perforation (HR, 2.079; 95% CI, 1.013 to 4.267; P=.046), bone marrow involvement of the disease (HR, 3.134; 95% CI, 1.136 to 8.651; P=.0274), performance status equal to or more than 2 (HR, 3.988; 95% CI, 1.763 to 8.882; P=.0007), the International Prognostic Index (IPI) more than low-intermediate (HR, 3.317; 95% CI, 1.304 to 8.441; P=.0119), Prognostic Index for T-cell lymphoma (PIT) scores more than 2 (HR, 8.166; 95% CI, 2.574 to25.904; P=.004), CD8 positivity (HR, 2.041; 95% CI, 1.032 to 4.037; P=.0404), and intestinal case (HR, 2.955; 95% CI, 1.493 to 5.849; P=.0019). Multivariate analysis with individual factors confirmed that PIT scores was a significant (HR, 6.622; 95% CI, 1.108 to 39.566; P=.0382) and platelet level (<10.0 /μl) was a marginally significant (HR, 5.343; 95% CI, .837 to 34.116; P=.0765) prognostic factors independent from other clinical factors. In conclusion, Japanese intestinal lymphoma patients were in keeping with characteristics of Enteropathy type T-cell lymphoma other than an association with celiac disease and monomorphic histology. However, gastric T-cell lymphomas were distinct from intestinal ones, and were separately considered.

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

Blood ◽

10.1182/blood.v120.21.1577.1577 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1577-1577

Author(s):

Aiko Kato ◽

Yukihiro Imai ◽

June Takeda ◽

Nobuhiko Yamauchi ◽

Yuki Funayama ◽

...

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

Prognostic Score ◽

Univariate Analysis ◽

Bone Marrow Involvement ◽

Prognostic Index ◽

T Cell Lymphoma ◽

Poor Survival ◽

Risk Of Death ◽

Serum Iga

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

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Validation of nomogram-revised risk index and comparison with other models for extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era: indication for prognostication and clinical decision-making

Leukemia ◽

10.1038/s41375-020-0791-3 ◽

2020 ◽

Vol 35 (1) ◽

pp. 130-142 ◽

Cited By ~ 6

Author(s):

Si-Ye Chen ◽

Yong Yang ◽

Shu-Nan Qi ◽

Ying Wang ◽

Chen Hu ◽

...

Keyword(s):

T Cell ◽

Validation Cohort ◽

Cell Lymphoma ◽

Risk Index ◽

Prognostic Index ◽

Curve Analysis ◽

T Cell Lymphoma ◽

Decision Curve Analysis ◽

Nasal Type ◽

Ann Arbor

AbstractDerived from our original nomogram study by using the risk variables from multivariable analyses in the derivation cohort of 1383 patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL) who were mostly treated with anthracycline-based chemotherapy, we propose an easily used nomogram-revised risk index (NRI), validated it and compared with Ann Arbor staging, the International Prognostic Index (IPI), Korean Prognostic Index (KPI), and prognostic index of natural killer lymphoma (PINK) for overall survival (OS) prediction by examining calibration, discrimination, and decision curve analysis in a validation cohort of 1582 patients primarily treated with non-anthracycline-based chemotherapy. The calibration of the NRI showed satisfactory for predicting 3- and 5-year OS in the validation cohort. The Harrell’s C-index and integrated Brier score (IBS) of the NRI for OS prediction demonstrated a better performance than that of the Ann Arbor staging system, IPI, KPI, and PINK. Decision curve analysis of the NRI also showed a superior outcome. The NRI is a promising tool for stratifying patients with ENKTCL into risk groups for designing clinical trials and for selecting appropriate individualized treatment.

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Clinicopathologic Characteristics of Angioimmunoblastic T-Cell Lymphoma: Analysis of the International Peripheral T-Cell Lymphoma Project

Journal of Clinical Oncology ◽

10.1200/jco.2011.37.3647 ◽

2013 ◽

Vol 31 (2) ◽

pp. 240-246 ◽

Cited By ~ 159

Author(s):

Massimo Federico ◽

Thomas Rudiger ◽

Monica Bellei ◽

Bharat N. Nathwani ◽

Stefano Luminari ◽

...

Keyword(s):

T Cell ◽

Survival Data ◽

Cell Lymphoma ◽

Risk Group ◽

Bone Marrow Involvement ◽

International Prognostic Index ◽

Prognostic Index ◽

T Cell Lymphoma ◽

Peripheral T Cell Lymphoma ◽

Angioimmunoblastic T Cell Lymphoma

PurposeThe International Peripheral T-Cell Lymphoma Project was undertaken to better understand the subtypes of T-cell and natural killer (NK) –cell lymphomas.Patients and MethodsAngioimmunoblastic T-cell lymphoma (AITL) was diagnosed according to the 2001 WHO criteria by a central review process consisting of panels of expert hematopathologists. Clinical, pathologic, immunophenotyping, treatment, and survival data were correlated.ResultsOf 1,314 patients, 243 (18.5%) were diagnosed with AITL. At presentation, generalized lymphadenopathy was noted in 76% of patients, and 89% had stages III to IV disease. Skin rash was observed in 21% of patients. Hemolytic anemia and hypergammoglobulinemia occurred in 13% and 30% of patients, respectively. Five-year overall and failure-free survivals were 33% and 18%, respectively. At presentation, prognostic models were evaluated, including the standard International Prognostic Index, which comprised the following factors: age ≥ 60 years, stages III to IV disease, lactic dehydrogenase (LDH) > normal, extranodal sites (ENSs) > one, and performance status (PS) ≥ 2; the Prognostic Index for Peripheral T-Cell Lymphoma, comprising: age ≥ 60 years, PS ≥ 2, LDH > normal, and bone marrow involvement; and the alternative Prognostic Index for AITL (PIAI), comprising: age > 60 years, PS ≥ 2, ENSs > one, B symptoms, and platelet count < 150 × 109/L. The simplified PIAI had a low-risk group (zero to one factors), with 5-year survival of 44%, and a high-risk group (two to five factors), with 5-year survival of 24% (P = .0065).ConclusionAITL is a rare clinicopathologic entity characterized by an aggressive course and dismal outcome with current therapies.

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