burkitt lymphoma/leukaemia (BL) (How i treat 2014)
Ki67 >99%, CD10+/-, CD19+, CD20+, CD22+, CD38++, CD81++, CD43+, CD79a+, Ig+, BCL6+
TdT-, CD5-, BCL2-, CD23-
t(8;14) MYC-IGH, t(8;22) MYC-LambdaLC, t(2;8) MYC-KappaLC
Aggressive B-cell non-Hodgkin lymphoma, uniformly associated with MYC translocations.
Doubling time of 25 hours – probably fastest growing of any cancer
Endemic (African) BL
Uniformly EBV positive
3-6 cases per 100,000 children per year in equatorial Africa
Incidence is increasing in line with increasing HIV and malaria
Classically presents with jaw or facial bone tumours
2-3 cases per million per year in Europe
30% of paediatric lymphomas, 1% of adult NHL
Men > Women (4:1)
Occurs independently of CD4 count and so incidence has not fallen with introduction of HARRT.
Complete effacement of normal tissue architecture
Medium sized, highly monomorphic cells with round nuclei, prominent nucleoli and basophilic cytoplasm with prominent cytoplasmic lipid vacuoles.
Interspersed between these cells are benign histiocytes that have become enlarged and irregular due to ingestion of cellular debris —> Starry sky appearance
t(8;14) present in >80% of cases. Brings MYC under the control of IGH enhancer elements —> increased MYC expression. Further 15% of cases have other MYC rearrangements.
Additional mutations – CCND3, TP53, CDKN2A, TCF-3 (E2A), ID3
EBV mechanism is poorly understood. BL cells express a latent viral protein, EBNA1, which is not known to be directly oncogenic.
Clinical trials – 75-90% OS
Real world data – 56% 5-yr OS
Tumour lysis syndrome
Blood product support
2 cycles each of CODOX-M and IVAC, alternating
Includes high dose cytarabine and high dose MTX
Autograft in first remission?
PFS appears to be the same as for aggressive chemotherapy alone