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Acute Myeloid Leukemia, Blog

Acute Myeloid Leukemia Treatment


The treatment for AML is one of the most complex and intensive cancer therapy programs. The treatment of AML depends on many factors, including but not limited to, the type of disease, patient’s age, WBC count, immunophenotypic/cytogenetic abnormality involved, CNS involvement, and response to induction therapy. AML treatment generally includes the following phases:

1.Induction: The main aim of induction therapy is to achieve remission, that is, depletion of leukemia cells from the blood and bone marrow. However, this does not mean a cure as some leukemia cells may still exist that are undetectable by conventional diagnostic techniques. Thus, further treatment is usually recommended. Induction treatment usually depends upon the type of AML, age and performance status of the patient. For a healthy individual, induction treatment usually includes multiagent chemotherapy with or without a targeted agent depending upon the type of AML.
The treatment for AML may also include CNS treatment with intrathecal chemotherapy if the leukemia cells have spread to the CNS. Patients also generally require supportive treatment with blood product transfusion, antibiotics, antifungals, and drugs that raise blood cell count.

 

2.Consolidation: The main aim of consolidation treatment is to wipe out any remaining leukemia cells in the body after induction treatment. Consolidation treatment for otherwise healthy young patient usually includes chemotherapy with or without a targeted drug depending upon the type of AML. Allogenic or autologous stem cell transplant (SCT) may be considered in high risk and some intermediate risk patients who are good candidates for the same. Older patients with poor performance status usually receive low-intensity therapy based upon the risk-benefit analysis.

 

3.Maintenance: The main aim of maintenance treatment is to avoid disease recurrence after induction and consolidation therapy. The maintenance treatment is not recommended for all types of AML but usually given to patients with APML.

 

Based on the results obtained from various clinical research studies carried out so far, following are the preferred treatment approach for different types of diseases and different patient population:

Type/Risk Group Preferred Treatment
Acute Promyelocytic Leukemia (APL) The translocation of the PML gene on chromosome 15 to the RARA gene on chromosome 17 [t(15;17] producing a PML-RARA fusion gene is the characteristic feature of APL. Patient with APL may have fatal coagulopathy and it is recommended to start treatment even before confirmation of the disease with cytogenetic testing.

The preferred induction treatment regimens include ATRA + arsenic trioxide (ATO); ATRA + daunorubicin + cytarabine; or ATRA + idarubicin (AIDA). The preferred consolidation treatment regimens include cytarabine with daunorubicin; cytarabine with AIDA; and ATRA plus ATO.

After consolidation therapy, bone marrow samples from patients are assessed for MRD using PCR technique.

Some patients may receive maintenance therapy with ATRA with or without 6-mercaptopurine and methotrexate for around 1 to 2 years. The benefit of maintenance therapy is less clear. However, a periodic monitoring of MRD with PCR technique is recommended for up to 2 years.

 

Treatment for APL is frequently associated with differentiation syndrome (constellation of symptoms and physiologic abnormalities, including fluid retention, dyspnea, episodic hypotension, pulmonary infiltrates, and pulmonary or pericardial effusions) which should be managed with prophylactic corticosteroid treatment.

Coagulopathy, another common complication encountered in patients with APL, should be managed by transfusion support to maintain platelet counts >/=50,000/microliters, by fibrinogen replacement with cryoprecipitate and frozen plasma to maintain a fibrinogen level of 150 mg/dL, and by the maintenance of prothrombin time and partial thromboplastin time close to normal.

AML in patients younger than 60 years and good performance status For patients with age less than 60 years and who are otherwise healthy (without accompanying comorbidities), the preferred induction treatment regimen include cytarabine + anthracycline. Targeted drug – midostaurin may be included in the chemotherapeutic regimen for patients with an FLT3 gene mutation. In case of CNS involvement, intrathecal chemotherapy may be included as well.

Human leukocyte antigen (HLA) typing and allogenic stem cell transplant is recommended to be performed in high risk and some intermediate risk patients who are the good candidate for it.

A bone marrow aspirate or biopsy should be performed 14 to 21 days after the start of induction therapy to assess the response.

If patient achieves a CR after induction therapy, consolidation treatment is started. The preferred consolidation treatment regimen mainly includes HiDAC (high dose Ara-C). Treatment with midostaurin may be continued for patients who received the targeted drug during the induction phase.

AML in patients older than 60 years or poor performance status For patients with age more than 60 years OR who are not overall healthy (have accompanying comorbidities), the preferred induction treatment regimen includes lower-intensity therapy with hypomethylating drugs 5-azacitidine or decitabine, or low-dose cytarabine.

 

For patients who are the candidate for intensive induction therapy, standard-dose cytarabine and anthracycline, with midostaurin for patients with FLT3-mutation–positive AML can be employed.

A bone marrow aspirate or biopsy should be performed 14 to 21 days after the start of induction therapy to assess the response.

If patient achieves a CR after induction therapy, consolidation treatment is started. Non-myeloablative or reduced-intensity (RIC) SCT can be a good option for selected patients who are good candidates for it.

 

Following is the brief description of various treatment types employed for AML:

1.Chemotherapy: Chemotherapy means treatment with anti-cancer drugs that kill or decrease the growth of rapidly-growing cancer cells. Chemotherapy may be employed in combination with targeted drugs for the management of AML having certain genetic abnormalities for which targeted drugs are available. It may also be injected directly in the CSF for CNS prophylaxis/treatment. Many pharmaceutical companies are conducting a number of clinical trials to find out new drugs and drug-combinations with increased efficacy and specificity to target ALL cells. Chemotherapy may be associated with side effects due to its effect on normal body cells apart from cancerous cells.

 

2.Targeted Therapy: Targeted drugs are designed to target a specific gene or protein characteristic of the AML cells. Examples of targeted drugs for AML include Midostaurin that targets FLT3 gene abnormality, Enasidenib that targets IDH2 gene abnormality, etc. These drugs are generally used in combination with other therapeutic agents for the treatment of AML.

Certain drugs which bring about differentiation in the immature blast cells have been used successfully to overcome the differentiation block and counteract the coagulopathy. Following 2 differentiation agents are used for the treatment of APL:

 

  • All-trans-retinoic acid (ATRA): It is a form of vitamin A, which brings about conformational changes in PML-RARA. This causes the differentiation in immature myeloid cells by removing the differentiation block. Common side effects include headache, fever, dry skin and mouth, skin rash, swollen feet, sores in the mouth or throat, itching, and irritation in eyes.
  • Arsenic trioxide (ATO): It’s exact mechanism of action is unknown. It is postulated to have differentiation and cytotoxic effects that help in reducing the myeloid blasts. Common side effects include fatigue, nausea, vomiting, diarrhea, abdominal pain, and nerve damage leading to numbness and tingling in the hands and feet.

 

3.Radiation Therapy: Radiation therapy (or radiotherapy) uses high-energy x-rays or other high-energy radiations which are directed to the affected area to kill cancerous cells. An external beam radiation therapy can sometimes be employed for the treatment of CNS leukemia; with high dose chemotherapy before SCT; to reduce bone pain in bones invaded by leukemia cells; and to shrink a tumor in the trachea causing breathing problem.

 

4.Stem Cell Transplant (SCT): SCT is considered as the standard of care for high risk and some intermediate risk patients who are a good candidate for the same. Following are major types of stem cell transplant techniques used for the treatment of AML:

 

  • Autologous SCT: In this technique, the patient’s own stem cells are first collected from the bone marrow tissue or peripheral blood (preferred nowadays). Then, the patient receives high-dose chemotherapy with or without radiation therapy to kill the leukemia The collected stem cells are re-administered to the patient which slowly replenish the blood cells in the patient’s body.
  • Allogeneic SCT: In this technique, healthy stem cells to be administered to the patient after high dose chemotherapy are obtained from another person known as the donor. It is very important that donor is a close blood relative (preferably a sibling) so that donor HLA closely matches with that of the patient.
  • Non-myeloablative transplant (RIC or mini-transplant): In case of older individuals or individuals who cannot tolerate a standard allogeneic transplant procedure, a non-myeloablative transplant can be employed. In this technique, a relatively lower dose of chemotherapy/radiotherapy is used to partially kill the cells in the bone marrow. Then, the patient is infused with stem cells from a donor and newly generated immune cells identify and kill any remaining leukemia cells due to the graft versus leukemia effect. Chances of fatal complication due to graft-versus-host disease still exist.

It is very important to assess the benefits of each treatment option versus the possible risks and side effects before making a treatment decision. Sometimes patient’s choice and health condition are also important to make a treatment choice. Following are ultimate goals of treating stomach cancer:

  • Prolongation of life
  • Reduction of symptoms
  • Improvement in quality of life

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