Introduction:

• It is a highly aggressive B cell lymphoma charectorised by the translocation and deregulation of c-myc gene on chromosome 8.
• If bone marrow contains more than 25% tumor cells, then the condition is called as Burkitt leukemia 
• Accounts for 30-50% of pediatric lymphomas

Pathogenesis: 

• Genetic aberrations during immunoglobulin rearrangements or attempted immunoglobulin class switching in B cell precursor 
• Juxtaposing MYC to the IGH locus by t(8;14)à Translocation between MYC and an immunoglobulin promoter à Constitutive expression of MYC
• Other translocations include: t(8;22) and t(2;8)

Classification: 

• Endemic 
  • Commonly involves jaws and facial bones 
  • Seen in equatorial Africa 
  • EBV associated 
  • Seen at 4-7 years 
• Sporadic 
  • Usually presents as abdominal mass in ileocecal region 
  • Low EBV association 
  • Median age- 30 years 
• Immunodeficiency associated BL – Seen in HIV patients 

Clinical Features: 

• Endemic – Loosening of teeth and extrusion of eye – occurs due to mandibular and maxillary bone involvement. 
• Sporadic – Bulky mass per abdomen – Due to involvement of kidney, adrenals, ovary and lymph nodes. 

Investigations:

• Biopsy of lesion/ lymph node mass
  • Diffuse monotonous pattern of infiltration of medium sized tumour cells.
  • Nuclei are round with clumped chromatin  and relatively clear parachromatin. Multiple basophilic centrally located nucleoli are seen. Cytoplasm is deeply basophilic  and contains lipid vacuoles
  • High mitotic count 
  • Multiple apoptotic bodies 
  • “Starry sky pattern” – Imparted by numerous benign macrophages that have ingested apoptotic tumor cells 
• Immunophenotype
  • Positive – Membrane IgM with light chain restriction, CD45, B cell associated Antigens(CD19, 20, 22, 79a, PAX 5), CD10, TCL1, BCL6, CD38, Cd77, CD21, BCL6
  • Ki67 (High growth fraction >95%) 
  • Negative- CD5,   CD3, CD23,  TdT, BCL1, BCL2, MUM1, CD44, CD138, CD25, CD30 
• Molecular studies
  • Clonal rearrangements of immunoglobulin heavy a light chain genes
  • Somatic mutations of Ig genes are found 
• Cytogenetics/ FISH 
  • t(8:14)- Translocation of MYC on 8q24 to immunoglobulin heavy chain region on 14q32. 
  • cMYC expression by FISH is required for confirmation of diagnosis 
  • Less common – t (2:8),  t (8:22) 

Staging by Murphy &Hustu 

Prognosis: 

• Highly aggressive but potentially curable (up to 90%) 
• Patients without relapse for 2 years can be considered as cured
• Poor prognostic markers: 
  • Higher stage 
  • BM or CNS involvement 
  • Unresected tumor measuring >10cm in diameter 
  • High LDH 

Pretreatment Work-up: 

• History 
  • B-Symptoms 
• Examination 
  • LN: 
  • Spleen: 
• WHO P. S. 
• BSA 
• IHC/Flow cytometry 
• BMA and Bx 
• CT (CAP) 
• Stage 
• Hemoglobin 
• TLC, DLC 
• Platelet count 
• LFT- Bili- T/D   SGPT:    SGOT: Albumin:   Globulin: 
• Creatinine 
• Electrolytes: Na:       K:   Ca: Mg:     PO4:   
• Uric acid: 
• LDH 
• HIV: 
• HBsAg: 
• HCV: 
• LP- CSF- IT MTX 
• UPT 
• Cytogenetics 
• FISH- t (8;14) 
• Risk category 
• ECHO (If anthracyclines planned) LVEF-               %
• Chemotherapy consent after informing about disease, prognosis, cost of therapy, side effects, hygiene, food and contraception
• Fertility preservation
• PICC line insertion and Chest X ray after line insertion
• Tumor board meeting and decision
• Attach supportive care drug sheet
• Inform primary care physician

Treatment Plan: 

Paediatric Burkitt: Refer to R-LMB Intergroup B NHL 2010 trial protocol in NHL Section. Click here

Risk stratification: 

Low risk: Both criteria must be met

• Normal LDH 
• Stage 1 and completely resected abdominal mass 

Or Single extra-abdominal mass <10cm 

High risk: 

• Stage I with mass >10cm 
• Stage II to IV 

Monitoring After Treatment/ Follow-up: 

• History, examination and labs- every 2-3 months for 1 year, then 3 monthly for 1 year and then every 6 monthly 
• CT (C/A/P)- Only if clinically indicated  

Figures:

Figure 6.16.1- Burkitt leukemia/ lymphoma- Bone marrow biopsy

Recent advances:

R-CODOX-M/R-IVAC versus DA-EPOCH-R in patients with newly diagnosed Burkitt lymphoma

This multicentre, phase 3, open-label, randomised study compared two treatment regimens for newly diagnosed high-risk Burkitt lymphoma: R-CODOX-M/R-IVAC and DA-EPOCH-R. The study closed prematurely due to slow accrual. Of the 89 enrolled patients, 84 were included in the modified intention-to-treat analysis. The 2-year progression-free survival was 76% in the R-CODOX-M/R-IVAC group and 70% in the DA-EPOCH-R group. While DA-EPOCH-R did not demonstrate superior progression-free survival, it was associated with fewer toxic effects and supportive care requirements. The study suggests that DA-EPOCH-R is a valid therapeutic option for high-risk Burkitt lymphoma without CNS involvement.

https://doi.org/10.1016/S2352-3026(23)00279-X