Acute myeloid leukemia (AML) treatment is a complex process typically divided into distinct phases to effectively combat this aggressive cancer. For patients requiring acute care inpatient services, understanding these phases is crucial for navigating their treatment journey. Chemotherapy remains the cornerstone of AML treatment, although targeted therapies and other interventions are increasingly integrated into care plans.
It’s important to note that acute promyelocytic leukemia (APL), a subtype of AML, follows a unique treatment path. Due to AML’s rapid progression, treatment often commences swiftly after diagnosis. In certain situations, immediate interventions may be necessary even before chemotherapy can exert its full effect.
Addressing Leukostasis in Acute Care Settings
Upon initial diagnosis, some AML patients present with markedly elevated leukemia cell counts in their blood. This condition, known as leukostasis, can impede normal blood circulation and necessitates urgent medical attention within an acute care environment.
When immediate induction chemotherapy is not feasible, medications like hydroxyurea or cytarabine can be administered to rapidly reduce leukemia cell burden.
Image alt text: Leukapheresis procedure diagram showing blood being drawn from patient, processed through a machine to remove white blood cells, and returned to the patient, illustrating a key treatment for leukostasis in acute myeloid leukemia.
Leukapheresis, also referred to as pheresis, is another valuable option employed before chemotherapy initiation. This procedure involves channeling the patient’s blood through a specialized device that selectively removes white blood cells, including leukemia cells, before returning the remaining blood components to the patient. This rapid reduction of leukemia cells offers temporary relief, effectively bridging the gap until chemotherapy can take effect.
Induction Therapy: The First Phase of Inpatient AML Treatment
The primary goal of the induction phase, the initial stage of AML treatment, is to aggressively eliminate as many leukemia cells as possible. Given the intensity of this phase, it is predominantly managed in an inpatient acute care setting.
Treatment intensity is carefully tailored, considering factors such as patient age and overall health. Younger individuals often receive more intensive chemotherapy regimens, while some healthier older patients may also benefit from similarly robust or slightly less intensive approaches. However, for significantly older or frail patients, intensive chemotherapy may not be suitable, and alternative strategies are considered.
Beyond age and health, other considerations influence treatment decisions. AML subtypes can vary in prognosis, impacting the intensity of treatment required. Furthermore, specific genetic or chromosomal abnormalities within leukemia cells can predict responsiveness to particular therapies.
For younger patients, induction therapy commonly involves a combination of two chemotherapy agents:
- Cytarabine (ara-C)
- An anthracycline drug, such as daunorubicin (daunomycin) or idarubicin
This combination is frequently termed the “7 + 3 regimen,” denoting continuous cytarabine administration for seven days, coupled with short anthracycline infusions during the first three days.
In select cases, a third agent may be incorporated to enhance remission induction rates:
- For patients with FLT3 gene mutations in their leukemia cells, targeted therapy drugs like midostaurin (Rydapt) or quizartinib (Vanflyta) may be combined with chemotherapy.
- For patients whose leukemia cells express the CD33 protein, the targeted drug gemtuzumab ozogamicin (Mylotarg) may be added to the chemotherapy regimen.
Patients with compromised heart function may not be candidates for anthracyclines. In such instances, alternative chemotherapy drugs such as fludarabine or cladribine may be utilized.
In rare scenarios where leukemia has spread to the brain or spinal cord, intrathecal chemotherapy, involving direct drug administration into the cerebrospinal fluid (CSF), may be necessary. Radiation therapy might also be considered in these cases.
Hospitalization is typically required throughout the induction phase and potentially for a period thereafter. Induction therapy, while targeting leukemia cells, also non-selectively destroys normal bone marrow cells. Consequently, patients often experience dangerously low blood counts and may become severely ill, necessitating antibiotics and blood product transfusions. Growth factors, medications that stimulate white blood cell production, may also be administered. Blood counts usually remain depressed for several weeks.
Approximately one to two weeks post-chemotherapy, a bone marrow aspiration and biopsy are performed to assess treatment efficacy. Successful induction is indicated by hypocellular bone marrow with a minimal blast percentage (less than 5%).
Image alt text: Illustration depicting a bone marrow aspiration and biopsy procedure, a critical diagnostic and monitoring step in acute myeloid leukemia treatment to assess remission status.
While most patients achieve remission after the initial induction cycle, persistent leukemia cells may necessitate a second chemotherapy cycle, termed reinduction, using the same or alternative drug regimens. A stem cell transplant may be considered at this juncture. If bone marrow biopsy findings remain inconclusive, a repeat biopsy may be performed within a week.
Over subsequent weeks, normal bone marrow function should recover, leading to the production of new blood cells. Bone marrow biopsies may be repeated during this recovery period. Once blood counts normalize, a bone marrow sample is reassessed to confirm remission status.
It’s crucial to recognize that remission induction typically does not eradicate all leukemia cells. A small residual population often persists, underscoring the necessity of post-remission therapy (consolidation) to prevent relapse.
Consolidation Therapy: Sustaining Remission in AML Patients
Successful induction, marked by leukemia remission, paves the way for consolidation therapy. This phase aims to eradicate any remaining leukemia cells and minimize the risk of disease recurrence.
Consolidation Strategies for Younger AML Patients
For younger patients, typically under 60 years of age, primary consolidation options include:
- Multiple cycles of high-dose cytarabine chemotherapy (HiDAC)
- Allogeneic (donor) stem cell transplant
- Autologous stem cell transplant
Alternative chemotherapy regimens may also be considered. The optimal consolidation strategy is individualized, taking into account relapse risk and other patient-specific factors.
HiDAC involves administering very high cytarabine doses, typically over five days, repeated approximately every four weeks for a total of three to four cycles. Due to the potential for significant side effects, each HiDAC cycle usually necessitates inpatient hospital care.
For patients who received targeted therapy, such as midostaurin or quizartinib, during induction, these agents are typically continued throughout consolidation. Similarly, gemtuzumab ozogamicin, if used during induction, may be incorporated into consolidation regimens.
Another post-induction approach involves high-dose chemotherapy followed by either allogeneic or autologous stem cell transplantation. Stem cell transplants have demonstrated superior relapse reduction compared to standard chemotherapy, albeit with a higher risk of serious complications, including treatment-related mortality.
Consolidation Approaches for Patients Not Undergoing Intensive Induction
Similar to induction, older or frail patients may not tolerate intensive consolidation therapy. In these individuals, more aggressive consolidation may increase the risk of severe side effects without substantial incremental benefit. Alternative, less intensive regimens are employed in these cases.
Factors Guiding Consolidation Treatment Selection
Determining the most appropriate consolidation strategy is multifaceted. Each option presents unique advantages and disadvantages. Physicians consider several factors when recommending consolidation therapy, including:
- Number of induction cycles to achieve remission: Multiple induction cycles to achieve remission may prompt consideration of more intensive consolidation, potentially including stem cell transplantation.
- Availability of a matched sibling or unrelated donor: A suitable tissue match facilitates allogeneic stem cell transplantation, particularly for younger patients.
- Feasibility of collecting leukemia-free bone marrow cells: Remission status allows for autologous stem cell collection for potential autologous transplantation. Purging collected stem cells in the laboratory aims to eliminate residual leukemia cells and reduce relapse risk.
- Presence of adverse prognostic factors: Factors such as specific genetic or chromosomal abnormalities, elevated initial white blood cell counts, AML evolving from prior blood disorders or cancer treatment, or central nervous system involvement may warrant more aggressive consolidation, such as stem cell transplantation. Conversely, favorable prognostic factors may lead to deferral of transplantation unless relapse occurs.
- Patient age and overall health: Older or comorbid patients may be less tolerant of the toxicities associated with high-dose chemotherapy or stem cell transplantation.
- Patient preferences: Quality-of-life considerations are paramount. The increased risk of severe side effects, including life-threatening complications, associated with intensive consolidation must be thoroughly discussed between patient and physician.
Stem cell transplantation represents intensive therapy with potential for serious complications, including mortality. While allogeneic transplantation, when feasible and tolerated, is often considered to offer the best chance for long-term survival by many physicians, the precise role of transplantation in AML management remains under ongoing investigation. Ongoing research seeks to refine patient selection criteria for stem cell transplantation and optimize transplant modalities.
Maintenance Therapy: Prolonging Remission After Consolidation
In certain situations, maintenance therapy, also known as post-consolidation therapy, may be considered as further treatment. This phase involves prolonged treatment administration, often at lower doses, with the goal of sustaining remission for as long as possible.
Maintenance therapy is not universally indicated for all AML patients. However, it may be beneficial for patients at higher relapse risk or those unable to undergo or complete intensive initial treatment.
Oral chemotherapy drugs like azacitidine (Onureg) or similar agents may be considered for maintenance in patients who achieve remission after induction or consolidation. For patients who received targeted therapy as part of their initial treatment, continuation of the targeted agent (without chemotherapy) may be an option.
Treatment Considerations for Frail, Older Patients, and Those Declining Intensive Therapy
Standard AML treatment protocols are well-defined for younger, healthy patients willing to undergo intensive therapy. These protocols typically involve intensive chemotherapy cycles, sometimes combined with targeted therapy or stem cell transplantation. Many older patients, if otherwise healthy, can tolerate similar treatment approaches, although chemotherapy intensity may be adjusted.
However, for significantly older or frail patients, intensive treatment may be poorly tolerated and potentially detrimental, even shortening lifespan. Furthermore, some patients may decline intensive treatment due to concerns about severe side effects. Treatment for these individuals is often less phase-structured and may be administered intermittently as needed.
Options for these patients may include less intensive chemotherapy regimens or targeted therapies, depending on the specific AML subtype and patient characteristics. Clinical trials may also offer access to novel treatment approaches.
Some patients may opt against chemotherapy and other directed therapies, choosing instead for supportive (or palliative) care. This approach prioritizes symptom management, complication treatment, and maximizing patient comfort and quality of life.
