A 55-year-old man presented in 2002 with severe tiredness, developing over a period of 4 months, associated with weight loss of 5 kg and night sweats. He had no previous medical history of note and was taking no medication. He had two brothers who were both well. On examination he looked pale and had a palpable spleen 4 cm below the left costal margin. Lymph nodes were palpable up to 2 cm in diameter in both axillae and in both sides of his neck. At presentation his white cell count was 60.0 × 109/l, neutrophils 2.4 × 109/l, lymphocytes 56 × 109/l, haemoglobin 9.8 g/dl and platelets 88 × 109/l. Immunophenotyping confirmed that the lymphocytes were clonal (CD19+, CD5+, CD23+, CD20weak, surface immunoglobulin κweak). His bone marrow trephine biopsy was replaced by small lymphocytes. A computed tomography scan confirmed the presence of widespread lymphadenopathy and splenomegaly. His direct Coombs’ test (DCT) was negative.
What is the diagnosis?
What stage is his disease?
How would you manage his case?
His presentation and immunophenotyping are typical of chronic lymphocytic leukaemia (CLL).1 He has advanced stage disease in view of his bone marrow failure (either Binet’s stage C or Rai stage IV [Table 20.1] – Binet’s staging system2 is generally used in Europe and the Rai system3 in the USA) and he therefore requires therapy. If he had presented in 2007 he would have been treated with fludarabine plus cyclophosphamide, as this has been proven in three large, randomized trials to be superior to fludarabine alone in terms of response rates and progression-free survival.4–6 In 2009, the addition of rituximab, the monoclonal antibody to CD20, to FC (FCR) was shown to improve response rates, progression-free survival and overall survival and has now become the standard therapy for patients with CLL who require treatment and are relatively fit.7,8 However, in 2002 these trials were in progress and he was entered into one of them, the LRF CLL4 trial. This was a randomized trial in which he was assigned to the fludarabine monotherapy arm. In 2001 the National Institute of Clinical Excellence issued a Technology Appraisal for fludarabine9 and recommended that it should be given orally rather than intravenously at a dose of 40 mg/m2/day for 5 days every 4 weeks.
Table 20.1Rai staging system (USA) |Favorite Table|Download (.pdf) Table 20.1 Rai staging system (USA)
|Stage ||Definition |
|0 ||Blood lymphocyte count 15 × 109/l or more, with 40% or more lymphocytes in marrow differential count |
|I ||Stage 0 plus enlarged lymph nodes |
|II ||Stage 0 plus enlarged spleen, or liver, or both; lymph nodes may or may not be enlarged |
|III ||Stage 0 plus ...|