Acute Lymphoblastic Leukemia

1. Acute Lymphoblastic Leukemia Introduction: Acute Lymphoblastic Leukemia may be called by other names, including ALL and acute lymphoid leukemia. ALL can occur at any age, it is the most common type of leukemia in children as well as young adults younger than aged 20 years. The improved remission rates can be achieved with the help of advanced treatment of ALL. What is Acute Lymphoblastic Leukemia (ALL): ALL, one of the four main types of leukemia, is kind of blood cancer that begins in the bone marrow and moves into the blood quickly. ALL is an aggressive type of leukemia; in absence of getting treatment, most patients with acute leukemia would survive only for a few months. Symptoms of Acute Lymphoblastic Leukemia: The signs and symptoms of ALL are variable and include: •Weakness •Feeling tired •Anemia •Dizziness •Headache •Vomiting •Lethargy •Neck stiffness •Cranial nerve palsies •Weight loss •Loss of appetite •Bone pain •Joint pain •Breathlessness •Enlarged lymph nodes •Testicular enlargement •Mediastinal mass •Frequent fever and infection •Excessive and unexplained bruising Risk Factors: The risk of developing ALL is greater in children younger than 5 years of age. Overall, approximately 4 of every 10 cases of acute lymphoid leukemia are in adults. The possible risk factors for acute lymphoblastic leukemia include: •Being male •Being older than 70

2. •Being Caucasian •Previously treated with chemotherapy or radiation therapy. •High dose radiation exposure (e.g., survivor of an atomic bomb blast or nuclear reactor accident). •Certain genetic disorders, such as Down syndrome. Diagnosis: ALL diagnosis is usually done with the help of blood and bone marrow tests, based on the information on blood cell counts, blood chemistry studies and bone marrow sampling. Patients with acute lymphoblastic leukemia often have numerous non- specific symptoms, including fever, weight loss, fatigue, night sweats and loss of appetite. Who treats Acute Lymphoblastic Leukemia? On behalf of your existing treatment options, you may have different types of doctors on your treatment team. These doctors could include: A hematologist: a specialist who treats disorders of the blood. A medical oncologist: a specialist who treats cancer with medicines. You might have many other specialists on your treatment team as well, including physician assistants, nurses, nurse practitioners, nutrition specialists, social workers, and other healthcare professionals. Treatment: Long-term chemotherapy and various combination chemotherapy regimens are widely used to treat first line ALL. Additional treatment options include targeted therapies, T-cell therapies and tyrosine kinase inhibitors (TKIs). Because leukemia cells have potential in order to spread widely throughout the bone marrow and to several other organs, surgery can not be used. For patients who do not respond to chemotherapy and have an advanced case of ALL, stem cell transplant may be the best chance for a cure. Additional therapeutic options are needed to help patients achieve hematologic remission, which may help them become eligible for transplant. Chemotherapy for ALL (Acute Lymphocytic Leukemia): Chemo is considered as the main treatment for treating the acute lymphocytic leukemia (ALL). Due to its potential adverse reactions, chemo might not be given for those patients who are in poor health, but advanced age by itself is not a barrier to getting chemo. Chemo is typically recommended to be given in cycles, with each period of treatment followed by a rest period to allow the body time to recover.

3. The chemo drugs are injected into a vein (IV), into a muscle, or under the skin, or are taken by mouth. These medicines enter the blood and reach leukemia cells all over the body. Chemo for acute Lymphoblastic leukemia uses a combination of anti- cancer medications. The most recommended chemo drugs include: •Methotrexate •Cyclophosphamide •Prednisone •Dexamethasone •Nelarabine (Arranon) •Cytarabine (cytosine arabinoside, ara-C) •Vincristine or liposomal vincristine (Marqibo) •Daunorubicin (daunomycin) or doxorubicin (Adriamycin) •Pegaspargase or Oncaspar •6-mercaptopurine (6-MP) Patients typically get some of these drugs at different times during a treatment course, but they can not take all of them. Possible side effects: Chemo drugs may also affect a few healthy/normal cells which can be responsible for causing side effects. The adverse reactions of chemo depend on the type as well as dose given and the length of time they are consumed. Common side effects may include: •Hair loss •Mouth sores •Loss of appetite •Nausea •Vomiting •Diarrhea •Constipation Targeted Therapy for ALL (Acute Lymphocytic Leukemia): Targeted therapy drugs attack the specific parts of the cancer cells. Targeted drugs are different from standard chemo drugs. They're effective when the chemo doesn't, and have different adverse reactions. Some of these drugs can be useful when taken daily as pills in certain cases of ALL. Imatinib (Gleevec): Apart from ALL, it is also used for Chronic Myeloid Leukemia (CML) that are Philadelphia chromosome-positive (Ph+). The imatinib 400 mg works by stopping the Bcr-Abl tyrosine-kinase. Dasatinib (Sprycel): It works by blocking a number of tyrosine kinases such as Bcr-Abl and the Src kinase family. Nilotinib (Tasigna): It is used both in the initial cases of the chronic phase CML as well as in the accelerated and chronic phase CML that has not responded to the imatinib.

4. Ponatinib (Iclusig): It is a multi-targeted tyrosine-kinase inhibitor. Bosutinib (Bosulif): Bosutinib 500 mg is an ATP-competitive Bcr-Abl TKI with an additional inhibitory effect on the SRc family kinases (including Src, Lyn and Hck). In Ph+ Acute Lymphoblastic Leukemia patients, adding a tyrosine kinase inhibitor to chemo helps increase the chance that the leukemia will go into remission. Keep taking one of these medications may help prevent the leukemia from coming back. If one TKI doesn't seem effective, another one might be recommended. Possible side effects: Side effects are generally mild. Common side effects include: •Diarrhea •Nausea •Muscle pain •Fatigue •Skin rashes Some other possible adverse reactions include lower platelet and red blood cells counts at the initial phase of treatment. All of these adverse reactions can get worse due to the higher doses of the drug. Immunotherapy: Some of the immunotherapy drugs used to treat ALL might also be considered forms of targeted therapy, because they work by attaching to specific parts of leukemia cells. Drugs include: •Blinatumomab (Blincyto) •Inotuzumab ozogamicin (Besponsa) Blinatumomab and Inotuzumab ozogamicin are the monoclonal antibodies. These antibodies are proteins made by the body’s immune system to help fight infections. Possible Side Effects: The common side effects of Blinatumomab are: •Fever •Headache •Nausea •Tremor •Rash •Constipation •Seizures •Difficulty in speaking •Blurred speech •Passing out •Confusion •Loss of balance

5. •Low blood potassium levels •Swelling of the feet and hands •Low white blood cell counts Apart from this, the common side effects of Inotuzumab ozogamicin (Besponsa) are: •Fever •Nausea •Headache •Abdominal (belly) pain •Low levels of blood cells •High blood levels of bilirubin Surgery for ALL: In order to treat ALL, surgery has a very limited role. Because the leukemia cells are specifically spread widely throughout the blood and bone marrow, the cure is not possible with surgery. In ALL, surgery is basically used to insert the catheters (tubes) into the body to make it quite easier in order to give chemo, which is the main treatment for ALL. •Placement of a central venous catheter. •Placement of an Ommaya reservoir. Radiation Therapy for Acute Lymphocytic Leukemia (ALL): Radiation therapy uses high-energy radiation to kill cancer cells. It is not considered as the main treatment in order to treat ALL, but it is recommended in certain conditions: This therapy is sometimes recommended for leukemia that has spread to the testicles or brain and spinal fluid. •Radiation to the entire body is often an important part of treatment prior to a bone marrow or peripheral blood stem cell transplant. •Radiation is rarely used to shrink a tumor if it is pressing on the windpipe and causing breathing problems. But chemo is often recommended instead, as it can work rapidly. •Radiation is also helpful for reducing the pain in an area of bone invaded by the leukemia, if chemotherapy hasn’t helped. Possible Side Effects: The possible side effects of radiation therapy depend on where the radiation is aimed. They include: •Fatigue •Headaches •Skin changes in the treated area •Hair loss in the area being treated •Nausea and vomiting (treatment of head or belly) •Diarrhea (treatment of belly or pelvis) •Mouth sores and trouble swallowing (treatment of head and neck area).

6. Stem Cell Transplant for Acute Lymphocytic Leukemia (ALL): The stem cell transplant (SCT) allows doctors in order to use higher doses of chemo (sometimes along with radiation) to kill the cancerous cells. Following these treatments, the patient gets an infusion (transplant) of blood-forming stem cells for restoring the bone marrow. Blood-forming stem cells used for a transplant are taken from the blood, bone marrow, or from a baby's umbilical cord blood. Most oftenly, stem cells from the blood are recommended. Types of stem cell transplants: The two most recommended stem cell transplants are: Allogeneic stem cell transplant: In this the stem cells come from someone else. This is one of the preferred transplants in order to treat ALL. Autologous stem cell transplant: In the autologous transplant, patients get back his or her own cells. Prognosis: Prognosis for the ALL remains poor. While approximately 80% to 90% of adult patients will have complete remissions at some point during the treatment, about half will relapse, so the overall cure rate is approximately 40%. Source: https://ikrispharmanet.wixsite.com/blog/post/acute-lymphoblastic-leukemia