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Analysis of Acute Lymphoblastic Leukemia Treatment

KEY HIGHLIGHTS :

  • Acute lymphoblastic leukemia can also be addressed as acute lymphocytic leukemia (ALL). 
  • ALL is a highly progressive blood cancer. In this disease, the bone marrow produces unnecessary immature lymphocytes known as lymphoblasts. This makes it tough for blood to function properly.
  • Signs and symptoms of adult acute lymphoblastic leukemia include feeling tired, fever, and easy bruising or bleeding.
  • Previous chemotherapy and exposure to radiation may be responsible for increasing the risk of developing the disease.
  • Tests that examine the blood and bone marrow are used to diagnose adult acute lymphoblastic leukemia.
  • To be diagnosed with this disease, 20% or beyond lymphoblasts must be available in the bone marrow. This simply means that at least two out of every ten marrow cells are lymphoblasts.
  • There is more than one type of acute lymphoblastic leukemia (ALL). It is based on the type of lymphocyte, genetic mutations, and certain other features.
  • Those with acute lymphoblastic leukemia should be treated at experienced cancer centers.

Acute Lymphoblastic Leukemia (ALL) and Its Treatment

Acute lymphoblastic leukemia is a highly progressive blood cancer that typically starts in disease-fighting lymphocytes of the immune system. In ALL, bone marrow creates excess immature lymphocytes named lymphoblasts. Lymphoblasts can disarrange other blood cells causing blood to not act as it should. Acute leukemias arise more quickly than chronic leukemias. The disease most typically affects B or T cells. ALL can be discovered in blood, bone marrow, and other organs such as the testicles or the central nervous system (CNS).

Treatment typically depends on the type of acute lymphoblastic leukemia, age at diagnosis, and certain other factors. ALL Treatments may include Chemotherapy, Steroids, Targeted therapy, Immunotherapy, Radiation therapy, and Stem cell transplant. 

Chemotherapy:

Chemotherapy is the backbone of acute lymphoblastic leukemia (ALL) treatment and is often combined with certain other drug therapies. It is a kind of systemic drug therapy that kills quickly progressive cells throughout the body, including unhealthy cells and healthy cells. Chemotherapy can be given as follows:

  • Oral (PO): taken orally either as a liquid or pill
  • Subcutaneous (SQ): given under the skin
  • Intramuscular (IM): uses a needle to inject the drug into the muscle of the arm or leg (like the flu shot)
  • IV (intravenous) infusion: chemotherapy given through a vein using IV push, gravity infusion, or infusion pump.
  • Intrathecal (IT): chemotherapy is given into the spinal fluid. In addition to other forms of chemo, it can be injected into the cerebrospinal fluid (CSF) to demolish any leukemia cells that might have progressed to the spinal cord and brain. This kind of treatment is administered through a spinal tap or lumbar puncture.

Types of Chemotherapy: Chemotherapies used for the treatment of Acute lymphoblastic leukemia (ALL) disrupt the life cycle of unhealthy (cancer) cells. There are several types of chemotherapy used to treat the disease (ALL). Typically chemotherapies are combined. This is known as multiagent chemotherapy. Some types of chemotherapies used for the treatment of ALL are mentioned next. 

Alkylating agents: Alkylating agents are used to damage DNA by adding a chemical to it. This group of medicinal products includes cyclophosphamide. 

Anthracyclines: Anthracyclines are used to damage and disrupt the creation of DNA causing cell death of both unhealthy and healthy cells. Some anthracyclines include:

Idarubicin (Idamycin PFS)
Daunorubicin (Cerubidine)
Doxorubicin (adriamycin)
 
Antimetabolites: Antimetabolites are used to prevent the “building blocks” of DNA from being used. Some antimetabolites include:
  • Nelarabine (Arranon)
  • Fludarabine (Fludara)
  • Clofarabine (Clolar)
  • 6-MP (6-mercaptopurine)
  • Cytarabine (Cytosar-U)
  • Methotrexate
Enzyme Therapy: Calaspargase (Asparlas), pegaspargase (Oncaspar), or asparaginase derived from Erwinia chrysanthemi (Erwinaze or ERW) are a few types of enzyme therapy used in chemotherapy treatment.
 
Plant alkaloids: Plant alkaloids are formulated from plants. These are cell-cycle specific. Vincristine (also known as Oncovin or Vincasar PFS) falls under the class of medicines known as vinca alkaloids. It is also a microtubule inhibitor, which stops a cell from dividing into a couple of cells.
 
Steroids: Steroids are man-made versions of hormones formulated by the adrenal glands. They also are toxic to lymphoid cells and are a vital part of acute lymphoblastic leukemia chemotherapy. Some steroids may include:
  • Prednisone
  • Hydrocortisone
  • Dexamethasone
Targeted Therapy:
This is a form of systemic therapy that acts throughout the body. It is a kind of drug therapy that focuses on unique/specific features of cancerous cells. This therapy seeks out how cancer cells grow, divide, and progress in the body. This group of medicines stops the action of molecules that assist cancer cells to grow and survive.
 
Tyrosine Kinase Inhibitor: This is a type of targeted therapy that inhibits the signals that cause cancer to progress and spread. These might be used alone or along with other systemic therapies like chemo. TKIs work in a bit different ways. Sometimes, a tyrosine kinase inhibitor will stop working when there’s a new mutation in acute lymphocytic leukemia cells. Switching to a different tyrosine kinase inhibitor may help.
TKIs used for the treatment of ALL: TKIs that might be used for the treatment of ALL:
  • Imatinib (Gleevec)
  • Dasatinib (Sprycel) 
  • Nilotinib (Tasigna)
  • Ponatinib (Iclusig)
  • Bosutinib (Bosulif) 
TKIs are classified into first, second, and even third generation. Each generation of the medication gets more specific and better at attacking certain mutations. This means that the next-generation TKIs are typically more promising as well as faster in order to offer a response. However, they might have more adverse reactions. In case the disease doesn’t seem to be responding to one tyrosine kinase inhibitor, then another tyrosine kinase inhibitor will be tried.
 
Immunotherapy:
Immunotherapy is a targeted therapy that is designed to increase the activity of the immune system. Doing so helps improve the body’s potential to detect and kill cancerous cells. Immunotherapy can be used alone or along with with other sorts of treatment. It is sometimes used for relapsed or refractory disease.
 
Monoclonal Antibody Therapy: This therapy typically uses antibodies to fight cancer, infection, or other diseases. Monoclonal antibodies are a sort of antibody developed in the lab. In cancer treatment, these may demolish cancer or leukemia cells directly, they may inhibit the formation of tumor blood vessels, or they may help the immune system destroy cancerous cells. 
  • The medicine Inotuzumab ozogamicin (Besponsa) binds to CD22 on leukemia cells and then releases a toxic agent once it’s inside the cells. 
  • Rituximab (Rituxan) acts against the protein CD20 found on the B cell’s surface. When it binds to this protein it triggers the death of cells.
  • Blinatumomab (Blincyto) allows healthy T-cells to attack unhealthy B cells by bringing them close together. It mainly targets the CD19 antigen that exists in B cells. Blinatumomab may be responsible for causing severe, life-threatening, or fatal reactions. This medicinal product comes in the form of injection: 35 mcg of lyophilized powder in a single-dose vial for reconstitution. The proposed dosage of Blincyto 35 mcg injection should be administered intravenously.
CD19-targeting CAR T-cell Therapy: This type of immunotherapy is formulated from your own T-cells. T cells will be taken out from the body, and in the lab, a CAR will be added to them. This programs the T cells to detect leukemia cells. The programmed T cells will be infused back into the body to detect and destroy cancerous cells. This therapy is not for everyone. There can be serious and life-threatening reactions. 
Tisagenlecleucel (Kymriah) is a type of CD19-targeting CAR T-cell therapy. This treatment is only recommended in those under 26 years of age with refractory B-ALL or two or more relapses. 
 
Radiation Therapy:
This therapy uses high-intensity radiation from x-rays, gamma rays, protons, and other sources to kill unhealthy cells and shrink tumors. It can be given alone or along with certain systemic therapies. It may be considered supportive care in order to help reduce pain or discomfort caused by cancer. 
  • Individuals with leukemia in the central nervous system (CNS) at diagnosis may receive radiation to their brain area. 
  • Individuals with the testicular disease at diagnosis that remains after induction therapy may receive radiation therapy to the testes.
Stem Cell Transplant:
A stem cell transplant (SCT) typically replaces the bone marrow stem cells. Sometimes, it can be also known as hematopoietic cell transplant (HCT). There are a couple of types of stem cell transplants:
  • Autologous: stem cells typically come from you
  • Allogeneic: stem cells typically come from a donor who may or may not be related to you
Only an allogeneic stem cell transplant (allo-SCT) is used as a treatment option for acute lymphoblastic leukemia. A stem cell transplant typically depends upon donor availability and your health at the time of a potential stem cell transplant. 
 
Reference:
https://www.cancer.gov/types/leukemia/patient/adult-all-treatment-pdq#:~:text=Treatment%20of%20Adult%20Acute%20Lymphoblastic%20Leukemia%20in%20Remission,-For%20information%20about&text=Chemotherapy.,radiation%20therapy%20to%20the%20brain.
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  • On January 23, 2023
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