Types of Treatment for Acute Lymphocytic Leukemia

Executive Summary

Treatment (acute lymphocytic leukemia) recommendations depend upon the patient’s state of Acute Lymphocytic Leukemia. Treatments recommendations depend on the size, grade, and type of tumor, metastasis, possible side effects, and patient’s preferences and overall health. The common treatments for acute lymphocytic leukemia include chemotherapy (remission induction therapy, remission consolidation or intensification therapy, remission maintenance or continuation therapy, central nervous system (CNS) prophylaxis (preventive treatment), re-induction chemotherapy), targeted therapy, radiation therapy (external-beam radiation therapy), and stem cell transplantation or bone marrow transplantation. Palliative care includes medication, nutritional changes, emotional and spiritual support, and other relaxation therapies. Treatment for recurrent ALL includes surgery, chemotherapy, radiation therapy, and targeted therapy.

Treatment for Acute Lymphocytic Leukemia

“Standard to care” refers to the best-known treatment. In cancer care, a multidisciplinary team where different doctors work together to bring out an overall treatment plan for the patient.

Treatments recommendations depend on many factors ​1​:

  • The size, grade and type of tumour
  • Whether the tumour is applying pressure on vital parts of the brain
  • If the tumour has increased to other parts of the body
  • Possible side effects
  • The patient’s preferences and overall health

Chemotherapy 

Chemotherapy uses medicine to kill or stop the growth of cancerous cells. However, the type of chemotherapy will depend upon the stage. Hence, the point that makes a difference is how the chemotherapy enters the body and which cells it affects.

A chemotherapy schedule usually consists of a certain number of cycles over a fixed period. It can be one frug or a combination of drugs simultaneously depending on the condition of the patient. Patients with ALL receive various drugs throughout the treatment. A patient can receive chemotherapy during different stages of treatment.

Remission induction therapy

is the first round of treatment is during the first 3 to 4 weeks after diagnosis. It is to destroy the leukemia cells, stop symptoms of the disease, and return the blood counts to normal levels.

The specific treatments used may include ​2​:

  • Doxorubicin (Adriamycin), vincristine (Vincasar), or cyclophosphamide (Neosar), given by an injection into a vein
  • Daunorubicin (Cerubidine)
  • Asparaginase (Elspar) or Pegasparaginase (Oncaspar), provided by injection into a muscle, under the skin or into a vein
  • Dexamethasone (multiple brand names) or prednisone (numerous brand names) by mouth
  • Treatments that targeted the Philadelphia chromosome 
  • Methotrexate (various brand names) or cytarabine (Cytosar-U) as an injection into the spinal fluid

The goal of induction therapy is complete remission. This means that the blood counts have come back to normal, leukemia is not visible in a bone marrow sample under the microscope, and there are no more symptoms and signs of ALL . Greater than 95% of children and 75% to 80% of adults with ALL will have a complete remission.

However, tiny amounts of leukemia can remain after treatment which might not be visible under a microscope. For this reason, it is necessary to give additional therapy to prevent the ALL from returning. Techniques such as minimal residual disease (MRD) help in finding small amounts of leukemia. This help predicts a patient’s prognosis and guides treatment options.

Remission consolidation or intensification therapy

This stage of therapy involves using a combination of drugs. The drugs may be different or have different doses than those used to achieve remission. Some drugs may be similar to what was provided during remission induction therapy. Depending on the subtype of the ALL, the doctor may suggest several courses of consolidation therapy.

Remission maintenance or continuation therapy

Treatment is given orally and by IV for 2 to 3 years to keep the ALL from returning. These drugs are generally given in lower doses. And so they have fewer side effects.

Central nervous system (CNS) prophylaxis (preventive treatment)

It uses drugs to prevent leukemia from spreading from the blood to the spinal cord or brain ​3​. They are given straight spinal fluid by spinal tap (lumbar puncture) or vein. This treatment can be used for a few patients with leukemia in the CNS when first diagnosed or for some patients with recurrent ALL. This treatment can be given along with radiation therapy to the spine and head. 

Re-induction chemotherapy

It is to treat ALL, in case of recurrence. And also in cases,where a person still has ALL signs after remission induction therapy.

Chemotherapy attacks rapidly dividing cells, like those in healthy tissue like the hair, intestines, lining of the mouth, and bone marrow. This means that patients having chemotherapy may have certain side effects such as, losing hair or can cause nausea and vomiting.

Because of modifications in the blood counts, most patients will need transfusions of platelets and red blood cells at some point during their treatment. At the same time, treatment with antibiotics to prevent or treat infection is necessary as well. Chemotherapy may lower the body’s resistance to infection by reducing the count of neutrophils. It can also cause bleeding and bruising because of the decrease in platelets and other problems related to blood clotting. Therefore, chemotherapy may cause fatigue by lowering the count of red blood cells.

Chemotherapy can affect fertility, which can have a child in the future, increasing the risk of developing second cancer. Patients may want to talk to a fertility specialist before treatment begins, as there are options available to help preserve fertility.

Targeted Therapy

Targeted therapy aims at any factor contributing to the growth and development of cancer cells. It can be a specific protein, gene or tissue environment. This treatment blocks the growth and spread of tumour cells while limiting damage to healthy cells.

For ALL, targeted therapy is suggested in addition to standard chemotherapy for patients with Philadelphia chromosome-positive ALL (Ph+ ALL). Such drugs include-

  • Nilotinib (Tasigna)
  • Imatinib (Gleevec)
  • Dasatinib (Sprycel)

Other targeted therapy drugs include –

  • Nelarabine (Arranon), a new drug targeting T-cell ALL
  • Inotuzumab ozogamicin
  • Ponatinib (Iculsig) for Philadelphia chromosome-positive ALL
  • Blinatumumab (Blincyto)
  • Rituximab (Rituxan), used in addition to chemotherapy for the treatment of B-cell ALL

The side effects of targeted therapy include vomiting, nausea, diarrhea, edema or swelling around the eyes or in the legs, and, rarely, fluid in the lungs. The side effects of targeted therapy are generally not severe and are manageable.

Radiation Therapy

Radiation therapy uses high-energy X-rays or particles to destroy cancer cells. The most common radiation treatment type is external-beam radiation therapy. In this, the radiation is given from the machine outside the body ​4​. A radiation therapy schedule consists typically of a specific number of treatments offered over a set period. For ALL, radiation therapy to the brain helps to kill cancerous cells around the brain and spinal column.

There can be side effects from radiation therapy such as mild skin reactions, upset stomach, fatigue, and loose bowel movements.

Stem cell Transplantation/Bone marrow Transplantation

A stem cell transplant is a medical process in which bone marrow that contains the cancer is replaced by highly specialized cells. These cells, known as hematopoietic stem cells, develop into healthy bone marrow. Hematopoietic stem cells are the blood-forming cells found in the bloodstream and the bone marrow. These stem cells form all of the healthy cells in the blood. Presently, this procedure is more commonly called a stem cell transplant than a bone marrow transplant because it is the stem cells in the blood typically being transplanted, not the actual bone marrow tissue ​5​.

Before suggesting transplantation, doctors talk to the patient and family members regarding the risks of this treatment. They will also consider several other factors, like age and general health, cancer type, and previous treatment results.

There are two types of stem cell transplantation depending on the source of the replacement blood stem cells – autologous (AUTO) and allogeneic (ALLO). AUTO uses the patient’s stem cells, while ALLO uses donated stem cells. In both types, the target is to destroy all cancer cells in the blood, marrow, and other body parts using high doses of chemotherapy or radiation therapy and then allow replacement blood stem cells to create healthy bone marrow.

Side effects depend on the child’s general health, the type of transplant, and other factors.

Palliative Care 

Cancer and its treatment have side effects that can be mental, physical, or financial, and managing the effects are palliative or supportive care. Palliative care includes various aspects such as medication, nutritional changes, emotional and spiritual support and, other relaxation therapies. 

Palliative care focuses on alleviating how you feel during treatment by managing symptoms and supporting patients and their families with other non-medical needs. Regardless of type and stage of Cancer age, any person may receive this type of care.

Refractory ALL

Refractory ALL occurs when there is no complete remission. This is mostly because the drugs did not destroy enough leukemia cells. These patients generally continue to have low blood counts, need transfusions, and risk bleeding or infection.

Remission and chance of recurrence

When there are no traces of cancer after diagnosis, then the patient is in remission. This may be called having ‘no evidence of disease’.

A remission can be temporary or permanent. Many people worry about the recurrence of cancer. The doctor performs another round of tests to know the extent of the recurrence.

Mainly the treatment plan includes the treatments explained above, like surgery, chemotherapy, radiation therapy, and targeted therapy.

Treatment for recurrent ALL depends on the duration of the remission and is typically given in cycles for 2 to 3 years. If a recurrence happens after a long remission, leukemia may respond to the initial treatment again. In case the remission occurs after a short period, other drugs might be more effective.

An ALLO stem cell transplant is typically recommended for patients whose leukemia has returned after a second remission. The drug clofarabine (Clolar) is mostly effective for patients between age 1 and 21 who have recurrent or refractory ALL after receiving at least two types of chemotherapy. Liposomal vincristine (Marqibo) can be an option. Supportive care will also be essential to help relieve symptoms and side effects.

Care and Concern

It is vital to have straightforward conversations with your health care team to express your feelings, preferences, and concerns. The health care team has unique skills, knowledge, and experience to assist patients and their families. Ensuring that a person is physically comfortable, free from pain, and emotionally supported is extremely important.

B-cell acute lymphoblastic leukemia

The B-cell ALL with several genetic flaws (gene or chromosome changes). B-cell acute lymphoblastic leukemia (B-cell ALL) is a form of ALL that causes you to have a lot of immature white blood cells called B-cell lymphoblasts in your circulation and bone marrow. According to the Leukemia and Lymphoma Society, B-cell acute lymphoblastic leukemia is the most prevalent subtype of acute lymphocytic leukemia, accounting for 75 percent of ALL occurrences in adults. It generally moves along rapidly.

When you have B-cell acute lymphoblastic leukemia, your body produces immature white blood cells rather than the mature white blood cells that the body requires. Immature cells are incapable of performing essential functions such as combating infections, T-cells attack and kill the infected cells directly. To fight infections, your body needs both T- and B-cells.

  • Hypodiploidy in B-cell ALL (the leukemia cells have fewer than 44 chromosomes [normal cells have 46]) Hyperdiploidy in B-cell ALL (the leukemia cells have more than 50 chromosomes)
  • B-cell ALL [t(9;22)] caused by a translocation between chromosomes 9 and 22. (the BCR-ABL1 fusion gene is produced by the Philadelphia chromosome)
  • The B-cell ALL with chromosome 11 translocation to another chromosome
  • B-cell ALL [t(12;21)] having a translocation between chromosomes 12 and 21.
  • B-cell ALL with a chromosome 1–19 translocation [t(1;19]
  • The B-cell ALL with chromosomes 5 and 14 translocation [t(5;14)]
  • Amplification of a region of chromosome 21 (too many copies) in B-cell ALL (iAMP21) 
  • B-cell ALL with tyrosine kinase or cytokine receptor translocations (sometimes called “BCR-ABL1–like ALL”)
Acute Lymphocytic Leukemia
B-cell Acute Lymphocytic Leukemia

Prevention and Risk factors

B-cell acute lymphoblastic leukemia has no known cause, and there is no method to avoid it. It is important to eliminate risk factors such as smoking. However, there’s no assurance that you won’t have B-cell acute lymphoblastic.

Even though the origin of the cellular DNA mutation that leads to B-cell acute lymphoblastic leukemia is unknown, several risk factors might enhance your chances of acquiring the illness.

  • Down syndrome and other genetic abnormalities are possible risk factors. The chromosomal variations that produce diseases like Down syndrome can cause a high risk of developing B-cell acute lymphoblastic leukemia.
  • Chemotherapy and other cancer therapies are among the most common. Chemotherapy or radiation therapy for cancer patients increases the chance of acquiring B-cell acute lymphoblastic leukemia.
  • Radiation at high doses. Exposure to nuclear reactor accidents or other high amounts of radiation enhances the chances of contradicting B-cell acute lymphoblastic leukemia.
  • Smoking. Many cancers, including B-cell acute lymphoblastic leukemia, have been related to smoking.

Treatments

There are various treatments available for B-cell acute lymphoblastic leukemia.

Induction therapy is the initial step of treatment, and it attempts to kill lymphoblasts and regulate blood cell production. Once this happens, you’ll be in remission, but you’ll still require therapy. Following that, the post-remission therapy will help to eliminate any residual cancer cells in your body. The maintenance therapy following it will help control the further proliferation of the cancer cells.

During these stages, you may receive the following treatments:

  • Chemotherapy. During the initial phase of treatment, you’ll get chemotherapy to kill cancer cells. In the post-remission and maintenance therapy periods, you may additionally get chemotherapy.
  • Radiation. X-ray-like beams in radiation treatment helps to kill cancer cells. If your cancer has spread, you could require radiation.
  • Therapy with a specific focus. This medication specifically targets cancer cells. They may perish as a result. In most cases, targeted therapy is utilized in conjunction with chemotherapy in the early phase of treatment.
  • Transplants of stem cells Stem cell transplants replace diseased bone marrow with healthy fresh bone marrow.
  • Immunotherapy. Immunotherapy works by boosting your body’s natural immune system to aid in the battle against cancer. If you experience a relapse, this therapy can be an option.
  • CAR-T cell treatment is a kind of chimeric antigen receptor (CAR)-T cell therapy. CAR-T cell therapy is a treatment that manipulates your body’s T-cells to combat cancer cells. Children and young adults are the most often recipients of this therapy.

For B-cell acute lymphoblastic leukemia, there are additional experimental therapies and clinical trials available. Keep in mind that because these therapies are still in the early stages of development, they may pose a considerable risk.

T-Cell ALL

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and rapidly progressing form of acute leukemia. It affects lymphoid-cell-producing stem cells, namely T lymphocytes, a kind of white blood cell, as opposed to B lymphocytes, which are usually affected by acute lymphoblastic leukemia (ALL).

Although there is no clear reason in the majority of T-ALL instances, it is crucial to remember that it is not a contagious disease. It is also not a generational disease, that is it cannot be inherited.

Risk factors

Age – Most types of leukemia are more frequent in persons over the age of 50. However, in the case of ALL, it has a peak occurrence in children between the ages of 2 and 5. T-ALL is most frequent in children who are a little older.

T-ALL is classified as high-risk, standard, or low-risk using a system. It’s crucial to emphasize that this relates to the likelihood of a positive response to conventional therapy. Many individuals with high-risk illnesses will perform well if therapy is caters to their risk category. Even so, a patient with a low-risk illness may not necessarily have a good outcome.

The risk group is just one of the elements that influence treatment outcomes. The majority of T-ALL patients are classified as high-risk. This means that, they have a very strong chance of cure T-ALL is classified as high-risk, standard, or low-risk using a system. It’s crucial to emphasize that this relates to the likelihood of a positive response to conventional therapy. Many individuals with high-risk illnesses will perform well if therapy is caters to their risk category. Even so, a patient with a low-risk illness may not necessarily have a good outcome. The risk group is just one of the elements that influence treatment outcomes. The majority of T-ALL patients are classified as high-risk. This means that , they have a very strong chance of cure with the right therapy.

Treatment

T-ALL patients will almost all begin therapy right away. The only exception would be if a patient is gravely unwell and unable to obtain treatment due to other medical issues. In younger and/or fitter people, acute leukemia is typically curable with conventional therapy. While patients respond well to therapy at first, but the problem will most likely return, or relapse. There are various treatments available for acute lymphocytic leukemia.

  • Chemotherapy is a term that refers to the use of medicines that destroy cells. T-ALL is typically treated with steroids in addition to chemotherapy.
  • Radiation treatment — In T-ALL, it is usually only used in conjunction with a stem cell transplant.
  • A stem cell transplant may be administered to younger/fitter patients (bone marrow transplant). Healthy stem cells from a donor are used in this procedure. If chemotherapy does not cure T-ALL, this procedure is performed.
  • T-cell ALL lymphoblastic leukemia with early T-cell precursors* * It’s unclear whether there’s sufficient proof that it’s a distinct group (meaning it’s still a “provisional entity”).

Acute leukemias of mixed phenotype

A few acute leukemias have both lymphocytic and myeloid characteristics. Myeloid and lymphocytic characteristics can coexist in leukemia cells. Other times, a person’s leukemia cells may have myeloid and lymphocytic characteristics. Mixed lineage leukemia, acute undifferentiated leukemia, or mixed phenotypic acute leukemia are all terms used to describe these kinds of leukemia (MPAL). According to most research, these leukemias are thought to have a worse prognosis than typical ALL or AML subtypes.

Conclusion

There are some factors that determine the prognosis for B-cell acute lymphoblastic leukemia . Children under the age of 15 are, for example, far more likely to have successful therapy and attain full remission. On the other hand, new cancer therapies are assisting more patients than ever before in achieving remission. According to the Leukemia and Lymphoma Society, all forms of leukemia had a five-year survival rate of about 14% decades ago.

In today’s world, the five-year survival rate for acute lymphocytic leukemia is 71.7 percent. However, in children, the incidence is considerably greater. B-cell acute lymphoblastic leukemia usually goes into remission. Many patients, however, may relapse and require further therapy. If you have been in remission for 5 years or longer for B-cell acute lymphoblastic leukemia there is a high chance of cure.

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