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Periphere T-Zell Lymphome

Periphere T-Zell Lymphome. Wien, 13.10.2008 Gerald Wulf. 1%. 14%. 2%. 23%. 2%. 5%. 11%. 18%. 6%. 7%. 12%. PTCL-U. AILT. NK/T. ALK+ ALCL. ALK - ALCL. ATLL. ETTL. Cut ALCL. HSTCL. SCPTCL. Other/Unclass. Biologie systemischer T-NHL: Heterogenität und Epidemiologie.

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Periphere T-Zell Lymphome

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  1. Periphere T-Zell Lymphome Wien, 13.10.2008 Gerald Wulf

  2. 1% 14% 2% 23% 2% 5% 11% 18% 6% 7% 12% PTCL-U AILT NK/T ALK+ ALCL ALK - ALCL ATLL ETTL Cut ALCL HSTCL SCPTCL Other/Unclass Biologie systemischer T-NHL: Heterogenität und Epidemiologie Armitage et al. JCO 2008

  3. Expressionsprofil von PTCL: Assoziation mit maturen T-Zelltypen AILT Geissinger et al. J Path 2006

  4. Genexpressionsprofil von PTCL Piccalagua et al. JCI 2007 Martinez-Delgado Hemtol Oncol 2006

  5. Genexpressionprofil von PTCL: Identifikation von Zielstrukturen Piccalagua et al. JCI 2007

  6. Prognose des anaplastisch großzelligen Lymphoms Gisselbrecht et al. Blood 1998

  7. Anaplastisch großzelliges Lymphom: Bedeutung von ALK-Positivität FFS OS Savage et al. Blood 2008

  8. Prognose des kutanen anaplastisch großzelligen T-Zell Lymphoms Bekkenk et al. Blood 2002 Savage et al. Blood 2008

  9. kutanes ALCL versus lymphomatoide Papulose Bekkenk et al. Blood 2002 Savage et al. Blood Reviews2007

  10. Prognose systemischer T-NHL: klinische Faktoren IPI Age, PS, LDH, ES, stage PIT Age, PS, LDH, BM Gallamini et al. Blood. 2004

  11. PTCL: approaches to improved treatment efficacy 6 x CHOP14 addition of humoral immunotherapy: consolidation/maintenance alemtuzumab 6-8 x CHO/E/P14 addition of humoral immunotherapy: alemtuzumab addition of cellular immunotherapy: allogeneic SC transplantation DHAP FBC12 dose escalation: HD therapy / autologous tx novel agents: antibodies small compounds Mega CHOEP Dexa BEAM TBI Cy

  12. Standard chemotherapy in PTCL: anthracycline-based ? PTCL NOS AILT Armitage et al. JCO 2008

  13. Periphere T-Zell Lymphome (PTCL): CX + Alemtuzumab

  14. 8x CHOP-21 + Alemtuzumab OS PFS Gallamini et al. Blood 2007

  15. DSHNHL Trial 2003-1 DSHNHL 2003-1: phase II alemtuzumab consolidation in PTCL peripheral T-NHL 18 – 60 years: 6 x CHOEP-14 + Peg-F 60 – 70 years: 6 x CHOP-14 + Peg-F CR / PR no infection Alemtuzumab- consolidation 133 mg in / 4 wks 36 Gy Bulk/E RTx

  16. DSHNHL 2003-1: treatment outcome (ITT) DSHNHL Trial 2003-1 DSHNHL 30.07.07

  17. BII RE F RE F D S C C C C C C C C C C C C C C C C C C H H H H H H H H H H H H O O O O O O O O O O O O P P P P P P P P P P P P CHOP + Alemtuzumab phase III: DSHNHL 2006-1B / ACT-2 documentation progress : death : forms : BI PT T-cell lymphoma 61-80 years eligible for chemotherapy all stages, except stage I IPI 0 w/o bulk R A A A A A A days 57 1 15 29 43 71

  18. EBV-associated secondary NHL post CHOP w alemtuzumab • caseprimarysecondaryinterval post outcome • histologyhistologyalemtuzumab • m, 41y PTCL NOS EBV + (endoth.) 10 monthsrefractoryto CT, CD2+,3+,5+ death • recurr. EBV – • f, 32y PLTCL EBV+, CD20+ • - cerebralmass 9 months RX • cerv. DLBCL 12 months RX, rituximab • cut. ind B-NHL 21 months • PLTCL 21 monthsalive • m, 59y AILT EBV+, CD20+ 23 monthsearlydeath • B-lymphoprol. • AILT n = 20, HOVON 69 trial, 8x CHOP-21 w 8x 90 mg alemtuzumab Kluin-Nelemans et al. Blood 2008: 02-138800

  19. EBV associated secondary NHL post CHOP w alemtuzumab HOVON 69 GITIL-trial ACT-2 DSHNHL 2003-1 CX 8x CHOP-21 8x CHOP-28 6x CHOP-14 6x CHO(E)P-14 alemtuzumab 720 240 (n=20) 360 133 cumulative 120 (n=4) time of cx 24 32 12 12 / 4 [weeks] observation 24+ 11 (5-42) 24+ [months] n 20 24 41 / 29 EBV-associated 3 0 0 sec. NHL

  20. Hochdosistherapie und autologe SZT bei PTCL

  21. HD Therapie bei PTCL phase II: Probleme sekundär refraktär primär refraktär stabile Remission 100% 65-75% 35…% 3yEFS Dx HDT

  22. HD Therapie bei PTCL phase II: MegaCHOEP II / III n=36 1.5 year rate 95%CI total 31 % (16%;46%) 3 year rate 24 % (9%;38%) DSHNHL 08.03.07

  23. HD Therapie bei PTCL phase II: autologe versus allogene SZT

  24. Allogene SZT bei rezidiviertem aggressiven NHL: konv. Konditionierung n=111 Sung-Won et al. Blood 2006

  25. PTCL im Rezidiv: allogene SCT nach Dosis-reduzierter Konditionierung n=17 Corradini et al. JCO 2004

  26. allogeneic SCT in relapsed PTCL: Göttingen experience indication: relapsed peripheral T-cell lymphoma, chemosensitive conditioning: fludarabin/busulfan (12 mg/kg bw)/cyclophosphamide n: 20 OS: 11/20, median observation 4 months (range 1-47 months) early death (TRM100): 3 / 20 late death (relapse): 3 / 20 late death (non-relapse): 3 / 20

  27. novel substances agent target indication ORR author [%] Gemcitabine nucleosid PTCL 60 Sallah 2001 AraG 506U78 analoga PTCL 14 Czucsman 2004 a Denileukin Il-2R PTCL 50 Dang 2004 a Difitox Depsipeptide HDAc PTCL 26 Piekarz 2005a SAHA SGN30 CD30 ALCL 33 Forero-Torres 2004a Zanolimumab (CD4), Daclizumab (Il-2R), Bevacizumab Sorafenib (TKI), Thalidomide (IMID), Bortezomib (proteasome)

  28. Zusammenfassung PTCL heterogene Gruppe von histologisch, immunologisch und nach Expressionsprofil klassifizierbaren Typen ALK pos. ALCL: unter Anthracyclin-haltige Chemotherapie gute Prognose, ansonsten Ergebnisse der konventionellen Therapie unbefriedigend Primärtherapie in Studien Evaluation von Alemtuzumab (DSHNHL 20061B, ACT-2) HD-Therapie mit autologer bzw. allogener Stammzelltransplantation (DSHNHL 2006-1A) Sekundärtherapie allogene SZT (DSHNHL 2003-R4); innovative, zielgerichtete Therapien (Studien)

  29. Vielen Dank DSHNHL Kompetenznetz maligne Lymphome Ihnen für Ihre Aufmerksamkeit

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