Efficacy of Pegaspargase, Etoposide, Methotrexate and Dexamethasone (PEMD) in Newly-Diagnosed Advanced-Stage Extra-Nodal Natural Killer (NK)/T-Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4148-4148
Author(s):  
Wei Xu ◽  
Jin-Hua Liang ◽  
Li Wang ◽  
Lei Fan ◽  
Hua-Yuan Zhu ◽  
...  
Keyword(s):  
T Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Elevated Serum ◽  
Early Death ◽  
T Cell Lymphoma ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Muscle Involvement ◽  
Nk T Cell

Abstract Objective: Determine efficacy and safety of PEMD (pegaspargase, etoposide, methotrexate, dexamethasone) in persons with newly-diagnosed advanced-stage extra-nodal NK/T-cell lymphoma. Subjects and methods: Twenty-seven consecutive subjects with newly-diagnosed advanced-stage (stage III-IV) extra-nodal NK/T-cell lymphoma were prospectively studied from July, 2010 to August, 2015. All subjects received PEMD (methotrexate, 3.0 g/m2 IV over 6 h on day 1, etoposide, 100 mg/m2 IV on days 2-4, dexamethasone, 40 mg IV on days 1-4 and pegaspargase, 2500 U/m2 IM on day 2). Courses were given every 3 week. Primary co-endpoints were response and survival. Secondary endpoints were proportion of subjects completing planned therapy (4 to 6 cycles of PEMD regimen) and frequencies of adverse events. Results: Median age was 46 y (range, 17-73 y). There were 21 males (78%). Nine subjects (33%) had non-nasal NK/T-cell lymphoma including 5 of the skin involvement, 1 of the testis involvement, 1 of the muscle involvement and 2 of the gastrointestinal tract involvement. Thirteen subjects (48%) had elevated serum LDH levels. Eleven subjects (41%) had higher level of EBV-DNA in blood (>5000 copies/mL). Twenty-one subjects (78%) had B-symptoms and 13 (48%) had an IPI score of 3-5. Subjects received a median of 4 courses of PEMD (range, 1-6). Median follow-up is 48 mo (range, 13-74 mo). Three patients had early death (within 3 mo after the diagnosis). Overall response rate (ORR) was 74% (95%CI 54%-89%) in the 27 subjects with advanced-stage disease including complete response (CR)/unconfirmed CR (CRu) in 12 (44% [95%CI 26%-65%]) and a partial response (PR) in 8 (30% [95%CI 14%-50%]). Four-year progression-free survival (PFS) was 44% (95%CI 25%-63%) and overall survival (OS) 51% (95%CI 32%-70%) (Figure 1). PFS and OS were not correlated between nasal and non-nasal types of ENKTL. There was no treatment-related death or serious allergic reactions. The most common grade-3/-4 hematologic complication was neutropenia (37% [95%CI 19%-58%]). The most common non-hematologic complications were infection (16% [95%CI 4%-34%]) and hypo-fibrinogenemia (12% [95%CI 2%-29%]). Conclusion: PEMD is effective and safe in persons with newly-diagnosed advanced-stage extra-nodal NK/T-cell lymphoma. Figure 1. PFS and OS for all the patients (N=27). Figure 1. PFS and OS for all the patients (N=27). Disclosures No relevant conflicts of interest to declare.

scholarly journals Efficacy of combined gemcitabine, oxaliplatin and pegaspargase (P-gemox regimen) in patients with newly diagnosed advanced-stage or relapsed/refractory extranodal NK/T-cell lymphoma

Oncotarget ◽  
2016 ◽  
Vol 7 (20) ◽  
pp. 29092-29101 ◽  
Author(s):  
Jing-hua Wang ◽  
Liang Wang ◽  
Cheng-cheng Liu ◽  
Zhong-jun Xia ◽  
Hui-qiang Huang ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Nk T Cell

scholarly journals A Clinically-Indolent Variant of Extranodal NK/T Cell Lymphoma with Unique Immunophenotypic Profile and Superior Outcome

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5278-5278
Author(s):  
Fabiola Valvert ◽  
Elizabeth Solorzano ◽  
Edward Briercheck ◽  
Marcos Mauricio Siliézar Tala ◽  
Yasodha Natkunam ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Elevated Serum ◽  
T Cell Lymphoma ◽  
Nasal Type ◽  
Aggressive Disease ◽  
Ebv Infection ◽  
Nk T Cell ◽  
Indolent Disease

Introduction Extranodal NK/T-cell lymphoma, nasal type (ENKTL), is the most frequent NK-cell malignancy. It is typically associated with a highly aggressive course and extensive local tissue destruction. ENKTL, nasal type, is most common among East Asians and indigenous persons in Latin America, which may result from genetic predisposition, shared strains of EBV infection or other factors. We noted that a subset of patients with ENKTL in Guatemala present with more indolent disease. The clinical and histologic features of these indolent cases, including outcomes after treatment, have not been defined. Methods We reviewed clinical data from 68 patients with ENKTL at INCAN, the largest public cancer hospital in Guatemala, who underwent evaluation between 2006-2018. We confirmed the diagnosis of ENKTL using available paraffin-embedded biopsies based on immunohistochemistry and in situ hybridization for 46 markers at Stanford University (O.S., Y.N.). We defined indolent cases as those lacking macroscopic necrosis, palate perforation, distant lesions (i.e. Stage II or greater), hemophagocytic lymphohistiocytosis (HLH) and B symptoms. Aggressive cases had one or more of these characteristics. Statistical analysis on categorical data was performed using Fisher's exact test. Results Fifty-three patients were confirmed to have ENKTL. The median age at the time of diagnosis was 43 years (range: 11-83) and 36 patients were male (68%). 75.7% of patients self-identified as Mayan ancestry and 85% were born or lived in central or western Guatemala. As outlined in the Table, 14 cases were classified as indolent and 39 were aggressive. Patients with indolent NKTCL were older (mean, 51 years vs. 41.5 years in the aggressive group; p=0.04). Patients with aggressive disease more commonly had anemia, lymphocytopenia and elevated serum LDH. Both indolent and aggressive cases typically had NK cell immunophenotype, including positivity for CD56, granzyme, perforin and TIA-1. All 53 NKTCLs expressed EBER, consistent with EBV infection, with a subset in each group also expressing EBV LMP1. In contrast, greater than 40% of aggressive cases expressed CXCL13 compared to 0% of indolent cases (p=0.005). Aggressive cases were more commonly BCL2 positive (67% versus 31%, p = 0.048). A subset of aggressive cases had Ki67 >50% (6/39 versus 0/14 indolent cases) but there were also aggressive cases with Ki67 <10%. A multiple correspondence analysis using 14 clinical and 18 IHC markers was performed on 33 patients with complete data available. Variables contributing to categorization of aggressive versus indolent ENKTL included palate perforation, peripheral blood lymphocyte count < 0.8 K/uL, B symptoms, anemia, cachexia and macroscopic necrosis. Median survival was markedly better for patients with indolent disease compared to those with aggressive disease (median not reached vs. 2 years, p<0.05). Twelve of (92.9%) thirteen treated patients in the indolent group achieved a complete response compared to only 8 (40%) of 22 treated for aggressive disease (p=0.04). In fact, 9 patients with aggressive disease died before receiving treatment compared to 0 with indolent disease (23.0% vs. 0%; p=0.04). Three of the deaths in patients with indolent disease were due to toxicity from chemotherapy (infection, pancytopenia). Conclusion Approximately one-quarter of patients with extranodal NK/T cell lymphoma, nasal type, in our cohort have a unique variant associated with the absence of aggressive clinical features. These patients have a more indolent clinical course, better outcome with treatment, have less frequent expression of BCL2, and lack CXCL13 expression. Patients with the indolent variant may benefit from less aggressive therapeutic approaches to minimize unnecessary treatment-associated toxicity. Efforts to define genetic and transcriptional characteristics of these cases are underway. Table Disclosures Weinstock: Celgene: Research Funding.

Alemtuzumab in Combination with CHOP and ESHAP as First-Line Treatment in Peripheral T-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4740-4740 ◽  
Author(s):  
Tanin Intragumtornchai ◽  
Udomsak Bunworasate ◽  
Thanyaphong Na Nakorn ◽  
Ponlapat Rojnuckarin
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Pneumocystis Carinii ◽  
Elevated Serum ◽  
T Cell Lymphoma ◽  
Newly Diagnosed ◽  
Bulky Disease ◽  
T Cell Lymphomas ◽  
Hodgkin's Lymphomas ◽  
Cmv Disease

Abstract Patients diagnosed with peripheral T-cell lymphomas (PTCL) generally had a poorer prognosis compared to B-cell non-Hodgkin’s lymphomas. With conventional treatment, the 5-year overall and failure-free survivals (OS and FFS) were 36% and 23%, respectively (Vose et al, Blood2005;106:abstract 811). Between February 2005 and January 2006, 13 consecutive patients newly diagnosed with PTCL (5, extranodal nasal NK/T-cell lymphoma, 4 subcutaneous panniculitis-like, 3 PTCL, unspecified and 1 enteropathy type) were enrolled. The median age was 44 years (range, 21–56) and male:female was 1.6:1. Fifty-four percent had stage III/IV, 31%, PS 2–3, 69%, B-symptoms, 15%, bulky disease, 46%, &gt; 1 extranodal site, 38%, elevated serum LDH and 39%, aaIPI 2–3. Twenty-three percent had thrombocytopenia. Patients were treated with alemtuzumab 30 mg. sc. D1-3 of cycle 1–5 plus CHOP (day 1 of cycle 1, 3, 5) and ESHAP (day 1 of cycle 2, 4, 6) at 28-day intervals. Valacyclovir 500 mg tid and trimethoprim/sulfamethoxazole were given for prophylaxis of CMV and Pneumocystis carinii infection, respectively. Of the evaluable 10 patients, complete remission was obtained in 8 patients, 1 had partial remission and 1 had CNS progression while on treatment. Infection was a major adverse complication: 54% had CMV reactivation (1 had CMV disease), 54%, febrile neutropenia and 15%, tuberculosis. With a median follow-up time of 8 months, the 2-year OS and FFS were 75% (95%CI, 41–92) and 48% (95%CI, 14–76), respectively. From the standpoint of this result, alemtuzumab in combination with CHOP and ESHAP is an effective front-line therapy for patients newly diagnosed with PTCL.

NK/T Cell Versus Peripheral T Cell Lymphoma: Significant Differences in Clinical Characteristics and Survival.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4600-4600
Author(s):  
Soon-Thye Lim ◽  
Fei Gao ◽  
Lay-Cheng Lim ◽  
Richard Quek ◽  
Daryl Lim ◽  
...  
Keyword(s):  
T Cell ◽  
Who Classification ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Advanced Stage ◽  
Peripheral T Cell Lymphoma ◽  
Nk T Cell

Abstract Background: To compare the clinico-pathologic characteristics and prognosis of Natural Killer/T cell lymphoma (NK/TL) with peripheral T cell lymphoma (PTCL). Methods: A total of 556 resident patients (pts) with lymphoma were treated in the departments of medical oncology and hematology in an Asian institution from 2000 to 2005. Of these pts, 71 (12.8%) had NK/TL or PTCL and were included in this analysis. Pathology was centrally reviewed and classified according to the WHO classification. Results: NK/TL and PTCL comprised of 4.7% (26/556) and 7.9% (45/556) of all cases. Of the PTCL cases, histology was PTCL-NOS in 21, anaplastic large cell in 12 (5 were ALK-1 positive) and angioimmunoblastic T cell in 8 pts. Subcutaneous panniculitis T cell and γ/δ T cell lymphoma accounted for one case each. There were no significant differences between the two groups of pts in terms of sex, performance status, extranodal involvement and LDH level at presentation. However, more patients with NK/TL presented with stage I/II disease (65% vs. 31%, p=0.003). Among pts with NK/TL, 17 (65%) received CHOP-based chemotherapy, 4 received radiation alone and 5 received palliative chemotherapy. In the PTCL group, 39 (87%) received CHOP-based chemotherapy, 2 received radiation alone and 3 received palliative treatment only. Compared to PTCL, NK/TL was associated with a significantly inferior rate of complete remission (27% vs. 58%, p=0.01) and inferior overall survival (5 vs. 28.4 mos, p=0.001). Although age &gt; 60, ECOG ≥ 2, elevated LDH, advanced stage, IPI ≥ 2 and NK/T cell histology were each associated with decreased survival on univariate analysis, only NK/T cell histology and advanced stage were independently associated with decreased survival (see table 1). Conclusions: Contrary to expectation, the incidence of PTCL based on WHO classification in this Asian series is not higher than that reported in Western series. Compared to PTCL, the NK/T subtype is associated with a paricularly inferior prognosis and overrides the prognostic significance of IPI. These data suggest that NK/TL should be considered as a seperate entity and should not be considered together with other subtypes of T cell lymphoma in clinical trials. Table 1. NK/TL vs. PTCL: Univariate and Multivariate Analyses Univariate Analysis Multivariate Analysis Median (yr) P Hazard Ratio 95% CI P Male vs. Female 1.03 vs. Not reached 0.06 0.62 0.28 to 1.40 0.25 Age&lt;60 vs. ≥ 60 2.37 vs. 0.51 0.01 1.41 0.70 to 2.83 0.33 ECOG 0/1 vs. ≥ 2 1.99 vs. 0.36 0.002 1.52 0.63 to 3.65 0.354 LDH normal vs. High Not reached vs. 0.75 0.03 1.29 0.53 to 3.13 0.57 Stage I/II vs. III/IV 1.99 vs. 1.41 0.16 2.91 1.17 to 7.2 0.02 IPI 0/1 vs. ≥ 2 Not Reached vs. 0.42 0.002 2.22 0.82 to 5.99 0.12 PTCL vs. NK/TL 2.37 vs. 0.42 0.001 5.8 2.36 to 14.24 &lt;0.001

A Nationwide Prospective Multicenter Study of Clinical Features and Outcomes of Non-Hodgkin Lymphoma in Thailand: An Analysis of 939 Cases

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2064-2064 ◽  
Author(s):  
Udomsak Bunworasate ◽  
Noppadol Siritanaratanakul ◽  
Archrop Khuhapinant ◽  
Arnuparp Lekhakula ◽  
Pairaya Rujirojindakul ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Clinical Features ◽  
Cell Lymphoma ◽  
Elevated Serum ◽  
Clinical Information ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
T Cell Lymphoma ◽  
Nk T Cell

Abstract Abstract 2064 OBJECTIVE: Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy in Thailand. The objective of the study was to evaluate clinical features, histopathology, treatment outcomes and prognostic factors in Thai adult patients with NHL. METHODS: Using web-based registry system, we prospectively collected clinical information of newly diagnosed NHL patients from eleven major medical centers situated in various geographic regions of Thailand. All histopathological diagnoses were reviewed by consensus meeting of panels of 6 expert hematopathologists and classified according to the 2008 WHO classification of the lymphoid neoplasms. Clinical features and treatment outcomes were analyzed using STATA program. RESULTS: Between January 2007 and May 2009, there were a total of 939 NHL patients whose clinical information including follow-up data and tissue samples were readily available for analysis. The median age was 58 years (range, 15–99). Forty six percent of the patients were ≥60 years of age. Male:female was 1.18:1. The six leading subtypes were diffuse large B-cell lymphoma (67%), extranodal marginal zone lymphoma of MALT type (7%), follicular lymphoma (6%), mantle cell lymphoma (4%), peripheral T-cell lymphoma, not otherwise specified (NOS) (3%) and extranodal NK/T-cell lymphoma, nasal type (3%). T-cell lymphoma constituted 10% of all NHL. The three most common subtypes in T-cell lymphomas were peripheral T-cell lymphoma, NOS (26%), extranodal NK/T-cell lymphoma, nasal type (25%) and angioimmunoblastic T-cell lymphoma (15%). Fifty-eight percent of all patients had advanced disease (stage III, IV), 42% had B symptoms and 54% had elevated serum LDH. The IPI risk groups were 23% low, 30% low-intermediate, 30% high-intermediate and 17% high-risk. HIV-associated NHL was seen in 4.4% of the patients. Of the 801 patients who received chemotherapy, 90% were treated with anthracycline-containing regimen. Twenty-five percent of the patients received rituximab. Of the 663 evaluable patients, the rate of objective tumor response was 75% (CR+CRu, 59%). At a median follow-up time of 13 months, the 4-year projected overall survival (OS) was 73% (95% CI 69–77%). The OS of patients with T-cell lymphoma was inferior to B-cell lymphoma (58% vs. 74%, p = 0.04). With multivariate analysis, the independent adverse prognostic factors for OS in B-cell lymphoma were poor performance status (HR 2.4, 95% CI 1.7–3.5), elevated serum LDH (HR 2.1, 95% CI 1.4–3.1), stage III/IV (HR 1.6, 95% CI 1.1–2.3), WHO subtype (HR 1.1, 95% CI 1.0–1.2), no chemotherapy (HR 3.1, 95% CI 1.9–5.1) and no rituximab treatment (HR 1.7, 95% CI 1.1–2.6). The independent adverse factors for OS in T-cell lymphoma were elevated serum LDH (HR 3.7, 95% CI 1.2–11.1) and male sex (HR 3.4, 95% CI 1.3–8.8). CONCLUSIONS: This study confirmed the characteristic features of NHL among Thai population, i.e., a preponderance of diffuse large B-cell lymphoma and a low incidence of follicular lymphoma within B-cell lymphoma; a relatively high incidence of nasal NK/T-cell lymphoma within T-cell lymphoma. The IPI risk-groups and survival outcomes were comparable to most previously published reports. Disclosures: Bunworasate: Novartis Pharmaceutical: Research Funding. Off Label Use: Nilotinib is a safe and effective treatment for patients with CML. Chuncharunee:Novartis: Research Funding.

Phase II study of SMILE chemotherapy for newly-diagnosed stage IV, relapsed or refractory extranodal NK/T-cell lymphoma, nasal type: NKTSG study.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 8044-8044 ◽  
Author(s):  
M. Yamaguchi ◽  
Y. Kwong ◽  
Y. Maeda ◽  
C. Hashimoto ◽  
W. Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Stage Iv ◽  
T Cell Lymphoma ◽  
Newly Diagnosed ◽  
Nasal Type ◽  
Nk T Cell
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