Consolidation Therapy in Acute Myeloid Leukemia (AML)

Treatment of acute myeloid leukemia (AML) with chemotherapy may be classified into two phases: induction of remission and post-remission therapy.

In nearly 80% of AML patients, induction therapy induces complete remission, though the percentage tends to decrease with increase in age and other factors, such as genetic abnormalities.

Once complete remission is achieved, post remission therapy is started and it involves consolidation therapy and maintenance. In the absence of therapy post remission, disease relapse occurs in more than 90% of AML patients within a few weeks to months.

While induction chemotherapy aims to lower the number of AML cells, the main aim of post remission therapy is to prevent disease recurrence.

Consolidation therapy involves intensive chemotherapy given right after recovery from induction. It is administered as quickly as possible after induction. The closer together induction and consolidation are given, the lesser the chance of leukemia recurrence. In case of younger patients, key options for consolidation therapy are (a) multiple cycles of high-intensity chemotherapy using cytarabine and (b) allogeneic or autologous stem cell transplant.

In terms of drugs, the key difference between consolidation chemotherapy and induction chemotherapy is that in induction therapy cytarabine and anthracycline are used, while in consolidation only cytarabine is used. This drug is administered at high doses over a period of 5 days, repeated every 4 weeks, normally for 3 or 4 cycles.

Stem Cell Transplant

In another approach, once induction therapy is over, high intensity chemo is given followed by either an allogeneic or autologous stem cell transplant. In patients with unfavorable prognostic factors, such as genetic abnormalities, disease spreading to the central nervous system, or the presence of other disorders, doctors usually recommend very intensive therapy. For example, a stem cell transplant may be advised. In healthy people with favorable prognostic factors, doctors might recommend a stem cell transplant only when there is disease recurrence.

Autologous Stem Cell Transplant

In autologous stem cell transplant, the patient’s own stem cells are used. Autologous stem cell transplant is an option only if the patient is in remission and gathering the patient’s own leukemia-free stem cells is a possibility. Stem cells taken from the patient will need to be treated to destroy any leukemic cells that may be present so as to decrease the chances of disease recurrence.

Allogeneic Stem Cell Transplant

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. Intensive radiation or chemo causes serious side effects and also impairs the ability to produce one’s own stem cells. The key objectives of this intensive chemotherapy are to kill as many leukemic cells as possible and to deactivate the immune system and thus reduce the possibility of a graft rejection.

Studies have shown that stem cell transplants are more effective than chemotherapy in reducing the risk of disease relapse. However, stem cell transplantation is highly complicated and can be fatal in some cases, including older and fragile patients who might not tolerate intensive treatment. In some cases, stem cell transplant may be recommended when remission is not achieved using induction therapy.

Determining the best treatment option for consolidation is not easy 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. They may be treated with low intensity chemotherapy usually involving 1 to 2 cycles of cytarabine or 1 to 2 cycles of standard dose cytarabine usually along with daunorubicin or idarubicin.

References

• http://www.texasoncology.com/types-of-cancer/leukemia/acute-myeloid-leukemia/acute-myeloid-leukemia-consolidation/
• http://www.cancer.org/cancer/leukemia-acutemyeloidaml/detailedguide/leukemia-acute-myeloid-myelogenous-treating-typical-treatment-of-aml
• http://jco.ascopubs.org/content/31/17/2067.full