NCCN Guidelines Insights: T-Cell Lymphomas, Version 1.2021

Featured Updates to the NCCN Guidelines

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Steven M. HorwitzMemorial Sloan Kettering Cancer Center;

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Stephen AnsellMayo Clinic Cancer Center;

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Weiyun Z. AiUCSF Helen Diller Family Comprehensive Cancer Center;

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Jeffrey BarnesMassachusetts General Hospital Cancer Center;

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Stefan K. BartaAbramson Cancer Center at the University of Pennsylvania;

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Mark W. ClemensThe University of Texas MD Anderson Cancer Center;

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Ahmet DoganMemorial Sloan Kettering Cancer Center;

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Aaron M. GoodmanUC San Diego Moores Cancer Center;

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Gaurav GoyalO'Neal Comprehensive Cancer Center at UAB;

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Joan GuitartRobert H. Lurie Comprehensive Cancer Center of Northwestern University;

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Ahmad HalwaniHuntsman Cancer Institute at the University of Utah;

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Bradley M. HaverkosUniversity of Colorado Cancer Center;

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Richard T. HoppeStanford Cancer Institute;

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Eric JacobsenDana-Farber/Brigham and Women's Cancer Center;

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Deepa JagadeeshCase Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute;

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Allison JonesSt. Jude Children's Research Hospital/The University of Tennessee Health Science Center;

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Youn H. KimStanford Cancer Institute;

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Neha Mehta-ShahSiteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine;

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Elise A. OlsenDuke Cancer Institute;

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Barbara ProRobert H. Lurie Comprehensive Cancer Center of Northwestern University;

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Saurabh A. RajguruUniversity of Wisconsin Carbone Cancer Center;

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Sima RozatiThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins;

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Jonathan SaidUCLA Jonsson Comprehensive Cancer Center;

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Aaron ShaverVanderbilt-Ingram Cancer Center;

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Andrei ShustovFred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance;

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Lubomir SokolMoffitt Cancer Center;

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Pallawi TorkaRoswell Park Comprehensive Cancer Center;

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Carlos Torres-CabalaThe University of Texas MD Anderson Cancer Center;

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Ryan WilcoxUniversity of Michigan Rogel Cancer Center;

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Basem M. WilliamThe Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute;

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Jasmine ZainCity of Hope National Medical Center; and

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Mary A. DwyerNational Comprehensive Cancer Network.

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Hema SundarNational Comprehensive Cancer Network.

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Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of T-cell lymphoma associated with an aggressive clinical course and a worse prognosis. HSTCL develops in the setting of chronic immune suppression or immune dysregulation in up to 20% of cases and is most often characterized by spleen, liver, and bone marrow involvement. Diagnosis and management of HSTCL pose significant challenges given the rarity of the disease along with the absence of lymphadenopathy and poor outcome with conventional chemotherapy regimens. These Guidelines Insights focus on the diagnosis and treatment of HSTCL as outlined in the NCCN Guidelines for T-Cell Lymphomas.

Supplementary Materials

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  • 1.

    Swerdlow SH, Harris NL, Jaffe ES, et al.. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th ed. Lyon, France: IARC; 2017.

    • Search Google Scholar
    • Export Citation
  • 2.

    Foss FM, Horwitz SM, Civallero M, et al.. Incidence and outcomes of rare T cell lymphomas from the T Cell Project: hepatosplenic, enteropathy associated and peripheral gamma delta T cell lymphomas. Am J Hematol 2020;95:151155.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Gratzinger D, de Jong D, Jaffe ES, et al.. T- and NK-cell lymphomas and systemic lymphoproliferative disorders and the immunodeficiency setting: 2015 SH/EAHP workshop report–part 4. Am J Clin Pathol 2017;147:188203.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Pro B, Allen PB, Behdad A. Hepatosplenic T-cell lymphoma: a rare but challenging entity. Blood 2020;blood.2019004118.

  • 5.

    Parakkal D, Sifuentes H, Semer R, et al.. Hepatosplenic T-cell lymphoma in patients receiving TNF-α inhibitor therapy: expanding the groups at risk. Eur J Gastroenterol Hepatol 2011;23:11501156.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Yabe M, Medeiros LJ, Daneshbod Y, et al.. Hepatosplenic T-cell lymphoma arising in patients with immunodysregulatory disorders: a study of 7 patients who did not receive tumor necrosis factor-α inhibitor therapy and literature review. Ann Diagn Pathol 2017;26:1622.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Daver N, McClain K, Allen CE, et al.. A consensus review on malignancy-associated hemophagocytic lymphohistiocytosis in adults. Cancer 2017;123:32293240.

  • 8.

    Yabe M, Miranda RN, Medeiros LJ. Hepatosplenic T-cell lymphoma: a review of clinicopathologic features, pathogenesis, and prognostic factors. Hum Pathol 2018;74:516.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Farcet JP, Gaulard P, Marolleau JP, et al.. Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta. Blood 1990;75:22132219.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Weidmann E. Hepatosplenic T cell lymphoma. A review on 45 cases since the first report describing the disease as a distinct lymphoma entity in 1990. Leukemia 2000;14:991997.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Suarez F, Wlodarska I, Rigal-Huguet F, et al.. Hepatosplenic alphabeta T-cell lymphoma: an unusual case with clinical, histologic, and cytogenetic features of gammadelta hepatosplenic T-cell lymphoma. Am J Surg Pathol 2000;24:10271032.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Macon WR, Levy NB, Kurtin PJ, et al.. Hepatosplenic alphabeta T-cell lymphomas: a report of 14 cases and comparison with hepatosplenic gammadelta T-cell lymphomas. Am J Surg Pathol 2001;25:285296.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Yabe M, Medeiros LJ, Tang G, et al.. Prognostic factors of hepatosplenic T-cell lymphoma: clinicopathologic study of 28 cases. Am J Surg Pathol 2016;40:676688.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Shi Y, Wang E. Hepatosplenic T-cell lymphoma: a clinicopathologic review with an emphasis on diagnostic differentiation from other T-cell/natural killer-cell neoplasms. Arch Pathol Lab Med 2015;139:11731180.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Cooke CB, Krenacs L, Stetler-Stevenson M, et al.. Hepatosplenic T-cell lymphoma: a distinct clinicopathologic entity of cytotoxic gamma delta T-cell origin. Blood 1996;88:42654274.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Wang CC, Tien HF, Lin MT, et al.. Consistent presence of isochromosome 7q in hepatosplenic T gamma/delta lymphoma: a new cytogenetic-clinicopathologic entity. Genes Chromosomes Cancer 1995;12:161164.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Yao M, Tien HF, Lin MT, et al.. Clinical and hematological characteristics of hepatosplenic T gamma/delta lymphoma with isochromosome for long arm of chromosome 7. Leuk Lymphoma 1996;22:495500.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Alonsozana EL, Stamberg J, Kumar D, et al.. Isochromosome 7q: the primary cytogenetic abnormality in hepatosplenic gammadelta T cell lymphoma. Leukemia 1997;11:13671372.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Wlodarska I, Martin-Garcia N, Achten R, et al.. Fluorescence in situ hybridization study of chromosome 7 aberrations in hepatosplenic T-cell lymphoma: isochromosome 7q as a common abnormality accumulating in forms with features of cytologic progression. Genes Chromosomes Cancer 2002;33:243251.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Finalet Ferreiro J, Rouhigharabaei L, Urbankova H, et al.. Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma. PLoS One 2014;9:e102977.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Travert M, Huang Y, de Leval L, et al.. Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets. Blood 2012;119:57955806.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Nicolae A, Xi L, Pittaluga S, et al.. Frequent STAT5B mutations in γδ hepatosplenic T-cell lymphomas. Leukemia 2014;28:22442248.

  • 23.

    McKinney M, Moffitt AB, Gaulard P, et al.. The genetic basis of hepatosplenic T-cell lymphoma. Cancer Discov 2017;7:369379.

  • 24.

    Jerez A, Clemente MJ, Makishima H, et al.. STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia. Blood 2012;120:30483057.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Koskela HL, Eldfors S, Ellonen P, et al.. Somatic STAT3 mutations in large granular lymphocytic leukemia. N Engl J Med 2012;366:19051913.

  • 26.

    Ohgami RS, Ma L, Merker JD, et al.. STAT3 mutations are frequent in CD30+ T-cell lymphomas and T-cell large granular lymphocytic leukemia. Leukemia 2013;27:22442247.

  • 27.

    Blombery P, Thompson ER, Jones K, et al.. Whole exome sequencing reveals activating JAK1 and STAT3 mutations in breast implant-associated anaplastic large cell lymphoma anaplastic large cell lymphoma. Haematologica 2016;101:e387390.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Yabe M, Medeiros LJ, Wang SA, et al.. Distinguishing between hepatosplenic T-cell lymphoma and γδ T-cell large granular lymphocytic leukemia: a clinicopathologic, immunophenotypic, and molecular analysis. Am J Surg Pathol 2017;41:8293.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Malani A, Weigand R, Gupta V, et al.. Ehrlichiosis mimicking T-cell lymphoma/leukemia [abstract] Blood 2005;106:Abstract 4343.

  • 30.

    Marko D, Perry AM, Ponnampalam A, et al.. Cytopenias and clonal expansion of gamma/delta T-cells in a patient with anaplasmosis: a potential diagnostic pitfall. J Clin Exp Hematop 2017;56:160164.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Cho MW, Chin BB. 18F-FDG PET/CT findings in hepatosplenic gamma-delta T-cell lymphoma: case reports and review of the literature. Am J Nucl Med Mol Imaging 2018;8:137142.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Belhadj K, Reyes F, Farcet JP, et al.. Hepatosplenic gammadelta T-cell lymphoma is a rare clinicopathologic entity with poor outcome: report on a series of 21 patients. Blood 2003;102:42614269.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Falchook GS, Vega F, Dang NH, et al.. Hepatosplenic gamma-delta T-cell lymphoma: clinicopathological features and treatment. Ann Oncol 2009;20:10801085.

  • 34.

    Voss MH, Lunning MA, Maragulia JC, et al.. 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. Clin Lymphoma Myeloma Leuk 2013;13:814.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Klebaner D, Koura D, Tzachanis D, et al.. Intensive induction therapy compared with CHOP for hepatosplenic T-cell lymphoma. Clin Lymphoma Myeloma Leuk 2020;20:431437.e2.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Gopcsa L, Bányai A, Tamáska J, et al.. Hepatosplenic gamma delta T-cell lymphoma with leukemic phase successfully treated with 2-chlorodeoxyadenosine. Haematologia (Budap) 2002;32:519527.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Iannitto E, Barbera V, Quintini G, et al.. Hepatosplenic gammadelta T-cell lymphoma: complete response induced by treatment with pentostatin. Br J Haematol 2002;117:995996.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Corazzelli G, Capobianco G, Russo F, et al.. Pentostatin (2′-deoxycoformycin) for the treatment of hepatosplenic gammadelta T-cell lymphomas. Haematologica 2005;90:ECR14.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Jaeger G, Bauer F, Brezinschek R, et al.. Hepatosplenic gammadelta T-cell lymphoma successfully treated with a combination of alemtuzumab and cladribine. Ann Oncol 2008;19:10251026.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Ravandi F, Aribi A, O’Brien S, et al.. Phase II study of alemtuzumab in combination with pentostatin in patients with T-cell neoplasms. J Clin Oncol 2009;27:54255430.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Bennett M, Matutes E, Gaulard P. Hepatosplenic T cell lymphoma responsive to 2′-deoxycoformycin therapy. Am J Hematol 2010;85:727729.

  • 42.

    Rashidi A, Cashen AF. Outcomes of allogeneic stem cell transplantation in hepatosplenic T-cell lymphoma. Blood Cancer J 2015;5:e318.

  • 43.

    Tanase A, Schmitz N, Stein H, et al.. Allogeneic and autologous stem cell transplantation for hepatosplenic T-cell lymphoma: a retrospective study of the EBMT Lymphoma Working Party. Leukemia 2015;29:686688.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Domm JA, Thompson M, Kuttesch JF, et al.. Allogeneic bone marrow transplantation for chemotherapy-refractory hepatosplenic gammadelta T-cell lymphoma: case report and review of the literature. J Pediatr Hematol Oncol 2005;27:607610.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45.

    Sumi M, Takeda W, Kaiume H, et al.. Successful treatment with reduced-intensity cord blood transplant in a patient with relapsed refractory hepatosplenic T-cell lymphoma. Leuk Lymphoma 2015;56:11401142.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 46.

    Pan H, Huang J, Li JN, et al.. Successful second allogeneic stem-cell transplantation from the same sibling donor for a patient with recurrent hepatosplenic gamma-delta (γ/δ) T-cell lymphoma: a case report. Medicine (Baltimore) 2018;97:e12941.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
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