Specific treatment

Initial aim of therapy is to eliminate the leukaemic cells and achieve a complete haematological remission (CR), defined as normal BM cellularity with blast cells <5% and normal representation of trilineage haematopoiesis, normalisation of peripheral blood count with no blast cells, neutrophils >1.5 x 109/L, platelets >100 x 109/L and Hb>10g/dL. Leukaemia is undetectable by conventional morphological techniques but may be demonstrated by more sensitive molecular techniques (when available) and CR is not synonymous with cure. CR may result from a three-log kill from 1012 leukaemic cells at diagnosis to 109 at CR.

Treatment consists of 3 phases: (1) remission induction to achieve CR 156 (usually 1-2 courses of combination chemotherapy); (2) consolidation therapy to reduce leukaemia burden further and reduce risk of relapse (optimum number unknown, usually 2-4 which may include an 'intensification' phase or an autologous or allogeneic stem cell transplant); (3) maintenance therapy has been abandoned in AML except in some elderly patients where intensive consolidation cannot be tolerated.

• Enter patient into MRC or other high quality trial if possible. MRC randomised studies in acute leukaemia are based on large patient numbers and compare incremental experimental therapy with best treatment arm from previous trials.

• Treatment protocols are age related; patients >60 only tolerate less intensive treatments and very rarely transplantation.

• Supportive treatment alone is a valid treatment option in the >75 age group or if there are coexistent serious general medical problems.

• Outline treatment for patients <60 years is 4-5 courses of intensive combination chemotherapy initially including daunorubicin or another anthracycline and cytosine arabinoside each lasting 5-10 days with a 2-3 week period of profound myelosuppression.

• Major complications are infective episodes which may be bacterial (Gram +ve and Gram -ve), fungal (Candida and Aspergillus), and less commonly viral (esp. HSV, HZV).

• APML (FABM3) is a distinct category of AML requiring different treatment. The risk of DIC prior to and during initial therapy due to release of thromboplastins from leukaemic cells is an indication for urgent treatment. The use of all-trans-retinoic acid (ATRA) with initial therapy reduces the risk of DIC. After this the prognosis is good. ATRA induces differentiation of the abnormal clone by overcoming the molecular block resulting from the t(15;17) translocation. ATRA alone cannot achieve sustained remission but in combination with chemotherapy 70% of patients may be cured. Arsenic trioxide appears to be a useful agent in those patients who relapse. Persistence of the fusion product after therapy detected by RT-PCR predicts relapse.

• Autologous stem cell transplantation is an option for intensive consolidation of younger patients (<60) with intermediate or poor-risk disease who achieve CR. It has lower procedure-related mortality or morbidity than an allograft but lacks a graft-versus-leukaemia effect and has a relapse rate of 40-50%.

• Allogeneic stem cell transplantation from a compatible sibling donor is an option for younger patients (<45) with intermediate or poor-risk disease. Significant mortality (7-13%) and morbidity may be reduced by non-myeloablative conditioning regimens and increase the age range. Unrelated donor grafts have higher toxicity. Donor lymphocyte infusion (DLI) is used to treat recurrence after an allogeneic transplant.

• In the longer term, relapse is the main complication.

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