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E-JCRT CORRESPONDENCE
Year : 2015  |  Volume : 11  |  Issue : 3  |  Page : 665

Efficacy of pegaspargase in extra nodal natural killer/T-cell lymphoma nasal type: A case report from China


1 Department of Pharmacology, The First Affiliated Hospital, Yangtze University, Jingzhou, Hubei, China
2 Department of Oncology, The First Affiliated Hospital, Yangtze University, Jingzhou, Hubei, China

Date of Web Publication9-Oct-2015

Correspondence Address:
Zhiqiang Cai
Department of Oncology, The First Affiliated Hospital, Yangtze University, Jingzhou, Hubei
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.140750

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 > Abstract 

Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is a rare and highly aggressive disease with a grim prognosis. There is no known satisfactory treatment. The author herein to report one case of L-asparaginase extranodal NK/T-cell lymphoma primary treated with L-asparaginase methotrexate and dexamethasone.

Keywords: Initial chemotherapy, L-asparaginase, natural killer/T-cell lymphoma


How to cite this article:
Xiong X, Cai Z, Yang J, Shu X. Efficacy of pegaspargase in extra nodal natural killer/T-cell lymphoma nasal type: A case report from China. J Can Res Ther 2015;11:665

How to cite this URL:
Xiong X, Cai Z, Yang J, Shu X. Efficacy of pegaspargase in extra nodal natural killer/T-cell lymphoma nasal type: A case report from China. J Can Res Ther [serial online] 2015 [cited 2019 Nov 13];11:665. Available from: http://www.cancerjournal.net/text.asp?2015/11/3/665/140750


 > Introduction Top


Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is a rare and severe malignancy. It is an extranodal lymphoma usually with an immature NK-cell phenotype and Epstein-Barr virus positivity. It is classically characterized by a cytoplasmic CD3 ε phenotype, with no surface CD3 or T-cell receptor expression, no T-cell receptor gene rearrangements, an activated cytotoxic profile with perforin, granzyme B, and T-cell intracellular antigen-1 expression, and frequent CD56 expression. [1],[2],[3]

There is a geographic predominance in Asia, where it comprises 3-8% of nonHodgkin's lymphoma, and in Central and South America. [4] More common in males, it may affect children, or adults, with a median age of diagnosis the fifth decade. [5] There are two clinical entities, nasal and extranasal NK/T cell lymphoma, which diverge in clinical presentation, treatment, and prognosis. [6] Because disease incidence is rare even in prevalent areas, there has been no randomized controlled trial, and most treatment protocols are consensus-guided. [7] Localized NK/T-cell lymphomas often respond to radiotherapy [8],[9] or to concurrent radiation and chemotherapy, [10] but relapse is common. Chemotherapy protocols used for lymphomas of other histologic subtypes are poorly effective, at least in part, because of frequent multidrug resistance gene expression by tumor cells. [11]

We report one case of initial treated with L-asparaginase-containing regimen for patients with disseminated NK/T lymphoma. We combine L-asparaginase with methotrexate, a drug insensitive to the multidrug resistance pathway, because of its well-known synergistic effect with asparaginase in acute lymphoblastic leukemia and its ability to prevent central nervous system involvement. Dexamethasone was added because T-cell lymphomas are usually sensitive to corticosteroids and dexamethasone seems to be associated with a lower risk of thrombosis when given with L-asparaginase. [12]


 > Case report Top


A 73-year-old Chinese man noted fullness in the left nasal cavity and difficulty breathing on that side. Computed tomography (CT) scan revealed a soft tissue opacity filling the left maxillary frontal and ethmoid sinuses [Figure 1]. Excisional biopsy showed extranodal NK/T-cell lymphoma. Immunophenotyping revealed CD3 + , CD45RO + , CD79α , CD56 + , GranzymeB + , CD30 , CyclinD1 , Ki67 + :50-60%, EBER (By fluorescence in situ hybridization)- [Figure 2]. He denied fevers, chills or night sweats, but had 7-8 pound weight loss over 2 months. His physical exam was remarkable only presented with left neck mass. Excisional biopsy showed extranodal NK/T-CELL lymphoma. Bone marrow biopsy and CT scan showed no other evidence of lymphoma. He was diagnosed with stage II E extranodal NK/T lymphoma, nasal type. He received two 21-day cycles AspaMetDex (pegaspargase with methotrexate and dexamethasone) regime. Pegaspargase was initiated at 2500 units/m 2 of body surface area on days 1, 14, intramuscularly, plus methotrexate 2 g/m 2 on day 1, and oral dexamethasone 20 mg from day 1 to 4. After two cycles, the patient can breath well, responses assessed by CT scan is a partial response, [13] there are a little soft tissue in the left nasal cavity according the CT scan [Figure 3]. Physical examination showed that the mass in the left neck also almost disappeared. Unfortunately, the treatment discontinued because of health expense.
Figure 1: Nasal computed tomography scan after chemotherapy

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Figure 2: Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) of tumor: CD3+, CD45RO+, CD79α−, CD56+, GranzymeB+, CD30−, CyclinD1−, Ki67+:50-60%, EBER (By FISH)−(IHC ×40) CD20−

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Figure 3: Nasal computed tomography scan before chemotherapy

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 > Discussion Top


In a recent international multicenter series reported by the International Peripheral T-cell Lymphoma Project, the median survival time was only 7.8 months. [14] There is no consensus on the optimal therapeutic regimen in the salvage setting. Etoposide, ifosfamide, and methotrexate based regimens exhibited a complete response rate of ~40% with median disease free survival of 12 months in one study, [15] and a 44% response rate in 32 patients with median overall survival of 8.2 months and time to treatment failure of 3.7 months in another. [16] Chinese group who first reported the use of asparaginase to treat NK/T-cell lymphoma, in four retrospective series. [17],[18],[19],[20] However, in these studies, the patients had localized disease and received irradiation after asparaginase, making it impossible to determine whether asparaginase or irradiation was responsible for the excellent response rate. Jaccard et al. [21] had reported that L-asparaginase with methotrexate and dexamethasone in patients with refractory or relapsing extranodal NK/T-cell lymphoma is more effective. Reyes et al. [22] show that L-asparaginase is a viable treatment alternative in relapsed NK/T-extranodal lymphoma.


 > Conclusion Top


There are many research has proved the efficacy in relapsed NK/T-extranodal lymphoma. In our case, we first report the L-asparaginase is also effective in the initial treatment of extranodal NK/T-cell lymphoma nasal type. Because of the limited cases, so first-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma initial treatment need further study.

 
 > References Top

1.
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Kluin PM, Feller A, Gaulard P, Jaffe ES, Meijer CJ, Müller-Hermelink HK, et al. Peripheral T/NK-cell lymphoma: A report of the IX th Workshop of the European Association for Haematopathology. Histopathology 2001;38:250-70.  Back to cited text no. 2
    
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Jaffe ES, Lee Harris N, Stein H, Vardiman JW. Tumors of Haematopoietic and Lymphoid Tissues: World Health Organization Classification of Tumors. Lyon, France: IARC Press; 2001.  Back to cited text no. 3
    
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Liang R, Todd D, Chan TK, Chiu E, Lie A, Kwong YL, et al. Treatment outcome and prognostic factors for primary nasal lymphoma. J Clin Oncol 1995;13:666-70.  Back to cited text no. 4
    
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Chim CS, Ma SY, Au WY, Choy C, Lie AK, Liang R, et al. Primary nasal natural killer cell lymphoma: Long-term treatment outcome and relationship with the International Prognostic Index. Blood 2004;103:216-21.  Back to cited text no. 5
    
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Kwong YL. Natural killer-cell malignancies: diagnosis and treatment. Leukemia 2005;19:2186-94.  Back to cited text no. 6
    
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Kwong YL, Anderson BO, Advani R, Kim WS, Levine AM, Lim ST, et al. Management of T-cell and natural-killer-cell neoplasms in Asia: Consensus statement from the Asian Oncology Summit 2009. Lancet Oncol 2009;10:1093-101.  Back to cited text no. 7
    
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Li YX, Yao B, Jin J, Wang WH, Liu YP, Song YW, et al. Radiotherapy as primary treatment for stage IE and IIE nasal natural killer/T-cell lymphoma. J Clin Oncol 2006;24:181-9.  Back to cited text no. 8
    
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Isobe K, Uno T, Tamaru J, Kawakami H, Ueno N, Wakita H, et al. Extranodal natural killer/T-cell lymphoma, nasal type: the significance of radiotherapeutic parameters. Cancer 2006;106:609-15.  Back to cited text no. 9
    
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Kim SJ, Kim K, Kim BS, Kim CY, Suh C, Huh J, et al. Phase II trial of concurrent radiation and weekly cisplatin followed by VIPD chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell Lymphoma: Consortium for Improving Survival of Lymphoma study. J Clin Oncol 2009;27:6027-32.  Back to cited text no. 10
    
11.
Yamaguchi M, Kita K, Miwa H, Nishii K, Oka K, Ohno T, et al. Frequent expression of P-glycoprotein/MDR1 by nasal T-cell lymphoma cells. Cancer 1995;76:2351-6.  Back to cited text no. 11
    
12.
Nowak-Göttl U, Ahlke E, Fleischhack G, Schwabe D, Schobess R, Schumann C, et al. Thromboembolic events in children with acute lymphoblastic leukemia (BFM protocols): Prednisone versus dexamethasone administration. Blood 2003;101:2529-33.  Back to cited text no. 12
    
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Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol 2007;25:579-86.  Back to cited text no. 13
    
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Au WY, Weisenburger DD, Intragumtornchai T, Nakamura S, Kim WS, Sng I, et al. Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: A study of 136 cases from the International Peripheral T-Cell Lymphoma Project. Blood 2009;113:3931-7.  Back to cited text no. 14
    
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Cabanillas F, Hagemeister FB, Bodey GP, Freireich EJ. IMVP-16: An effective regimen for patients with lymphoma who have relapsed after initial combination chemotherapy. Blood 1982;60:693-7.  Back to cited text no. 15
    
16.
Kim BS, Kim DW, Im SA, Kim CW, Kim TY, Yoon SS, et al. Effective second-line chemotherapy for extranodal NK/T-cell lymphoma consisting of etoposide, ifosfamide, methotrexate, and prednisolone. Ann Oncol 2009;20:121-8.  Back to cited text no. 16
    
17.
Yong W, Zheng W, Zhang Y. Clinical characteristics and treatment of midline nasal and nasal type NK/T cell lymphoma. Zhonghua Yi Xue Za Zhi 2001;81:773-5.  Back to cited text no. 17
    
18.
Yong W, Zheng W, Zhang Y, Zhu J, Wei Y, Zhu D, et al. L-asparaginase-based regimen in the treatment of refractory midline nasal/nasal-type T/NK-cell lymphoma. Int J Hematol 2003;78:163-7.  Back to cited text no. 18
    
19.
Yong W, Zheng W, Zhu J, Zhang Y, Wei Y, Wang X, et al. Midline NK/T-cell lymphoma nasal-type: treatment outcome, the effect of L-asparaginase based regimen, and prognostic factors. Hematol Oncol 2006;24:28-32.  Back to cited text no. 19
    
20.
Yong W, Zheng W, Zhu J, Zhang Y, Wang X, Xie Y, et al. L-asparaginase in the treatment of refractory and relapsed extranodal NK/T-cell lymphoma, nasal type. Ann Hematol 2009;88:647-52.  Back to cited text no. 20
    
21.
Jaccard A, Gachard N, Marin B, Rogez S, Audrain M, Suarez F, et al. Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study. Blood 2011;117:1834-9.  Back to cited text no. 21
    
22.
Reyes VE Jr, Al-Saleem T, Robu VG, Smith MR. Extranodal NK/T-cell lymphoma nasal type: efficacy of pegaspargase. Report of two patients from the United Sates and review of literature. Leuk Res 2010;34:e50-4.  Back to cited text no. 22
    


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  [Figure 1], [Figure 2], [Figure 3]



 

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