バーキットリンパ腫と類縁疾患 - harasanshin.or.jp

1 2015 12 14 Version (MYC ) MYC B Ex) Small non-cleaved cell lymphoma, non-BurkittHigh-grade B-cell lymphoma, Burkitt-likeBurkitt-like lymphoma, etc 2008 WHO 4 BurkittLymphoma (BL) B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkittlymphoma (BCLU) Diffuse large B-cell lymphoma (DLBCL)BCLU DLBCL Double hit lymphoma(DHL) 2000 WHO 3 BurkittLymphoma/leukemia BurkittLymphoma + Burkittleukemia variant MYC BL DLBCL BL DLBCL BL BCLU MYC BL BL BCLU MYC DLBCL IG-MYC t(11;14), t(14.

2 19) , BCL6 BCL2 t(14;18), BCL6 IntermediatelymphomasDouble-hitDouble-hi t: +MYCBCL6 , CD10 , BCL2+MIB1 > 90%, MYC + Double-hit BCL6-, CD10-, BCL2+MIB1 < 95%MYC c-myc RNA II iPS c-myc Zeidler R et al. Genes Chrom. Cancer 1994; 9: 282-287 cMYCt(8;14)BCL1/cyclinD1 t(11;14)BCL6 t(3;14)BCL2 t(14;18)API2-MALT1 t(11.

3 18)BLBCLUDLBCL small/mediumSmall/medium/largelargeStarr y sky +++( )-CD10 / / Bcl-2 / Ki-67(MIB-1) > 90% MYC ( 95%, IG)35 50%(IG/non-IG)<10%BCL2/BCL6 Double hit MYC- BL BCLU DLBCL (BL) c-myc (8q24) B 1-2% 60 2000 WHO Burkittlymphoma/leukemia2008 WHO BurkittlymphomaBurkittleukemia/ALL(L3) Burkittleukemia variant (BL) ALL(L3) CHOP-like regimen (Starry skyappearance) Starry sky appearance ( )

4 B +, CD10+, BCL6+, IgM+, BCL2-, MUM1/IRF- Ki67/MIB1 95% (IG) c-MYC IgH (14q32) 80%, (2p12) <5%, (22q11) 10% BL BCLU Endemic BLSporadic BLImmunodeficiency-associatedBL , , HIV , , , , , , , , , EBV 100% 5 10%30 40%Co-factorEBV, HIV , T VH SHM+++++ Memory B ?

5 GCB?Memory B ? I , 1 ( , )II ( , )IIR III ( , , ) , ( )IIIA IIIB IV , <25%Murphy SB. Semin Oncol. 1980; 7: 332-9 Ann Arbor (40 ) LDH +7q del(13) BFM FAB UKLG R1 : CSI/II, Group A : CSI CSIILow risk : LDH PS 2 CS III 10cm R2 : CSI/II, CSIII with LDH 500R3 : CSIII with LDH 500 1000 CSIV with LDH 1000 CNS Group B : Group A C R4 : CSIII/IVwith LDH 1000 CNS Group C : ( 25%) CNS High risk : Divine M et al.

6 Ann Oncol 2005; 16: 1928-35 LMB95 (FAB )18 HIV N = 7233 37 (51%) et al. Ann Oncol 2002; 13: 1264-1274LY06 (UKLG )Low RiskCODOX-M 3 High RiskCODOX-M/IVAC 4 N = 52 Median age 38CR risk2yrEFS 60%2yrOS 70% CHOP-like regimen 10 20% 40 BL Rituximab 60 HIV CR Wasterlid T et al.

7 Ann Oncol 2013 Jul; 24(7): 1879-86 CHOP-like regimen nordic lymphoma group, BL/BLLN = 258(R+ 163) 56 BFM 36%HyperCVAD 15%CODOX-M/IVAC 16%CHOP/CHOEP 25%Other9%2yr OS<40 86%40-65 65%>60 23% 2013(BL)NCCN 2015 (BL) CALGB10002 CODOX-M ( ), CODOX-M/IVAC ( ) RituximabDA-EPOCH + RituximabHyperCVAD/MA + Rituximab R-ICE, DA-EPOCH-R, R-IVAC, R-GDP, HD-AraC+RCALGB10002 BL+ Burkitt-like lymphomaCALGB9251 Rituximab G-CSF (CPA, PSL, IFO, Dexa, MTX, VCR, VP16, DXR, G-CSF, Rit)Rizzieri DA et al.

8 Br J Haematol. 2014 April; 165(1): 102-111N = 105aged 19-79, >60yr 27% 7 (1), (4), (2)CR 83%, 4yr EFS 74%, OS 78%(modified) CODOX-M/IVAC Rituximab CODOX-M/IVACS mall non-cleaved-cell lymphoma 41 ( 21 , 20 )CR 39 (95%), 2yrEFS 85% / 100% modified CODOX-M/IVAC (LY10, Dana-farbor, ) , BL + BCLU(Burkitt-like) MTX 3g/sqm 2yrEFS 85%, OS 88%, 2yrEFS 49%, OS 52%65 3/10 4 BL 4 BCLU 11 , 39 , 5yr EFS/OS 87%Magrath I et al. JCO. 1996 March; 14(3): 925-34 Mead GM et al.

9 Blood. 2008; 112:2248-60 Lacasce A et al. Leuk Lymphoma. 2004 April; 45(4): 761-7 Maruyama D et al. Int J Hematol. 2010 Dec; 92(5): 732-43 HyperCVAD/MA + Rituximab MDACC, BL/Burkitt-like + B-ALL N = 31 (BL/BLL 17, B-ALL 14), 46 (17-77)CR 28 (86%), 3yrOS 89%, DFS88%Rituximab 65 (n=9) Thomas DA et al. Cancer. 2006 ; 106: 1569-80 OSDFS ( ), BL+ BCLU N = 43 (BL/BLL 17, B-ALL 14), 51 (20-83), >60 12 CR 24 ( ), 2yrOS , 6 ADM, VCR, MTX, AraC (RDI) 60-65%80% dose 25% HyperCVAD/MA + RituximabJunsik Hong et al.

10 Cancer Res Treat. 2015 ; 47: 173-181DA-EPOCH-R/SC-EPOCH-RR Burkittlymphoma (sporadic 17, immunodeficiency 13)N = 30, 33 (15-88), 40 40%LMB Low risk 17%, High risk 10% Sporadic DA-EPOCH-R 86 Freedom from progression 95%OS 100%Immunodeficiency-associated SC-EPOCH-RR 73 Freedom from progression 100%OS 90%Dunleavy K et al. N Engl J Med. 2013 ; 369: 1915-25BL EBMT BL + Burkitt-like lymphoma 117 17 3yr OS 53% , disease status1stCR 3yr OS 72%Chemosensitiverelapse 3yr OS 37%Chemoresistant3yrOS 7% BL Chemosensitiverelapse ASCT Sweetenham JW et al.