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

 

Three categories

  • Endemic (African)

  • Sporadic

  • Immunodeficiency-associated (HIV)

 

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