A 24-year-old male presents with priapism and is found to have a grossly elevated white cell count of 450 × 109/l. Haemoglobin is 10.4 g/dl and platelets 620 × 109/l. Clinical examination reveals splenomegaly at 7 cm below the costal margin and subsequently a diagnosis of chronic myeloid leukaemia (CML) is made following bone marrow examination and cytogenetic analysis. The patient has two brothers who are fit and well.
What would be the optimum initial management of this patient?
How should his response to treatment be monitored?
What is the role of allogeneic stem cell transplantation in the management of this condition?
Management of CML has been revolutionized in the last few years by the emergence of tyrosine kinase inhibitors, notably imatinib mesylate, which has been shown to be superior in terms of haematological, cytogenetic and molecular responses to the previous best non-transplant treatment with interferon-α.1 This major advance in the management of the disease was recognized in the UK by the National Institute for Clinical Excellence in 2002, when it announced that imatinib therapy was the recommended first-line treatment for all newly diagnosed patients.2 Subsequent follow-up of patients treated with imatinib has confirmed that cytogenetic responses are durable, with 85% of patients expected to achieve a major cytogenetic response within 1 year of therapy. Recent data that have emerged following the 5-year analysis of imatinib-treated patients have confirmed that responses are not only durable but that cytogenetic and molecular responses, as measured by reduction in quantitative real-time reverse transcription–polymerase chain reaction (RT–PCR) testing for the BCR-ABL gene, may improve with time.3 The question for the management of young patients with the disease is what, if any, is the continued role for allogeneic stem cell transplantation (alloSCT).
Allogeneic stem cell transplantation is by convention the only proven curative treatment for the disease, with 5-year survival rates of 75% for sibling transplants performed in the first chronic phase of the disease within 1 year of diagnosis. However, the toxicity associated with transplantation may be increased when using an unrelated donor, and quality of life may be significantly affected by the complications of bone marrow transplantation, notably graft-versus-host disease. There are a variety of donor and transplant factors that may impact on outcome which have been evaluated to produce a prognostic scoring system – the European Blood and Marrow Transplantation (EBMT) or ‘Gratwohl’ score – which may help in selecting patients for transplant based on expected outcome (Table 21.1).
Table 21.1The European Blood and Marrow Transplantation (EBMT) score |Favorite Table|Download (.pdf) Table 21.1 The European Blood and Marrow Transplantation (EBMT) score
|Risk factor || ||Score |
|Disease stage ||chronic phase ||0 |
| ||accelerated phase ||1 |
| ||blast crisis ||2 |
|Age ||<20 years ||0 |
| ||20–40 years ||1 |
| ||>40 years ||2 |
|Donor/recipient sex combination...|