Lymphoma Flashcards
How is lymphoma divided?
Lymphoma is divided into:
(a) Hodgkin Lymphoma (30%)
- Nodular sclerosing( best prognosis), mixed cellularity, lymphocyte rich, lymphocyte epeletion
- Nodular lymphoma predominant HL
(b) Non-Hodgkin Lymphoma
- Diffuse large B cell lymphoma (aggressive)
- Follicular lymphoma (indolent)
Non-Hodgkin Lymphoma is further divided into
- B cell NHL: aggressive DLBC NHL, indolent (follicular NHL)
- T cell NHL
Between B cell and T cell lymphoma, which one is more likely to cause cutaneous manifestations?
T cell lymphoma
Clinical classification of NHL
(A) Indolent / Low grade NHL (“incurable”) (What is cure?) Survival of the untreated disease is measured in years
- Follicular, MALT, Marginal
(B) Aggressive / Intermediate NHL (>50% cured)
Survival of the untreated disease is measured in months
- Diffuse Large B cell and Peripheral T cell lymphomas
- Mantle cell?
(C) Highly aggressive / High grade NHL (>70% cured) Survival of the untreated disease is measured in weeks
- Burkitt Lymphoma, T Lymphoblastic Lymphoma
Presentation for lymphoma
- Incidental finding of lymphadenopathy in neck, axilla, groin
- Abdominal pain with bulky disease
- Systemic symptoms: weight loss, fever, sweats
- Abnormal blood finding uncommon (compared with leukemia)
Investigations for lymphoma
Clinical:
• Detailed history and exam
• Performance status (PS) [ECOG scale]
• B symptoms (weight loss, fever, night sweats)
Pathology:
• Node (EXCISIONAL preferred, or core biopsy) and Bone marrow biopsy + immunohistochemistry, immunophenotyping, cytogenetics
- Specialized investigations e.g. gastrointestinal endoscopy, MRI Brain where appropriate
- CT/PET (staging)
Measurement of tumor masses to establish more accurate stage
•Prognosis (tumor ≥7cm)
•Baseline status for response evaluation
Exploratory lumbar puncture in aggressive lymphomas + intrathecal chemotherapy/prophylaxis
(Specific chemo protocol for CNS disease)
Pretreatment laboratory screening: •Full blood count and film review •Hepatic, renal and cardiac workup •Serum lactic dehydrogenase (LDH) level •Serum β2-microglobulin level Systematic HIV, HCV and HBV testing: prognostic and therapeutic implications of positivity
Chromosomal changes in lymphoma
t (14:18) - follicular lymphoma BCL2
t (8:14) - Burkitts lymphoma MYC oncogen
t (11:14) - mantle cell lymphoma cyclin D1
Myc + BCL2 or BCL6 mutation - “double hit” lymphoma, poor prognosis
Staging for Lymphoma
Ann Arbor Classification
- Stage 1: lymphoma located in a single region, usually one lymph node and the surrounding area
- Stage 2: lymphoma is located in 2 separate regions, confined to one side of the diaphragm
- Stage 3: lymphoma involves nodes or organs on both sides of the diaphragm or the spleen
- Stage 4: diffuse or disseminated involvement of one or more extra lymphatic organs, including any involvement of the liver, bone marrow or nodular involvement of the lungs
A or B: the absence of constitutional (B type) symptoms (fever, night sweats, weight loss) is denoted by adding an “A” to each stage and presence as “B”
Features of Hodgkin Lymphoma
TYPES
- Nodular sclerosing, mixed cellularity, lymphocyte rich, lymphocyte depleted
PRESENTATION
- Typically localised at presentation
- Preferentially involves cervical nodes, mediastinal involvement
DIAGNOSIS
- Reed sternberg cells - derived from mature B cells
- CD15 and CD30 expression of Reed Sternberg cells (others include TARC, MUM1)
RISK STRATIFICATION
- Early Stage: stage I-II, non bulky, no B symptoms
- Advanced Stage: stage IIB, III-IV, bulky disease, B symptoms
Treatment for Hodgkin lymphoma
2 choices
(1) AVBD (every 14 days in 28 day cycle)
(2) Esclated BEACOPP (every 21 days) - cures more but more intensive, can’t use in elderly, more premature menopause and long term risk MDS/AML
Early Stage
- ABVD + involved field radiotherapy
Advanced Stage
- ABVD +/- IFRT utilising RATHL approach
- Escalated dose BEACOPP
Relapsed/Refractory Disease
- Salvage chemotherapy
- Brentuximab (anti-CD30) - key toxicity is peripheral neuropathy
- Autologous stem cell transplant
- PD1 check point inhibitor. eg: pembrolizumab
Tox: immune related response, rash, pyrexia, arthralgia, autoimmune hepatitis, pneumonitis, itch, diarrhoea
ABVD: adriamycin [doxorubicin], bleomycin, vinblastine, and dacarbazine
- Alopecia, neutropenia, cardiotoxicity (doxorubicin), lung toxicity (blemoycin), low risk of infertility
BEACOPP: bleomycin, etoposide, Adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone
- More intense, increased risk of infertility
Unfavourable features in Hodgkin Lymphoma
- Bulky mediastinum: >1/3 thoracic diameter
- > /= 4 nodal areas involved
- B symptoms
- Age > 50
- Elevated ESR
Complications of treatment for Hodgkin Lymphoma
Secondary cancers develop
- AML
- NHL
- Breast cancer
- Other solid cancers, eg: lung, brain
Features of follicular lymphoma
- Most common indolent low grade lymphoma
- BCL-2 overexpression
- t (14:18) - translocation between IGH and BCL2 genes
- CD 10+/19+/20+
BCL 2/6
Treatment of Follicular Lymphoma
- Watch and wait
- Radiotherapy for Stage 1 or contiguous stage II with curative intent
- Chemoimmunotherapy if fulfill GELF criteria
- Rtiux or obtintuzumab + CVP (cyclophsophamide, vincristine, pred
- Rituximab or obintuzumab + endmustine
RCHOP
- Rituxumab or Orbintuzumab + CHOP (Cyclophosphamide, Adriamycin, Vincristine (Oncovin) + Prednisone
Poor prognosis for follicular lymphoma
Poor Prognostic Factors
- Age >60
- Ann Arbor stage III/IV
- Hb< 120
- Number of nodal areas > 4
- Elevated LDH
- B2 microglobulin
- Lonest diameter of largest LN > 6cm
Features of diffuse large B cell lymphoma (DLBCL) - AGGRESSIVE B CELL LYMPHOMA
- Rapidly enlarging tumour mass at single or multiple nodal or extranodal sites
- B symptoms
- Extranodal disease: CNS, gastric, prostate, testes
Diagnosis
- Histological diagnosis of LN or affected organ
Prognosis
- Age >60yo
- Ann Arbor Stage III/IV
- ECOG > 2
- Serum LDH
- Extranodal sites (BM, skin, liver, lung)
- DOUBLE HIT LYMPHOMA - MYC+ and BCL2/BCL6 - very poor prognosis
CNS IPI
- Risk of CNS progression/relapse
- Specific extranodal sites associated with elevated risk: kidneys and adrenals
TREATMENT
- Chemoimmunotherapy
- Radiotherapy to bulk
- R-CHOP
- CNS prophylaxis if high CNS IPI (inPternational prognostic index)
