The Clinical Significance Of Activated p-AKT Expression In Peripheral T-Cell Lymphomas

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4315-4315
Author(s):  
Jung Yong Hong ◽  
Min Eui Hong ◽  
Seok Jin Kim ◽  
Jun Ho Jang ◽  
Kihyun Kim ◽  
...  

Abstract Background The oncogenic phosphatidylinositol-3-kinase/serine-threonine kinase (PI3K/AKT) pathway mediates diverse prosurvival signals and promotes the malignant phenotype of cancer cells through multiple downstream pathways. We aimed to define the prognostic role and clinical significance of p-AKT expression in peripheral T-cell lymphomas (PTCLs). Methods We evaluated the p-Akt expression in patients with PTCLs using tissue microarray(TMA) technology. The intensity of p-AKT staining was scored as 0, 1, 2, and 3 and the proportion of p-AKT positive cells was scored from 0% to 100%. p-AKT expression score was expressed as arbitrary units (AUs), calculated by multiplying the intensity score by the proportion score. Results A total of 63 PTCL patients were analyzed (PTCL not otherwise specified [PTCL-NOS, n=16], angioimmunoblastic T-cell lymphoma [AITL, n=19], and anaplastic large cell lymphoma [ALCL, n=11] and natural killer T-cell lymphoma [NKTCL, n=17]). The upper limit of the third quartile (Q3) of the AU values was 120. High p-AKT group (AU>Q3) included a higher proportion of NKTCL (41.7%) and ALCL (33.3%) subtypes, while low p-AKT group (AU≤Q3) included higher proportion of AITL (37.3%) and PTCL-NOS (25.0%) subtypes. High p-AKT group showed substantially poorer overall survival (OS) (median OS, 2.3 months vs. 25.2 months, P< 0.001) compared with the low p-AKT group. Multivariate analysis showed that high p-AKT group retained its significance as an independent prognostic factor for poor OS (hazard ratio [HR] 6.5; 95% confidence interval [CI], 2.7 – 15.9; P< 0.001) and poor PFS (HR 4.7, 95% CI; 2.1 – 10.6, P< 0.001).< 0.001) compared with the low p-AKT group. Conclusion PTCLs having high p-AKT expression showed a significantly worse survival than patients with low p-AKT expression. Thus, more effective treatment approaches are needed for this subset of patients with PTCLs, and we suggest inhibition of PI3K/AKT pathway may be a promising therapeutic strategy in PTCLs. Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2003 ◽  
Vol 102 (6) ◽  
pp. 2213-2219 ◽  
Author(s):  
Marcel W. Bekkenk ◽  
Maarten H. Vermeer ◽  
Patty M. Jansen ◽  
Ariënne M. W. van Marion ◽  
Marijke R. Canninga-van Dijk ◽  
...  

Abstract In the present study the clinicopathologic and immunophenotypic features of 82 patients with a CD30– peripheral T-cell lymphoma, unspecified, presenting in the skin were evaluated. The purpose of this study was to find out whether subdivision of these lymphomas on the basis of cell size, phenotype, or presentation with only skin lesions is clinically relevant. The study group included 46 primary cutaneous CD30– large cell lymphomas and 17 small/medium-sized T-cell lymphomas as well as 17 peripheral T-cell lymphomas with both skin and extracutaneous disease at the time of diagnosis. Patients with primary cutaneous small- or medium-sized T-cell lymphomas had a significantly better prognosis (5-year-overall survival, 45%) than patients with primary cutaneous CD30– large T-cell lymphomas (12%) and patients presenting with concurrent extracutaneous disease (12%). The favorable prognosis in this group with primary cutaneous small- or medium-sized T-cell lymphomas was particularly found in patients presenting with localized skin lesions expressing a CD3+CD4+CD8– phenotype. In the primary cutaneous T-cell lymphoma (CTCL) group and in the concurrent group, neither extent of skin lesions nor phenotype had any effect on survival. Our results indicate that peripheral T-cell lymphomas, unspecified, presenting in the skin have an unfavorable prognosis, irrespective of the presence or absence of extracutaneous disease at the time of diagnosis, cell size, and expression of a CD4+ or CD8+ phenotype. The only exception was a group of primary cutaneous small- or medium-sized pleomorphic CTCLs with a CD3+CD4+CD8– phenotype and presenting with localized skin lesions.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4477-4477 ◽  
Author(s):  
Jae-Sook Ahn ◽  
Deok-Hwan Yang ◽  
Yee Soo Chae ◽  
Sang Kyun Sohn ◽  
Jae-Yong Kwak ◽  
...  

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


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2721-2721 ◽  
Author(s):  
Eckhart Weidmann ◽  
Georg Hess ◽  
STefan W. Krause ◽  
Marion Subklewe ◽  
Judith Kruse ◽  
...  

Abstract The majority of entities of peripheral (mature) T-cell lymphomas (PTCL) have an unfavourable prognosis as compared to aggressive B-cell lymphomas. This difference has become even more pronounced since the introduction of CD20 antibodies in B-cell lymphoma therapy. The purpose of the present study was to investigate the feasibility and efficacy of the combination of the monoclonal antibody alemtuzumab with chemotherapy consisting of fludarabine, cyclophosphamide and doxorubicin in PTCL. Patients were treated with alemtuzumab 3, 10, 30, 30 mg, days 1–4, fludarabine 25 mg/m2 days 2–4, cyclophosphamide 600 mg/m2 day 3, and doxorubicin 50 mg/m2 day 4. Initially, patients with primary diagnosis, with first relapse, or with primary refractory disease were included. Excluded were patients with primary cutaneous T-cell lymphomas and ALK-positive large cell anaplastic T-cell lymphomas. So far, 37 patients have been included and 30 are evaluable for response and toxicity: 13 patients with PTCL-unspecified, 9 with angioimmunoblastic lymphoma, two with ALK negative anaplastic large cell lymphoma, two with enteropathy-associated T-cell lymphoma, two with nasal-type NK-/T-cell lymphoma, one with an NK-cell lymphoma, and one with a T-PLL. 19/30 patients were enrolled with primary diagnosis of PTCL and 11/30 patients with relapse or refractory disease. The median age was 56 years (range 21–77); 69% of the patients had an intermediate high or high prognostic score according to the international prognostic index. In patients with primary diagnosis the remission rate was 63% (12/19; CR 58%, PR 5%), four patients were primary progressive, and three patients dropped out because of treatment associated complications. Of the 12 responding patients 10 are in ongoing remission at 2+, 2+, 3+, 6+, 12+, 14+, 26+, 27+, 38+, and 39+ months, respectively. Two patients relapsed after being in CR for 23 and 34 months, respectively. In the group of relapsed or refractory patients three CR and two PR (45% overall response) were observed. The main toxicity was leukocytopenia (65% grade III and IV of all evaluable treatment cycles), other grade III and IV toxicities included anemia (17%), thrombocytopenia (35%), infections (16%), pruritus/skin reactions (11%), nausea/emesis (6%), mucositis (4%), and cardiac toxicity (4%, two patients with relapsed disease after pre-treatment with CHOP-like regimens developed severe heart failure and died). 12 (40%) patients reactivated CMV, however, 10 without developing CMV-related disease. In conclusion, the combination is an effective first-line regimen for peripheral T-cell lymphoma, however, regarding the general outcome a longer follow-up period of a larger patient population is required. Because the results were not convincing in relapsed and refractory disease and because of two heart failures in this group, the study was closed for relapsed and refractory patients, but is ongoing for first-line treatment of peripheral T-cell lymphomas.


Blood ◽  
1999 ◽  
Vol 93 (10) ◽  
pp. 3487-3493 ◽  
Author(s):  
Dan Jones ◽  
Christopher D.M. Fletcher ◽  
Karen Pulford ◽  
Aliakbar Shahsafaei ◽  
David M. Dorfman

The tumor necrosis factor (TNF) receptor family includes several important markers of activation in T cells. We examined expression patterns of two T-cell-associated members of these receptors, namely CD30 and OX40/CD134, in 148 cases of T-cell lymphoma to identify possible objective immunohistochemical criteria for subclassification of these tumors. CD30 expression was characteristic of tumors with an anaplastic (46/47 cases [98%]) or large-cell (10/21 [48%]) morphology and was seen in only scattered cells in other tumor types. In contrast, large numbers of OX40/CD134+ tumors cells were typical of angioimmunoblastic lymphoma (15/16 [94%]), angiocentric lymphoma (4/4), a subset of large-cell lymphomas (10/21 [48%]), and lymphomas with a prominent histiocytic component (6/7 [86%]). Strong OX40/CD134 and CD30 coexpression was seen in only 4% of tumors, typically those with an anaplastic/Hodgkin’s-like appearance. OX40/CD134 expression was characteristic of tumors composed of activated CD4+ T cells and was not seen in small-cell T-cell lymphomas, lymphoblastic lymphomas, or other tumor types, including B-cell lymphomas or carcinomas. These results suggest that immunostaining for OX40/CD134 may be helpful in subclassification of peripheral T-cell lymphomas and that the patterns of TNF receptor family expression in these tumors may parallel those seen within nonneoplastic helper T-cell subsets.


2020 ◽  
pp. 107815522096861
Author(s):  
Lucie Oberic ◽  
Faustine Delzor ◽  
Caroline Protin ◽  
Sophie Perriat ◽  
Camille Laurent ◽  
...  

Introduction Brentuximab vedotin (Bv) has been approved for the treatment of Refractory/Relapsed (R/R) Anaplastic Large Cell Lymphomas (ALCL) and cutaneous T-Cell Lymphomas, but is also effective in other CD30+ malignancies. We report here the outcomes of patients with various R/R Peripheral T Cell Lymphoma (PTCL) treated with Bv in real life practice. Method This was a retrospective, single-center study based on medical records of patients with R/R PTCL treated either with Bv alone or in combination with chemotherapy. Results Among 27 patients treated with Bv, neutropenia was the main serious adverse event observed in particular when Bv was used as combination treatment. The complete Response Rates (CRR) was 40.7%; it was significantly improved when Bv was used as combination treatment. The majority of eligible patients (7/10) underwent Stem Cell Transplantation. Median Progression Free Survival (PFS) and Overall Survival (OS) were 5.2 months and 12.5 months respectively. Conclusion Our current study shows that Bv used in combination with chemotherapy provides a high CRR and thereby allows SCT in R/R PTCL. The use of Bv treatments in this setting warrants further investigation.


2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Caiqin Xie ◽  
Xian Li ◽  
Hui Zeng ◽  
Wenbin Qian

AbstractPeripheral T-cell lymphomas (PTCLs) are biologically and clinically heterogeneous diseases almost all of which are associated with poor outcomes. Recent advances in gene expression profiling that helps in diagnosis and prognostication of different subtypes and next-generation sequencing have given new insights into the pathogenesis and molecular pathway of PTCL. Here, we focus on a broader description of mutational insights into the common subtypes of PTCL including PTCL not other specified type, angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, and extra-nodal NK/T cell lymphoma, nasal type, and also present an overview of new targeted therapies currently in various stages of clinical trials.


Hematology ◽  
2006 ◽  
Vol 2006 (1) ◽  
pp. 317-322 ◽  
Author(s):  
Elaine S. Jaffe

Abstract Peripheral T-cell lymphomas (PTLs) are uncommon, accounting for fewer than 10% of all non-Hodgkin lymphomas. Success in therapy of the PTLs has lagged behind that of aggressive B-cell lymphomas, and most PTLs have a poor prognosis. The molecular pathogenesis of most PTLs is also poorly understood. In the WHO classification, clinical features, in conjunction with morphological and immunophenotypic criteria, are relied on to define most disease entities. Functionally, T-cell lymphomas are related to the two major arms of the immune system, the innate and adaptive immune systems. NK cells and T cells of the innate immune system recognize antigen in the absence of MHC antigens and are involved in mucosal immunity. The lymphomas derived from these cells often involve cutaneous and mucosal sites. The expression of cytotoxic molecules in these lymphomas may predispose to apoptosis by tumor cells and normal bystander cells. Hepatosplenic T-cell lymphoma is a systemic disease derived from functionally immature innate effector cells, most often of γδ T-cell origin. In contrast, most nodal T-cell lymphomas belong to the adaptive immune system. Angioimmunoblastic T-cell lymphoma (AILT) is mostly likely derived from follicular helper T-cells (TFH), a finding that explains many of its pathological and clinical features. Studies of these neoplasms may assist in further unraveling the functional diversity of their normal counterparts.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2399-2399 ◽  
Author(s):  
Steven M. Horwitz ◽  
Francine Foss ◽  
Shari Goldfarb ◽  
Ana Molina ◽  
Paul A. Hamlin ◽  
...  

Abstract FDG-PET is emerging as a standard staging study for diffuse large B-cell lymphoma and Hodgkin’s disease. There is little experience with PET in staging T-cell lymphomas (TCL). TCL often involve extranodal sites not well imaged by standard CT. We hypothesized that PET would add to staging by detecting additional sites of disease. To address this question we reviewed our TCL database to identify patients (pt) who had PET as part of complete staging at initial diagnosis or at relapse. Each pt was included once. Staging included physical exam, CT scan of the chest/abdomen/pelvis alone or as part of a PET/CT combination, and bone marrow (BM) biopsy. Studies such as MRI of the sinus or ultrasound of the testes were done as clinically indicated. We reviewed 107 pt who met the above criteria. Histologies were as follows: peripheral T-cell lymphoma NOS (PTCL), angioimmunoblastic T-cell lymphoma (AILT), anaplastic large cell lymphoma, ALK-1-, (ALCL−), anaplastic large cell lymphoma, ALK-1+, (ALCL+), mycosis fungoides (MF), subcutaneous panniculitis-like T-cell lymphoma (SPTCL), adult T-cell lymphoma (ATL), NK lymphoma nasal type (NK-Nas), lymphoblastic lymphoma (LL), enteropathy associated T-cell lymphoma (EATCL), blastic NK lymphoma (BLNK), primary cutaneous ALCL (ALCL-Cut), and hepatosplenic T-cell lymphoma (HSPTCL). All pt with MF had suspicion of extracutaneous disease. Overall 95/107 (89%) had a PET interpreted as positive by visual review. Standard uptake values (SUV) varied from 1.1–20.5 g/ml. Of the 12 pt with negative PET scans, 7(58%) had no evidence of disease on CT including PTCL (n=3, stage I resected), HSPTCL (n=2, liver, spleen, BM disease only), ALCL-Cut (n=2, skin only). T-cell Lymphoma-PET Results Histology N PET + % positive SUV Range (g/ml) ALL PT 107 95 89% 1.1–20.5 PTCL 27 24 88% 2–20 AILT 19 16 84% 2–11.7 ALCL− 12 12 100% 3–19.6 ALCL+ 4 4 100% 4–12 MF 12 10 83% 1.8–17.6 SPTCL 8 8 100% 1.4–13.1 ATL 5 5 100% 2.9–19.7 NK-Nas 5 5 100% 3.4–13.1 LL 3 3 100% 5.5–20.5 EATCL 3 3 100% 3.5–9.9 ALCL-Cut 5 3 60% 1.1–1.4 BLNK 2 2 100% 1.929.5 HSPTCL 2 0 0 N/A PET detected additional sites of disease in 34/107 (32%). These sites detected by PET were skin/subcut (n=9), bone (n=7), lymph node (n=6), spleen (n=3), nasopharynx/sinus (n=2), liver (n=2), BM (n=1), bowel (n=1), muscle (n=1), kidney (n=1), tonsil (n=1), testes (n=1). Three new malignancies were incidentally detected by PET including lung cancer (n=1), metastatic renal cell to the parotid (n=1), and mantle cell lymphoma (n=1 in a pt with ALCL-cut). Despite these additional sites, stage was changed in only 10/107 (9%). We did not use negative PET to downstage. Sites resulting in higher stage included bone (n=3), lymph node (n=2), subcut/muscle (n=3), testes (n=1), liver (n=1). Skin lesions were noted on physical exam and therefore did not change stage. In conclusion, TCL are almost universally PET positive. PET often adds information by identifying extranodal disease. However, partly due to many pt being stage IV by other modalities, PET resulted in a change of stage in <10% of pt. PET may be particularly useful in assessing of skin sites. These data suggest that it may be beneficial to include PET in the response assessment of TCL, as has been proposed for DLBCL and HL in revised NHL response criteria.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4392-4392
Author(s):  
Frederick Lansigan ◽  
Stuart Seropian ◽  
Dennis Cooper ◽  
Francine Foss

Abstract Peripheral T-cell Lymphomas (PTCL) are a heterogenous group of malignanices that represent 10–15% of non-Hodgkin lymphoma (NHL). This group has a worse prognosis with conventional chemotherapy compared to B-cell lymphomas. Both autologous (AutoSCT) and allogeneic stem cell transplantation (AlloSCT) have been used as consolidation in first remission and at relapse, but the role of transplantation has not been clearly defined. We report a retrospective analysis of 42 patients with PTCL who underwent AutoSCT (24) or AlloSCT (18) between 8/1997 and 12/2007. The AlloSCT group consisted of 4 PTCL unspecified (PTCLu), 3 angioimmunoblastic T-cell lymphomas (AITL), 2 panniculitic T-cell lymphomas, 2 cutaneous T-cell lymphomas (CTCL) with large cell transformation, 2 NK-cell lymphomas, 2 anaplastic large cell lymphomas (ALCL, 1 Alk+, 1 Alk unknown), 1 hepatosplenic T-cell lymphoma, 1 enteropathic T-cell lymphoma, and 1 refractory CTCL. The AutoSCT group consisted of 6 PTCLu, 12 ALCL (5 Alk+, 5 Alk−, 2 Alk unknown), 4 AITL, 1 CTCL with transformation, and 1 T-lymphoblastic lymphoma. The median age of the AlloSCT and AutoSCT groups was 51 (range 29–72) and 52 years (range 19–67), respectively. The median number of prior treatments of the AlloSCT and AutoSCT groups were 3 (range 1 to 5) and 1 (range 1 to 5), respectively. Within the AlloSCT group there were 14 matched-related donor transplants, and 4 matched-unrelated donor transplants; 7 were ablative and 11 were reduced-intensity transplants; the AlloSCT conditioning regimens varied. The AutoSCT group predominantly received BEAM as their conditioning regimen. Median time from diagnosis to AlloSCT or AutoSCT was 18.4 (range 6.9 to 109) and 7.5 (range 3.9 to 25) months, respectively. Median follow-up times for the AlloSCT and AutoSCT groups were 28.6 and 23.5 months, respectively. The day 100 transplant-related mortality rates in the AlloSCT and AutoSCT groups were 11% and 0%, respectively. Within the AlloSCT group the relapse and non-relapse mortalities were 11% and 33%, respectively. In the AutoSCT group, the relapse mortality was 33%. The 1- and 2-year overall survival (OS) rates were similar within the AlloSCT and AutoSCT groups (78% vs 74%, and 67% vs 60%, respectively). The 1- and 2-year progression-free survival (PFS) rates for the AlloSCT vs AutoSCT groups were 68% vs 52%, and 53% vs 45%, respectively (p = 0.28). Within the AutoSCT group, 14 patients (58%) were transplanted in first complete remission (CR1), and 10 (42%) in second complete remission (CR2), beyond CR2, or partial remission (PR). Patients in CR1 had significantly better PFS (57 vs 17 months, p=0.007) and OS (76 vs 29 months, p=0.004) than those in CR2, PR2, or beyond. Within the AlloSCT group, there was a trend toward poorer OS in 6 patients (33%) who had prior AutoSCT (32 vs 60 months, p=0.15). One patient (6%) was transplanted in CR1, and is still alive. We conclude that outcomes for AutoSCT are best in CR1. For patients with resistant or relapsed disease, AlloSCT should be strongly considered rather than AutoSCT. Prior AutoSCT may affect the outcome of AlloSCT. These results suggest that a prospective randomized trial comparing AutoSCT and AlloSCT for aggressive PTCL in first remission is warranted.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1610-1610
Author(s):  
Alex F Herrera ◽  
Allison Crosby-Thompson ◽  
Jonathan W. Friedberg ◽  
Gregory A. Abel ◽  
Myron S. Czuczman ◽  
...  

Abstract Abstract 1610 Background: T-cell lymphomas (TCL) are an uncommon group of diseases recently updated in the WHO classification. Accurate diagnosis requires immunophenotyping and molecular techniques. Diagnostic accuracy of TCLs utilizing the WHO classification has not previously been evaluated. Methods: The NCCN NHL database prospectively collects clinical, treatment, and outcome data for patients seen at 7 comprehensive cancer centers. Using this unique resource, we evaluated diagnostic concordance between referring and NCCN centers for TCLs, including peripheral T-cell lymphoma, NOS (PTCL NOS), angioimmunoblastic T-cell lymphoma (AITL), ALK-positive anaplastic large cell lymphoma (ALK+ ALCL), and ALK-negative ALCL utilizing pathology reports, immunohistochemical stains, flow cytometry, fluorescence in situ hybridization/cytogenetics, T-cell gene rearrangement, and progress notes. Results: Of 98 eligible patients enrolled from April 2007 to March 2011, 38 (39%) cases were concordant and 60 (61%) were non-concordant. Among non-concordant cases, 34 (57%) had a provisional diagnosis before referral, 6 (10%) were discordant with no additional studies performed, 17 (28%) were discordant with additional studies performed, and 3 (5%) required an additional biopsy. Concordance was highest for ALK+ ALCL at 73%, while the remaining subtypes had low concordance: PTCL NOS 28%, AITL 28%, ALK- ALCL 47%. In 13 (13%) discordant cases (referral diagnosis was benign, a B-cell NHL, or ALK status was undefined) patients may have experienced a significant change in treatment with pathologic reclassification. Conclusions: In patients with TCL, the likelihood of a concordant final diagnosis at a referring institution was low. Among non-concordant cases, the majority were referred with provisional diagnoses, and many referral diagnoses were discordant. Establishing a precise diagnosis is critical for prognosis and impacts both therapeutic decisions and clinical trial enrollment. As current and future therapies, such as brentuximab vedotin, target subsets of TCLs, our data suggest that all suspected TCLs may benefit from evaluation by an expert hematopathologist. Disclosures: Kaminski: Allos: Consultancy, Honoraria.


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