Acute myeloid leukaemia (AML)

This is the most common acute leukaemia in adults and represents a heterogeneous disease with the outcome heavily influenced by acquired genomic abnormalities. Median age at diagnosis is 66 years.

In younger patients (<60 years) and selected older patients without adverse disease features or significant co-morbidities, intensive therapy is given with curative intent. Therapy is generally divided into a remission induction and a consolidation phase. The mainstay of induction therapy for the last 40 years has been intravenous chemotherapy with cytosine arabinoside (Ara-C) in combination with an anthracycline, usually given for two cycles. The consolidation phase generally consists of regimens containing high-dose Ara-C for one to three cycles and/or, in patients with adverse disease factors, allogeneic stem cell transplantation. With current treatments, remission induction is successful in greater than 80% of patients [2]. A 5-year OS is 42% but varies considerably by disease risk status. For example, acute myeloid leukaemia (AML) with core binding factor translocations or isolated nucleophosmin-1 (NPM1) mutations has a 5-year survival greater than 60%, whereas corresponding survival for patients with adverse chromosome abnormalities is less than 20%. The main complications of treatment are infections due to the prolonged period of severe neutropenia. Infections are usually bacterial and less commonly fungal in origin.

In older patients (>60 years), survival remains less satisfactory with cure rates of less than 10% and a disappointing median survival of less than 1 year overall. Swedish registry data indicate that for most patients up to 79 years of age, intensive therapy produces a better outcome with remission rates around 50% and a 2-year survival of 20% [3]. The relatively poorer outcome in older patients is not strongly influenced by age per se [4] but is due both to patient-related factors, i.e. co-morbidities, and disease-related factors, i.e. higher rate of adverse cytogenetic abnormalities. For frailer patients, low-intensity treatment, for example, with subcutaneous Ara-C or oral hydroxycarbamide, can achieve disease control for a period of weeks or months.

An important subtype of AML (10%) is acute promyelocytic leukaemia (APL), which enjoys a markedly superior long-term OS of greater than 80%. Treatment is based on chemotherapy with an anthracycline in combination with all-trans-retinoic acid (ATRA), which induces terminal differentiation of the abnormal promyelocytes. Recent data suggests that combination treatment of ATRA with arsenic trioxide can achieve similar outcomes and may allow cure without cytotoxic chemotherapy. Early death rate is still greater than 10%, mainly due to coagulopathy (fibrinolysis) and thrombocytopenia leading to haemorrhage. Aggressive management of such early complications is essential as patients surviving these will have an excellent long-term prognosis (see Chapter 4 for acute management of suspected APL).

Acute lymphoblastic leukaemia (ALL)

In contrast to children and adolescents, acute lymphoblastic leukaemia (ALL) is uncommon in adults. Similar to AML, the outcome for ALL patients differs significantly between patients less than 60 years and older patients. Treatment with curative intent consists of an induction phase usually containing dexamethasone, vincristine, asparaginase and daunorubicin, followed by exposure to cyclophosphamide and Ara-C. The consolidation phase generally contains agents to prevent central nervous system (CNS) relapse, e.g. intravenous methotrexate, and may include periods of intensification using similar agents as during induction phase. Treatment is completed by a long maintenance phase of oral mercaptopurine and methotrexate in addition to intermittent intravenous vincristine and intrathecal chemotherapy. Overall, in patients not undergoing allogeneic stem cell transplant, total treatment duration is around 24–30 months. Remission can be achieved in 80–95% of patients. However, the majority will relapse. Despite recent improvements, outcome in adults remains strikingly inferior to paediatric results, and long-term survival, even with intensive treatment, can only be achieved in around 30–40% of patients. Allogeneic stem cell transplantation instead of maintenance is considered for eligible patients with high-risk and standard-risk disease and results in long-term survival of around 50%.

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