The chemotherapeutic management of acute myeloid leukemia (AML) consists of two parts: remission induction and post-remission therapy. Remission induction involves intense chemotherapy to induce remission in the bone marrow. Key drugs used in induction chemotherapy are cytarabine and anthracycline.
Anthracyclines cannot be used in patients with heart disease and hence other drugs, such as topotecan or fludarabine, need to be used. These drugs induce complete remission in nearly 80% of AML patients, though this percentage tends to decrease with increasing age and other factors, such as genetic abnormalities.
After about 1 to 2 weeks of induction chemotherapy, a bone marrow biopsy may be done and it should ideally show few bone marrow cells and a tiny amount of blasts. However, if biopsy shows presence of leukemic cells, more chemotherapy may be administered. If the biopsy does not show the presence or absence of leukemia clearly, it may be repeated after a week’s time.
Once complete remission is achieved, post remission therapy is started. While induction chemotherapy aims to lower the number of AML cells present at the time of diagnosis to undetectable levels, the main aim of post remission therapy is to prevent disease recurrence. In the absence of therapy after remission, disease relapse occurs in more than 90% of AML patients within a few weeks to months.
Post remission therapy involves consolidation and maintenance. Consolidation therapy involves intensive chemotherapy given right after recovery from induction therapy. It is administered as quickly as possible after induction. The closer together induction and consolidation are given, the lesser the chance of leukemia recurrence. The possibility of disease relapse is also inversely proportional to the intensity of chemotherapy; lower drug doses do not have the same impact as higher doses.
Consolidation therapy involves multiple courses of myelosuppressive chemotherapy or intensive chemotherapy followed by stem cell transplantation, which can be either autologous or allogeneic.
In consolidation therapy only cytarabine is given in high doses over a period of 4 to 5 days and it is repeated every 4 weeks, for about 3 or 4 cycles. In the second approach, once induction therapy is over, high intensity chemotherapy is given followed by either an allogeneic or autologous stem cell transplant.
In autologous stem cell transplant, patient’s own stem cells are used. Allogeneic stem cell transplant involves the transfer of stem cells from a healthy donor to the patient’s body after intensive radiation or chemotherapy. It can be risky due to the high intensity chemotherapy or radiation given prior to stem cell transplantation. The key objectives of this intensive chemotherapy is to deactivate the immune system and prepare it for receiving new stem cells from donor and reduce the possibility of a graft rejection.
Studies have shown that stem cell transplants are more effective than chemo in reducing the risk of disease recurrence. However, stem cell transplantation is highly complicated. It can be fatal in some cases, including older and fragile patients who might not be able to tolerate intensive treatment. In some cases, stem cell transplant is recommended when remission is not achieved at the end of induction therapy.
Another phase of post remission therapy is maintenance therapy. This involves low-dose chemotherapy and is beneficial to patients having acute lymphoblastic leukemia. Maintenance therapy is rarely employed in AML.
Determining the best treatment option for consolidation is complicated and each approach has its own pros and cons. Physicians need to consider a number of factors such as age and health status before recommending the best therapy for each patient. Older adults in poor health may not tolerate intensive chemotherapy.
Reviewed by Jonas Wilson, Ing. Med.