Peripheral T-cell Lymphoma, Unspecified Research Articles

Clinical case of a 44-year-old patient with newly diagnosed peripheral T-cell lymphoma unspecified (Lennert’s lymphoma) and Loeffler’s endocarditis

Peripheral T-cell lymphoma unspecified (PTCLu) in most cases has an aggressive clinical course and is characterized by a high frequency of extranodal lesions. One of the manifestations of PTCLu, in particular Lennert’s lymphoma, is eosinophilia. Regardless of the development mechanism, eosinophilia can be accompanied by heart damage, leading to endomyocardial fibrosis, ventricular thrombosis and, in the final stage, to restrictive cardiomyopathies, which are manifestations of Loeffler’s endocarditis (LE). The presence of LE aggravates the course and prognosis of PTCLu, primarily limiting the possibilities of antitumor drug therapy. A multidisciplinary approach to managing a patient with PTCLu and concomitant LE makes it possible to diagnose and start both specific and cardiotropic therapy in a timely manner, ultimately improving the prognosis. A clinical case of a 44‑year-old patient with newly diagnosed PTCLu (Lennert’s lymphoma) and LE is presented.

Complete remission of an unusual form of unspecified peripheral T-cell lymphoma: a case report and review of the literature

Introduction: Peripheral T-cell lymphomas have a poor prognosis with less common sustainable remissions after standard anthracycline-based chemotherapy. We report a case of isolated skin involvement of an unspecified peripheral T-cell lymphoma with an unremarkable outcome under chemotherapy. Observation: A 72-year-old hypertensive patient under treatment was seen in a hematology consultation for the management of a postero-lateral mass on theleft-hand first metacarpal, ulcerative-bulging with a clean background, rounded, firm, mobile, painless, measuring around 12 cm in length, and evolving for 4 months. Peripheral lymph nodes and other organs were unremarkable on examination. The patient underwent a biopsy of the mass.Histological examination of the specimen showed a malignant proliferation made up of medium-sized rounded cell layers with reduced cytoplasm and irregular nuclei with nucleated patterns sometimes. The stroma was densely fibrous and mitoses were quite frequent. On immunohistochemistry, the cells were CD3 positive, CD5, CD4, CCD8, CD7, CD25, CD20 and melan A negative. Perforin, FOXP3, CD30, and Pan cytokeratins were also negative. Ki67 was 80%. The hand X-raydidn’tidentify bone involvement. The biological work-up was unremarkable. The thoracic-abdominal-pelvic CT scan was normal. The diagnosis of nonspecific T-lymphoma stage IE Ann Arbor and IPI 2 was set. After 6 cycles of Cyclophosphamide-Doxorubicin-OncovinPrednisone chemotherapy, we obtainedcomplete tumor remission. MRI of the left hand aftermanagement showed a focal subcutaneous thickening opposite the 1st ray, without any underlying mass syndrome. After 3 months, the patient had a good general condition with no clinical recurrence. Conclusion: This case illustrates an unusual location of an unspecified peripheral T-cell lymphoma with a complete response after standard anthracycline-based chemotherapy. The short-term prognosis is unremarkable.

Aspectos anatomopatológicos do linfoma cutâneo em cães – revisão

Lymphoma is one of the most prevalent forms of cancers in dogs, however, it is uncommon on the skin. Cutaneous lymphoma can present as erythematous and exfoliative superficial lesions or raised masses. Histologically, cutaneous lymphomas are subdivided into epitheliotropic and non-epitheliotropic. Epitheliotropic lymphomas is mostly seen as mycosis fungoides and more rarely as pagetoid reticulosis or Sézary syndrome. Non-epitheliotropic lymphomas include anaplastic large T-cell lymphoma, unspecified peripheral T-cell lymphoma, lymphomatoid granulomatosis, intravascular lymphoma, and subcutaneous panniculitis-like T-cell lymphoma. This literature review presents macroscopic and histopathological aspects of canine cutaneous lymphomas.

Unspecified skin peripheral T-cell lymphoma: diagnostic difficulties

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) have an aggressive, life-threatening course. 5‑year survival rate is less than 20 %, which may be due to not timely diagnosis. PTCL-NOS can histologically and immunophenotypically mimic other T-cell lymphomas of the skin, including mycosis fungoides. In this connection, the correct diagnosis is most often established in the late stages of the disease. We present a clinical case of PTCL-NOS misdiagnosed as mycosis fungoides.

Clinical outcomes of peripheral blood stem cell transplantation for aggressive peripheral T-cell lymphoma

目的研究外周血造血干细胞移植治疗外周T细胞淋巴瘤（PTCL）的疗效。方法回顾性分析解放军总医院血液科2007年6月至2017年6月接受外周血造血干细胞移植PTCL患者的临床资料。结果共有41例PTCL患者纳入研究，男30例，女11例，中位年龄38（13~57）岁。17例行自体外周血造血干细胞移植（auto-PBSCT），24例行异基因外周血造血干细胞移植（allo-PBSCT）。auto-PBSCT组ALK阳性间变大细胞淋巴瘤占47.1%（8/17），allo-PBSCT组NK/T细胞淋巴瘤和外周T细胞淋巴瘤-非特指型占66.7%（16/24）。auto-PBSCT组患者移植前疾病处于完全缓解（CR）状态者占58.8%（10/17），疾病进展（PD）状态者占11.8%（2/17）；allo-PBSCT组移植前疾病状态为CR者8.3%（2/24），PD者45.8%（11/24）。auto-PBSCT组和allo-PBSCT组移植后2年总生存率、无病生存率差异均无统计学意义[（64.0±10.8）%对（53.5±9.7）%，P=0.543；（57.1±12.4）%对（53.5±10.6）%，P=0.701]。auto-PBSCT组6例死亡，5例死于复发；allo-PBSCT组12例死亡，其中5例死于复发，7例为移植相关死亡。结论auto-PBSCT和allo-PBSCT均是PTCL的有效治疗方法。

The correlation between platelet-lymphocyte ratio and the prognosis of patients with peripheral T-cell lymphoma, unspecified

Objective: To identify the correlation between pre-treatment peripheral blood platelet-lymphocyte ratio (PLR) and the clinicopathological features of the patients with peripheral T cell lymphoma, unspecified (PTCL-U), and to explore the prognostic significance of PLR in these patients.Methods: The clinical characteristics and survival state of 163 patients diagnosed of PTCL-U in Tianjin Medical University Cancer Institute and Hospital were analyzed retrospectively. All patients were divided into low PLR group (PLR < 170, n = 80) and high PLR group (PLR ≥ 170, n = 83) based on the receiver operating characteristic (ROC) curve’s cut-off value. The relationship between pre-treatment PLR and the prognosis of these patients was analyzed. Results: In all 163 patients with PTCL-U, the 5-year overall sarvival (OS) and progression-free survival (PFS) rates of patients in low PLR group (76.3% and 60.0%, respectively) were higher than those in high PLR group (10.8% and 8.4%, respectively, both P < 0.05). Age, Eastern Cooperative Oncology Group performance status (ECOG PS), B symptoms, serum lactate dehydrogenase (LDH) level, platelet and PLR were remarkably relevant to OS (all P < 0.01). Age, serum LDH level, platelet and PLR were independent prognostic features for patients with PTCL-U (all P < 0.05). Conclusion: The peripheral blood PLR at pre-treatment is distinctly relevant to the prognosis of patients with PTCL-U. An elevated PLR predicts poor prognosis of these patients. DOI:10.3781/j.issn.1000-7431.2017.33.768

The Neutrophil-to-Lymphocyte Ratio Is Prognostic in Patients with Early Stage Peripheral T-Cell Lymphoma

Introduction: Peripheral T-cell lymphoma (PTCL) encompasses a group of rare and aggressive lymphomas. PTCL, unspecified (PTCLU) is the most common subtype of PTCL, and carries a poor prognosis. The International Prognostic Index (IPI) and the Prognostic Index for PTCLU (PIT) scoring systems are powerful risk-stratification tools in patients with PTCL. The neutrophil-to-lymphocyte ratio (NLR) has shown to be prognostic in patients with advanced stage PTCLU (Beltran Leuk Lymphoma 2016). The aim of this study was to evaluate whether the NLR is a prognostic factor in patients with early stage PTCLU.Methods: We included patients with a pathological diagnosis of PTCLU who were diagnosed and treated at our institution between 2001-2016. We excluded cases with stage 3 or 4 disease. IRB approval was obtained prior to research. Pathological samples were reviewed by hematopathologists to confirm the diagnosis. Pertinent clinicopathological data were collected through chart review, and are presented using descriptive statistics. The NLR was calculated by dividing the neutrophil by the lymphocyte count, and dichotomized in NLR>=4 and NLR<4. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate Cox models were fitted to evaluate hazard ratios (HR) for overall survival (OS).Results: 48 patients with a diagnosis of early stage PTCL were included in this analysis. Histologically, 40 patients (83%) were PTCL, unspecified, 7 (15%) were anaplastic large cell lymphoma, and 1 (2%) was enteropathy-associated T-cell lymphoma. The median age at diagnosis was 60 years (range 18-83 years) with a slight male predominance (82%). Clinically, 49% of patients were 60 or older, 34% presented with ECOG>1, 36% with elevated LDH, and 65% with extranodal disease; 44% had stage II and 56% had stage I disease. No patient had bone marrow involvement. 30% of patients presented with high/high-intermediate IPI score and 34% with high/high-intermediate PIT score. 27% of patients had a NLR >=4. There were no differences in age, LDH levels, extranodal involvement and stage between NLR>=4 and NLR<4. There was a trend towards worse ECOG performance status in NLR>=4 patients (p=0.06). The 3- and 5-year OS rates were 67% (95% CI 50-80%) and 52% (95% CI 29-71%), respectively. High/high-intermediate IPI score was associated with a worse outcome (HR 4.9, 95% CI 1.7-14.2; p=0.004), as well as high-high-intermediate PIT score (HR 3.9, 95% CI 1.2-12.7; p=0.03). According to NLR, NLR>=4 patients had a higher risk of death (HR 9.9, 95% CO 3.2-30.1; p<0.001). In a multivariate analysis adjusting for IPI and PIT scores, NLR>=4 was the only independent factor associated with a worse survival (HR 6.2, 95% CI 1.9-20.9; p=0.003).Conclusion: The NLR appears as a novel and easy to use prognostic factor for OS in previously untreated patients with early-stage PTCL. Our findings support the need for validation of the NLR in larger retrospective or prospective studies in patients with PTCL. DisclosuresCastillo:Otsuka: Consultancy; Pharmacyclics: Honoraria; Abbvie: Research Funding; Millennium: Research Funding; Janssen: Honoraria; Biogen: Consultancy.

Efficacy of CHOP chemotherapy on unspecified peripheral T cell lymphoma in patients aged 80 years and over and its prognostic analysis

Objective To evaluate the efficacy of CHOP(cyclophosphamide, doxorubicin, vincristine, and prednisone)chemotherapy on peripheral T cell lymphomas-unspecified(PTCL-U)in patients aged 80 years and over, and investigate the chemotherapy adverse effects and its prognostic factors. Methods Clinical data of 57 patients with PTCL-U confirmed by pathology and immunohistochemistry in Guangzhou First People's Hospital from January 2008 to January 2015 were retrospectively analyzed. The efficacy and adverse effects of CHOP chemotherapy, and its prognostic factors were evaluated. Results Of 57 patients, 11(19.3%)achieved complete remission, 23(40.4%)had partial remission, 14(24.6%)had stable disease, and 9(15.8%)had progressive disease after CHOP chemotherapy, with a total effective rate of 59.6%(34 cases). The expected 1-year, 2-year and 3-year overall survival(OS)rate was 70.2%(40 cases), 36.8%(21 cases) and 17.5%(10 cases), respectively. The median survival time was 18.2 months. Among the 57 patients, 40(70.2%)had hypoplasia of bone marrow at degreeⅠ-Ⅱ, 17(29.8%)at degree Ⅲ-Ⅳ, 49(86.0%)had mild nausea and vomiting(degreeⅠ-Ⅱ), 8(14.0%)had severe nausea and vomiting(degree Ⅲ-Ⅳ), 7 had liver dysfunction, 2 had cardiac toxicity and 7 had disturbance of blood coagulation. Univariate analysis showed that the alkaline phosphatase, Ki-67 percentage, lymphoma international prognostic index(IPI)score, extranodal involved sites(>1), as well as the efficacy and course of chemotherapy were the prognostic factors for survival time in very elderly patients. Multivariate analysis indicated that IPI score>2(95%CI: 1.12~6.35, χ2=5.45, P 1)(95%CI: 2.58-15.32, χ2=16.42, P 4)(5%CI: 0.18~0.79, χ2=7.28, P<0.01)were the independent prognostic factors for the median survival time in very elderly patients. Conclusions PTCL-U patients aged 80 years and over have poor prognosis. CHOP chemotherapy has a certain effect on PTCL-U in very elderly patients, and chemotherapy side effects can be tolerated. IPI score>2 and extranodal involved sites(>1)are the important prognostic factors in very elderly PTCL-U patients. The completion of full course of chemotherapy with remission occurrence is important to prolong survival time in very elderly PTCL-U patients. Key words: Lymphoma, T-cell, Peripheral; Antineoplastic combined chemotherapy protocols; Elderly, aged over 80 years; Prognosis

Efficacy comparison of gemcitabine-based and anthracycline-based chemotherapy regimens in unspecified peripheral T-cell lymphoma

Objective To compare the efficacy and toxicity of gemcitabine-based and anthracycline-based chemotherapy regimens in the treatment of peripheral T-cell lymphoma unspecified (PTCL-U). Methods The data of 37 eligible patients with PTCL-U were analyzed retrospectively. The patients were classified into two groups: trial group including 17 patients treated with gemcitabine-based regimen, and control group including 20 patients treated with anthracycline-based regimen. The response rate (RR), time to progression (TTP), overall survival (OS) and toxicity were assessed. Results RR and complete response rate (CR) were significantly higher in the trial group than those in the control group [88.2 % (15/17) vs 55.0 % (11/20), 76.5% (13/17) vs 40.0 % (8/20), P 0.05). The median TTP was significantly longer in the trial group than that in the control group (10.1 months vs 5.3 months, P < 0.05). The median OS in the trial group was longer than that in the control group (19.3 months vs 12.4 months, P < 0.05). Major toxicity reactions included myelosuppression, gastrointestinal reaction, alopecia and cardiotoxicity. The incidence of thrombocytopenia (grade Ⅰ-Ⅱ) in the trial group was significantly higher than that in the control group (P < 0.05). The incidences of alopecia and cardiotoxicity in the trial group were significantly lower than those in the control group (P < 0.05). No chemotherapy-related death occurred. Conclusion Gemcitabine-based chemotherapy regimens may be more effective for PTCL-U than anthracycline-based chemotherapy regimens, and it can be well tolerated, which requires further clinical study. Key words: Lymphoma, T-cell, peripheral; Gemcitabine; Treatment outcome; Untoward reaction

Clinical analysis of 25 patients with aggressive peripheral T-cell lymphoma in advanced stage treated with autologous stem cell transplantation

目的探讨大剂量化疗联合自体造血干细胞移植（ASCT）治疗侵袭性外周T细胞淋巴瘤（PTCL）的疗效。方法回顾性分析1997年5月至2013年6月于完全缓解（CR）期接受ASCT治疗的25例侵袭性PTCL患者的临床资料。结果①25例患者中男16例，女9例，中位发病年龄30(12~54）岁。病理类型包括PTCL非特指型（PTCL-U) 16例、血管免疫母细胞淋巴瘤（AITL）4例、间变大细胞淋巴瘤（ALCL）3例和肝脾T细胞淋巴瘤（HSTL) 2例。临床分期Ⅲ期和Ⅳ期分别为8例和17例；其中合并骨髓侵犯者9例。移植前19例处于CR1期，另6例为CR2期。②2例HSTL均为骨髓侵犯、国际预后指数评分高危患者，联合化疗后获得CR1并行ASCT巩固治疗，但均于移植后12个月内早期复发、死亡。其余23例患者中位随访38(14~110）个月，3年无进展生存（PFS）率和总体生存（OS）率分别为（63.1±10.5）%和（71.8±9.9）%。CR1期（17例）移植者的生存有优于CR2期（6例）移植者的趋势[3年PFS率（74.9±11.0）％对（33.3±19.2）%，P=0.092; 3年OS率（80.2±10.4）％对（50.0±20.4）%，P=0.043]。无骨髓侵犯者的生存有优于骨髓侵犯者的趋势[3年PFS率（77.9±11.3）%对（40.0±17.4）%，P=0.142；OS率（84.4±10.2）％对（53.3±17.3）%，P=0.076]。结论ASCT改善化疗敏感侵袭性PTCL患者的生存。移植前非CR1状态和淋巴瘤骨髓侵犯可能是影响ASCT疗效的不良预后因素。HSTL患者预后差，ASCT后早期复发率高，需要进一步探索有效的治疗方案。

Peripheral T-Cell Lymphomas (PTCL) Treated With Or Without Upfront Autologous Stem Cell Transplantation: Results Of a Retrospective Single Center Analysis

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare diseases, characterized by an aggressive behavior and a poor clinical outcome. High-dose therapy followed by autologous stem cell transplantation (ASCT) has been used as salvage and upfront treatment with conflicting results. However, no standard therapy has so far been established due to the lack of randomized studies.The records of 54 untreated patients with a confirmed diagnosis of PTCL managed at our Institute between 2001 and 2011 were reviewed. The histologic subtypes were: 37 (68%) peripheral T-cell lymphomas unspecified (PTCL-U), 13 (24%) anaplastic large cell lymphomas (ALCL), of which 4 (30%) ALK-positive, 2 (4%) angio-immunoblastic lymphomas (AITL) and 2 (4%) enteropathy-associated T-cell lymphomas (EATL). The clinical characteristics were: median age 56 years (range 18-79); 40 men and 14 women; 13 (24%) and 41 (76%) patients were, respectively, in Ann Arbor stages I-II and III-IV. An elevated serum LDH was present in 33% of patients, 48% had B symptoms and 24% had a bone marrow involvement. The ECOG performance status was 2-3 in 28% of patients. According to the International Prognostic Index (IPI) and the prognostic index for T-cell lymphomas (PIT), 11% and 22% were classified as low risk, 30% and 33% as low-intermediate risk, 12% and 33% as high-intermediate risk and 29% and 12% as high risk, respectively. CHOP-like regimens were given to 32 (59%) patients, 14 of whom received the CHOEP regimen. The remaining 22 (41%) patients were treated with more intensive third generation regimens (MACOP-B like). ASCT was planned as upfront consolidation therapy for 16/54 (30%) patients.A complete response (CR) was obtained in 30/54 (55.5%) patients, a partial response in 7 (13%), while 17 (31.5%) patients showed a lymphoma progression during induction therapy. No difference in terms of CR rate was observed between the CHOP-like and MACOP-B-like regimens. At a median follow-up of 19 months (range 3-138), the 5-years OS and 5-years PFS were 32% (95% CI 25.3-38.5) and 27% (95% CI 20.2-34.5), respectively. At univariate analysis, bone marrow involvement (p=0.003), PIT high risk group (p<0.001) and lymphocytopenia (p=0.06) predicted a shorter PFS. Five of 16 (31%) patients did not receive the planned ASCT consolidation due to early progression. Patients who received an ASCT as consolidation therapy presented a slightly better 5-year PFS than patients treated with chemotherapy alone (95% CI 37.7% vs 25%; p=0.08).The prognosis of PTCLs remains poor despite the use of intensive chemotherapy regimen including upfront ASCT. More active induction chemotherapy regimens, including novel agents, should be designed in an attempt to increase the quality of response before ASCT consolidation therapy. Disclosures:No relevant conflicts of interest to declare.

Activating Mutations In Fyn Kinase In Peripheral T-Cell Lymphomas

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of aggressive non Hodgkin lymphomas with poor prognosis. Molecular and cytogenetic studies have shown a prominent role for kinase fusion oncogenes, mostly NPM-ALK, in ALK+ anaplastic large cell lymphomas (ALCLs) and ITK-SYK kinase in unspecified PTCLs. To gain further insight on the genetics and pathogenic mechanisms of aggressive PTCLs we performed an integrated mutation analysis using whole exome sequencing (n=12) and RNAseq (n=35) data. This analysis identified 288 candidate coding somatic mutations in 268 genes including known recurrent mutations in the TET2, DNMT3A and IDH2 epigenetic factor genes and pointed to the FYN kinase gene as a new recurrently mutated oncogene in T-cell transformation. The FYN tyrosine kinase is, with LCK, the predominant SRC family kinase found in T lymphocytes and plays an important role in T-cell activation upon T-cell receptor (TCR) stimulation. FYN mutations in PTCL included a FYN L174R mutation detected in one AITL patient sample, a FYN R176C allele recurrently found in two PTCL NOS cases and a FYN Y531H mutation present in a PTCL NOS sample. Notably, each of these alleles are predicted to specifically disrupt the inhibition of FYN kinase activity by the C terminal SRC kinase (CSK). Thus, structure analysis of FYN and FYN mutant proteins predicted that FYN L174R and, most prominently, FYN R176C and FYN Y531H can disrupt the inhibitory interaction of the FYN SH2 domain with the CSK-phosphorylated Y531. Consistently, pull down assays using GST-FYN-SH2 recombinant proteins and biotinylated C-terminal FYN peptides encompassing Y531 showed abrogation of the interaction between FYN-SH2 and P-Y531 in each of these mutants. In agreement with these results, expression of FYN L174R, FYN R176C and FYN Y531H resulted in increased levels of FYN activation. Moreover, CSK expression effectively inhibited wild type FYN, but failed to abrogate FYN L174R, FYN R176C or FYN Y531H activation. In contrast, pharmacologic kinase inhibition with dasatinib, a multikinase inhibitor which blocks ABL1 and SRC kinases, effectively abrogated the activity of FYN L174R, FYN R176C and FYN Y531H mutant proteins and suppressed the growth of cells transformed via expression of activated FYN mutant alleles. Overall these results support an oncogenic role for FYN activating mutations in the pathogenesis of PTCL and support a role for SRC kinase inhibitors for the treatment of this disease. Disclosures:No relevant conflicts of interest to declare.

Fasting Blood Glucose As Prognostic Factor In Peripheral T-Cell Lymphoma: A Study Of 250 Cases

BackgroundPeripheral T-cell lymphoma (PTCL) is a heterogeneous familyof entities with a worse prognosis, stage by stage, than theirB-cell counterparts. Fasting blood glucose (FBG) level at diagnosis has recently been described as a novel, independent prognostic factor for survival in patients with extranodal natural killer/T-cell lymphoma (NKTCL). The goal of this study is to retrospectively investigatethe prognostic value of FBG at lymphoma diagnosis in the survival of patientswith PTCL. MethodsA total of 250 cases of aggressive, non-primary cutaneous PTCLdiagnosed at our institution between January 1997 and December 2012 were reviewed,reevaluated according to their morphological, immunologicaland clinical characteristics, and reclassified according tothe 2008 WHO classification of lymphoid neoplasms. Characteristics are presented descriptively. For the evaluation of FBG, patients were divided in 2 categories; those patients with an FBG at diagnosis >100 mg/dl (hyperglycemia) and those with an FBG at diagnosis <100 mg/dl (normoglycemia). Overall survival (OS) was defined as the time elapsed between lymphoma diagnosis and death or last follow-up. The Kaplan-Meiermethod was used to estimate OS curves, which were then comparedusing the log-rank test. P-values less than 0.05 were considered statistically significant. ResultsAccording to the new WHO classification, 104 cases (41%) were classified as adult T-cell leukemia/lymphoma (ATLL), 103 cases (41%) as PTCL, unspecified (PTCLU), 26 cases (11%) as anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL), 10 cases (4%) as extranodal NKTCL, nasal type, 4 cases (2%) as angioimmunoblastic lymphoma (AIL), 2 cases (1%) as ALK-positive ALCL, and 1 case (0.4%) as hepatosplenic T-cell lymphoma. The median age at diagnosis was 57 years (range 14-92 years); 47% of patients were >60 years. The male-to-female ratio was 1:1. ECOG performance status >1 was seen in 51%, LDH was elevated in 67%, advanced stage was seen in 73%, and >1 extranodal sites were seen in 22% of the patients. Bone marrow involvement was reported in 30% and B symptoms in 64% of patients. FBG >100 mg/dl was seen in 34% and FBG <100 mg/dl in 66%. An International Prognostic Index (IPI) score 3-5 was seen in 52%, and a Prognostic Index for PTCLU (PIT) score of 2-4 in 62%. Response evaluation was performed only in patients who received chemotherapy (n=161). The overall response rate (ORR) was 47% (n=76) with complete response (CR) in 32% (n=52) and partial response (PR) in 15% (n=24). FBG was no associated with ORR or CR (p=0.25 and p=0.43, respectively. We then evaluated FBG separately in patients with ATLL and PTCL except ATLL. In ATLL patients, the median OS was 8 months with a 3-year OS of 33%. In PTCL patients, the median OS was 17 months with a 3-year OS of 49%. FBG >100 appeared as an adverse prognostic factor only in PTCL patients with a median OS that was not reached vs. 27 months in patients with FBG <100 mg/dl (Figure; log-rank p=0.035). No difference was seen in patients with ATLL; patients with FBG >100 mg/dl has a median OS of 16 months vs. 18 months in patients with FBG <100 mg/dl (log-rank p=0.95). ConclusionsBased on the results of our single-center retrospective study, FBG >100 mg/dl appears as a prognostic factor in PTCL but not in patients with ATLL. Additional studies are needed to investigate the role of hyperglycemia in patients with PTCL, and to evaluate if controlling hyperglycemia during therapy could improve the survival on such patients. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Two subcutaneous nodules over the right fifth finger in a patient with peripheral T-cell lymphoma

A 70-year-old woman with unspecified peripheral T-cell lymphoma on chemotherapy presented with a 1-month history of enlarging lesions on her right hand. On examination, 2 whitish, firm, nontender, cystic nodules were noted on her right small finger (Fig 1). The patient was otherwise well and denied any history of traumatic injury. The skin biopsy specimen revealed 2 subcutaneous cysts with fibrocollagenous capsules and central suppurative necrosis. A foreign body was identified in the larger cyst (Fig 2).

Monocytosis As Prognostic Factor in Aggressive, Non-Primary Cutaneous Peripheral T-Cell Lymphoma: A Study of 251 Cases

Abstract 1608 Background:Peripheral T-cell lymphoma (PTCL) is a heterogeneous family of entities with a worse prognosis, stage by stage, than their B-cell counterparts. We have previously reported that an absolute lymphocyte count (ALC) <1000/uL is associated with a worse prognosis in Peruvian patients with PTCL (Castillo et al. 2010). The goal of this study is to investigate the prognostic value of absolute monocyte count (AMC) in the survival of patients with PTCL. Methods:A total of 251 cases of aggressive, non-primary cutaneous PTCL diagnosed at our institution between January 1997 and January 2012 were reviewed, reevaluated according to their morphological, immunological and clinical characteristics, and reclassified according to the 2008 WHO classification of lymphoid neoplasms. Characteristics will be presented descriptively. Kaplan-Meier method was used to estimate overall survival (OS) curves, which were compared using the log-rank test. The multivariate analysis was performed using the Cox proportional-hazard regression test. Results:According to the new WHO classification of lymphoid neoplasms, 104 cases (41%) were classified as adult T-cell leukemia/lymphoma (ATLL), 103 cases (41%) as PTCL, unspecified (PTCLU), 27 cases (11%) as analplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL), 11 cases (4%) as extranodal NK/T-cell lymphoma (NKTCL), nasal type, 4 cases (2%) as angioimmunoblastic lymphoma (AIL), and 2 cases (1%) were diagnosed with ALK+ ALCL. The median age at diagnosis was 57 years (range 14–92 years); 47% of patients were >60 years. The male-to-female ratio was 1:1. ECOG performance status >1 was seen in 51%, LDH was elevated in 67%, advanced stage was seen in 73%, and >1 extranodal sites were seen in 22% of the patients. Bone marrow involvement was reported in 30% and B symptoms in 64% of patients. An International Prognostic Index (IPI) score 3–5 was seen in 55%, and a Prognostic Index for PTCLU (PIT) score of 2–4 in 63%. The median overall survival (OS) for the whole group was 10 months. The IPI score, the PIT score, ALC <1000/uL and AMC >800/uL (Figure) showed statistical significance in the univariate survival analysis (p<0.001, p<0.001, p=0.001 and p=0.001, respectively). In the multivariate analysis, PIT score and AMC >800/uL showed statistical significance (p=0.006, p=0.046, respectively). Conclusions:Monocytosis, defined as AMC >800/uL, and the PIT score were independent prognostic factors for OS in patients with aggressive, non-primary cutaneous PTCL. Disclosures:No relevant conflicts of interest to declare.

Comparison of the Transforming Effect of Different SYK Oncogenes in Vivo Reveals TEL-SYK As Inducer of an MDS/MPS Overlap Syndrome in Mice

AbstractAbstract 1310The spleen tyrosin kinase (SYK) was shown to be overexpressed in various human hematologic malignancies like B-cell lymphomas and acute myeloid leukemias. There are two known translocations involving the SYK kinase: ITK-SYK and TEL-SYK. ITK-SYK was identified in unspecified peripheral T-cell lymphomas, whereas the TEL-SYK fusion had been discovered in a patient with myelodysplastic syndrome (MDS). Methods:All SYK containing oncogenes, ITK-SYK, TEL-SYK and SYK wt, were cloned into a pMSCV-IRES-GFP retroviral vector. All oncogenes and a GFP control vector were overexpressed in bone marrow of 5-flurouracil-pretreated mice and oncogene containing bone marrow was transplanted into irradiated recipient mice. Disease development was monitored over 1 year. Additionally the three SYK oncogenes were overexpressed in a myeloid (32D), B-lymphoid (BaF3) and T-cell lineage (Jurkat) to monitor cell context specific differences in cell signaling. Results:Here, we demonstrate that the overexpression of 3 SYK containing oncogenes, SYK wt, TEL-SYK and ITK-SYK in a murine bone marrow transplantation model induces the development of 3 different hematologic (pre)diseases. While ITK-SYK exclusively induced T-cell lymphomas in mice, we found that the TEL-SYK fusion induced an MDS/MPS overlapsyndrom. The mice developed an anemia and thrombopenia with signs of dysplasia of megakaryocytes and the erythroid lineage in the bone marrow and spleens. In addition those mice showed a strong expansion of the myeloid lineage, with leucocytosis in the peripheral blood mainly consisting of differentiated neutrophils. The bone marrow shows expansion of differentiated myeloid cells, but also myeloid progenitors and expansion of HSCs. Interestingly, also SYK wt induced a relative expansion of the myeloid compartment without inducing a leucocytosis or a lethal disease indicating a premalignant myeloproliferative state. Only TEL-SYK was able to induce IL-3 independent growth of BaF3- and 32D cells and could activate STAT5, STAT6, ERK, PLCγ2 and SLP76 in those cell lines. SYK and ITK-SYK were able to activate PLCγ2 and SLP76, but no STAT transcription factors. STAT5 activation by TEL-SYK was detectable also in vivo, which might indicate STAT5 as the major driver of TEL-SYK induced transformation.Our results demonstrate, that the various SYK oncogenes can induce different hematologic diseases in mice and reveales TEL-SYK as the first oncogene inducing an MDS/MPS overlap syndrome in mice. Disclosures:No relevant conflicts of interest to declare.

Cutaneous Manifestations of Unspecified Peripheral T-Cell Lymphoma May Be Indicative of Disease Activity and Predict Response to Therapy

Cutaneous manifestations of internal malignancy encompass both direct extension of tumor to the skin and indirect involvement (the so-called paraneoplastic syndromes). Direct cutaneous manifestations parallel systemic disease in progression, remission, and response to treatment. Peripheral T-cell lymphoma (PTCL) comprises a group of mature T-cell malignancies that together make up less than 15% of all non-Hodgkin's lymphoma; PTCL has been reported to directly involve the skin in a minority of cases.1 Unspecified PTCL (PTCL-u) makes up the majority of these lymphomas (60% to 70%).2 We report a patient with PTCL-u with secondary cutaneous involvement who was treated with a new histone deacetylase inhibitor, romidepsin (Istodax; Celgene, Summit, NJ). Because skin manifestations correlate with systemic disease activity, cutaneous manifestations can aid in monitoring of the systemic responses to therapy and can be a first warning sign of relapse.

The spectrum of T‐cell and natural killer/T‐cell neoplasms with leukaemic presentation in a single institution in Taiwan

T cell and natural killer (NK)/T-cell neoplasms are rare and may occasionally present as leukaemia. We retrospectively searched T cell and NK/T-cell tumours in a single institution in Taiwan from January 2000 to December 2009 and identified 137 (19.1%) patients with T cell and NK/T-cell tumours among 718 patients with lymphoid neoplasms. Among these 137 patients, 18 (13.1%) presented with leukaemia including T-lymphoblastic lymphoma/leukaemia (T-LBL), T-cell prolymphocytic leukaemia, aggressive NK-cell leukaemia, adult T-cell lymphoma/leukaemia (ATLL), T-cell large granular lymphocytic (T-LGL) leukaemia and unspecified peripheral T-cell lymphoma. Cases with concurrent lymphoma, higher absolute leukaemic cell counts and elevated lactate dehydrogenase level carried a poorer prognosis. The survival was dichotomous, with a very poor prognosis for patients with T-LBL, T-cell prolymphocytic leukaemia, aggressive NK-cell leukaemia, ATLL in acute phase and unspecified peripheral T-cell lymphoma, while those with T-LGL leukaemia and ATLL in chronic phase had a favourable outcome.

イレウスを来した小腸原発非特異型末梢性T細胞性リンパ腫の1例

イレウスを来した小腸原発非特異型末梢性T細胞性リンパ腫の1例

Cytokine/Chemokine Expression with Protein Arrays Identifies Three Subsets of T-Cell Lymphomas with Differented Immunological Profiles,

Abstract 3473 Background:Only a few studies have addressed the expression of cytokine/chemokine in T-cell lymphomas. The aim of this study was to analyze the cytokine/chemokine protein expression profiles and to correlate them with the pathological manifestation of T-cell lymphomas. Patients and methods: Samples at diagnosis from 19 patients were T-cell lymphoma (unspecified peripheral T-cell lymphomas (PTCL), 10 cases; angioimmunoblastic (AITL), 4; ALK-negative anaplastic large-cell (ALCL), 3 and ALK-positive ALCL, 2) and were studied by protein microarrays. The characteristics of the patients were as follows: 11/8 M/F; median age, 55 years. 50% of patients were stage IV, 69% had extranodal involvement, 79% high LDH and 66% high β2 microglobulin. The high or high-intermediate risk IPI and PIT score were 62% and 61%, respectively. We have analyzed the expression of 174 cytokines by using a highly sensitive and specific antibody array containing single band specific primary antibodies duplicate. Chemolumiscence detection was performed by a HRP-conjugated streptavidin in an image analysis system. Densitometry analysis of unsaturated pixels was performed with Image Gauge software and an endogenous housekeeping gene was used to normalize results. Unsupervised clustering analysis was then performed. Results: Three clusters were obtained. Cluster 1 included 5 ALCL, 2 PTCL and 1 AITL, with a cytokine/chemokine profile that had high expression of IL21R, MIG, PDGF AA/AB, LIGHT, IL10, MIP1γ, MIP3α and IL13. Cluster 2 was composed by 5 PTCL and 1 AITL and exhibited a profile characterized by the high expression of L-SELECTIN, MMP1, IL1RII, SIGLEC 5, IL10R, IL1β, IL18BPA, FGF7, IL13RAα2, GMCSF, SDF1β, LIF, IL1Rα and IL11. Finally, the analysis defined a cluster 3 constituted by 2 AITL and 3 PTCL with a cytokine/chemokine profile that showed the high expression of TIMP1, NT4, ITAC and IGBP6. Detailed initial features and outcome of the patients according to the clusters are detailed in the table. Cluster 1 had better survival than the other groups (p=0.01). Summary: T-cell lymphomas show three different cytokine/chemokine patterns as was determined by protein microarrays. Cluster 1 was well characterized with the presence of all ALCL and better survival.VariablesCluster 1Cluster 2Cluster 3N=8*N=6*N=5*Median age525454Sex (M/F)6/24/21/4Histologic subtypeALCL500Other365Advanced stage % (IV)605040Extranodal involvement %606760High LDH %8050100IPI %Low20330Intermediate205060High601740CR rate (%)806705-year OS60330 Disclosures:No relevant conflicts of interest to declare.