Chemotherapy For Leukemia

Overview

Leukaemia is a type of blood cancer originating from the bone marrow, resulting in the overproduction of abnormal white blood cells. Chemotherapy is the primary treatment for acute lymphocytic leukaemia and acute myeloid leukaemia, which are two of the most severe types of Leukaemia. In some cases, people with chronic myeloid leukaemia may also need chemotherapy. This treatment is becoming increasingly important in the fight against cancer-related symptoms and to extend life. It uses cytotoxins, anti-cancer drugs, to circulate throughout the body and destroy cancer cells. This article aims to provide a simple yet thorough understanding of chemotherapy in the context of leukaemia treatment. 

Understanding leukaemia

Definition and types of leukaemia

Leukaemia is a cancer affecting the hematopoietic system, leading to rapid uncontrolled production of abnormal white blood cells. There are different classifications of leukaemia, based on what type of white blood cells it is affecting such as myeloid or lymphoid, and by the percentage of leukaemia cells in bone marrow or blood, as chronic or acute. Myeloid cells include platelets, red blood cells and some white blood cells such as neutrophils, mast cells, monocytes, basophils and eosinophils. Lymphoid cells are adaptive immunity, responsible for specific targeted responses to pathogens, such as B cells, T cells and natural killer cells. Acute conditions are considered severe and rapidly growing, whereas chronic conditions are long-term health issues, often throughout an individual's life. The four main classifications of leukaemia are:

• Acute lymphocytic leukaemia (ALL)
• Chronic lymphocytic leukaemia (CLL)
• Acute myeloid leukaemia (AML)
• Chronic myeloid leukaemia (CML)¹

Causes and risk factors

The genetic mutation causing leukaemia

Leukaemia is caused by a mutation, genetic change, in the cells of bone marrow. What causes the mutation leading to leukaemia is still under research. During the process of cell division, replication of chromosomes (long linear DNA molecules) happens. Errors can occur during this process, affecting certain genes in the chromosome, causing mutations that turn on oncogenes or turn off tumour suppressor genes, leading bone marrow cells to grow abnormally and stopping them from maturing.² This mutation can be different for leukaemia patients even though they have the same type. 

Risk factors

Some common risk factors include:

• Exposure to radiation such as from medical treatments, work, or wartime activities; therapeutic radiation exposes patients with primary pelvic cancers or benign disorders like cervical polyps and endometrial hyperplasia
• Genetic disorders such as Down syndrome
• Chemotherapy
• Genetic syndromes and abnormalities
• Chemical exposures, such as formaldehyde, a chemical found in many household products and disinfectants, have a strong association with myeloid leukaemia
• Family history
• Smoking

Understanding chemotherapy

What is chemotherapy?

Chemotherapy, also called “chemo” is a type of cancer treatment that uses drugs against various types of cancer. Cancer cells grow and divide abnormally. The role of chemotherapy in the treatment is that it destroys the cancer cells and prevents them from multiplying. Chemotherapy can be used along with radiation therapy or surgery to treat cancer. For instance, in patients with locally advanced disease, radiation and chemotherapy are frequently combined to enable surgical resection, and removal of tissue, part or full organ,  later on. This kind of combined modality treatment has improved clinical outcomes. Currently, the first diagnosis of cancer can be treated in roughly 50% of cases. Nevertheless, the success rate drops to less than 10% of cancer patients whose tumour is discovered at an advanced stage if chemotherapy is employed alone. 

How is chemotherapy used?

Oncologists may use chemotherapy in many different ways. Some important ways are as follows:

• Primary chemotherapy: Chemotherapy is administered as the primary treatment in patients with advanced cancer; this helps to relieve tumour-related symptoms by improving their life quality and prolonging tumour progression
• Neoadjuvant chemotherapy: Chemotherapy administered in patients, whose cancer is only found in a tissue or organ, where it began and has not spread to other parts of the body; the role of chemotherapy is to reduce the size of the primary tumour to simplify surgical resection
• Adjuvant chemotherapy: Chemotherapy administered after surgery has been performed to improve patient survival

Chemotherapy treatments and drug therapy for leukaemia

Chemotherapy for acute lymphoblastic leukaemia

Chemotherapy is one of the main treatments for acute lymphoblastic leukaemia (ALL) because of its rapid growth. The chemotherapy treatments are outlined below.

Induction therapy

It is the first treatment provided to destroy as many cancer cells as possible to decrease symptoms. This treatment requires 4 to 6 weeks of hospital stay and generally includes the following drugs:

• Vincristine
• Corticosteroids
• Anthracyclines
• Cyclophosphamide 
• Pegaspargase 

The goal of the therapy, complete remission, is reached when there are no more than 5% of leukaemia cells in the bone marrow, no leukaemia cells circulating in the blood, the blood cell count is normal and all signs and symptoms are gone.

Postremission therapy

This treatment is provided after the induction therapy and when the disease is in complete remission. This therapy is used to deal with the residual leukaemia cells in the body. Certain factors can influence the therapy like age, the body’s ability to tolerate the treatment, cytogenetic findings and the availability of stem cell donors. This therapy consists of two phases described below.

Consolidation therapy: During this therapy, doctors administer higher doses of chemo drugs than the ones given during the induction therapy. The duration and combination of drugs vary, however drug combinations can be similar to the drugs provided during induction. Some drug examples are: 

• Vincristine
• High-dose methotrexate
• Cytarabine
• 6-mercaptopurine 
• Cyclophosphamide
• Corticosteroids 
• Pegaspargase

Maintenance therapy: This is the second phase of postremission therapy. The goal is to prevent the cancer cells from relapsing after the first two therapy sessions. The maintenance therapy drugs are mostly oral drugs and patients generally do not need to be hospitalised. The chemotherapy drug doses are also lowered to avoid side effects. Some examples of maintenance drugs are:

• Methotrexate (used in a weekly manner)
• 6-mercaptopurine (administered daily)
• Vincristine
• Corticosteroids

Therapy to prevent central nervous system

To prevent Leukaemia from spreading into the central nervous system (CNS), brain and spinal cord, they are provided with CNS prophylaxis to prevent leukaemia cells from spreading in the CNS. This is given throughout the treatment, even during the induction and postremission therapy. This therapy may include:

• Intrathecal chemotherapy: Injecting anticancer drugs between thin layers that cover the brain and spinal cord (drugs include cytarabine, methotrexate and corticosteroids)
• Systemic chemotherapy: Circulating anti-cancer drugs throughout the body (drugs include (pegaspargase, cytarabine and methotrexate)
• Cranial irradiation: Radiation therapy targeting the brain

Chemotherapy for acute myeloid leukaemia

Induction therapy

During Induction therapy for acute myeloid leukaemia, doctors mostly follow the “7+3 regimen”, which includes the cytarabine drug administered over 7 days and the anthracycline drug over 3 days during the initial week of treatment. Both the drugs are given using IV infusion. These drugs are not always prescribed by the oncologist. Some drugs are also given orally. This treatment is continued till complete remission is achieved. The other drugs that can be substituted or added are:

• Midostaurin
• Gemtuzumab ozogamicin
• Quizartinib
• Daunorubicin and cytarabine

Post-remission therapy

The first type is consolidation therapy for patients with favourable risk factors and frequently entails intensive chemotherapy combined with high-dose cytarabine and other medications. Based on their prognostic criteria, patients with high-risk AML are treated more aggressively with allogeneic stem cell transplantation among other treatments.

The other type is maintenance therapy during which adult patients are normally prescribed quizartinib and azacitidine. 

Treatment to prevent central nervous system (CNS)

The doctor may request imaging studies and a lumbar puncture if neurologic symptoms are present in order to check for leukaemia cells in the spinal fluid. "intrathecal chemotherapy", a treatment in which chemotherapy medications are injected directly into the spinal fluid, is used if leukaemia cells are discovered in the spinal fluid.

Chemotherapy for chronic lymphocytic leukaemia

Chemotherapy drugs prescribed during chronic lymphocytic leukaemia are mostly:

• Antimetabolites (cladribine, pentostatin and fludarabine)
• Alkylating agents (bendamustine hydrochloride, chlorambucil)
• DNA-damaging agents (cyclophosphamide)
• Treatment may also include corticosteroids like prednisone and dexamethasone

Oncologists mainly focus on targeting specific parts of the cancer cells. They mostly administer oral drugs for lower bioavailability. Drugs mainly provided are 

• Ibrutinib
• Venetoclax
• Zanubrutinib
• Idelalisib
• Acalabrutinib

Chemotherapy for chronic myeloid leukaemia

Treatment for the chronic phase: Tyrosine Kinase inhibitor (TKI) therapy is a standard therapy for the chronic phase of CML and it is very helpful in managing CML for an extended period of time. Drugs used during TKI are imatinib, dasatinib, bosutinib and nilotinib. If this treatment is not working, doctors may ask you to do a BCR::ABL1 kinase domain mutation analysis to check for mutation at the BCR::ABL1 gene. 

• Treatment for accelerated phase: The goal of this treatment is to eliminate all BCR::ABL1 genes to reach complete remission. 
• Treatment for blast phase: The blast phase CML could be considered to be very abnormal and is similar to acute leukaemia with severe symptoms. Treatments may include TKI therapy and then an allogeneic stem cell transplantation or clinical trial.

Side effects of chemotherapy

Common side effects include:

• Mouth sores
• Hair loss
• Nausea
• Headaches
• Fatigue
• Loss of appetite
• Diarrhoea

Summary

Leukaemia is a type of blood cancer that affects the bone marrow, producing abnormal white blood cells. There are four kinds of leukaemia. Acute leukaemias are more severe than chronic leukaemia; however, patients must reach out to a doctor and receive proper treatment immediately if diagnosed. The role of chemotherapy in the treatment is that it destroys the cancer cells and prevents them from multiplying and spreading more. Treatment for acute leukaemia includes induction therapy, postremission therapy, and then therapy to prevent the spread to the CNS. Postremission therapy has two phases: consolidation and maintenance therapies. Treatment for chronic leukaemia could be completely different. Some doctors may not go for chemotherapy with patients suffering from chronic lymphocytic leukaemia. Drug combinations and doses prescribed during treatment for leukaemia could be completely different between patients, even if they have the same type of leukaemia.