Patients with progressive or relapsed leukemia remain curable despite failing initial treatment. Patients failing initial treatment can be divided into two broad categories. Patients who fail to achieve an initial complete disappearance or remission of their cancer following two or more courses of remission induction chemotherapy are referred to as “induction failures.” Patients who achieve a complete remission to initial treatment and then experience a cancer recurrence are said to have relapsed leukemia. Relapse of leukemia may occur several months to years after the initial remission; however, the majority of relapses occur within 2 years of initial treatment.
A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.
The following is a general overview of the treatment of relapsed/refractory acute myeloid leukemia. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.
Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.
If a remission is not achieved or a recurrence occurs, there are essentially two choices of therapy. Since subsequent treatment with chemotherapy is rarely curative, a palliative approach can be adopted where drugs are administered in non-toxic doses to keep the disease under control for as long as possible. In this situation, the emphasis is on the quality of life and supportive care measures.
The alternative approach is to receive more intensive treatment in an attempt to produce a complete remission. There are two main intensive strategies available. For younger patients, a bone marrow or blood stem cell transplant offers a possibility for control or cure of the leukemia. The other approach is to participate in clinical trials evaluating new treatments. Both of these alternatives are discussed below.
Patients Failing Induction or Relapsing after a Complete Remission
High-dose chemotherapy and autologous stem cell transplant is rarely a treatment option for patients who fail remission induction therapy because the bone marrow contains many leukemia cells. Treatment for patients failing remission induction is currently allogeneic stem cell transplant or chemotherapy.
Patients with AML that relapses after an initial complete remission can be cured with autologous stem cell transplant. Many centers have reported cure rates of 25-50% for patients with AML transplanted in second remission or early in first relapse. These results are often obtained because patients elected to have their stem cells collected and stored at the time of their initial remission. Collecting stem cells after relapse is less successful since less than half of patients receiving reinduction chemotherapy will achieve a second remission. Patients without previously stored stem cells, therefore, are often treated with allogeneic stem cell transplant or additional chemotherapy.
In these settings, allogeneic stem cell transplantation offers the only prospect of long-term disease-free survival. If a compatible family member donor or autologous stem cells are not available, there should be a search for an unrelated donor or an umbilical cord source of stem cells.
Strategies to Improve Treatment
While significant progress has been made in the treatment of leukemia, many patients still succumb to cancer and better treatment strategies are still needed. Future progress in the treatment of leukemia will result from continued participation in appropriate clinical studies. Currently, there are several areas of active exploration aimed at improving the treatment of leukemia.
Stem Cell Transplant: High-dose chemotherapy and autologous or allogeneic stem cell transplantation are currently superior treatment options for many patients. To learn about new developments with these therapies, go to strategies to improve Allogeneic Stem Cell Transplant or Autologous Stem Cell Transplant.
Phase I Trials: New chemotherapy drugs continue to be developed and evaluated in patients with recurrent leukemia in phase I clinical trials. The purpose of phase I trials is to evaluate new drugs in order to determine the best way of administering the drug and whether the drug has any anti-leukemia activity in patients.
New Chemotherapy Regimens: Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies for use as treatment of leukemia is an active area of clinical research.
For example, physicians at MD Anderson Cancer Center evaluated a treatment regimen utilizing standard AML drugs Novantrone® and cytarabine, combined with a new chemotherapy drug, Fludara® for the treatment of 55 adult patients with refractory acute leukemia. The complete remission rate was 27% and the time to achieve a complete response was only 42 days. The major side effects from treatment were low blood counts and minor abnormalities of the liver, all of which resolved. This new chemotherapy regimen may be able to prepare patients for an allogeneic bone marrow or peripheral blood stem cell transplant or provide improved treatment for patients unable to receive a stem cell transplant. Clinical trials are ongoing to confirm the anti-cancer activity for this and other new treatment regimens for leukemia.
Arsenic is a potential anti-cancer compound that has recently been evaluated in clinical trials. Physicians from China reported results of a treatment program utilizing arsenic in patients with acute promyelocytic leukemia who had failed initial therapy. Eighty-five percent of patients achieved a complete remission and the estimated leukemia-free survival at 2 years was 42%. The major side effect was liver toxicity, which resulted in 2 patients dying. Additional clinical trials are ongoing in order to determine the safest way to use arsenic.
Multiple Drug Resistance Inhibitors: Patients with AML fail to achieve a remission or relapse because of chemotherapy drug resistance that can be present at the time of diagnosis or are induced by treatment. Several drugs are being tested to determine if they will overcome or prevent the development of multiple drug resistance in AML.
Biological Modifier Therapy: Biologic response modifiers are naturally occurring or synthesized substances that direct, facilitate or enhance the body’s normal immune defenses. Biologic response modifiers include interferons, interleukins and monoclonal antibodies. In an attempt to improve survival rates, these and other agents are being tested alone or in combination with chemotherapy in clinical studies. Interleukin-2 is currently being evaluated as a maintenance agent after consolidation therapy. Newer biologic agents are in the developmental phase.
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