Second remissions are more difficult to achieve and are virtually never durable. The decision to treat a person at the time of recurrence will therefore (even more than at presentation) depend on the patient’s overall situation and his/her wishes. In younger patients, provided a second remission can be achieved, cure is still a possibility for a proportion, with the use of myeloablative therapy with allogeneic/autologous BMT. In older patients, the options lie between further intensive combination chemotherapy and keeping the person as well as possible for as long as possible, with supportive measures such as blood transfusions for anaemia, antibiotics for infection and the judicious use of palliative oral drugs that help to lower the circulating blast cell count.
Acute promyelocytic leukaemia
APML has a specific association with disseminated intravascular coagulation (DIC) . Patients may present with severe bleeding and this tends to increase when treatment is started as the leukaemic blast cells break down, leading to further consumption of clotting factors and platelets. Treatment consists of regular, twice daily, platelet transfusions and maintenance of the fibrinogen level with fresh frozen plasma. Provided remission can be achieved, patients with APML (which is associated with the chromosome translocation t(l5; 17» have a somewhat better prognosis overall than patients with other subtypes of AML. Ensuring that they survive this early period of DIC is therefore critical. It has recently been demonstrated that the use of a differentiating agent, all-trans-retinoic acid (ATRA), given orally can lead to the achievement of CR in some patients with APML. ATRA has a differentiating effect on leukaemic promyelocytes, both in vitro and in vivo. It does not appear to be effective in other subtypes of AML. Unfortunately such remissions do not last and need to be consolidated with conventional chemotherapy. The advantage is that patients receiving ATRA do not usually develop DIC, with a decrease in the risk of fatal haernorrhage.
Acute lymphoblastic leukaemia
Predominantly a disease of children, ALL is also potentially curable. Overall, 90% of children respond to treatment and 50-60% are cured. The results in adults are not as good, with only approximately 30% being cured. ALL is classified on the basis of the morphology of the leukaemic blast cells into subtypes Ll-L3.
There is also an ‘immunological’ classification which is continually evolving as more sophisticated techniques are developed for detecting the B- or T-cell origin of lymphoid cells.
The principles of treatment are the same as for AML, the aim being to return the bone marrow to normal and the person to a normal state of health. The sequence of treatment is, however, somewhat different because ALL has a propensity for involvement of the central nervous system (CNS); thus treatment also includes prophylactic intrathecal drugs (methotrexate or cytosine arabinoside) with or without prophylactic cranial radiotherapy to the meninges. Most patients also receive oral maintenance therapy for 2-3 years. The sequence of treatment is shown.
Cyclical combination chemotherapy comprising vincristine, prednisolone and an anthracycline such as doxorubicin forms the basis of most treatment regimens. Other drugs such as r.-asparaginase, cyclophosphamide and/or cytosine arabinoside (also known as cytarabine) are also increasingly being used in patients (both adults and children) considered to be at high risk of recurrence.
Although a proportion of adult patients are cured with the initial therapy, in the rest the disease recurs and ultimately proves fatal unless secondary remission can be achieved and further treatment involving BMT given, when a further 20-30% of patients will survive long term.