Current Treatment Options in Oncology

, Volume 5, Issue 4, pp 289–303 | Cite as

Treatment of T-cell non-hodgkin’ lymphoma

  • Andrew M. Evens
  • Ronald B. Gartenhaus

Opinion statement

T-cell non-Hodgkin’s lymphoma (NHL) represents approximately 10% to 15% of all lympho-mas in Western countries. Patients with T-cell NHL are often treated similarly to patients with intermediate grade B-cell NHL, although many reports have demonstrated lower overall survival rates in patients with T-cell NHL compared to patients with B-cell NHL. Updated classifications have recognized specific clinical and pathologic T-cell entities, such as peripheral T-cell lymphoma, not otherwise characterized, angioimmunoblastic lymphoma, systemic anaplastic T-cell lymphoma, adult T-cell leukemia/lymphoma, subcutaneous panniculitis-like T-cell lymphoma, hepatosplenic T-cell lymphoma, extranodal natural killer (NK)/T-cell lymphoma nasal type, and enteropathy-type intestinal T-cell lymphoma. Furthermore, these distinct T-cell NHL subtypes often warrant individual-ized diagnostic and therapeutic strategies, such as the associated cytophagic histiocytic panniculitis and hemophagocytic syndrome with subcutaneous panniculitis-like T-cell lymphoma, the chromosomal translocation t(2;5), leading to the nucleophosmin anaplastic lymphoma kinase fusion protein, viral pathogenesis of Epstein-Barr virus, human T-cell lymphotropic virus type-1 associated with extranodal NK/T-cell lymphoma nasal type and adult T-cell leukemia/lymphoma, respectively, and the role of radiation therapy in extra-nodal NK/T-cell lymphoma nasal type. Other active therapeutic agents in T-cell NHL include purine and pyrimidine antimetabolite agents eg, nucleoside analogues and gemcitabine, respectively), denileukin diftitox, and antinucleoside or retinoic acid with interferon-α combination treatment. The exact role of transplantation in patients with T-cell NHL is unknown, but several case series have documented the feasibility of autologous and allogeneic transplant with reported long-term survival rates similar to transplanted B-cell NHL. Identification of relevant proto-oncogenes and tumor suppressor genes involved in the pathogenesis of T-cell NHL, such as the nucleophosmin anaplastic lymphoma kinase fusion protein, p53 and retinoblastoma gene, cyclin-dependent kinase inhibitors, histone deacetylation inhibitors, and infectious etiologies (eg, Epstein-Barr virus and Helicobacter pylori), in addition to their interplay with the various regulatory pathways of cell-cycle progression and apoptosis, represent potential candidates for molecular-based therapy. Prospective multi-institution clinical trials are critically important to determine the most effective treatment regimens that will continue to improve cure rates in these aggressive, yet treatable and often curable, diseases.


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References and Recommended Reading

  1. 1.
    Melnyk A, Rodriguez A, Pugh WC, Cabannillas F: Evaluation of the Revised European-American Lymphoma classification confirms the clinical relevance of immunophenotype in 560 cases of aggressive non-Hodgkin’s lymphoma? Blood 1997, 89:4514–4520. A large report on the importance of T-cell phenotype in NHL with associated prognostic variables and impact on survival.PubMedGoogle Scholar
  2. 2.
    Armitage JO, Weisenburger DD: New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin’s Lymphoma Classification Project? J Clin Oncol 1998, 16:2780–2795.PubMedGoogle Scholar
  3. 3.
    Gisselbrecht C, Gaulard P, Lepage E, et al.: Prognostic significance of T-cell phenotype in aggressive non-Hodgkin’s lymphomas. Groupe d’Etudes des Lym-phomes de l’Adulte (GELA)? Blood, 1998. 92:76–82. A large report on the importance of T-cell phenotype in NHL with associated prognostic variables and impact on survival.PubMedGoogle Scholar
  4. 4.
    Rudiger T, Weisenburger DD, Anderson JR, et al.: Peripheral T-cell lymphoma (excluding anaplastic large-cell lymphoma): results from the Non-Hodgkin’s Lymphoma Classification Project? Ann Oncol 2002, 13:140–149. A multi-institution review on classification, clinical features, and outcomes from a large T-cell NHL database.PubMedCrossRefGoogle Scholar
  5. 5.
    Harris NL, Jaffe ES, Diebold J, et al.: World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clini-cal Advisory Committee meeting-Airlie House, Virginia, November 1997? J Clin Oncol 1999, 17:3835–3849.PubMedGoogle Scholar
  6. 6.
    Siegel RS, Pandolfino T, Guitart J, et al.: Primary cutaneous T-cell lymphoma: review and current con-cepts? J Clin Oncol 2000, 18:2908–2925.PubMedGoogle Scholar
  7. 7.
    Pellatt J, Sweetenham J, Pickering RM, et al.: A single-centre study of treatment outcomes and survival in 120 patients with peripheral T-cell non-Hodgkin’s lymphoma? Ann Hematol 2002, 81: 267–272.PubMedCrossRefGoogle Scholar
  8. 8.
    Itoyama T, Chaganti RS, Yamada Y, et al.: Cytogenetic analysis and clinical significance in adult T-cell leukemia/lymphoma: a study of 50 cases from the human T-cell leukemia virus type-1 endemic area, Nagasaki? Blood 2001, 97:3612–3620.PubMedCrossRefGoogle Scholar
  9. 9.
    Anagnostopoulos I, Hummel M, Stein H: Frequent presence of latent Epstein-Barr virus infection in peripheral T-cell lymphomas: a review? Leuk Lymphoma 1995, 19:1–12.PubMedGoogle Scholar
  10. 10.
    Luppi M, Barozzi P, Maiorana A, et al.: Human herpes-virus-8 DNA sequences in human immunodeficiency virus-negative angioimmunoblastic lymphadenopa-thy and benign lymphadenopathy with giant germinal center hyperplasia and increased vascularity? Blood 1996, 87:3903–3909.PubMedGoogle Scholar
  11. 11.
    d’Amore F, Johansen P, Houmand A, et al.: Epstein-Barr virus genome in non-Hodgkin’s lymphomas occur-ring in immunocompetent patients: highest preva-lence in nonlymphoblastic T-cell lymphoma and correlation with a poor prognosis. Danish Lymphoma Study Group, LYFO? Blood 1996, 87:1045–1055.PubMedGoogle Scholar
  12. 12.
    Hayday AC, Barber DF, Douglas N, Hoffman ES: Signals involved in gamma/delta T cell versus alpha/beta T cell lineage commitment? Semin Immunol 1999, 11: 239–249.PubMedCrossRefGoogle Scholar
  13. 13.
    Evens AM, Gartenhaus RB: Molecular etiology of mature T-cell non-Hodgkin’s lymphomas? Front Biosci 2003, 8:D156-D175.PubMedCrossRefGoogle Scholar
  14. 14.
    Reiser M, Josting A, Soltani M, et al.: T-cell non-Hodgkin’s lymphoma in adults: clinicopathological characteristics, response to treatment and prognostic factors? Leuk Lymphoma 2002, 43:805–811. A recent report describing clinical factors, prognostic variables, and treatment outcomes for T-cell NHL.PubMedCrossRefGoogle Scholar
  15. 15.
    Karakas T, Bergmann L, Stutte HJ, et al.: Peripheral T-cell lymphomas respond well to vincristine, adriamy-cin, cyclophosphamide, prednisone and etoposide (VACPE) and have a similar outcome as high-grade B-cell lymphomas? Leuk Lymphoma 1996, 24:121–129.PubMedGoogle Scholar
  16. 16.
    Ansell SM, Habermann TM, Kurtin PJ, et al.: Predictive capacity of the International Prognostic Factor Index in patients with peripheral T-cell lymphoma? J Clin Oncol 1997, 15:2296–2301.PubMedGoogle Scholar
  17. 17.
    Jemal A, Murray T, Samuels A, et al.: Cancer statistics, 2003? CA Cancer J Clin 2003, 53:5–26.PubMedCrossRefGoogle Scholar
  18. 18.
    Gordon LI, Harrington D, Andersen J, et al.: Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin’s lymphoma? N Engl J Med 1992, 327:1342–1349.PubMedCrossRefGoogle Scholar
  19. 19.
    Fisher RI, Gaynor ER, Dahlberg S, et al.: Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma? N Engl J Med 1993, 328:1002–1006.PubMedCrossRefGoogle Scholar
  20. 20.
    Kurzrock R: Therapy of T-cell lymphomas with pentostatin? Ann N Y Acad Sci 2001, 941:200–205.PubMedCrossRefGoogle Scholar
  21. 21.
    Iannitto E, Barbera V, Quintini G, et al.: Hepatosplenic gammadelta T-cell lymphoma: complete response induced by treatment with pentostatin? Br J Haematol 2002, 117:995–996.PubMedCrossRefGoogle Scholar
  22. 22.
    Sallah S, Wan JY, Nguyen NP: Treatment of refractory T-cell malignancies using gemcitabine? Br J Haematol 2001, 113: 185–187.PubMedCrossRefGoogle Scholar
  23. 23.
    Zinzani PL, Magagnoli M, Bendandi M, et al.: Therapy with gemcitabine in pretreated peripheral T-cell lymphoma patients? Ann Oncol 1998, 9:1351–1353.PubMedCrossRefGoogle Scholar
  24. 24.
    LeMaistre CF, Saleh MN, Kuzel TM, et al.: Phase I trial of a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for interleukin-2? Blood 1998, 91: 399–405.PubMedGoogle Scholar
  25. 25.
    Talpur R, Apisarnthanarax N, Ward S, Duvic M: Treatment of refractory peripheral T-cell lymphoma with denileukin diftitox (ONTAK)? Leuk Lymphoma 2002, 43:121–126.PubMedCrossRefGoogle Scholar
  26. 26.
    Huang CL, Lin ZZ, Su IJ, et al.: Combination of 13-cis retinoic acid and interferon-alpha in the treatment of recurrent or refractory peripheral T-cell lymphoma? Leuk Lymphoma 2002, 43:1415–1420.PubMedGoogle Scholar
  27. 27.
    Siegert W, Nerl C, Agthe A, et al.: Angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma: prognostic impact of clinical observations and laboratory findings at presentation. The Kiel Lymphoma Study Group? Ann Oncol 1995, 6:659–664.PubMedGoogle Scholar
  28. 28.
    Sallah S, Gagnon GA: Angioimmunoblastic lymph-adenopathy with dysproteinemia: emphasis on patho-genesis and treatment? Acta Haematol 1998, 99:57–64.PubMedCrossRefGoogle Scholar
  29. 29.
    Siegert W, Agthe A, Griesser H, et al.: Treatment of angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma using prednisone with or without the COPBLAM/IMVP-16 regimen: a multicenter study. Kiel Lymphoma Study Group? Ann Intern Med 1992, 117: 364–370.PubMedGoogle Scholar
  30. 30.
    Quintini G, Iannitto E, Barbera V, et al.: Response to low-dose oral methotrexate and prednisone in two patients with angio-immunoblastic lymphadenopathy-type T-cell lymphoma? Hematol J 2001, 2:393–395.PubMedCrossRefGoogle Scholar
  31. 31.
    Tsatalas C, Margaritis D, Kaloutsi V, et al.: Successful treatment of angioimmunoblastic lymphadenopathy with dysproteinemia-type T-cell lymphoma with fludarabine? Acta Haematol 2001, 105: 106–108.PubMedCrossRefGoogle Scholar
  32. 32.
    Stein H, Foss HD, Durkop H, et al.: CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features? Blood 2000, 96:3681–3695. An excellent overall review of anaplastic lymphoma.PubMedGoogle Scholar
  33. 33.
    Tilly H, Gaulard P, Lepage E, et al.: Primary anaplastic large-cell lymphoma in adults: clinical presentation, immunophenotype, and outcome? Blood 1997, 90:3727–3734.PubMedGoogle Scholar
  34. 34.
    Kutok JL, Aster JC: Molecular biology of anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma? J Clin Oncol 2002, 20:3691–3702.PubMedCrossRefGoogle Scholar
  35. 35.
    Gascoyne RD, Aoun P, Wu D, et al.: Prognostic significance of anaplastic lymphoma kinase (ALK) protein expression in adults with anaplastic large cell lymphoma? Blood 1999, 93:3913–3921.PubMedGoogle Scholar
  36. 36.
    Suzuki R, Kagami Y, Takeuchi K, et al.: Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype? Blood 2000, 96:2993–3000.PubMedGoogle Scholar
  37. 37.
    Falini B, Pileri S, Zinzani PL, et al.: ALK+ lymphoma: clinico-pathological findings and outcome? Blood 1999, 93:2697–2706.PubMedGoogle Scholar
  38. 38.
    Seidemann K, Tiemann M, Schrappe M, et al.: Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin-Frankfurt-Munster Group Trial NHL-BFM 90? Blood 2001, 97:3699–3706.PubMedCrossRefGoogle Scholar
  39. 39.
    Bekkenk MW, Geelen FA, van Voorst Vader PC, et al.: Primary and secondary cutaneous CD30(+) lympho-proliferative disorders: a report from the Dutch Cuta-neous Lymphoma Group on the long-term follow-up data of 219 patients and guidelines for diagnosis and treatment? Blood 2000, 95:3653–3661.PubMedGoogle Scholar
  40. 40.
    Kumar S, Krenacs L, Medeiros J, et al.: Subcutaneous panniculitic T-cell lymphoma is a tumor of cytotoxic T lymphocytes? Hum Pathol 1998, 29:397–403.PubMedCrossRefGoogle Scholar
  41. 41.
    Salhany KE, Macon WR, Choi JK, et al.: Subcutaneous panniculitis-like T-cell lymphoma: clinicopathologic, immunophenotypic, and genotypic analysis of alpha/ beta and gamma/delta subtypes? Am J Surg Pathol 1998, 22:881–893.PubMedCrossRefGoogle Scholar
  42. 42.
    Marzano AV, Berti E, Paulli M, Caputo R: Cytophagic histiocytic panniculitis and subcutaneous panniculitis-like T-cell lymphoma: report of 7 cases? Arch Dermatol 2000, 136:889–896.PubMedCrossRefGoogle Scholar
  43. 43.
    WY, Ng WM, Choy C, Kwong YL: Aggressive subcutaneous panniculitis-like T-cell lymphoma: complete remission with fludarabine, mitoxantrone and dexamethasone? Br J Dermatol 2000, 143:408–10.PubMedCrossRefGoogle Scholar
  44. 44.
    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, 88:4265–274.PubMedGoogle Scholar
  45. 45.
    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, 14:991–97.PubMedCrossRefGoogle Scholar
  46. 46.
    Hanson MN, Morrison VA, Peterson BA, et al.: Post-transplant T-cell lymphoproliferative disorders: an aggressive, late complication of solid-organ transplantation? Blood 1996, 88:3626–633.PubMedGoogle Scholar
  47. 47.
    Cheung MM, Chan JK, Lau WH, et al.: Primary non-Hodgkin’s lymphoma of the nose and nasopharynx: clin-ical features, tumor immunophenotype, and treatment outcome in 113 patients? J Clin Oncol 1998, 16:70–7. A large collection of patients with nasal T-cell NHL with description of clinical and treatment outcome.PubMedGoogle Scholar
  48. 48.
    Kim GE, Cho JH, Yang WI, et al.: Angiocentric lymphoma of the head and neck: patterns of systemic failure after radiation treatment? J Clin Oncol 2000, 18:54–3.PubMedGoogle Scholar
  49. 49.
    Li YX, Coucke PA, Li JY, et al.: Primary non-Hodgkin’s lymphoma of the nasal cavity: prognostic significance of paranasal extension and the role of radiotherapy and chemotherapy? Cancer 1998, 83:449–56.PubMedCrossRefGoogle Scholar
  50. 50.
    Kim GE, Lee SW, Chang SK, et al.: Combined chemo-therapy and radiation versus radiation alone in the management of localized angiocentric lymphoma of the head and neck? Radiother Oncol 2001, 61: 261–69.PubMedCrossRefGoogle Scholar
  51. 51.
    Gale J, Simmonds PD, Mead GM, et al.: Enteropathy-type intestinal T-cell lymphoma: clinical features and treatment of 31 patients in a single center? J Clin Oncol 2000, 18:795–03. The largest available collection of patients with intestinal T-cell NHL with emphasis on clinical features and treatment.PubMedGoogle Scholar
  52. 52.
    Quintanilla-Martinez L, Lome-Maldonado C, Ott G, et al.: Primary non-Hodgkin’s lymphoma of the intestine: high prevalence of Epstein-Barr virus in Mexican lymphomas as compared with European cases? Blood 1997, 89:644–51.PubMedGoogle Scholar
  53. 53.
    Hoffmann M, Vogelsang H, Kletter K, et al.: 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) for assessment of enteropathy-type T cell lymphoma? Gut 2003, 52:347–51.PubMedCrossRefGoogle Scholar
  54. 54.
    El-Sabban ME, Nasr R, Dbaibo G, et al.: Arsenic-inter-feron-alpha-triggered apoptosis in HTLV-I transformed cells is associated with tax down-regulation and reversal of NF-kappa B activation? Blood 2000, 96:2849–855.PubMedGoogle Scholar
  55. 55.
    Bazarbachi A, El-Sabban ME, Nasr R, et al.: Arsenic triox-ide and interferon-alpha synergize to induce cell cycle arrest and apoptosis in human T-cell lymphotropic virus type I-transformed cells? Blood 1999, 93:278–83.PubMedGoogle Scholar
  56. 56.
    Dierov J, Sawaya BE, Prosniak M, Gartenhaus RB: Retinoic acid modulates a bimodal effect on cell cycle progression in human adult T-cell leukemia cells? Clin Cancer Res 1999, 5:2540–547.PubMedGoogle Scholar
  57. 57.
    Matutes E, Taylor GP, Cavenagh J, et al.: Interferon alpha and zidovudine therapy in adult T-cell leukaemia lymphoma: response and outcome in 15 patients. Br J Haematol 2001, 113: 779–84.PubMedCrossRefGoogle Scholar
  58. 58.
    Hermine O, Allard I, Levy V, et al.: A prospective phase II clinical trial with the use of zidovudine and interferon-alpha in the acute and lymphoma forms of adult T-cell leukemia/lymphoma? Hematol J 2002, 3:276–82.PubMedCrossRefGoogle Scholar
  59. 59.
    Besson C, Panelatti G, Delaunay C, et al.: Treatment of adult T-cell leukemia-lymphoma by CHOP followed by therapy with antinucleosides, alpha interferon and oral etoposide? Leuk Lymphoma 2002, 43:2275–279.PubMedCrossRefGoogle Scholar
  60. 60.
    Philip T, Guglielmi C, Hagenbeek A, et al.: Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma? N Engl J Med 1995, 333:1540–545.PubMedCrossRefGoogle Scholar
  61. 61.
    Kahl C, Leithauser M, Wolff D, et al.: Treatment of periph-eral T-cell lymphomas (PTCL) with high-dose chemo-therapy and autologous or allogeneic hematopoietic transplantation? Ann Hematol 2002, 81: 646–50.PubMedCrossRefGoogle Scholar
  62. 62.
    Blystad AK, Enblad G, Kvaloy S, et al.: High-dose therapy with autologous stem cell transplantation in patients with peripheral T cell lymphomas? Bone Marrow Transplant 2001, 27:711–16.PubMedCrossRefGoogle Scholar
  63. 63.
    Rodriguez J, Munsell M, Yazji S, et al.: Impact of high-dose chemotherapy on peripheral T-cell lymphomas? J Clin Oncol 2001, 19:3766–770.PubMedGoogle Scholar
  64. 64.
    Song KW, Mollee P, Keating A, Crump M: Autologous stem cell transplant for relapsed and refractory peripheral T-cell lymphoma: variable outcome according to pathological subtype? Br J Haematol 2003, 120:978–85.PubMedCrossRefGoogle Scholar
  65. 65.
    Deconinck E, Lamy T, Foussard C, et al.: Autologous stem cell transplantation for anaplastic large-cell lymphomas: results of a prospective trial? Br J Haematol 2000, 109: 736–42.PubMedCrossRefGoogle Scholar
  66. 66.
    Fanin R, Sperotto A, Silvestri F, et al.: The therapy of primary adult systemic CD30-positive anaplastic large cell lymphoma: results of 40 cases treated in a single center? Leuk Lymphoma 1999, 35:159–69.PubMedGoogle Scholar
  67. 67.
    Okamura T, Kishimoto T, Inoue M, et al.: Unrelated bone marrow transplantation for Epstein-Barr virus-associated T/NK-cell lymphoproliferative disease? Bone Marrow Transplant 2003, 31: 105–111.PubMedCrossRefGoogle Scholar
  68. 68.
    Nagata S, Onda M, Numata Y, et al.: Novel anti-CD30 recombinant immunotoxins containing disulfide-stabi-lized Fv fragments? Clin Cancer Res 2002, 8:2345–355.PubMedGoogle Scholar
  69. 69.
    Hatta Y, Koeffler HP: Role of tumor suppressor genes in the development of adult T cell leukemia/lym-phoma (ATLL)? Leukemia 2002, 16:1069–1085.PubMedCrossRefGoogle Scholar
  70. 70.
    Hofmann WK, Tsukasaki K, Takeuchi N, et al.: Methylation analysis of cell cycle control genes in adult T-cell leuke-mia/ lymphoma? Leuk Lymphoma 2001, 42:1107–1109.PubMedCrossRefGoogle Scholar
  71. 71.
    Piekarz RL, Robey R, Sandor V, et al.: Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T-cell lymphoma: a case report? Blood 2001, 98:2865–868.PubMedCrossRefGoogle Scholar
  72. 72.
    Bariol C, Field A, Vickers CR, Ward R: Regression of gastric T cell lymphoma with eradication of Helicobacter pylori? Gut 2001, 48:269–71.PubMedCrossRefGoogle Scholar
  73. 73.
    Fillmore GC, Lin Z, Bohling SD, et al.: Gene expression profiling of cell lines derived from T-cell malignancies? FEBS Lett 2002, 522:183–88.PubMedCrossRefGoogle Scholar
  74. 74.
    Passoni L, Scardino A, Bertazzoli C, et al.: ALK as a novel lymphoma-associated tumor antigen: identification of 2 HLA-A2.1-restricted CD8+ T-cell epitopes? Blood 2002, 99:2100–106.PubMedCrossRefGoogle Scholar
  75. 75.
    Thirdborough SM, Radcliffe JN, Friedmann PS, Stevenson FK: Vaccination with DNA encoding a single-chain TCR fusion protein induces anticlonotypic immunity and protects against T-cell lymphoma? Cancer Res 2002, 62:1757–760.PubMedGoogle Scholar

Copyright information

© Current Science Inc 2004

Authors and Affiliations

  • Andrew M. Evens
  • Ronald B. Gartenhaus
    • 1
  1. 1.Division of Hematology/Oncology, Department of MedicineNorthwestern University Feinberg School of Medicine Medical School and the Robert H. Lurie Comprehensive Cancer Center of Northwestern UniversityChicagoUSA

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