Case 44 – summary

Chronic lymphocytic leukaemia

Our case began with a blood film demonstrating small mature lymphocytes, and smear cells, which are findings typical of CLL.

The flow cytometry confirmed this diagnosis with a CLL score of 5/5.

CD5 +

CD23+

Fmc7 negative

CD79b negative

Surface Ig weak.

A score of 5/5 can be found in CLL, SLL, and monoclonal B lymphocytosis

The patient was found to be anaemic on review, as well as being symptomatic with widespread lymphadenopathy and night sweats.  Therefore the decision was to commence chemotherapy.

Assessment of the patient should include:

  • History and examination
  • On diagnosis of CLL patients should be advised to receive vaccination against s.pneumoniae, h.influenzae and influenza.
  • Comorbidity assessment and review of performance status. This should aid in determining whether the patient is fit for treatment.
  • FBC – indications for treatment are a HB <100g/l, plt <100. However the patient should also be investigation for a possible autoimmune cause – AIHA, ITP and Evans syndrome can occur in patients with CLL
  • A biopsy is indicated if there has been sudden progression of one area of disease – suggesting Rickters transformation (transforming to either DLBCL or Hodgkins)
  • Pre- treatment – patients should have cytogenetic analysis, specifically looking for TP53 disruption, which if present in > 20% cells, would alter management of the patient.
  • Hepatitis B and C serology should be checked.
  • Bone marrow should be considered pre and post treatment to assess response.

Cytogenetics

Poor risk Good risk
Unmutated IGHV Deletion 13p
ZAP70+, CD38+
TP53 disruption – 17p deletion
Deletion 11q

First line standard treatment in a patient fit for chemotherapy would be FCR (CLL8 and CLL10 trials have suggested this should be first line treatment).  If there are concerns with regard to the patients fitness for treatment, alternative treatment plans could include: bendamustine + rituximab, chlorambucil + CD 20 antibody (rituximab, obinutuzumab, ofantuzumab), or chlorambucil as monotherapy.   Chlorambucil + obinutuzumab or ofantuzumab have been found to produce an improved response when compared with chlorambucil + rituximab, and a better overall survival is achieved if a CD20 antibody is added to chlorambucil.

This case was designed to prompt discussion of management for a newly diagnosed patient who is found to have TP53 disruption in >20% of cells.  Treatment of patients with TP53 disruption with standard chemotherapy is associated with significantly worse outcomes in terms of disease response, duration of response and overall survival

Current BCSH guidelines have recently been updated.  Previously the first line therapy for patients with TP53 disruption was alemtuzumab + steroids.  The new guidelines suggest that first line treatment should be:

  • Ibrutinib – side effects include: myelosupression, infection, haemorrhage, secondary malignancy, embryo-foetal toxicity and renal toxicity.
  • Or idelalisib +rituximab – diarrhoea/colitis, elevated liver enzymes, pneumonitis, rash, and neutropenia.

The majority of the data available for these patients come from trials of patients with relapsed disease.  However small numbers of patients have been treated first line with these agents and show similar response.   These are licensed for first line treatment, however there is no agreed national funding.  The choice of agent is dependent on a number of factors, including patient co-morbidities and funding.  The role of allogeneic transplant now appears unclear with the advent of these new agents

These agents are also suggested for relapsed disease.  Ibrutinib may be consider if the patient has had at least one line of chemotherapy and relapsed within 24 months.  Idelalisib + rituximab can be used if the patient has had previous treatment with two cytotoxic regimes and has relapsed within 24 months.

BCSH guidelines, CLL interim statement. http://www.bcshguidelines.com/documents/Interim_statement_CLL_guidelines_version6.pdf

CLL 10 trial, interim analysis  http://www.bloodjournal.org/content/122/21/526?sso-checked=true

CLL 11 trial Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions  http://www.nejm.org/doi/full/10.1056/NEJMoa1313984

About TeamHaem

Online education and discussion about all things haematological
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