Lymphomas

Blair McLaren

Oncologist, Southern DHB

2008 NZ Cancer Registrations

*Excludes basal and squamous cell skin cancers.Source: Cancer: New Registrations and Deaths. MOH 2011

Men

9647

Women

8963

• 28% Breast

• 14% Colon & rectum

• 11% Melanoma of skin

• 9% Lung & bronchus

• 4% Uterine corpus

• 4% Non-Hodgkinlymphoma

• 3% Ovary

• 3% Leukaemia

• 2% Pancreas

• 2% Thyroid

• 20% All Other Sites

Prostate 28%

Colon & rectum 14%

Melanoma of skin 11%

Lung & bronchus 9%

Non-Hodgkin 4% lymphoma

Kidney 3%

Leukaemia 3%

Urinary bladder 2%

Stomach 2%

Head & Neck 2%

All Other Sites 22%

Non-Hodgkins lymphoma

(NHL)

• Incidence of NHL increasing

• Life time incidence c2% (rising)

• Generally disease of aging (median age onset

50-60) but bimodal for Hodgkins and

aggressive NHL

Clinical Presentation

• Symptoms and signs

– History

• Painless lymphadenopathy

• Systemic symptoms

– Pruritis

– Fever, weight loss, night sweats (“B symptoms”)

• Pain

• Local symptoms from mass effect

– Examination

• Nodes

• Tonsils and oropharynx

• Occipital, posterior auricular, shotty inguinal nodes often

benign

Basic rules of oncology

• What is it (tissue)?

• How much of it is there (staging)?

• What sort of nick is the patient in?

(performance status/ comorbid conditions)

• What are my treatment options?

• What is my treatments aim?

• What does the patient want?

NHL staging

• History, examination

• Diagnostic biopsy (FNA inadequate)

• Bloods – FBC, U + E, LFT, SPE, ß2microglobulin

• LDH

• CT chest

• CT abdo/pelvis

• Bone marrow aspirate/trephine

NHL special staging (selected)

• ENT exam

• Endoscopy +/- small bowel studies

• CSF exam (esp high grade with +ve bone

marrow, paranasal sinus or testicular NHL)

• PET scanning

Histopathology

Generous biopsy of fresh tissue (molecular studies)

please surgeon

• WHO classification - cell size, appearance,

architecture

• Immunophenotype (markers on cells)

• Real clinical entities

Immunophenotype (tissue stains

by pathologist)

• Help distinguish from carcinoma and

confirm clonal

• Specific combinations of markers allow you

to determine specific types of lymphomas

B cell differentiation

NHL - classificationIndolent Aggressive Highly Aggressive

B-Cell lymphomas

SLL/CLL Follicular lymphoma (G3) Burkitt's lymphoma

Follicular Grade 1 & 2 Diffuse Large B-cell lymphoma Precursor B lymphoblastic

leukemia/lymphomaLymphoplasmacytic Mantle-cell lymphoma

Plasmacytoma/myeloma

Hairy cell leukaemia

Marginal B-Cell lymphoma / MALT

Mantle Cell lymphoma

T-cell Lymphomas

T-cell large granular lymphocyte

leukaemia

Peripheral T-cell lymphoma Adult T-cell lymphoma/leukaemia

Mycosis fungoides Anaplastic large cell lymphoma, T/null

cell

Precursor T lymphoblastic

leukemia/lymphomaT-cell promyelocytic leukaemia

NK cell neoplasms

NK cell large granular lymphocyte

leukaemia

Adapted from Harris et al JCO 1999

Generalisations

• FOLLICULAR - usually indolent, low grade, incurable (except localised)

Treatment options – observation, chemo,

radiotherapy

• DIFFUSE - usually aggressive and potentially curable with chemotherapy +/-radiotherapy

Follicular lymphoma (22% NHL)

• Usually widespread

(51% stage IV)

• Median survival >8 years

FLIPI score prognostic

(nodes, LDH, age, stage, Hb)

Diffuse large B cell (33% NHL)

• Mixed group

• Curable with chemo

(potentially)

• Prognosis by International prognostic index (IPI)

• Use of rituximab + CHOP chemotherapy

MALToma (8% NHL)

• Mucosa associated lymphoid tissue

(MALT)

• Usually localised and indolent (may be

curable by radiotherapy or surgery)

Gastric MALToma

• Commonest extranodal NHL

• Presence of H. Pylori infection in >60% of

gastric lymphoma

• Regression can occur with antibiotics alone

(75%)

• Can transform to aggressive grade NHL

Mycosis fungoides

• Cutaneous T cell

lymphoma

• Indolent (very)

• Can progress to

T cell leukaemia

Burkitt’s lymphoma

• Median age = 30 in adults

• Highly aggressive but curable

• Doubling time can be 7 days

• Associated with tumour lysis syndrome; ↑uric acid, K+, PO4 - can cause renal failure)

Burkitt’s lymphoma

• Endemic (Africa and PNG); facial, jaw,

abdo, associated with EBV

• Sporadic ; generally abdominal, 30% EBV

• HIV associated; usually lymph nodes

Prognosis in NHL

Depends on

• Tumour factors

• Patient’s response to tumour

• Patient’s ability to tolerate treatment

Prognosis - NHL

• Age

• Advanced stage

• Low Hb

• LDH

• Extensive nodal involvement (>4 areas)

• Poor ECOG performance status

• More than one extranodal area

Ann Arbor staging for lymphoma

IPI prognosisIPI prognosis Survival %

Risk

group

Risk

factor

CR

rate

5

year

Low 1 87 73

Low/

int

2 67 51

High/

int

3 55 43

High 4,5 44 26

Treatment of NHLKey Questions

• Stage and histologic subtype

• Clinical aggressiveness

• Is it curable? – all Stage I potentially

- all aggressive NHL (regardless

of stage)

• Which treatment is “best” to achieve cure or

palliation

Radiation treatment

• Potentially curative for

- Stage I indolent

• Addition to chemotherapy – bulky disease

or localised aggressive disease

• Palliation (high response rates)

Chemotherapy (lots of options)Intensity depends on treatment goal

• Oral alkylating agents e.g. chlorambucil in very

indolent NHL and frail patients

• Minimally intensive chemo e.g. CVP in progressive

indolent (+/- rituximab)

• Moderately intensive chemo e.g. CHOP or R-CHOP

• Highly intensive chemo – leukaemia like (includes

intrathecal);

Rituximab

• Monoclonal Antibody

• Reacts with CD20 on B lymphocytes

( > 90% express CD20)

• Uses immune system

• May promote apoptosis

Mechanism of action of rituximab

R

Killerleukocyte

MalignantB-cell

CD20

Rituximab

CD20

Complement

Rituximab

Rituximab - clinical

• For diffuse large B cell NHL better survival in patients treated with R-CHOP

• Indolent lymphoma - better response rate, prolongs remission and survival with chemotherapy or when used as maintenance treatment

• Toxicities – fever, rigors, headache, bronchospasm, hypotension (1st dose)

High dose chemotherapy treatment

• Big dose chemotherapy with autologous or

allogeneic peripheral blood stem cell (PBSC) rescue

• Proven in chemo-sensitive relapse for diffuse large

cell (survival 53% vs. 32% for standard chemo)

Hodgkins disease

• All potentially curable

• Chemo (ABVD) +/- radiotherapy

• ?More intensive chemo (e.g. BEACOPP) for poor risk disease

• High dose chemo with autologous stem cell rescue effective for 1st relapse

Hodgkin Lymphoma

• Bimodal incidence: 20’s, and >50

• EBV associated

• Reed-Sternberg cells pathognomic

(“Owl Eyes”)

•Mediastinal mass in younger person common

•BM and CNS involvement rare

•Increased incidence w HIV

HD: Prognosis and Treatment

Risk factor Score 5 year PFS

Hb <105 0 84%

WBC > 15 1 77%

L <0.6 2 67%

Stage 4 3 60%

Albumin < 40 4 51%

Age > 45 5+ 42%

Male gender

Treatment:

- Early disease = short chemo + XRT

- Advanced disease = more chemo, XRT to bulk areas only

- Transplant at first relapse

Long term effectsShort-medium term

- Tiredness, depression, anxiety and hyper-vigilance

Consider late effects (high rates of survival)

– fertility (ABVD relatively spares fertility compared to other regimens)

–Second cancers

- Organ damage from treatments