What You Must Know About Lymphoma?

CME INDIA Presentation by Dr. Avinash Kumar Singh, DM (Hematology), Consultant haematologist and BMT physician, Paras HMRI hospital and Patna Haematology clinic, Patna, Bihar.

Based on a talk at APICON-2022, Jaipur.

Cancer Prediction is Frightening

What is Lymphoma?

Lymphoma is a group of hematological malignancy arising from lymphocytes. Broadly they are divided into Non-Hodgkin’s lymphoma and Hodgkin’s lymphoma.
Depending upon cell of origin lymphoma can be divided in B cell, T cell or NK/T cell lymphoma.
Depending upon aggressiveness, lymphoma can be divided in to indolent, aggressive and highly aggressive lymphoma.

Know about Primary and Secondary Lymphoid Organs

What are the Risk Factors?

Male Sex
Late middle-aged and older persons with a median age at diagnosis of approximately 65 years.
Body mass index,
Tobacco and Alcohol use, and inflammatory states.

Risk factors for lymphoma include:

Age

Family history

Certain infections

A lowered immune system

Autoimmune conditions

Other factors.

Causes of lymphoma

In most cases, there is no known cause for lymphoma.
For or a few types of lymphoma, scientists have identified a cause.
Most cases of gastric MALT lymphoma are caused by a common bacterial infection called Helicobacter pylori
Almost all people who get gastric MALT lymphoma have Helicobacter pylori infection.
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is caused by having textured breast implants.
Most people with breast implants do not develop BIA-ALCL – but everyone who develops BIA-ALCL has breast implants.

How Lymphoma develops?

Origin of Non-Hodgkin B cell lymphomas and mechanisms related to their development During development B cells can acquire translocations, deletions or mutations that make a subtype of lymphoma.
Pre-germinal centre derived lymphomas are CLL unmutated and mantle cell lymphoma and some follicular lymphomas.
Germinal centre derived lymphomas are derived by transformation from either variable region gene recombination (BCL-2-IgH) in follicular lymphoma, somatic hypermutation (BCL-6) in diffuse large B cell lymphoma, or class switching in c-myc sporadic Burkitt ́s lymphoma.
Post-germinal centre B cell lymphomas are marginal zone lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukaemia and plasmacytoma and are derived from memory B cells and plasma cells.
B-Cell Lymphoma: A hallmark of many types of B-cell lymphoma is reciprocal chromosomal translocations involving one of the immunoglobulin loci and a proto-oncogene. As a consequence of such translocations, the oncogene comes under the control of an active immunoglobulin locus, causing deregulated, constitutive expression of the translocated gene.

Presentations

Asymptomatic
Symptomatic
- Non-responding fever
- B symptoms
- Pain/breathlessness
- Persistent painless node enlargement
- Skin rash
- Can involve any organ from head to toe

Difference between NHL and Hodgkins

	Non Hodgkin’s	Hodgkin’s
COMMON AGE	ADULTS AND ELDERLY	BIMODAL
NODE PATTERN	NON-CONTIGUOUS	CONTIGUOUS
NODE CONSISTENCY	FIRM	RUBBERY
PEL EBSTEIN FEVER	NO	MAY HAVE
RELATION WITH ALCOHOL	NO	PAINFUL NODES
INCIDENCE	MORE COMMON	RELATIVELY LESS COMMON

Diagnosis and Classification

FNAC is not sufficient
Don’t use steroid in suspected case of lymphoma
Urgent referral should be done in cases of aggressive or very aggressive lymphoma
BIOPSY IS MUST to know D/D

KOCHS/BENIGN LPD/INDOLENT/HODGKINS/METASTASIS/NON-SPECIFIC/VIRAL

IHC is must: MCL/FL/PTCL/PBL/HL

Molecular Tests are Must: DHL/THL/TARGETS

Courtesy: Management of Lymphomas: Consensus Document 2018 by an Indian Expert Group Indian J Hematol Blood Transfus (July-Sept 2018) 34(3):398–421 https://doi.org/10.1007/s12288-018-0991-4

Staging

Management

Performance status – ECOG/KARNOFSKI
Co morbidity
Emergencies –TLS/SVC/Pericardial tamponade/Luminal obstruction
Counselling
Consent before chemotherapy
Definitive Treatment – as Per Type of Lymphoma – NCCN Guideline
Chemotherapy –CHOP/MOPP/ABVD etc.
Chemo Immunotherapy-RCHOP/BR/ABVD etc.
Immunotherapy-MABS/CPI
Cellular Therapy – HSCT/CAR T Cell Therapy

Survival Trend DLBCL

See a Case

30 years old male presented with infradiaphragmatic multiple lymphadenopathy with fever and weight loss for 1 month
Work up confirmed as DLBCLL stage IIi non-bulky R IPI good
What treatment options?

Received 4 cycles of RCHOP
iPET CT –CR
2 more R
Follow Up
In Remission for Last 4 Years

See Case 2

40 yrs. old lady without any co morbidity presented with right cervical persistent painless lad 2X3 CM for 1 month associated with weight loss fever.
Work up confirmed it as classical Hodgkin’s lymphoma mixed cellularity type stage 1A Favourable
What Treatment Options?

Received 2 Cycle ABVD
IPET –CR
Received 2 More Cycle Of ABVD
Follow Up
In Remission for Last 6 Years

Relapse/Refractory

Case 1 Of DLBCL Relapsed After 4 Years
What Options???

What is new in lymphoma management?

Engineering Patients’ Immune Cells to Treat Their Cancers

A type of treatment in which a patient’s T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells.
T cells are taken from a patient’s blood.
Then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added to the T cells in the laboratory.
The special receptor is called a chimeric antigen receptor (CAR).
Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. CAR T-cell therapy is used to treat certain blood cancers, and it is being studied in the treatment of other types of cancer.

Final Points

Lymphoma is a common hematological malignancy encountered in day-to-day practice.
Awareness is the key to detect cases on time.
Signs and symptoms are mostly nonspecific and difficult to differentiate from infections.
For diagnosis tissue biopsy/IHC is must and molecular tests too are important
PET CT is important for staging and response assessment.
With better understanding of tumor biology, newer targets and therapy survival has improved.
Relapse refractory disease is a challenge and most of the time ASCT is needed to consolidate.

References: