1.2.

1 NHL IPI------------------------------------------------------------------- 0 1------------------------------------------------------------------- 60 60 01 234Ann Arbor LDH 2 2-------------------------------------------------------------------

: B

: B-Cell Small lymphocytic/CLL LymphoplamacyticFollicular, any typeMarginal Zone MALT nodal(monocytoid) splenic T-Cell Mycoses fungoides Anaplastic large cell,cutaneous T-cell granular lymphocytic leukemia

Indolent Lymphoma: Clinical findings SLL FL LPL MZLAge (median,y) 65 59 63 60M:F 2:1 1:1.7 1:1 1:1Frequency(%) 5 33 1-2 5Stage advanced(%) 90 90 100 25Marrow positive(%) 95 40 95 20IgM paraprotein(%) 1-2 0 80-90 5

Indolent Lymphoma: Immunophenotyping SLL FL LPL MZL MCLSurf Ig + +++ ++IgM +++ +++Cyclin D1 - - - - +++CD5 +++ - - - +++ CD10 - +++ - - -CD19 ++ +++ +++ +++ +++CD20 + +++ ++ +++ +++CD22 + +++ +++ CD23 +++ - ++ - +

:

watch and wait

535%~40%

4-6mg/d2-32-3CXT150-200 mg/d5-72-3Pred

Fludarabine Alone CR CR+PRTondini, 2000 54 1 48 68Falkson,1996 21 1-2 33 62Moskowitz,1994 32 2 6 50Hiddermann,1993 38 3(1-11) 13 31Pigaditou,1993 45 3(1-7) 9 44Redman,1992 38 3(1-4) - 55Leiby,1987 25 2.6 4 32 Fludara: 25mg/m2/d, VD 5d; 1/4W

CHOP/CHOPE/CHOP-BCTX800-1200mgd1EPI80-120mg d1VCR2mg d1Pred1mg/kg/d d1-5

VP16/VM26100mg/dd3-5 Blem10-15mg d1

ProMACE-CytoBOM etcCTX: 650mg/m2 d1Doxorubicin: 25mg/m2 d1VP16: 120mg/m2 d1Pred: 60mg/m2 d1-14Ara-C: 300mg/m2 d8Bleomycin: 5U/m2 d8VCR: 1.4mg/m2 d8MTX: 120 mg/m2 d8Calcium folinate: 25mg/m2 q6hX6

ProMACE-CytoBOM WHO

51: 25mg/m2/d,d1310 mg/m2,d120 mg/dd151/4W8SMZco.2447%CR2447%PRCR21PR9LDH2FND: 12%82

Peter McLaughlin, et al. JClin. Oncol 141262-1268. 1996

FND

Fludarabine Combined CR CR+PR

Hochster, 1994 27 Flu 20mg/m2/d 5d 1/4w 89 100 CTX 600-1000mg/m2 d1, 1/3-4WLazzariono,1999 25 Flu 25mg/m2/d 3d 32 72 CTX 350mg/m2/d 3d Dex 20mg/d 3d, 1/4WBocchia,1999 30 Flu 15mg/m2/d 4d 50 85 Epi 60mg/m2 d1 CTX 250mg/m2/d 4d 1/3-4W

: WHOAgae 60Normal organ functionGood performance status

: WHENFirst remissionFirst or subsequent relapseUp-front transplantation

ASCTRef n SC source purging TBI DFS(years)% OS (years)%

Freedman 153 BM + + 42(8) 66(8)Apostolidis 99 BM + + not done 45(5)Schouten 92 BM +/- +/- 52(5) not doneBrice 83 BM/PB - +/- 42(5) 58(5)Bierman 100 BM/PB - +/- 44(4) 65(4)Rohatiner 121 BM + + 55(4) 70(4)Weaver 59 PB - - 32(3.5) 57(3.5)Bastion 60 PB - +/- 53(2) 66(2)Schouten 89 BM/PB +/- + not done 80(2)

: HOWHigh dose regimens: TBI+CTX+/-VP16 TBI:12GyCBVBEAMICE

: HOWHematopoietic stem-cell sourcesBMT PBSCT FFSOSPBSCTBMT

: HOWImpact of ex vivo purging or CD34+ selection:FLBM 80%PCRFLBCL2100%CROSPCRBCL2

: HOWImprovement of ex vivo purging methods:CTXAra-CVP16++2-3 log+4 log

GVL GVHD

IBMTR11350 HLA TBI 82%CSA 74%

3DFS50% 16% 40%

(mini)WHO

Sibling donorAge65 yearsRelapsed disease2nd or 3rd relapse1st relapse with response duration 1 years1st relapse in failure after 3-4 salvage chemotherapy cyclesRelapse after ASCTPrimary refractory disease

(mini)MD Anderson Cancer Center10 50

CD20()

B2. 1. ADCC3.

() ()++

()375mg/m2500mg/m2 468q6m4

166CD20+78%/375mg/m21/w181522

Journal of Clinical Oncology. Vol 16 No 8,1998; P2825

87% 49% 32% 16% 14% 6% 6% 10% 18% 11% 8% 13% 10%

() COPP COPP+IFN P 27 28 2074% 2486% CR 1659% 2071% PR 4 15% 518% 7 74% 72% 0.2 CR7EFS 70% 100% 0.01

IFN-285MU3/W4W 91% Neri N et al, J. Hematother Stem Cell Res. 2001(10):669-74

() CVP CVP+IFN P 120 122 5 70% 70%

TTF 87 132 0.05

IFN-3MU3/W1 91% TTF: time to treatment failure.Hagenbeek et al, J. Clin. Oncol. 1998(16):41

NHLCycle 1 Cycle 2 Observation CR Rituximab n=14 PR n=56 Randomization MR n=13 Rituximab + IFN-2a NR n=13 Off study

NHLadditional 4 cycles of R or R + IFN- Complete 23% 48% Partial 59% 46% Minor 12% 6% Stable disease 3% 0 Progression 3% 0 Type of response Rituximab Rituximab+ Interferon 2a

Active Immunization for CancerLoading DCEx vivo Directly in vivoGene Gene, Protein/peptide Cell fragments RNA Whole tumor cellKnown limitedrepertoire of TAALarge repertoire of unknown antigensDNA vaccinationNeeds adjuvant:plasmid sequencesmuscle injury

BCL-2