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
Intro
Aggressive B-cell non-Hodgkin lymphoma, uniformly associated with MYC translocations.
Doubling time of 25 hours – probably fastest growing of any cancer
WHO-HAEM5 Classification
WHO-HAEM5 has two types: EBV postiive vs EBV negative
This replaces the previous classification of endemic / sporadic / immunodeficient
Notes below still use old calssficiation until I read some newer guidelines
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
Sporadic BL
2-3 cases per million per year in Europe
30% of paediatric lymphomas, 1% of adult NHL
Men > Women (4:1)
Immunodeficiency-Associated BL
Essentially HIV
Occurs independently of CD4 count and so incidence has not fallen with introduction of HARRT.
Pathophysiology
Histology
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
Genetics
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
EBV mechanism is poorly understood. BL cells express a latent viral protein, EBNA1, which is not known to be directly oncogenic.
Prognosis
Clinical trials – 75-90% OS
Real world data – 56% 5-yr OS
Treatment
Supportive
Tumour lysis syndrome
Renal impairment
Blood product support
GCSF
Neutropenic sepsis
Chemotherapy
R-CODOX-M/IVAC
2 cycles each of CODOX-M and IVAC, alternating
Includes high dose cytarabine and high dose MTX
Alternatives
R-da-EPOCH
HyperCVAD
ALL regimens
Autograft in first remission?
PFS appears to be the same as for aggressive chemotherapy alone