Leukemia Cancer

• Leukemia is cancer of the body's blood-forming cells; the bone marrow. They can be divided into acute and chronic leukemia depending upon the growth rate of cancer cells. Both types of leukaemia’s, result in increased number of abnormal immature blood cells in the body, that are unable to carry out their normal functions.

The type of leukaemia is based on how fast the cancer grows. It is divided into:

• Acute leukaemia
• Chronic leukaemia

Acute leukaemia progresses faster because the abnormal blood cells do not mature and hence are unable to carry out normal functions. Chronic leukaemia stages much slowly as compared to Acute leukaemia because the abnormal cells are much low in number as compared to the normal cells.

The four main types of leukaemia are:

• Acute Myelogenous leukaemia
• Acute Lymphocytic leukaemia
• Chronic Myelogenous leukaemia
• Chronic Lymphocytic leukaemia

Acute Myelogenous Leukaemia (AML) : AML affects myeloid stem cells. When healthy, these stem cells make three blood components:

• Granulocytes, a type of mature white blood cell that helps fight infection
• Red blood cells, which deliver oxygen throughout the body
• Platelets, which help blood form clots.

AML occurs when a myeloid stem cell becomes cancerous. In these cases, the myeloid stem cells produce diseased cells. These cells don’t do their job well and multiply so rapidly that they crowd out healthy cells. AML can severely weaken the patient’s immune system, leading to frequent infections.

AML is the most common acute leukemia in adults. While pediatric patients also can develop the disease. As an acute leukemia, AML is aggressive and can be particularly difficult to treat. Its five-year survival rate is less than 28%, though that figure differs based on the exact subtype of each person’s cancer.

Most of these AML subtypes are based on how the diseased cells differ from healthy cells and how far along they are in the development process. Specific chromosome abnormalities in the cancer cells and the disease’s own genetic mutations also impact the prognosis.

Acute lymphocytic leukaemia (ALL): is more common in children. Of the four primary types of leukemia, acute lymphoblastic leukemia (ALL) is the least common. While people of all ages develop ALL, a majority of new diagnoses are in people under age 20. The five-year survival rate is 68%.

ALL impacts lymphoid stem cells. In healthy bone marrow, lymphoid stem cells, or lymphoblasts, form mature lymphocytes, a type of disease-fighting white blood cell. In ALL, lymphoid stem cells make diseased lymphoblasts, which rapidly grow. They eventually take over the bone marrow and cause high counts in the blood. ALL cells are immature and grow rapidly. They are poor at fighting infection and crowd out healthy cells.

Chronic myelogenous leukaemia (CML) : Chronic myeloid leukemia (CML) primarily affects adults. About 68% of new cases are in people 55 or older, while the average age of diagnosis is 65.

CML involves myeloid stem cells. When healthy, these cells form neutrophils, a type of mature white blood cell. In CML, the myeloid stem cells become cancerous. The myeloid stem cells may not fully mature and are poor at doing their jobs. They can eventually crowd healthy blood cells out of the bone marrow and cause a high white blood cell count and an enlarged spleen.

As a chronic disease, CML is relatively slow to develop, and its five-year survival rate is nearly 68%. The patient’s exact subtype of CML can impact his or her prognosis and treatment plan.

Chronic lymphocytic leukaemia (CLL): Chronic lymphoblastic leukemia (CLL) is the most common type of adult leukemia. The disease is virtually unheard of in children and it primarily affects older adults. Almost 90% of new cases are in people age 55 and older, while the average age at the time of diagnosis is 72.

CLL develops from B cells. B cells start out as lymphoid stem cells, then mature into adult B cells. In CLL, a cancerous B cell grows and multiplies in the bone marrow, lymph nodes, liver, spleen and results in a high white blood cell count. These cancerous cells are not able to fight infection. They also crowd out healthy cells from the marrow, and cause enlargement of lymph nodes, liver and spleen.

As a chronic disease, CLL is less aggressive than acute forms of leukemia. It has a five-year survival rate of around 90%. The presence of specific genetic mutations and proteins produced by the diseased cells, however, can have a big impact on the patient’s prognosis.

For CLL patients, clinical studies have not shown a benefit to beginning treatment immediately after diagnosis versus when the disease develops to a set point, known as an indication for treatment. Because of this, doctors often recommend “watchful waiting” for early stage CLL.

Initial treatments can include targeted therapy and a combined chemotherapy/immunotherapy treatment. In most cases, these treatments put patients into remission. Some patients may need continued treatment to maintain remission. For others, remission is complete and they may stop treatment. All CLL patients in remission are at risk of recurrence, requiring that they undergo other treatments. Typically patients go through multiple courses of treatment through the span of their disease.

Hairy Cell Leukaemia: Lymphoid stem cells produce too many diseased B cells. Hairy cell leukemia is typically slow to develop and progress. Because of this, doctors often recommend “watchful waiting” in which they simply monitor the disease instead of immediately ordering treatments like chemotherapy or targeted therapy.

While there are many different types of leukemia, the symptoms among these types can be similar.

Because chronic leukemia develops slowly, these patients may go years without developing symptoms. In these cases, the disease is often found through a routine blood test ordered during a physical or for some other reason.

Acute leukemia progresses quickly, so patients almost always develop symptoms.

Common leukemia symptoms include:

• Weakness, tiredness and fatigue
• Fever and frequent infections
• Night sweats
• Easy bleeding and bruising, including bleeding of the gums
• Petechiae, a rash-like collection of pinpoint spots on the skin caused by bleeding into the skin
• Shortness of breath
• Swollen lymph nodes in the neck, underarm, stomach or groin
• Loss of appetite or a full feeling after eating very little food due to enlargement of the spleen
• Unexplained weight loss
• Bone and joint pain
• For female patients, longer than normal or heavier than normal menstruation

If you are experiencing symptoms that are mentioned above, you should get yourself tested and checked by our specialists

Our specialist may suspect you for having leukaemia if you are exposed to certain risk factors and experience a combination of these symptoms. The screening for leukaemia will include:

• A complete physical examination
• Complete medical history of the patients
• Complete family history of the patient.
• Blood Tests
• Imaging Tests such as CT scans, X-rays Ultrasounds or MRIs
• Biopsies

The tests to confirm diagnosis of leukaemia will include:

• Bone marrow aspiration and biopsy: It is done painless nowadays with the help of anaesthesia.
• Microscopic examination: This is done to determine the shape of the cell for any abnormalities.
• Tissue Biopsy: A biopsy is done of the tissue from the bone marrow to look for changes in the tissue anatomy. These biopsies can help our specialist identify for any small changes as well as the progression of cancer
• Flowcytometry: It is done to further characterize the type of leukemia
• Cytogenetics: To determine with genetic alterations which help in prognosticating leukemias
• Molecular studies: It is done to determine the mutations in the genome to assess the biology and prognosis of the disease.

Cancer Staging

As blood runs throughout the body, there is no specific staging for leukemias. Instead, they are classified into three categories according to their cytogenetic profile, namely; Good risk, Intermediate risk and Poor risk.

The goal of leukemia treatment is to put the disease into remission and ultimately cure the patient.

For leukemia, complete remission usually means that the patient’s bone marrow has no microscopic evidence of the disease and his or her blood counts have returned to normal. When evaluating for acute leukemia (AML and ALL) with the microscope, the pathologists are looking for immature cells, called blasts. Blasts normally make up less than 5% of healthy bone marrow. In active leukemia, the blast count is greater than 5%. Once patients with acute leukemia are in remission, they will need additional treatment to maintain the remission.

Patients who remain in continued complete remission for an extended period of time are considered cured. This means they have an extremely low chance of recurrence. The exact amount of time it takes to be considered cured differs among leukemia types, but it is typically measured in years.

• Remission induction: This is an intense phase of treatment designed to kill leukemia cells in the blood and bone marrow and can require a hospital stay. The goal is to bring the cancer into remission.
• Consolidation: This phase of chemotherapy is meant to kill any remaining cancer cells that survived the induction phase.

ALL patients undergo the remission induction and consolidation phases, as well as a third chemotherapy phase, maintenance. During the maintenance phase, patients receive additional lower doses of chemotherapy over a longer period of time to try to wipe out any remaining cells.

Patients with chronic leukemia can receive chemotherapy treatment, but targeted therapies are currently more commonly used for these leukemias.

Targeted therapy for leukemia

Targeted therapy is designed to stop or slow the growth of cancer by interfering with, or targeting, molecules or genes in cancer cells that help the disease survive, grow and spread. By targeting these particularly vulnerable features, the leukemia cells are ultimately eliminated. There are limited and minimal associated side effects of these treatments.

Immunotherapy for leukemia Cancer immunotherapy recruits the immune system to eliminate cancer. There are several types of immunotherapies, and each uses the immune system in a different ways. Immunotherapies for leukemia include:

• Antibody-drug conjugates: Antibody-drug conjugates use an immune molecule (antibody) that seeks and binds with cancer cells and a cancer-killing drug that is then directly delivered to those cells.
• Bi-specific monoclonal antibodies: These therapies use antibodies that seek and bind to proteins on the surface of cancer cells and to activation proteins on immune cells. By doing this, they form a bridge between these cells, triggering the immune cell to destroy the cancer cells.
• CAR T-cell therapy: In CAR-T cell therapy, patients are given T cells (a type of immune system cell) that have been engineered to recognize and attack cancer. For leukemia, CAR T-cell therapy is currently only FDA-approved for patients under age 25 with B-cell ALL. Only patients who have been treated unsuccessfully with at least two other cancer therapies are eligible. In addition to the FDA-approved treatments, there are a number of CAR T-cell therapy clinical trials currently underway at MD Anderson for patients with various forms of leukemia.

Radiation therapy for leukemia

Radiation therapy uses high energy beams to kill cancer cells. Though it’s not a primary treatment for leukemia, it may be used when the disease has affected the brain and central nervous system or is likely to spread to these areas.

Stem cell transplants for leukemia

A stem cell transplant may be needed for patients whose leukemia has returned or has not responded to standard treatments. It may also be recommended if the patient has a high-risk form of leukemia that would make a cure with standard treatments unlikely. This treatment can be physically challenging, so it is typically not given to patients who are older or otherwise unhealthy.

Stem cell transplantation is not a surgical procedure. It is typically done when patients are in remission. Most leukemia patients receive an allogeneic stem cell transplant, in which stem cells are taken from the blood (and on occasion the bone marrow) of a matched donor, then infused into the patient. Stem cells may also be collected from a newborn's umbilical cord and placenta and used for a cord blood transplant.

Before the transplant, the patient receives chemotherapy (or sometimes radiation therapy) to prepare the patient’s bone marrow to accept the transplanted stem cells. The donated stem cells are then given by an intravenous infusion and travel to the bone marrow. There, they grow to produce healthy stem cells, which in turn produce red and white blood cells and platelets found in blood.

What is minimal residual disease (MRD)?

MRD refers to cancer cells remaining after treatment that can’t be detected by those same scans or tests. Minimal residual disease is a small number of cancer cells left in the body after treatment. These cells have the potential to come back and cause relapse in our patients. MRD is quantified by next generation sequencing or cytogenetic studies or a flowcytometry.