1. Non-Hodgkin’s Lymphoma
M G R R e v i e w
Non-Hodgkin’s Lymphoma
Optimal therapeutic plan for Diffuse Large B-cell Type Lymphoma

2. What Is Non-Hodgkin’s lymphoma?
Solid tumor arising from lymphoid tissue except Hodgkin’s lymphoma
Lymphoid tissue Primary lymphatic tissue - bone marrow, thymus 2 Secondary lymphatic tissue : lymph node, spleen, mucosa-associated lymphoid tissue adenoid, tonsil
Various heterogeneous subtypes - according to each stages of differentiation of lymphocytes - representing malignant clonal expansion of lymphocytes at different stages of development

3. Antigen-dependent B cell maturation
DLBL
Myeloma
Marginal zone B-cell lymphoma

4. WHO/REAL Classification

5. Types Based on Growing Rate
From Treatment guidelines for patients : 2005 by the National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS)

6. Making Decision about Treatment
Accurate immunohistochemical pathologic confirmation
Identification of subtype
Stage
Prognostic factors
Assessment of treatment response

7. Cotswolds Modification of Ann Arbor Staging System
Stage
Area of Involvement I
Single lymph node group II
Multiple lymph node groups on same side of diaphragm
III
Multiple lymph node groups on both sides of diaphragm IV
Multiple extranodal sites or lymph nodes and extranodal disease X
Bulk > 10 cm E
Extranodal extension or single isolated site of extranodal disease
A / B
B symptoms: weight loss > 10%, fever, drenching night sweats

8. Prognostic Factors

9. Response Criteria for Lymphoma
Category
Physical
Examination
Lymph Nodes
Lymph Node
Masses
Bone Marrow CR
Normal
CRu
Indeterminate
> 75% decrease
Normal or Indeterminate PR
Positive
≥ 50% decrease
Irrelevant
Decrease in liver / spleen
Relapse / Progression
Enlarging liver / spleen, New site
New or increased
Reappearance

10. Treatment Options
Combination chemotherapy - CHOP cyclophosphamide + doxorubicin + vincristine + PDL : not inferior to other newer combination regimen with lower toxicity [ ProMACE-CytaBOM, BACOD, MACOP-B]
Rituximab - human-mouse chimeric monoclonal anti-CD20 antibody - destruction CD-20 positive cells
Radiotherapy - recommended for stage I~II with bulky disease (> 10cm) [ Category 1 NCCN Clinical Practice Guidelines in Oncology™ Non-Hodgkin’s Lymphoma V ] - benefit for time to progression but NO overall survival rate
High dose chemotherapy with autologous stem cell support

11. Treatment Options
First choice of combination chemotherapy for DLBL type NHL - RCHOP Rituximab + CHOP
Salvage chemotherapy - ESHAP : etoposie + MPD + cytarabine + cisplatin - ICE : ifosfamide + carboplatin + etoposide
High dose chemotherapy with autologous PBSC support with/without rituximab purging in vivo - indication for patient with relapsed after 1st CR with chemo-sensitive to second-line salvage regimen - controversial for survival benefit

12. Optimal Therapy for NHL, DLBL type Failed with First-line chemotherapy

13. NCCN® Practice Guidelines – v.2.2006

14. NCCN® Practice Guidelines – v.2.2006

15. NCCN® Practice Guidelines – v.2.2006

16. High-dose Therapy with PBSCT
Efficacy First-line chemotherapy : non-CR or eventually relapsed in 60~70% of patients Second-line (Salvage) chemotherapy : < 10% of long term survival rate Secondary(salvage) chemotherapy followed by high dose therapy with PBSC rescue : a little curative potential < 50% of relapsed or refractory disease especially in chemosensitive disease
Optimal time to initiation : no definite guideline

17. J Clin Oncol 20:2002,
Shortened standard therapy + early high-dose therapy < Conventional therapy

18. Abbreviated chemotherapy followed by HDT+ASCT
J Clin Oncol 21: 2003,
Abbreviated chemotherapy
followed by HDT+ASCT
: NOT superior to conventional Tx

19.  Improved outcome in patients with age-adjusted IPI 2 groups
Cancer 2003;98:983–92
Background - abbreviated standar management with early ASCT  not effective - need of adequate chemotherapy-based debulking
Study design - sequential high-dose chemotherapy followed by autologous BMT as initial treatment
 Improved outcome in patients with age-adjusted IPI 2 groups

20. HDT with ASCT as first-line treatment in disseminated aggressive disease : comparison with CHOP  superior to conventional treatment with CHOP

21. Conflicting result - survival benefit vs. no improvement
Annals of Oncology 9 (Suppl. 1): S5~S8, 1998
Definition of “PR” - presence of residual mass after induction chemotherapy - persistence of BM involvement
Conflicting result - survival benefit vs. no improvement

22. § Summary : Role of high-dose chemotherapy with ASCT
No advantage with high-dose chemotherapy with ASCT as first-line treatment at initial diagnosis or early initiation
Better outcome with ASCT after an adequate debulking disease by induction treatment
Effective to only poor-risk patients intermediate to high risk group [age-adjusted IPI score 2] - no survival benefit for low-risk patients

23. S 9704 : A Randomized Phase III Trial
For intermediate to high risk young patients with response by full-course CHOP/RCHOP #5 - arm A : additional 3 cycles of CHOP/RCHOP (total CHOP/RCHOP #8) - arm B : additional 1 cycles of CHOP/RCHOP and ASCT (CHOP/RCHOP #6  immediate high dose therapy + ASCT)
Conducted by
Southwest Oncology Group [SWOG]
Eastern Cooperative Oncology Group [ECOG]
Cancer and Acute Leukemia Group B [CALGB]
National Cancer Institute of Canada