CLL richters transformation (BSH 2021)

90% Diffuse Large B Cell Lymphoma (DLBCL-RT)

10% Hodgkin Lymphoma (HL-RT)

<1% Other lymphomas

 Intro

 

Definition of Richters Transformation (RT) - high grade lymphoma occurring on a background of CLL

Occurs in 2-10% of CLL patients

Look for new B symptoms, asymmetric rapidaly enlarging nodes, LDH rise

90% of cases are DLBCL, although Hodkin (10%) and other rare forms may occur

Clonality

  • Clonally related cases follow an aggressive course with poor response to treatment

  • Clonally-unrelated case outcomes much more in line with de novo DLBCL

  • Clonal relationship present in 70-80% of DLBCL-RT and 30-40% of HL-RT

 

Investigations

 

Biopsy for diagnosis

  • Surgical biopsy preferred. Core biopsy is alternative.

  • DLBCL-RT

    • Sheets of large neoplastic B cells with centroblastic or immunoblastic morphology

    • 80% ABC type, 20% GCB type

    • TP53, MYC, CDKN2A and NOTCH1 mutations all commonly seen

  • HL-RT

    • CD30+, CD15+, CD20- cassical Reed-Sternberg cells

    • Usually EBV positive

Virology

  • HIV, Hep B/C, EBV and CMV

PET-CT

  • Helpful to aid in targeting the area of node/mass of greatest uptake for biopsy

  • High sensitivity, low specificity for identifying RT

  • SUVmax cut offs of >5 and >10 have both been studied

Cytogenetics/Molecular

  • TP53 mutation and 17p deletion

  • Clonality studies - Performed by sequencing of IgHV genes of both tumours

 

Prognosis

Prognostic Factors:

  • Clonality - Median OS 14 vs 62 months for clonally-related vs clonally-unrelated DLBCL-RT

  • Prior CLL treatment - Median OS 8 vs 46 months for previously treated vs untreated CLL

  • Staging and Avidity on PET-CT

Clinical RT score (2006 J Clin Oncol)

  • PS >1, LDH >1.5x ULN, Plt <100, Bulk >5cm, 1+ prior line of therapy

  • Median OS ranges 0.3 - 1.1 years depending on score

A second score incorporating cytogenetics (2011 Blood)

  • ECOG PS, achievement of CR with induction, TP53 status

  • Median OS: high risk 8 months, intermediate risk 25 months, low risk 70% OS at 5 yrs

Management

 

DLBCL-RT

First line: R-CHOP

  • ORR 40-60%, median PFS 6-10 months

  • More intense regimens have generally proven too toxic

  • A minority of patients (previously untreated CLL, TP53-intact) achieve CMR and durable remissions

Consolidation Transplant? - Auto and Allo have been used. Consider in young, fit patients.

Relapse/Refractory

  • Clinical trial

  • Palliative care

  • 2nd line chemo, e.g. R-Gem-Ox

  • CAR-T - currently case-by-case basis, need to meet de novo DLBCL criteria before considering

HL-RT

First line: ABVD or CHOP+/-R

Only small case series for outcomes, but 2-yr OS 72% has been reported.