Specific treatment

The aims of treatment are outlined under specific treatment in AML. The regimens used in adult ALL have evolved from successful treatments for childhood ALL.

Treatment for ALL consists of four contiguous phases:

1. Remission induction using vincristine, prednisolone, daunorubicin and asparaginase to achieve complete remission; more intensive induction using more anthracycline improves leukaemia-free survival.

2. CNS prophylaxis generally combines cranial irradiation (18-24 Gy in 12 fractions over 2 weeks) and intrathecal (IT) chemotherapy (methotrexate ± cytarabine or prednisolone) given early in the consolidation phase; IT therapy is continued in the consolidation and maintenance phases; CNS prophylaxis reduces the rate of CNS relapse from 30%75%.

3. Consolidation therapy to reduce tumour burden further and reduce risk of relapse and development of drug-resistant cells; consists of alternating cycles of induction agents and other cytotoxics; usually includes one or two 'intensification' phases; combinations of methotrexate at high dose, cytarabine, etoposide, m-amsacrine, mitox-antrone (mitozantrone) and idarubicin are used.

4. Maintenance therapy is necessary for all patients who do not proceed to a stem cell transplant; daily 6-MP and weekly methotrexate for 2-3 years plus cyclical administration of IV vincristine and IT methotrexate.

(►► simultaneous administration of IV vincristine and IT methotrexate MUST be avoided as errors can be fatal)

Allogeneic stem cell transplantation: an option for adults <50 with a compatible sib; leukaemia-free survival is superior after first remission allograft in patients with high risk disease (40% vs. <10% for Ph+ ALL); treatment-related mortality up to 30%; in low risk patients SCT should be reserved for second CR.

Matched unrelated donor transplant: an option in younger patients (<40) with very high risk disease (Ph/BCR-ABL positive ALL) but has up to 48% treatment-related mortality.

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Autologous stem cell transplantation: an alternative for adults up to 60: lower treatment related mortality (up to 8%); no clear survival advantage over maintenance therapy in first remission for most patients but may improve survival in very high risk disease without option of allo-graft.

• Enter patient into MRC or other high quality trial if possible.

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

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

• Mature B-cell ALL is treated with shorter more intensive cycles including high dose methotrexate, high dose cytarabine and fractionated cyclophosphamide; it has a higher incidence of CNS disease at diagnosis and relapse.

• CNS leukaemia at diagnosis is treated by adding intensified intrathecal triple therapy to cranial irradiation; IT methotrexate, cytarabine and prednisolone 2-3 x times weekly over 3-4 weeks until 2 consecutive CSF samples are negative; insertion of an Ommaya reservoir facilitates such frequent IT therapy.

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