鼻型nkt细胞淋巴瘤的诊治课件

Pathogenesis and Treatment of Extranodal Natural Killer/T-Cell Lymphoma Semin Hematol. 2014, 51:4251. Li Ye PATHOGENESIS OF NK/T-CELL LYMPHOMA 1. Chromosomal abnormalities 2. Genetic aberrations 3. The Epstein-Barr virus(EBV) Chromosomal abnormalities Deletion of the long arm of chromosome 6 Br J Haematol. 1997;98:922-6. Chromosomal abnormalities Br J Haematol.1997;97:621-5. Genetic aberrations FOXO3, PRDM1, TP53,CDKN2A,FAS,SHP1,TP73, and KIT J Clin Exp Hematopathol. 2005;45:51-70. PATHOLOGY OF NK/T-CELL NEOPLASMS 1. diffuse proliferation of lymphoma cells with anangiocentric or angiodestructive growth pattern 2. Infiltration of inflammatory cells and sometimes accompany necrotic changes 3. NK cell markers (CD2, cytoplasmic CD3 (cyCD3), CD7, and CD56 ) 4. Cytotoxic molecules such as TIA-1, granzyme B, and perforin DISEASE FEATURES OF NK/T-CELL LYMPHOMA 1. origin for ENKL: the nose and paranasal area skin, gastrointestinal tract, et al. 2. Stage I/II : Approximately half of the patients 3. Nasal and extranasal ENKLs in the same category of disease according to the current WHO classification Ann Oncol. 2010;21:1032-40. Nasal ENKL more frequently presents as a localized disease, whereas extranasal ENKL is more frequently detected at an advanced stage. Blood.2009;113:3931-3937 A. Limited-stage (I/II) disease B. advanced-stage (III/IV) disease Blood.2009;113:3931-3937 TREATMENT OF EXTRANODAL NK/T-CELL LYMPHOMA 1. Limited Stages 2. Advanced Stages, Relapsed or Refractory State 3. Hematopoietic Stem Cell Transplantation (autologous and allogeneic HSCTs) Cancer. 1995;76:2351-6. the expression of P-glycoprotein (P-gp)/MDRlthe product of the multidrug resistance (MDR) 1 gene -actin MDR3 MDRl Drug : vincristine and doxorubicin J Clin Oncol. 2000;18:54-63. J Clin Oncol. 2000;18:54-63. (median 56 months)Treatment failure 57/92 (62%) (median 8 months) Relapsed rate 14/61 (23%) Ann Oncol. 2001;12:349-52. New treatment strategies, such as high-dose chemotherapy with stem-cell transplantation, early administration of radiation treatment, or concomitant chemo-radiotherapy, need to be investigated to improve the treatment outcomes, particularly in patients with patients with B symptoms. 1. The planned sequential chemo-radiotherapy 6/17 (35%) 2. Estimated overall three-year survival 59% 74 patients receiving CT 64 CHOP (cyclophosphaminde, doxorubicin, vincristine, prednisone) or CHOP-bleo (CHOP+bleomycin) 9 COBVP-16 (cisplatin, vincristine, bleomycin, prednisone) 1 COPP (cyclophosphaminde, vincristine, procarbazine, prednisone) 37 patients received RT after CT. Before RT, 20 one to two cycles of CT, 16 three to four cycles, 1 five cycles of CT J Clin Oncol. 2006;24:181-9. 1. Limited Stages J Clin Oncol. 2006;24:181-9. Response after initial therapy RT vs. CT 83% vs. 20% (P =0.0001) Response after therapy RT and RT+CT vs. CT+RT 92% vs. 81% (P=0.387) 1. Limited Stages RT as primary therapy resulted in good outcome in early-stage disease J Clin Oncol. 2009;27:5594-600. 1. Limited Stages J Clin Oncol. 2009;27:5594-600. CR 20/26 (77%) OS at 5 years 50% ORR 21/26 (81%) PFS at 5 years 50% (A)Overall survival and (B) progression-free survival of patients treated with radiotherapy and two thirds dose of dexamethasone, etoposide, ifosfamide, and carboplatin. J Clin Oncol. 2009;27:5594-600. J Clin Oncol. 2009;27:5594-600. The most common grade 3 nonhematologic toxicity was mucositis related to radiation (30%). No treatment-related deaths were observed. J Clin Oncol. 2009;27:6027-32. 1. Limited Stages J Clin Oncol. 2009;27:6027-32. J Clin Oncol. 2009;27:6027-32. CCRT CR 22/30 (73.3%) ORR 30/30 (100%) CCRT+VIPD CR 22/26 (84.6%) OS at 3 years 85.19% PFS at 3 years 85.19% J Clin Oncol. 2009;27:6027-32. Only one patient experienced grade 3 toxicity during CCRT (nausea), whereas 12 of 29 patients experienced grade 4 neutropenia. 2. Advanced Stages, Relapsed or Refractory State J Clin Oncol. 2011;29:4410-6. ORR 79% 1-year survival rate 55% A 3-year OS of 50% Hematol Oncol. 2013;31 suppl.S1:175 abstract 235. SMILE VS. historical controls L-asparaginase (Kidrolase, Eusa Pharma) 6000 units/m2 of body surface area on days 2, 4, 6, and 8, intramuscularly (unless contraindicated), methotrexate 3 g/m2 on day 1, oral dexamethasone 40 mg from day 1 to 4. ROLE OF EBV-DNA 1. To predict the prognosis 2. To predict the degree of adverse reactions Blood. 2011;118:6018-22.