Acute Myeloid Leukemia (AML) is a rapidly progressing cancer originating in the bone marrow, affecting healthy blood cell production. While initial treatments aim for remission, a significant challenge is the cancer’s return, known as relapse. AML relapse is the re-emergence of the disease after a period of no detectable cancer.
Understanding AML Relapse
AML relapse occurs when leukemia cells reappear in the bone marrow or blood after a patient achieves complete remission following initial treatment. Complete remission means no leukemia cells are found in the blood or bone marrow, and the patient has no disease symptoms. This differs from refractory AML, where the cancer never fully responded to initial treatment and persists.
Relapsed AML is a recurrence of the disease, which can happen months or even years after initial treatment, though it is more common within two years.
Why AML Relapse Occurs
AML relapse often stems from minimal residual disease (MRD), where a small number of leukemia cells survive initial treatment. Even if a patient appears to be in complete remission, these microscopic cells can remain undetected and later multiply, leading to a full relapse. Highly sensitive techniques like flow cytometry or quantitative polymerase chain reaction (qPCR) can detect these residual cells, which are associated with an increased risk of relapse.
Genetic mutations and clonal evolution also play a significant role in AML relapse. Cancer cells can acquire new mutations or changes in their genetic profile during or after initial treatment, making them resistant to previously effective therapies. For instance, certain mutations like FLT3 can be newly acquired at relapse, even if they were not present at diagnosis, further contributing to treatment resistance. This dynamic evolution of the leukemia cells allows them to evade the immune system and overcome drug effects.
Recognizing and Confirming Relapse
Recognizing AML relapse involves awareness of potential symptoms indicating the cancer’s return. These symptoms can be similar to those experienced at initial diagnosis, including:
- Unexplained fatigue
- Persistent infections
- Fever
- Unexpected bruising or bleeding
- Achy bones
- Swollen glands
- Headaches
- Shortness of breath due to low red blood cell counts (anemia)
Confirming a relapse requires specific diagnostic tests. Blood tests, such as a complete blood count (CBC), can reveal abnormal numbers of white blood cells, red blood cells, and platelets, often showing an increase in immature white cells called myeloblasts. A bone marrow biopsy is also performed to check for leukemia cells and analyze genetic changes. Advanced techniques like flow cytometry and genetic testing are used to detect residual leukemia cells and identify any new or altered genetic mutations that might influence treatment decisions.
Treatment Approaches for Relapsed AML
Treatment for relapsed AML is highly individualized, considering factors such as the patient’s age, overall health, previous treatments, and the duration of the initial remission. Re-induction chemotherapy, often using different drug combinations than initial treatment, is a common approach to achieve a second remission. For example, a repeat course of the 7-and-3 protocol, involving cytarabine and an anthracycline like daunorubicin or idarubicin, may be considered if the remission lasted over a year.
Targeted therapies are increasingly important, especially if specific genetic mutations are identified in the relapsed leukemia cells. For instance, if the FLT3 mutation is present, drugs like gilteritinib may be used, while gemtuzumab ozogamicin might be an option for AML with a CD33 protein marker. Allogeneic stem cell transplantation (also known as bone marrow transplant) is a potential curative option for some patients, particularly those who achieve a second remission. Clinical trials offer access to novel therapies and combinations under investigation, providing additional options for patients with relapsed AML.
Prognosis and Outlook After Relapse
Prognosis for relapsed AML varies considerably, influenced by several factors. A longer duration of initial remission, typically over one year, is associated with a more favorable outlook. Specific genetic mutations at relapse, such as FLT3-ITD, can impact prognosis, with some indicating a poorer outcome. Patient’s overall health and ability to tolerate intensive treatments also play a significant role.
Achieving a second complete remission after salvage therapy is a strong predictor of improved survival. Allogeneic hematopoietic stem cell transplantation (HSCT) after relapse, especially if performed in a second remission, improves outcomes compared to not undergoing transplantation. While challenges persist, ongoing research and advancements in understanding AML biology continue to offer new therapeutic strategies and hope for improving outcomes for patients facing relapse.