-악성림프종악성림프종

전남의대 혈액종양내과

화순전남대병원 혈액종양클리닉 이제중

혈액암의 위험도에 따른 치료 전략

- 악성 림프종

증례 1

•16세 여자

•주소: 7일전부터 발열감과 두통

•검사실 소견

WBC 1,000/mm3 (Neutrophil 22.3%, Lymphocyte: 63.3%) Hb 11.1 g/dL Platelet 165,000/mm3

LFT: W.N.L

LDH 750 IU/L (N: 218-472) CRP 1.6 mg/dL (N: 0-0.3) ANA (-)

증례 1

증례 1

판독소견: Multiple enlarged lymph nodes with homogeneously enhancement in right upper paratrachea, anterior mediastinum, right hilar, and right interlobar nodal area.

: Considered as lymphomatous involvement, more likely.

R/O Reactive hyperplastic lymph node, less likely.

증례 1 (the next plan?): Vote!!!

1. 추적 관찰 2. 조직 검사 3. PET/CT

4. 약제 투여: 소염진통제, 스테로이드 5. 기타

증례 1 (the next plan?): Vote!!!

1. 추적 관찰

4. 약제 투여: 소염진통제, 스테로이드 5. 기타

증례 1: PET/CT

Hypermetabolic LNs in right cervical II, III, right mediastinal & hilar area

 Consistent with lymphomatous invasion

증례 1: 병리소견

CD20 CD45RO

증례 1: 추적 관찰

•검사실 소견

LDH 335 IU/L (N: 218-472) CRP < 0.2 mg/dL (N: 0-0.3)

Kikuchi‘s lymphadentitis

• 21세 여자

• 경부 림프절종대

• 2-3주전 URI 병력

• 발열, 전신쇠약

Kikuchi‘s lymphadenitis

(Histiocytic necrotizing lymphadenitis)

Lymphadenopathy

 Routine P/E: 56% lymphadenopathy (+)

 LAP in primary care office:

> 2/3: nonspecific causes or upper respiratory illness (viral or bacterial)

< 1%: malignancy

 Patients referred for evaluation of LAP 84%: benign diagnosis

63%: nonspecific or reactive etiology Remainder: specific cause

(infectious mononucleosis, toxoplasmosis, tuberculosis) 16%: malignancy (lymphoma or metastatic adenocarcinoma)

Causes of Lymphadenopathy

Infection

Bacteria (e.g., all pyogenic bacteria, syphilis) Mycobacterial (e.g., tuberculosis, leprosy)

Fungal (toxoplasmosis, coccidiodomycosis), Chlamydial, Parasitic Viral (e.g., EBV, CMV, rubella, hepatitis, HIV)

Benign disorders of immune system: RA, SLE, Kikuchi‘s or Kimura‘s disease, HLH

Malignant disorders of immune system: leukemia, lymphoma, malignant histiocytosis

Other malignancies: breast, lung, head & neck, GI cancer, melanoma, sarcoma Storage diseases

Endocrinopathies: hyperthyroidism, adrenal insufficiencies, thyroiditis Miscellaneous: sarcoidosis, amyloidosis, dermatopathic lymphadenitis

Methods of LN evaluation

Physical examination Imaging

Chest radiography Lymphangiography Ultrasonography

Computed tomography

Magnetic resonance imaging Gallium scanning

Positron emission tomography Sampling

Needle aspiration: metastasis Cutting needle biopsy

Excisional biopsy: lymphoma

Diagnostic approach to lymphadenopathy

Atypical lymphocytes Leukemic cells

Perform ―Biopsy‖

of representative LN

Take history & examine the patient carefully:

Connective tissue diseases

Hypersensitivity reaction Infection

Endocrinopathies Other conditions Determine

anatomic location

score = 6

 2

no

generalized localized

normal abnormal

lymphadenopathy

CBS ‗Biopsy‘ score

abnormal chest x-ray: 5 LN > 2 cm: 3 ENT symptoms: -3 (constant: -2 (0 for normal of above )

* Cervical LAP > inguinal LAP

An approach to the patients with lymphadenopathy

1. Does the patient have a known illness that causes lymphadenopathy?

Treat & monitor for resolution

2. Is there an obvious infection to explain the lymphadenopathy (infectious mononucleosis)? Treat & monitor for resolution.

3. Are the nodes very large &/or very firm and thus suggestive of malignancy?

Perform a biopsy.

4. Is the patient very concerned about malignancy and unable to be reassured that malignancy is unlikely? Perform a biopsy.

5. If none of the preceding are true, perform a CBC and if it is unrevealing, monitor for a pre-determined period (usually 2 to 4 weeks).

If the nodes do not regress or if they increase in size, perform a biopsy.

증례 2

• 30세 여자

•주소: 3달전부터 시작된 우측 악하림프절 종창으로 내원

• PS score: 0, B 증상 (-)

• 조직 검사: Diffuse large B-cell lymphoma

CD20 (+), CD79a (+), CD3 (-), CD45RO (-), TIA (-), Granzyme B (-), CD56 (-), EBV in situ (-), CD21 (-), CD8 (-), Bcl-2 (+), Bcl-6 (-),

CD5 (-), CD10 (-), CD23 (-), CD43 (+), Cyclin D1 (-), Ki67 (+, 90%)

증례 2

• LDH 332 IU/L (N: 218-472)

• 다른 혈액 검사 소견: 정상

• HBsAg (-), Anti-HCV (-)

• 골수 천자 및 생검: 림프종 (-)

• IPI – 0 (low risk group)

Serum LDH < 1 x normal PS score 0

Stage IIA

Extranodal involvement (-)

증례 2 (치료 계획?): Vote!!!

1. 3-4 주기 R-CHOP + 침습부위 방사선 치료 2. 6-8 주기 R-CHOP 항암 요법

3. 기타 요법

• DLBCL

• IPI – 0 (low risk group)

• Stage IIA

증례 2 (치료 계획?): Vote!!!

1. 3-4 주기 R-CHOP + 침습부위 방사선 치료 2. 6-8 주기 R-CHOP 항암 요법

3. 기타 요법

• DLBCL

• IPI – 0 (low risk group)

• Stage IIA

증례 3

• 62세 남자

• PS Score: 0

• LDH 613 IU/L (N: 218-472)

• BM exam: lymphoma invasion (<10%)

• CSF exam: negative

• IPI: 3 (High/intermediate)

• R-IPI: 3 (poor)

CD20

증례 3: CNS prophylaxis 유무: Vote!!!

1. 시행한다

2. 시행하지 않는다 3. 잘 모르겠다

• DLBCL

• BM exam: lymphoma invasion (<10%)

증례 3: CNS prophylaxis 유무: Vote!!!

1. 시행한다

2. 시행하지 않는다

• DLBCL

• BM exam: lymphoma invasion (<10%)

증례 3

• 치료: 4주기 R-CHOP 항암요법

• Restaging: CR state

증례 3 (치료 계획?) : Vote!!!

1. 총 6-8 주기 R-CHOP 항암요법

2. 총 6-8 주기 R-CHOP 항암요법 + 자가 조혈모세포 이식 3. 총 6-8 주기 R-CHOP 항암요법 + 동종 조혈모세포 이식 4. 총 6-8 주기 R-CHOP 항암요법 + Radioimmunotherapy 5. 기타

• DLBCL

• IPI: 3 (High/intermediate)

• R-IPI: 3 (poor)

• BM involvement

증례 3 (치료 계획?) : Vote!!!

1. 총 6-8 주기 R-CHOP 항암요법

2. 총 6-8 주기 R-CHOP 항암요법 + 자가 조혈모세포 이식

• DLBCL

• IPI: 3 (High/intermediate)

• R-IPI: 3 (poor)

• BM involvement

증례 4 (Bulky lesion 치료 계획?): Vote!!!

1. 총 6-8 주기 R-CHOP 항암요법 2. 총 6-8 주기 R-CHOP 항암요법

+ Bulky 병변에 방사선조사 3. 총 6-8 주기 R-CHOP 항암요법

+ Radioimmunotherapy

4. 총 6-8 주기 R-CHOP 항암요법 + 자가 조혈모세포이식

5. 총 6-8 주기 R-CHOP 항암요법 + Bulky 병변에 방사선조사 + 자가 조혈모세포이식

IPI > 2

증례 4 (Bulky lesion 치료 계획?): Vote!!!

1. 총 6-8 주기 R-CHOP 항암요법

2. 총 6-8 주기 R-CHOP 항암요법

+ Bulky 병변에 방사선조사

+ Radioimmunotherapy

4. 총 6-8 주기 R-CHOP 항암요법 + 자가 조혈모세포이식

5. 총 6-8 주기 R-CHOP 항암요법 + Bulky 병변에 방사선조사 + 자가 조혈모세포이식

IPI > 2

증례 5 (위장관 침범 림프종): Vote!!!

항암치료전에 위장관 절제술 유무

2. 일반적으로 먼저 권고하지 않는다.

3. 증례에 따라 달리 시행한다.

4. 기타

증례 5 (위장관 침범 림프종): Vote!!!

항암치료전에 위장관 절제술 유무

2. 일반적으로 먼저 권고하지 않는다.

3. 증례에 따라 달리 시행한다.

4. 기타

Korean Society of Pathologist Study Group of Hematopathology 2005-2006, 3995 cases (31 institutes)

Relative frequency of histologic subtype of NHL in Korea

NHL: 95.6%

HL: 4.4%

Staging evaluation for Non-Hodgkin‘s lymphoma

Physical examination

Documentation of B symptoms Laboratory evaluation

Complete blood counts, liver function tests Uric acid, Calcium, LDH

Serum protein electrophoresis Serum 2-microglubulin

Chest radiograph

CT scan of abdomen, pelvis, and usually chest Bone marrow biopsy

Lumbar puncture in lymphoblastic lymphoma, Burkitt‘s, &

diffuse large cell lymphoma with positive marrow biopsy

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: Presence of at least one of the following:

unexplained weight loss 10% baseline during 6 months before staging; recurrent unexplained fever 38°C; recurrent night sweats

Cotswolds Modification of Ann Arbor Staging System

Lugano Staging System for GI TNM Staging System Ann Arbor Tumor extension

lymphomas adapted for gastric stage

lymphoma

Stage I Confined to GI tract (single T1 N0 M0 IE Mucosa, submucosa

primary or multiple, T2 N0 M0 IE Muscularis propria

noncontiguous) T3 N0 M0 IE Serosa

Stage II Extending into abdomen

II1 = local nodal involvement T1-3 N1 M0 IIE Perigastric lymph nodes

II2 = distant nodal involvement T1-3 N2 M0 IIE More distant regional lymph nodes Stage IIE Penetration of serosa to involve T4 N0 M0 IE Invasion of adjacent structures

adjacent organs or tissues

Stage Disseminated extranodal T1-4 N3 M0 IIIE Lymph nodes on both sides of the

III – IV involvement or concomitant T1-4 N0-3 M1 IVE diaphragm/distant metastases (eg, bone

supradiaphragmatic nodal marrow or additional extranodal sites

involvement

STAGING OF GASTRIC MALT LYMPHOMA

INTERNATIONAL PROGNOSTIC INDEX

ALL PATIENTS: INTERNATIONAL INDEX, ALL PATIENTS:

 Age > 60 years  Low 0 or 1

 Serum LDH > 1 x normal  Low intermediate 2

 Performance status 2-4  High intermediate 3

 Stage III or IV  High 4 or 5

 Extranodal involvement > 1 site

AGE-ADJUSTED INTERNATIONAL PROGNOSTIC INDEX

PATIENTS  60 YEARS: INTERNATIONAL INDEX, PATIENTS 60 YEARS:

 Stage III or IV  Low 0

 Serum LDH > 1 x normal  Low/intermediate 1

 Performance status 2-4  High/intermediate 2

 High 3

N Engl J Med. 329:987-994, 1993

International Prognostic Index (IP) for DLBCL

PFS (IPI)

OS (IPI)

PFS (R-IPI)

OS (R-IPI) PFS (No. of IPI factors)

Blood 2007

The revised International Prognostic Index (R-IPI)

for patients with DLBCL treated with R-CHOP

P<0.01

High (N=40)

Low-intermediate (N=48) High-intermediate (N=48)

Low (N=133)

Duration (Months)

Probability of OS Probability of OS

Duration (Months)

Very good (N=42) Good (N=139)

Poor (N=88) P<0.01

P<0.01

High (N=40)

Low-intermediate (N=48) High-intermediate (N=48)

Low (N=133)

Probability of PFS

Duration (Months)

Probability of PFS

Duration (Months) Very good (N=42) Good (N=139)

Poor (N=88)

P<0.01

IPI

IPI R-IPI

R-IPI

IPI vs. R-IPI for DLBCL patients treated with R-CHOP

(269 Korean from NUHSK group: 2003.7 – 2008.3)

FLIPI CRITERIA

 Age  60 y

 Ann Arbor stage III-IV

 Hemoglobin level < 12 g/dL

 Serum LDH level > ULN

 Number of nodal sites > 4

Risk group according to FLIPI chart

Number of factors

 Low 0-1

 Intermediate 2

 High  3

Blood 2004

Follicular lymphoma international prognostic index (FLIPI)

RISK FACTORS:

Age > 60 years

 Serum LDH > 1 x normal

 Performance status 2-4

 Bone marrow involvement

PROGNOSTIC RISK:

 Group 1 0

 Group 2 1

 Group 3 2

 Group 4 3 or 4

OS (IPI) OS (PI for PTCL-U)

Blood 2004

Prognostic index for PTCL-U

MIPI score = [0.03535 x age (years)]

+ 0.6978 (if ECOG > 1)

+ [1.367 x log10(LDH/ULN)]

+ [0.9393 x log10(WBC count)]

Points Age, y ECOG LDHULN WBC, 10⁹/L 0 <50 0-1 <0.67 < 6.700

1 50-59 — 0.67-0.99 6.700-9.999

2 60-69 2-4 1.000 -1.49 1.000-14.999

3 70 — 1.5000 15000

Simplified prognostic index

Low risk (LR): 0-3, Intermediate risk (LR): 4-5 High risk (HR): 6-11

Low risk (LR) < 5.7, Intermediate risk (LR): 5.7- High risk (HR): 6.1 6.2

OS (IPI)

OS (MIPI)

Blood 2008

MIPI for patients with advanced-stage mantle cell lymphoma (MCL)

Ann Arbor stage

IPI

LTI

Blood 2005

Local tumor invasiveness (LTI) in I_E/II_E extranodal NK/T-cell lymphoma, nasal type

RISK FACTORS:

 ―B‖ symptom (+)

 Stage  3

 LDH > 1 x UNL

 LN, N1 to N3, not M1

PROGNOSTIC RISK:

 Group 1 0

 Group 2 1

 Group 3 2

 Group 4 3 or 4

IPI New prognostic index

J Clin Oncol 2006

Extranodal NK/T-cell lymphoma, nasal type: New prognostic index

Response Criteria for Lymphoma (not including PET)

J Clin Oncol 1999

Recommended timing of PET scans in lymphoma clinical trials

J Clin Oncol 2007

Revised Response Criteria for Malignant Lymphoma

Stage I,II

Stage III, IV + aaIPI

Nonbulky (<10cm)

Bulky (10cm)

Adverse risk factors (+)

• LDH

• Stage II

• Age > 60 y

• PS score  2

Adverse risk factors (-)

RCHOP x 3-4 + IFRT (30-36Gy) or

RCHOP 6-8 cycles  IFRT (30-36 Gy) RCHOP x 3-4 + IFRT (30-36Gy)

or

RCHOP 6-8 cycles

when RT contraindicated

RCHOP 6-8 cycles + IFRT (30-40 Gy)

RCHOP 6-8 cycles or

Clinical trial (Preferred)

- May include high-dose therapy

CNS prophylaxis

: testicular, PNS, epidural, BM invol.

: 4-8 doses of IT MTXcytarabine during the course of treatment

Diffuse Large B-cell Lymphoma

Gastric DLBCL

• Primary surgery: debate – 25% risk of serious hemorrhage or perforation

• Patients with severe hemorrhage or perforation

– Partial gastrectomy + chemotherapy & irradiation

• Stage IAE or IIAE: chemotherapy + radiation

• B symptoms, bulky lesion, stage III or IV: full course of R-CHOPIFRT

Primary GI lymphoma

Intestinal DLBCL

• Localized disease: R-CHOP

• DLBCL that has been surgically removed, 1) 3 cycles of R-CHOP

2) when residual disease is present, 6-8 cycles of chemotherapy alone

6 vs. 8 bi-weekly CHOP-14  rituximab in elderly B-cell lymphoma : Phase III, RICOVER-60

Lancet Oncol. 2008;9(2):105-16

1 = 6×CHOP-14 2 = 8×CHOP-14 3 = 6×R-CHOP-14 4 = 8×R-CHOP-14

6×CHOP-14 8×CHOP-14 6×R-CHOP-14

8×R-CHOP-14 6×CHOP-14

8×CHOP-14 6×R-CHOP-14

8×R-CHOP-14

Relapse/

Refractory disease

Candidate for high-dose Therapy

Not

candidate for high-dose therapy

2nd line therapy

•DHAP  R

•ESHAP  R

•GDP  R

•GemOx  R

•ICE  R

•minBEAM  R

•MINE  R

High dose therapy with autologous SCT

 IFRT or

Clinical trial (allogeneic SCT) Clinical trial

or

Best supportive care

Diffuse Large B-cell Lymphoma

2nd line therapy

•Clinical trial

•Rituximab

•CEPP  R

•PEPC: PO

•EPOCH

CR or PR

NR

Salvage therapy for relapsed/refractory DLBCL

Biol Blood Marrow Transplant. 2008;14(3):259-67

Salvage Rx

Patients with aggressive

NHL

SCT (no.)

Relapsed/

Refractory (%)

ORR (%)

CR/PR (%)

OS (in SCT)

PFS (in SCT)

GDP × 2 51 26 92/8 49 16/33 NS NS

ESAHP × 3 65 23 37/63 62 NS 45% at 5 yrs NS

ICE × 3 163 96 52/48 66 24/42 65% at 3 yrs if had

CR, 30% if had PR

54% (CR), 29% (PR)

at 3 yrs

RICE × 3 34 24 64/36 78 53/25 67% at 2 yrs 54% at 2 yrs

DHAP × 2 43 23 69/31 68 29/39 39% at 4 yrs 35% at 4 yrs

DHAP × 2 4 54 100/0 58 NS 53% at 5 yrs 46% at 5 yrs

mini BEAM × 2-3 53 38 48/52 37 12/25 36% at 3 yrs NS

R-DHAP-VIM-DHAP 62 77 NS 77 NS 62% at 2 yrs 82% at 2 yrs

DHAP-VIM-DHAP 62 49 NS 49 NS 48% at 2 yrs 46% at 2 yrs

DHAP × 2 37 41 60/40 72 9/63 47% at 2 yrs (all pts) 25% (all pts)

IVAD × 2 7 NS 90/10 75 19/56 43% at 5 yrs

for IVAD responders NS

Rituximab  DHAP-VIM-DHAP & ASCT in relapsed/progressive aggressive CD20+ NHL: a randomized HOVON trial

Blood. 2008;111(2):537-43

54% 75%

50%

24%

Failure free survival

Failure free survival (CR/PR & BEAM/SCT)

R-DHAP DHAP

R-DHAP DHAP

90

Y-Ibritumomab tiuxetan & High-Dose Chemotherapy in NHL

J Clin Oncol 2008;26:90-95

Overall survival PFS

•Toxicity

•Tolerability

 Similar to BEAM alone

89.7%

84.6%

DLBCL

MCL 68.2%

68.4%

DLBCL MCL

BEAM/Rituximab  Zevalin: ?

Stage I,II

Stage III, IV

aaIPI low/low- intermediate

Clinical trial (preferred)(+) or

Multiagent

chemotherapy (6-8 cycl) + IFRT (30-40 Gy)

Observe High-dose therapy with SCT or

Observe

Peripheral T-Cell Lymphomas

aaIPI high/high- intermediate

Clinical trial (preferred)(+) or

Multiagent

chemotherapy (6-8 cycl)

CR

PR, NR,

•ALCL ALK-1 (+)

•ALCL ALK-1 (-)

•PTCL NOS

•AILT

Clinical trial or

2^nd line therapy

CR Observe

PR, NR,

Clinical trial or

2^nd line therapy

Peripheral T-Cell Lymphomas

Second-line therapy (candidate for SCT):

•Clinical trial preferred

•DHAP

•GDP

•ESHAP

•ICE

•miniBEAM

•MINE

Second-line therapy (non-candidates for SCT):

•Clinical trial preferred

•Alemtuzumab

•Bortezomib

•Denileukin diftitox

•Gemcitabine First-line therapy:

•Clinical trial preferred

•CHOP

•EPOCH

•HyperCVAD alternating with high-dose methotrexate and cytarabine

First-line Consolidation:

•All patients except low risk (aaIPI) should be consolidated with high dose therapy and SCT (autologous)

•ALK-1 ALCL is a subtype with good prognosis and does not need

consolidative transplant if in remission.

Novel emerging therapies for T-cell malignancies

Relatively New Interferon alfa Fludarabine Cladribine Pentostatin

New

Nelarabine Forodesine

Emerging

Denileukin diftitox Bexarotene

Gemcitabine Bendamustine Pralatrexate

HDAC inhibitors (eg, depsipeptide, suberoylanilide hydroxamic acid)

Lenalidomide

Apoptosis-inducing agents (eg, oblimersen, obatoclax, AT-101, ABT-737, Apo2L-TRAIL, YM155)

Abbreviation: HDAC, histone deacetylase

Semin Oncol 2007;34(Suppl 5):S3-S7

Alemtuzumab (Campath-1H) + CHOP for PTCL (1

line)

Blood 2007;110:2316-2323 Response Histopathology Total no. (%)

proportion CR

PTCL-U 7/14 17 (70.8)

AILD-T 6/6 —

ALCL 3/3 —

EATCL 1/1 —

PR

PTCL-U 1/14 1 (4.2)

Minor response

PTCL-U 1/14 1 (4.2)

Disease progression

PTCL-U 5/14 5 (20.8)

Major (WHO 4) infections

PTCL-U Invasive aspergillosis, J-C viral encephalitis ALK- Staphylococcus sepsis, Streptococcus sepsis PTCL-U Bacterial pneumonia, PC pneumonia

PTCL-U Bacterial pneumonia, invasive aspergillosis

Histologic Response (%)

Subtype CR PR SD PD

PTCL-U (10) 8 (80.0) 2 (20.0)

ENKT cells (3) 1 (33.3) 1 (33.3) 1 (33.3)

AILD-T (3) 2 (66.6) 1 (33.3)

ALK- (2) 1 (50.0) 1 (50.0)

SPLT (2) 1 (50.0) 1 (50.0)

NCI-CTC grade (n = 20) Grade 3 Grade 4 Hematologic

Anemia 5 (25.0) 1 (5.0)

Neutropenia 18 (90.0)

Lymphopenia 19 (95.0)

Thrombocytopenia 6 (30.0) Non-hematologic

AST/ALT 2 (10.0)

Febrile neutropenia 10 (50.0) 1 (5.0)

Cancer Chemother Pharmacol 2007;60(1):129-34

Autologous stem cell transplantation in PTCLs

Authors Histology aaIPI ≥ 2 (%)

Pre-transplant

CR (%) TRM (%) Survival (%) Median F/U (Months)

Rodrguez et al. 22 PTCL 28 38 13.7 3 yrs, OS 39 43

7 ALCL-Alk+ PFS 32

Rodriguez et al. 90 PTCL 52 32 CR1 8 5 yrs, OS 56 37

25 ALCL 24 ≥ 2CR DFS 49

Song et al. 23 PTCL na 42 17 3 yrs, OS 48 42

9 ALCL EFS 37

Blystad et al. 26 PTCL 45 27 CR1 7.5 3 yrs, OS 58 25

14 ALCL 42 ≥ 2CR EFS 48

Jantunen et al. 21 PTCL 51 49 CR1-PR1 16 5 yrs, OS 54 24

14 ALCL 38 CR2-PR2 PFS 44

Rodriguez et al. 51 PTCL 65 upfront 4 5 yrs, OS 68 67

23 ALCL na PFS 63

Corradini et al. 43 PTCL 71 upfront 4.8 12 yrs, OS 34 76

19 ALCL-Alk+ 56 EFS 30

Kim et al. 24 PTCL 52 7 CR1 7.5 1 yr, OS 46 16

5 ALCL 20 ≥ 2CR

Nademanee et al. 30 PTCL na 21 5.3 2 yrs, OS 53 22

26 ALCL DFS 45

Myeloablative allogeneic stem cell transplantation in PTCLs

Dhedin et al. Doocey et al. Kim et al.

No. 73 44 233

Pts with diagnosis of PTCL

(no) 16 (22%) 5 (11%) 51 (22%)

Chemosensitive disease 63% 79% 55%

Related donor 98% 75% 74%

Unrelated donor 2% 25% 26%

Conditioning TBI-based (100%) TBI + CTX (81%) TBI-based (83%)

NRM 44%, 5 years 25%, 1 year 42%, 2 years

OS 41%, 5 years 48%, 5 years 39%, 5 years

PFS or EFS 40%, 5 years 43%, 5 years 36%, 5 years

Specific outcome for PTCL

Not evaluated 80%, 5 years EFS 70%, 5 years OS PTCL unspecified

30%, 5 years OS NK/T

Leuk Lymphoma. 2007;48(8):1496-501

NST

Stage IE, H. pylori (+)

Currently accepted antibiotic therapy for H. pylori

Gastric MALT lymphoma

Stage III, IV;

(advanced- stage disease

uncommon)

Indications for treatment

•Candidate for clinical trial

•Symptoms

•GI bleeding

•Treatened end-organ function Induction chemo- Immunotherapy (Combination or single agent)

or Locoregional RT in specific setting Evaluate for H.pylori eradication

with endoscopy

Observe Stage IE or II,

H. pylori (-)

RT (30-33 Gy) (preferred) or

Rituximab

(if RT is contraindicated)

Endoscopy for restaging

No indication Indication present

*t(11;18): a predictor for lack of response to antibiotics

Stage IE-II

• Locoregional RT (20-30 Gy)

Locoregional RT

Non-gastric MALT lymphoma

Extranodal (multiple site)

Stage III, IV;

Extranodal disease

& multiple nodal sites

Manage per follicular lymphoma guideline for Advanced stage

Treat per diffuse large B-cell lymphoma guideline Stage IE-IV, MALT lymphoma,

Coexistent with large cell lymphoma

•Surgery may be considered (lung, breast, skin, thyroid,

colon/small bowel)

Consider

Locoregional RT Positive

margins Negative

margins Observe

Stage I,II

• Locoregional RT (preferred)

• Immunotherapychemotherapy

• ChemotherapyRT

• Observation (selected cases)

Follicular lymphoma (grades 1-2)

•Stage II, bulky

or abdominal disease

•Stage III,IV • 1^st line therapy

• Clinical trial

• Local RT (palliation) No

indication Observe Indications for treatment

•Candidate for clinical trial

•Symptoms

•Threatened end-organ function

•Cytopenia secondary to lymphoma

•Bulky disease

•Steady progression

•Patient preference

Indication present

Follicular lymphoma (grades 1-2)

First-line Therapy

•CHOP + rituximab (category 1)

•CVP + rituximab (category 1)

•Fludarabine + rituximab

•FND + rituximab

•Radioimmunotherapy (category 2B)

or CHOP followed by radioimmunotherapy (category 2B)

First-line for Elderly or Infirm

•Rituximab, preferred

•Single agent alkylators (eg, chlorambucil or cyclophosphamide)

First-line Extended Dosing

•Rituximab maintenance (category 2B)

Second-line and Subsequent Therapy

•Bendamustine (category 2B) ± rituximab

•Chemo-immunotherapy (as in first-line therapy)

•High dose therapy with autologous stem cell rescue

•High dose therapy with allogeneic stem cell rescue, for highly selected patients

•Radioimmunotherapy

Second-line Extended Dosing

•Rituximab maintenance (category 1)

Bendamustine + Rituximab for MCL & low-grade NHL

J Clin Oncol 2005;23(15):3383-3389

90

Y-Ibritumomab (Zevalin): 1

line indolent trial (FIT) in advanced FL

ASH2007

Newly diagnosed

FL (III–IV):

induction chemotherapy

CR/PR

Zevalin^®

No further treatment Start

Studyof (Phase III) NRPD Off study

Blood 2007

LMP2 DCs LMP2-specific CTL

Complete responses of relapsed lymphoma following genetic modification of tumor antigen presenting cells and T-lymphocyte transfer

Bone Marrow Transplant 2004

• 20-year-old man

• 2001. 3: Both cervical lymphadenopathies



•

• PBSC mobilization & collection after

•

•



Autologous transplantation + NST for poor risk or refractory lymphoma

Flu/CY regimen + NST from HLA- matched unrelated donor

CY/TBI regimen + Auto-PBSCT

Donor

(pre-NST) (post-NST)

VNTR

2 cycles of Hyper- CVAD & HDMTX with ara-C

CR

Recipient

CR

2003. 4

2003. 8 2004. 8

2002. 12

1 cycle of modified L2 chemotherapy

2003. 2

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