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:
- https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/risk-factors
- 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
- https://www.cancer.gov/publications/dictionaries/cancer-terms/def/car-t-cell-therapy
- Brentjens R, et al. “Driving CAR T cells forward.” Nat Rev Clin Oncol. 2016 13, 370–383.
- https://www.researchgate.net/figure/Origin-of-Non-Hodgkin-B-cell-lymphomas-and-mechanisms-related-to-their-development-During_fig3_221929542
- https://www.nature.com/articles/nrc1589

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