El desafío en el diagnóstico correcto de los linfomas T periféricos: a propósito de un caso

  • L Bullorsky Servicio de Hematología, 2Servicio Anatomía Patológica
  • MC Sernaque Servicio de Hematología
  • G Stemmelin Servicio de Hematología, Hospital Británico de Buenos Aires
  • J Méndez Servicio Anatomía Patológica
  • F Vigovich Servicio Anatomía Patológica
  • G Busnelli Servicio Cirugía General
  • R Maurette Servicio Cirugía General
  • A García Servicio Diagnóstico por Imágenes
  • C Fausti Servicio Diagnóstico por Imágenes
  • V Gutiérrez Servicio Clínica Médica, Resumen del Hospital Británico
  • F Bruetman Servicio Clínica Médica, Resumen del Hospital Británico
Palabras clave: linfomas T periféricos, linfoma T NOS, linfoma T hepato-esplénico, trasplante autólogo de células progenitoras hematopoyéticas (TAMO), CHOP, CHOEP, trasplante alogénico de médula ósea (TALLO).

Resumen

Los linfomas T periféricos (LTP) constituyen un grupo heterogéneo de patologías agresivas, poco frecuentes y de mal pronóstico. Pueden presentar manifestaciones clínicas, epidemiología e histología similares, por lo que el diagnóstico correcto tiene implicancias en la evolución y en el tratamiento.

Se presenta un paciente con hepato-esplenomegalia, pancitopenia leve, hipercalcemia, síntomas B y ausencia de adenopatías, cuyo diagnóstico resultó un desafío. El pronóstico de los LTP es desfavorable, a excepción del Linfoma anaplásico células grandes (LACG) ALK+. El tratamiento de 1ª línea continúa siendo el CHOP, con el agregado de etopósido en algunos pacientes. Todos los LTP se beneficiarían con consolidaciones con altas dosis de quimioterapia seguidas de trasplante autólogo de células progenitoras hematopoyéticas (TAMO) en 1ª RC; en LACG ALK+ no se utiliza por los buenos resultados sin éste. El TAMO demuestra mejores resultados cuanto mayor es la respuesta a la inducción y no estaría indicado en pacientes con quimio-resistencia. Se debe considerar al paciente recaído post TAMO o refractario como candidato a trasplante alogénico de médula ósea. En algunas patologías (leucemia linfoma T del adulto y en el Linfoma Hepato-esplénico (HSTCL) podría indicarse en 1ra RC, y con el uso de regímenes condicionantes de intensidad reducida se podría ampliar el número de candidatos por su menor toxicidad.

Referencias bibliográficas

1. Te Boekhorst PA, Van Lom K. Hepatosplenic T-cell lymphoma. Br J Haematol. 2013;163:422.
2. Gaulard P, Jaffe ES, Krenacs L, Macon WR. Hepatosplenic T-cell Lymphoma. In: Swerdlow SH, Campo E, Harris NL, et al, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC; 2016. p. 292-3.
3. Yabe M, Medeiros LJ, Tang G et al. Prognostic factors of hepatosplenic T-cell lymphoma (HSTCL): A clinicopathologic, immunophenotypic, and cytogenetic analysis of 28 patients. Am J Surg Pathol. 2016;40: 676-88.
4. 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;102:4261-9.
5. Falchook GS, Vega F, Dang NH et al. Hepatosplenic gamma-delta Tcell lymphoma: clinicopathological features and treatment. Ann Oncol. 2009;20:1080-5.
6. Thai A, Prindiville T. Hepatosplenic T-cell lymphoma and inflammatory bowel disease. J Crohns Colitis. 2010;4:511-22.
7. Yabe M, Medeiros LJ, Wang SA et al. Distinguishing between hepatosplenic T-cell lymphoma and gammadelta T-cell large granular lymphocytic leukemia: A clinicopathologic, immunophenotypic, and molecular analysis. Am J Surg Pathol. 2017;41:82-93.
8. 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;25:285-96.
9. Lu CL, Tang Y, Yang QP et al. Hepatosplenic T-cell lymphoma: clinicopathologic, immunophenotypic, and molecular characterization of 17 Chinese cases. Hum Pathol. 2011;42:1965-78
10. Swerdlow SH, Campo E, Harris NL et al. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, Francia. International Agency for Research on Cancer. 2008.
11. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H and Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. 2011; 117: 5019-5032.
12. Foss FM, Zinzani PL, Vose JM et al. Peripheral T-cell Lymphoma. Blood. 2011; 117: 6756-6767.
13. Weisenburger DD et al. Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project. Blood. 2011; 117: 3402-3408.
14. Vose JM, Armitage JO, Weisenburger DD. International peripheral Tcell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008; 26(25):4124-4130. 2008.
15. Armitage, JO. The aggressive peripheral T-cell lymphomas: 2013. Am J Hematol. 2013; 88:911-918.
16. Cacchione, R, Rodriguez, A, et al. Linfomas no Hodgkin T periféricos en Guías de diagnóstico y tratamiento de la Sociedad Argentina de Hematología, 2017: 513-526
17. Gutiérrez-García G, García-Herrera A, Cardesa T et al. Comparison of four prognostic scores in peripheral T-cell lymphoma. Ann Oncol. 2011; 22:397–404.
18. Abramson JS, Feldman T, Kroll-Desrosiers AR et al. Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy. Ann Oncol. 2014; 25:2211-2217.
19. Ellin F, Landström J, Jerkeman M and Relander T. Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry. Blood. 2014; 124:1570-1577.
20. Savage KJ, Chhanabhai M, Gascoyne RD and Connors JM. Characterization of peripheral T-cell lymphomas in a single North American institution by the WHO classification. Ann Oncol. 2004; 15(10):1467-1475.
21. Tilly H, Lepage E, Coiffier B et al. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poorprognosis agressive non-Hodgkin lymphoma. Blood. 2003; 102:4284- 4289.
22. Kim JG, Sohn SK, Chae YS et al. CHOP plus etoposide and gemcitabine (CHOP-EG) as front-line chemotherapy for patients with peripheral T cell lymphomas. Cancer Chemother Pharmacol. 2006; 58:35-39.
23. Savage KJ. Therapies for Peripheral T-Cell Lymphomas. Hematology Am Soc Hematol Educational Prog. 2011. 515-524.
24. O’Connor OA, Bhagat G, Ganapathi K et al. Changing the Paradigms of Treatment in Peripheral T-cell Lymphoma: From Biology to Clinical Practice. Clin Cancer Res. 2014; 20:5240-5254.
25. Reddy NM and Evens AM. Chemotherapeutic Advancements in Peripheral T-Cell Lymphoma. Seminars in Hematol. 2014; 51(1):17-24.
26. Moskowitz AJ, Lunning MA and Horwitz SM. How I treat the peripheral T-cell lymphomas. Blood. 2014; 123:2636-2644.
27. Nickelsen M, Ziepert M, Zeynalova S et al. High-dose CHOP plus etoposide (MegaCHOEP) in T-cell lymphoma: a comparative analysis of patients treated within trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Ann Oncol. 2009; 20:1977-1984.
28. Corradini P, Marchetti M, Barosi G et al. SIE-SIES-GITMO Guidelines for the management of adult peripheral T-and NK-cell lymphomas, excluding mature T-cell leukaemias. Ann Oncol. 2014; 00:1-12.
29. Karlin L and Coiffier B. The Changing Landscape of Peripheral T-Cell Lymphoma in the Era of Novel Therapies. Seminars in Hematol. 2014; 51:25-34
30. Foss F. Treatment strategies for peripheral T-cell lymphomas. Best Practice & Research Clinical Hematology. 2013; 26:43-56.
31. Mounier N, Gisselbrecht C, Briere J et al. All aggressive lymphoma subtypes do not share similar outcome after front-line autotransplantation: a matched-control analysis by the Group d’Etude des Lymphomes de l’Adulte (GELA). Ann Oncol. 2004; 15(12):1790-1797.
32. Corradini P, Tarella C, Zallio F et al. Long-term follow-up of patients with pepripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation. Leukemia. 2006; 20(9):1553-1538.
33. Rodríguez J, Conde E, Gutiérrez A et al. Frontline autologous stem cell transplantation in high-risk peripheral T-cell lymphoma: a prospective study from the Gel-Tamo Study Group. Eur J Haematol. 2007; 79(1):32- 38.
34. Mercadal S, Briones J, Xicoy B et al. Intensive chemotherapy (highdose CHOP/ESHAP régimen) followed by autologous stem-cell transplantation in previously untreated patients with peripheral T-cell lymphoma. Ann Oncol. 2008; 19(5):958-963.
35. Reimer, P, Rudiger T, Geissinger E et al. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: 62 results of a prospective multicenter study. J Clin Oncol. 2009; 27(1):106- 113.
36. D’Amore F, Relander T, Lauritzsen Gf et al. Up-front autologous stem cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol. 2012; 30(25):3093-3099.
37. Chen A, Mcmillan A, Negrin R et al. Long-term results of autologous hematopoietic cell transplantation for peripheral T-cell lymphoma: the Stanford experience. Biol Blood Marrow Transplant. 2008; 14(7):741-747.
38. Rodríguez J, Conde E, Gutiérrez A et al. The results of consolidation with autologous stem-cell transplantation in patients with peripheral Tcell lymphoma in first complete remission: the Spanish Lymphoma and Autologous Transplantation Group experience. Ann Oncol. 2007; 18(4):652-657.
39. Song K, Mollee P, Keating A and 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(6):978-985.
40. Yin J, Wei J, Xu JH et al. Autologous Stem Cell Transplantation as the First-Line Treatment for Peripheral T-Cell Lymphoma: Results of a Comprehensive Meta-Analysis. Acta Haematol. 2014; 131:114-125.
41. Perrone G, Farina L and Corradini P. Current state of art for transplantation paradigms in peripheral T-cell lymphomas. Expert Rev Hematol 2013; 6(4):465-474. 52. Perrone G and Corradini P. Autologous Stem Cell Transplantation for T-Cell Lymphomas. Seminars in Hematol. 2014; 51:59-66.
42. Smith SM, Burns LJ, van Besien K et al. Hematopoietic Cell Transplantation for Systemic Mature T-Cell Non-Hodgkin Lymphoma. J Clin Oncol. 2013; 31:3100-3109.
43. Gkotzamanidou M and Papadimitriou CA. Peripheral T-cell lymphoma: The role of hematopoietic stem cell transplantation. Critic Rev Oncol Hematol. 2014; 89:248-261.
44. Metha N, Maragulia JC, Moskowitz A et al. A Retrospective Analysis of Peripheral T-Cell Lymphoma Treated With the Intention to Transplant in the First Remission. Clin Lym Myel Leuk. 2013; 13(6):664-670.
45. Kharfan-Dabaja MA, Kumar A, Hamadani M et al. Clinical practice recommendations for use of allogeneic hematopoietic cell transplantation in chronic lymphocytic leukemia on behalf of the Guidelines Committee of the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2016;22:2117-2125
46. Fujiwara H, Fuji S, Wake A et al. Dismal outcome of allogeneic hematopoietic stem cell transplantation for relapsed adult T cell leukemia/lymphoma, a Japanese nation-wide study. Bone Marrow Transplant. 2017;52:484-488
Publicado
2019-01-21