Treatment of Leukemia

Acute lymphoblastic leukemia ◙

Remission induction ● At presentation , patients with acute leukaemia have a very high tumour burden and is at great risk from the complications of bone marrow failure and leukaemic infiltration.

●The aim of remission induction is to rapidly kill most of the tumour cells and get the patient into remission. ●This is defined as less than 5 % blasts in the bone marrow, normal peripheral blood count and no other symptoms or signs of the disease. ● In remission, however, a patient may still be harbouring large numbers of tumour cells and, without further chemotherapy, virtually all patients will relapse. ●Nevertheless, achievement of remission is a valuable first step in the treatment course. Patients who fail to achieve remission need to change to a more intensive protocol.

Minimal residual disease ● Even when the blood and bone marrow appear to be clear of leukaemia, small numbers of tumour cells may sometimes be detected by fluorescence activated cell sorter (FACS) analysis or molecular methods. ● A positive result indicates minimal residual disease (MRD) and the analysis of children for the presence of MRD at day 29 or adults after 3 months of treatment has prognostic significance and is now being used in planning therapy. ● More intensified therapy, or even allogeneic stem cell transplantation, is given to those with persistent MRD.

Acute myeloid leukemia (AML) ◙

● Maintenance therapy is of no value except in promyelocytic AML with ATRA. CNS prophylaxis is not usually given. ● New drugs such as FLT3 inhibitors are now being introduced for tumours with FLT3 mutations. ● Monoclonal immunoconjugates targeted against CD33 (e.g. Mylotarg R) or CD45 provide an additional therapeutic option for initial or consolidation AML therapy. Acute promyelocytic leukaemia (APML) has its own treatment protocol. ● A haemorrhagic syndrome can lead to catastrophic haemorrhage and may be present either at diagnosis or develop in the first few days of treatment.

● It is treated as for disseminated intravascular coagulation (DIC) with multiple platelet transfusions and replacement of clotting factors with fresh frozen plasma. ●In addition, all‐trans retinoic acid (ATRA) therapy is given for this disease subtype. ►The differentiation syndrome (also known as ATRA syndrome): ● It is a specific complication that may arise after ATRA treatment. ● Clinical manifestations : fever, hypoxia with pulmonary infiltrates and fluid overload. These manifestations are caused by the neutrophilia that follows differentiation of promyelocytes into mature neutrophils. ●Treatment of the differentiation syndrome is with steroids and ATRA is only discontinued in very severe cases.

CML Tyrosine kinase inhibitors ●Tyrosine kinase inhibitors (TKI) are the mainstay of the treatment of CML and several different drugs are now available . ●First‐line therapy for patients with chronic phase CML is usually Imatinib, Nilotinib or Dasatinib. ●Around 60 % of patients given imatinib achieve an excellent response.

CLL

1- Combination of Chemotherapy (e.g. chlorambucil and

cyclophosphamide) with a monoclonal antibody against CD20 (such as rituximab).

2- New drugs for B‐CLL :

A- Drugs which suppress signalling through the B cell receptor B- Drugs which suppress the activity of BCL‐2.

3- Radiotherapy : This is valuable in reducing the size of bulky lymph

node groups that are unresponsive to chemotherapy.