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Perth Haematology :: Dr Steven Ward

Non-Hodgkin's Lymphoma (NHL)

 

    NCCN Guidelines   NHL Therapy Algorithm

 

Introduction:

 

 

 

Classification:

NHL is classified into B-cell and T-/NK-cell disorders and by the cell of origin, most recently by the World Health Organisation (WHO).

The IWF (international Working Formulation) Classification is still useful clinically.

 

B-cell neoplasms

WHO

IWF

Precursor B-cell neoplasm

 

Precursor B-lymphoblastic leukaemia/lymphoma

I

Mature B-cell neoplasms

 

Chronic Lymphocytic Leukaemia / Small Lymphocytic Lymphoma

A

B-cell Prolymphocytic Leukaemia

NC

Lymphoplasmacytic lymphoma

A

Splenic marginal zone lymphoma

A,B,E

Hairy Cell Leukaemia

NC

Plasma cell neoplasms:

  Plasma cell myeloma

  Solitary plasmacytoma of bone

  Extraosseous plasmacytoma

  Ig deposition diseases [Amyloid]

  Heavy Chain disease

Other

Extranodal marginal zone B-cell lymphoma [MALT]

 

Nodal marginal zone B-cell lymphoma

 

Follicular Lymphoma

  Grade 1

  Grade 2

  Grade 3

 

B

C

D

Mantle Cell lymphoma

E,B

Diffuse large B-cell lymphoma

F,G,H

Mediastinal (thymic) large B-cell lymphoma

G,H

Intravascular large B-cell lymphoma

F,G,H

Primary effusion lymphoma

NC

Burkitt’s lymphoma/leukaemia

J

B-cell proliferations of uncertain malignant potential

 

Lymphomatoid Granulomatosis

NC

Post transplant lymphoproliferative disorders, polymorphic

NC

NC = Not Classified

 

T- and NK-cell neoplasms

 

WHO

IWF

 

Precursor T-cell neoplasms

 

 

Precursor T-lymphoblastic leukaemia/lymphoma

I

 

(Blastic NK-cell lymphoma)

NC

 

Mature T- and NK- cell neoplasms

 

Leukaemic

Disseminated

T-cell prolymphocytic leukaemia

NC

T-cell large granular lymphocytic leukaemia

NC

Aggressive NK-cell leukaemia

NC

Adult T-cell leukaemia/lymphoma

NC

Extranodal

Extranodal NK/T-cell lymphoma nasal type

E,F,G,H

Enteropathy-type T-cell lymphoma

G,H

Hepatosplenic T-cell lymphoma [γδ]

NC

Subcutaneous pannuculitis-like T-cell lymphoma

E,F,G,H

Cutaneous

Mycosis fungoides

Mycosis

Sezary Syndrome

Other

Primary cutaneous anaplastic large cell lymphoma [CD30+]

G,H

Nodal

Peripheral T-cell lymphoma, unspecified

E,F,G,H

Angioimmunoblastic T-cell lymphoma

F,G,H

Anaplastic large cell lymphoma

G,H

 

T-cell proliferations of uncertain malignant potential

 

Lymphomatoid papulosis

NC

 

Staging: (Ann Arbor system) 

Stage I   

Involvement of a single lymph node region

Stage II

 

Involvement of two or more lymph node regions on the same side of the diaphragm (II)

Stage III

Involvement of lymph node regions on both sides of the diaphragm (III)

Stage IV Multiple or disseminated foci of involvement of one or more extralymphatic organs or tissues with or without lymphatic involvement (IV) eg liver, BM

A

Without systemic symptoms (below)

"B" Symptoms

Drenching night sweats

Unexplained fever (>38°C)

Significant weight loss (>10% in 6 months)

E Local extranodal disease
S Splenic involvement (Stage IIIS)

 

Lymph node region map

Link to PDF: noderegions.pdf

 

International prognostic Index (IPI) :: For High Grade NHL

 

Risk factors:

bullet

Age >60yr

bullet

LDH > N

bullet

PS 2-4

bullet

Stage III, IV

bullet

Extranodal disease > 1 site

 

 

OUTCOME:

 

IPI

No of risk factors

% of patients

CR Rate

RFS 2yr

RFS 5 yr

OS 2yr

OS 5yr

Low

0 or 1

87%

79%

70%

84%

73%

Low-Intermediate

2

67%

66%

50%

66%

51%

High-Intermediate

3

55%

59%

49%

54%

43%

High

4 or 5

44%

58%

40%

34%

26%

CR = Complete Response; RFS = Relapse-Free Survival; OS = Overall Survival

 

 

Age-Adjusted International prognostic Index (aaIPI) :: For High Grade NHL

aaIPI

Divide by age ≤60 or >60 years

Factors:           Stage III or IV; High LDH; PS ≥2

 

Risk Group

No of Risk Factors

% of Pts

CR Rate %

5yr DFS %

5yr OS %

aaIPI age ≤60

 

 

 

 

 

Low

0

22

92

86

83

Low-Int

1

32

78

66

69

High-Int

2

32

57

53

46

High

3

14

46

58

32

 

 

 

 

 

 

aaIPI age >60

 

 

 

 

 

Low

0

18

91

46

56

Low-Int

1

31

71

45

44

High-Int

2

35

56

41

37

High

3

16

36

37

21

 

 

Follicular Lymphoma International prognostic Index (FLIPI)

 

Risk factors:

bullet

Age >60

bullet

Stage III, IV

bullet

Hb <120 g/L

bullet

Nodal areas >4

bullet

Hi LDH

 

 Outcome:

Risk group

No factors

% pts

5yr OS %

10yr OS %

RR

Low

0-1

36

90.6

70.7

1.0

Intermediate

2

37

77.6

50.9

2.3

High

3

27

52.5

35.5

4.3

 

 

 

Incidence of Lymphoma:

Follicular NHL   22%                                                   4% of new cancer diagnosis per year

Diffuse Large B-cell    31%                                        630,000 cases per year in USA

SLL   6%                                                                      5th commonest cancer overall

Mantle Cell   6%

Peripheral T-cell    6%

Marginal zone, MALT   5%

Lymphoplasmacytic   1%

 

 

SYMPTOMS OF LYMPHOMA

Lymphoma can present in many different ways depending on the sites affected, the growth rate, and general health of the patient. Common features are:

bullet

Enlarged lymph glands "lumps"

bullet

Systemic symptoms: fever, sweats, weight loss, itch, tiredness

bullet

Features of anaemia or thrombocytopenia

bullet

Effects of impingement of organ function by enlarged nodes - eg abnormal LFT, renal impairment, breathlessness

 

DIAGNOSIS OF LYMPHOMA

bullet

A tissue biopsy is required to make the diagnosis of lymphoma -  this may be lymph node, marrow, skin, blood, marrow

 

INVESTIGATIONS

The tests required to ensure that the correct diagnosis and stage are made include:

bullet

Tissue biopsy - usually an enlarged node

bullet

CT of chest and abdomen ± neck, pelvis and skull if required - to show enlarged nodes

bullet

PET scan [to show functional activity]

bullet

Bone marrow - to determine if marrow involvement is present

bullet

Blood Tests:

bullet

FBP

bullet

U&E

bullet

LFT

bullet

LDH -  marker of lymphoid activity; prognostic marker

bullet

Calcium

bullet

Tests to ensure adequate organ function/reserve prior to treatment: eg cardiac function by gated heart scan, pulmonary function tests, etc

 

TREATMENT

There are many differing treatments available depending on the exact subtype of disease and the individual patient characteristics.

Generally NHL therapy is as follows:

 

bullet

Low-grade disease:

bullet

Gentle therapy aimed at disease control as needed; treatment may not be required initially; often oral tablets when required; injections later

bullet

High-grade disease:

bullet

More aggressive therapy aimed at cure; usually injections

 

 

 

 

CUTANEOUS LYMPHOMA STAGING

 

T: Tumour

N: Nodes

M: Mets (organs)

B: Blood

T0

No skin Involvement

NP0

No abn periph nodes

M0

No visceral organ involved

B0

<5% circ Sezary cells and <250/mL

T1

Patches/plaques ≤ 10% surface

NP1-

Abn periph nodes (Bx neg) ie dermatopathic nodes

M1

Viseral organ involved

B1

≥5% circ Sezary cells or ≥ 250/mL

T2

> 10%

NP1+

Abn periph nodes Bx pos

 

 

 

 

T3

Tumours ± patches

NV0

No abn visceral nodes

 

 

 

 

T4

Generalised erythema

NV1

Abn visceral nodes (no Bx)

 

 

 

 

 

 

NV1-

Abn visceral nodes BX neg

 

 

 

 

 

 

NV1+

Abn visceral nodes Bx pos