By Dr Ananya Mandal, MD
Leukemia treatment is different for each of the types of leukemia. The major treatment plans and modalities for each type are outlined below.
Acute Myeloid Leukemia (AML)
AML is a rapidly progressive condition and treatment is usually begun a few days after a diagnosis has been made. Treatment for AML carried out in two stages – the initial stage or induction stage to kill the leukemia cells of the bone marrow and the consolidation stage to kill any remaining leukemia cells that may be present in the body.
Induction stage for AML
This stage usually requires hospitalization. Chemotherapy is given during this stage and there is a likelihood of severely depressing blood counts requiring blood and platelet transfusions. Isolation is also needed as the patient is vulnerable to infections. Chemotherapy during this phase is given intravenously or orally in combination. Some chemotherapy medication may also be directly administered into the cerebrospinal fluid (SCF) with injections into the spine (intra-thecal chemotherapy).
Chemotherapeutic drugs are usually associated with side effects because they kill rapidly dividing cells like cancer cells and do not distinguish these cancer cells from healthy cells. In other words, they also kill red blood cells leading to anemia, blood clotting platelets leading to excessive uncontrolled bleeding, hair follicles leading to hair loss and linings of the gastrointestinal tract leading to diarrhea, vomiting etc. Further, the damage to the white blood cells causes an increased risk of infections.
All trans retinoic acid (ATRA)
Patients with a sub-type of AML called acute promyelocytic leukaemia may benefit from all trans retinoic acid (ATRA). ATRA works by changing the immature blast cells into mature healthy blood cells, and can reduce symptoms very quickly. Side effects of ATRA include dry skin, mouth and eyes, headaches, bone pain, nausea etc.
Consolidation stage for AML
The aim of this phase is to kill the remaining leukemia cells in the body. Treatment involves receiving regular injections of chemotherapy medication. This is usually done on an outpatient basis and no admission is needed. The consolidation phase of treatment lasts several months.
Other therapies include radiation therapy that may include whole body radiation in advanced cases. This is used to kill off remaining cancer cells.
Bone marrow and stem cell transplants are an alternative option in patients who do not respond to chemotherapy. Before transplantation can take place, the person receiving the transplant will be given aggressive high-dose chemotherapy and radiotherapy to destroy any cancerous cells in their body. Bone marrow is then transplanted after killing off the cancer cells. Transplantations have better outcomes if the donor has the same tissue type as the person who is receiving the donation. Usually a genetic match from a sibling or related person is sought.
Acute lymphocytic Leukemia (ALL)
Except for those with mature-B ALL who receive short-term intensive chemotherapy, treatment for ALL typically consists of two phases of induction and consolidation. Chemotherapy and adequate supportive care results in complete remission rates of about 98% for children and 85% for adults. In mature B cell ALL however remission rates are only 30-40% with low long term survival.
Induction treatment for ALL
Current induction treatment for children with high-risk ALL and all adults contain chemotherapy agents including:
Glucocorticoid (prednisone, prednisolone or dexamethasone)
This is called the quadruple therapy and is given over the course of four to six weeks. In children with standard-risk ALL are given triple therapy with either anthracycline or asparaginase.
Consolidation treatment for ALL
In consolidation phase Imatinib (a tyrosine kinase inhibitor) has also been used as a single agent or part of combination therapy. It has been seen to increase survival. Common regimens for consolidation in childhood ALL include high dose methotrexate with mercaptopurine, high dose asparaginase over an extended period and a repetition of the initial induction therapy in the first few months of remission.
Patients with ALL may also have spread to the central nervous system. They need CNS prophylaxis in the form of cranial irradiation (less commonly used now), intrathecal (methotrexate, cytarabine, steroids) and high-dose systemic chemotherapy (methotrexate, cytarabine, L-asparaginase).
Stem cell transplantation is used to intensify the chemotherapies and radiotherapies as it replaces destroyed stem cells. It benefits subgroups such as those with a Philadelphia chromosome or poor initial response to treatment.
Chronic Myeloid Leukemia (CML)
The aim of treatment is remission. Drug treatment is superior to allogeneic stem cell transplantation in CML patients. The most widely used chemotherapeutic agents for the control of chronic phase CML are busulfan and hydroxyurea. Interferon alfa provides better results than traditional chemotherapy, with complete cytogenetic remission in a quarter of patients and improved survival.
In recent years, tyrosine kinase inhibitors are being used increasingly. Imatinib was one of the first drugs designed on an understanding of a disease's molecular biology. It is a selective inhibitor of the tyrosine kinase encoded by BCR-ABL fusion gene. Imatinib is now firmly established as an effective therapy for newly diagnosed patients with CML.
Despite these excellent results, several patients develop resistance to imatinib. This could be because the drug is not allowed entry into the cancer cell or the gene on which the drug acts undergoes modification and changes, making the drug inactive. This has led to the development of second-generation tyrosine kinase inhibitors (dasatinib, nilotinib) as an alternative for patients that develop resistance or are intolerant to imatinib.
Dasatinib is structurally unrelated to imatinib and is approved for therapy of all phases of CML in patients who are resistant or intolerant to imatinib. Nilotinib is a compound related to imatinib that has greater specificity and improved binding characteristics, and has clinical activity in case of imatinib failure.
Chronic lymphocytic Leukemia (CLL)
CLL in early stages may cause no symptoms. It may be detected on a routine blood test. Apart from Stem cell transplant there is no curative treatment currently available for CLL. The standard treatment of patients with early disease is a “watch and wait” strategy. Blood cell counts and clinical examinations should be performed every 3 to 12 months. Chemotherapy is advised in those with active, symptomatic disease.
Chemotherapy agents include alkylating agents (chlorambucil or cyclophosphamide) these reduce the total lymphocyte mass and may prevent bone marrow failure.
Combination regimens used include:
Cyclophosphamide, doxorubicin (Adriamycin) and prednisolone (CAP)
Cyclophosphamide, vincristine, and prednisolone (CVP)
Cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine (Oncovin®), and prednisolone (CHOP)
Other agents include Bendamustine, fludarabine etc. Fludarabine is the most commonly used purine analog. The combination of fludarabine and cyclophosphamide (FC) has shown higher response rates. The use of FC with rituximab (FCR) is now considered first-line treatment in patients able to tolerate this chemotherapy.
There are several monoclonal antibodies in use as well. Monoclonal antibodies are laboratory-produced antibodies (proteins) that locate and bind to specific substances (antigens) on cancerous cells and eventually destroy the cells. In other words, the monoclonal antibodies are programmed to make leukemia cells more visible to the immune system and to block their growth signals. Commonly used monoclonal antibodies for the treatment of CLL are rituximab and alemtuzumab
Reviewed by April Cashin-Garbutt, BA Hons (Cantab)