Periphere T-Zell-Lymphome - Diagnostik und Therapie

Zusammenfassung

Periphere T/NK-Zell-Lymphome (PTZL) sind eine heterogene Gruppe seltener Erkrankungen, die nur 10 - 15 % aller Non-Hodgkin-Lymphome ausmachen. Im Vergleich zu B-Zell-Lymphomen manifestieren sich PTZL häufiger extranodal und haben eine schlechtere Prognose. Wegen des zumeist günstigen Verlaufs sollten primär kutane T/NK-Zell-Lymphome von den übrigen PTZL getrennt betrachtet werden. Die Stadieneinteilung erfolgt nach der Ann-Arbor-Klassifikation. Der für B-Zell-Lymphome etablierte Internationale Prognostische Index (IPI) ist auch für PTZL relevant.

Eine befriedigende Standardtherapie der PTZL ist bisher nicht definiert. In der Primärtherapie führt eine konventionelle (Anthrazyklin-basierte) Chemotherapie zu Langzeitremissionen in 15 bis 42 % der Patienten. Abgesehen vom prognostisch deutlich günstigeren (ALK-positiven) anaplastischen großzelligen T-Zell-Lymphom bleiben die Ergebnisse somit hinter denen zurück, die bei aggressiven B-Zell-Lymphomen erreicht werden. Die Hochdosistherapie mit autologer Stammzelltransplantation (SZT) ist für rezidivierte und primär refraktäre PTZL eine sinnvolle Therapieoption, weil sie ähnlich effektiv ist wie bei aggressiven B-Zell-Lymphomen. Vielversprechend sind auch bisherige Studienergebnisse zur allogenen SZT nach dosisreduzierter Konditionierung bei Patienten im Rezidiv. Inwieweit die Primärtherapie der PTZL durch Hochdosiskonzepte oder den Einsatz neuerer Substanzen wie z. B. Alemtuzumab verbessert werden kann, ist bislang nicht geklärt. Patienten mit PTZL sollten daher nach Möglichkeit im Rahmen klinischer Studien behandelt werden.

Summary

Peripheral T/NK-cell lymphomas (PTCL) comprise a heterogeneous group of rare diseases accounting for approximately 10-15% of all non-Hodgkin"s lymphomas. Compared to B-cell lymphomas, PTCL more frequently involve extranodal sites and have a worse prognosis. Because of their usually indolent course, primary cutaneous T/NK-cell lymphomas should be distinguished from the other PTCL. Staging of PTCL is done according to the Ann Arbor staging system. The International Prognostic Index, established for aggressive B-cell lymphomas, has also proved relevant for PTCL. Standard therapy for PTCL has not been defined, yet. First line anthracycline-based chemotherapy brings about long-term remissions in 15 to 42% of patients. Apart from (ALK-positive) anaplastic large cell lymphoma it thus gives poorer results than those obtained in patients with aggressive B-cell lymphomas. Data for high-dosage therapy with autologous stem cell transplantation (autoSCT) for relapsing and refractory PTCL are similar to those reported for aggressive B-cell lymphomas. Thus this treatment seems to constitute a sensible salvage strategy. Allogeneic stem cell transplantation following reduced conditioning regimens has also given promising results in patients with relapse. However, the impact of high-dosage strategies and the implementation of newer agents, such as alemtuzumab, in first-line treatment are still uncertain. Hence patients with PTCL should be treated within clinical trials.

Literatur

• 1 Anonymous. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. The Non-Hodgkin’s Lymphoma Classification Project.  Blood. 1997;  89 3909-3918
• 2 Ansell S M, Habermann T M, Kurtin P J. et al . Predictive capacity of the International Prognostic Factor Index in patients with peripheral T-cell lymphoma.  J Clin Oncol. 1997;  15 2296-2301
• 3 Ascani S, Zinzani P L, Gherlinzoni F. et al . Peripheral T-cell lymphomas. Clinico-pathologic study of 168 cases diagnosed according to the R.E.A.L. Classification.  Ann Oncol. 1997;  8 583-592
• 4 Blystad A K, 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;  27 711-716
• 5 Chim C S, Ma S Y, Au W Y. et al . Primary nasal natural killer cell lymphoma: long-term treatment outcome and relationship with the International Prognostic Index.  Blood. 2004;  103 216-221
• 6 Coiffier B, Brousse N, Peuchmaur M. et al . Peripheral T-cell lymphomas have a worse prognosis than B-cell lymphomas: a prospective study of 361 immunophenotyped patients treated with the LNH-84 regimen. The GELA (Groupe d’Etude des Lymphomes Agressives).  Ann Oncol. 1990;  1 45-50
• 7 Corradini P, Dodero A, Zallio F. et al . Graft-versus-lymphoma effect in relapsed peripheral T-cell non-Hodgkin`s lymphomas after reduced-intensity conditioning followed by allogeneic transplantation for hematopoietic cells.  J Clin Oncol. 2004;  22 2172-2176
• 8 Dogan A, Attygalle A D, Kyriakou C. Angioimmunoblastic T-cell lymphoma.  Br J Haematol. 2003;  121 681-691
• 9 Elstrom R, Guan L, Baker G. et al . Utility of FDG-PET scanning in lymphoma by WHO classification.  Blood. 2003;  101 3875-3876
• 10 Enblad G, Hagberg H, Erlanson M. et al . A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas.  Blood. 2004;  103 2920-2924
• 11 Escalon M P, Liu N S, Yang Y. et al . Prognostic factors and treatment of patients with T-cell non-Hodgkin lymphoma: the M. D. Anderson Cancer Center experience.  Cancer. 2005;  103 2091-2098
• 12 Falini B, Pileri S, Zinzani P L. et al . ALK+ lymphoma: clinico-pathological findings and outcome.  Blood. 1999;  93 2697-2706
• 13 Gallamini A, Stelitano C, Calvi R. et al . Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study.  Blood. 2004;  103 2474-2479
• 14 Gascoyne R D, 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
• 15 Gisselbrecht C, Gaulard P, Lepage E. et al . Prognostic significance of T-cell phenotype in aggressive non-Hodgkin’s lymphomas. Groupe d’Etudes des Lymphomes de l’Adulte (GELA).  Blood. 1998;  92 76-82
• 16 Gisselbrecht C, Lepage E, Molina T. et al . Shortened first-line high-dose chemotherapy for patients with poor-prognosis aggressive lymphoma.  J Clin Oncol. 2002;  20 2472-2479
• 17 Greer J P, Kinney M C, Loughran T P. T cell and NK cell lymphoproliferative disorders.  Hematology (Am Soc Hematol Educ Program). 2001;  259-281
• 18 Haider K, Zamkoff K, Gentile T C. High dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) in peripheral T-cell lymphoma (PTCL). A single institution experience.   Blood. 1999;  94 (Supplement) #753
• 19 Haioun C, Lepage E, Gisselbrecht C. et al . Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin’s lymphoma: final analysis of the prospective LNH87 - 2 protocol - a groupe d’Etude des lymphomes de l’Adulte study.  J Clin Oncol. 2000;  18 3025-3030
• 20 Hast R, Jacobsson B, Petrescu A, Hjalmar V. Successful treatment with fludarabine in two cases of angioimmunoblastic lymphadenopathy with dysproteinemia.  Leuk Lymphoma. 1999;  34 597-601
• 21 Huang H Q, Peng Y L, Lin X B. et al . Clinical outcomes of 106 patients with peripheral T-cell lymphoma treated by standard CHOP regimen.  Ai Zheng. 2004;  23 (Suppl) 1443-1447
• 22 Jaffe E S, Harris N L, Stein H, Vardiman J W. Mature T-cell and NK-cell neoplasms. Washington D.C.: IARC Press In: Jaffe ES HN, Stein H et al., ed. World Health Organization Classification of Tumours. Pathology & Genetics. Tumours of Haematopoietic and Lymphoid Tissues 2001: 189-2355
• 23 Jagasia M, Morgan D, Goodmann S. et al . Histology impacts the outcome of peripheral T-cell lymphomas after high dose chemotherapy and stem cell transplant.   Leuk Lymphoma. 2004;  45 2261-2267
• 24 Jantunen E, Wiklund T, Juvonen E. et al . Autologous stem cell transplantation in adult patients with peripheral T-cell lymphoma: a nation-wide survey.  Bone Marrow Transplant. 2004;  33 405-410
• 25 Kim K, Kim W S, Jung C W. et al . Clinical features of peripheral T-cell lymphomas in 78 patients diagnosed according to the Revised European-American lymphoma (REAL) classification.  Eur J Cancer. 2002;  38 75-81
• 26 Kim K, Chie E K, Kim C W, Kim I H, Park C I. Treatment outcome of angiocentric T-cell and NK/T-cell lymphoma, nasal type: radiotherapy versus chemoradiotherapy.  Jpn J Clin Oncol. 2005;  35 1-5
• 27 Krych M, Dreyling M, Kneba M. et al . Prophylaxe und differentielle Therapie des Tumorlysesyndroms.  Dtsch Med Wochenschr. 2004;  129 1440-1445
• 28 Kutok J L, Aster J C. Molecular biology of anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma.  J Clin Oncol. 2002;  20 3691-3702
• 29 Lippman S M, Miller T P, Spier C M, Slymen D J, Grogan T M. The prognostic significance of the immunotype in diffuse large-cell lymphoma: a comparative study of the T-cell and B-cell phenotype.  Blood. 1988;  72 436-441
• 30 Lopez-Guillermo A, Cid J, Salar A. et al . Peripheral T-cell lymphomas: initial features, natural history, and prognostic factors in a series of 174 patients diagnosed according to the R.E.A.L. Classification.  Ann Oncol. 1998;  9 849-855
• 31 Melnyk A, Rodriguez A, Pugh W C, 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
• 32 Mounier N, Simon D, Haioun C, Gaulard P, Gisselbrecht C. Impact of high-dose chemotherapy on peripheral T-cell lymphomas.  J Clin Oncol. 2002;  20 1426-1427
• 33 Mounier N, Gisselbrecht C, Briére J. et al . All aggressive lymphoma subtypes do not share the same 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 1790-1797
• 34 Mounier N, Gisselbrecht C, Briére J. et al . Prognostic factors in patients with aggressive non-Hodgkin’s lymphoma treated by front-line autotransplantation after complete remission: a cohort study by the Group d`Etude des Lymphomes de l`Adulte (GELA).  J Clin Oncol. 2004;  22 2826-2834
• 35 Nakamura S, Suchi T, Koshikawa T. et al . Clinicopathologic study of 212 cases of peripheral T-cell lymphoma among the Japanese.  Cancer. 1993;  72 1762-1772
• 36 Pautier P, Devidas A, Delmer A. et al . Angioimmunoblastic-like T-cell non Hodgkin’s lymphoma: outcome after chemotherapy in 33 patients and review of the literature.  Leuk Lymphoma. 1999;  32 545-552
• 37 Reimer P, Schertlin T, Rüdiger T. et al . Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation (APBSCT) as first-line therapy in peripheral T cell lymphomas (PTCL). First results of a prospective multicenter study.  Hematol J. 2004;  5 304-311
• 38 Reimer P, Rüdiger T, Schertlin T. et al . Autologous stem cell transplantation as first-line therapy in peripheral T-cell lymphomas. A prospective multicenter study.  Blood. 2005;  105 (Supplement) #2074
• 39 Rodriguez J, Munsell M, Yazji S. et al . Impact of high-dose chemotherapy on peripheral T-cell lymphomas.  J Clin Oncol. 2001;  19 3766-3770
• 40 Rodriguez J, Caballero M D, Gutierrez A. et al . High-dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: the GEL-TAMO experience.  Ann Oncol. 2003;  14 1768-1775
• 41 Ross C W, Schnitzer B, Sheldon S, Braun D K, Hanson C A. Gamma/delta T-cell posttransplantation lymphoproliferative disorder primarily in the spleen.  Am J Clin Pathol. 1994;  102 310-315
• 42 Rüdiger T, Weisenburger D D, Anderson J R. 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
• 43 Savage K J, Chhanabhai M, Gascoyne R D, Connors J M. Characterization of peripheral T-cell lymphomas in a single North American institution by the WHO classification.  Ann Oncol. 2004;  15 1467-1475
• 44 Schetelig J, Fetscher S, Reichle A. et al . Long-term disease-free survival in patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation.  Haematologica. 2003;  88 1272-1278
• 45 Siegert W, Nerl C, Meuthen I. et al . Recombinant human interferon-alpha in the treatment of angioimmunoblastic lymphadenopathy: results in 12 patients.  Leukemia. 1991;  5 892-895
• 46 Song K W, 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;  120 978-985
• 47 Sonnen R, Schmidt S W, Müller-Hermelink H K, Schmitz N. The International Prognostic-Index determines the outcome of patients with nodal mature T-cell lymphomas.  Brit J Haematol. 2005;  129 366-372
• 48 Swerdlow S H, Habeshaw J A, Rohatiner A Z, Lister T A, Stansfeld A G. Caribbean T-cell lymphoma/leukemia.  Cancer. 1984;  54 687-696
• 49 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
• 50 Tsatalas C, Margaritis D, Kaloutsi V, Spanudakis E, Kaloutsi V, Bourikas G. Successful treatment of angioimmunoblastic lymphadenopathy with dysproteinemia-type T-cell lymphoma with fludarabine.  Acta Haematol. 2001;  105 106-108
• 51 Vose J M, Peterson C, Bierman P J. et al . Comparison of high-dose therapy and autologous bone marrow transplantation for T-cell and B-cell non-Hodgkin’s lymphomas.  Blood. 1990;  76 424-431
• 52 Weidmann E, Hess G, Krause S W. et al . Combination Chemoimmunotherapy using alemtuzumab, fludarabine, cyclophosphamide, and doxorubicine (Campath-FCD) is an effective first-line regimen in peripheral T-cell lymphomas.  Blood. 2004;  104 (Supplement) #2640
• 53 Willemze R, Jaffe E S, Burg G. et al . WHO-EORTC classification for cutaneous lymphomas.  Blood. 2005;  105 3768-3785
• 54 Wulf G G, Hasenkamp J, Jung W, Chapuy B, Trümper L, Glass B. Reduced intensity conditioning and allogeneic stem cell transplantation after salvage therapy integrating alemtuzumab for patients with relapsed peripheral T-cell non-Hodgkin’s lymphoma.  Bone Marrow Transplant. 2005;  36 271-273
• 55 You J Y, Chi K H, Yang M H. et al . Radiation therapy versus chemotherapy as initial treatment for localized nasal natural killer (NK)/T-cell lymphoma: a single institute survey in Taiwan.  Ann Oncol. 2004;  15 618-625
• 56 Zinzani P L, Alinari L, Tani M, Fina M, Pileri S, Baccarani M. Preliminary observations of a phase II study of reduced-dose alemtuzumab treatment in patients with pretreated T-cell lymphoma.  Haematologica. 2005;  90 702-703