Treatment. The main aim of the treatment is to get the blood counts back to normal. If this is achieved and the bone marrow looks healthy under the microscope the cancer is said to be in remission i.e the absence of any detectable cancer cells in the body. Over the past decade's effective treatments for acute lymphoblastic leukemia have been developed, hence survival rates have increased. There are many treatments available for ALL including steroids, chemotherapy, radiation, therapy, stem cell or bone marrow transplants etc www mountsinai org 37. Chemotherapy is the first treatment of choice with a goal of achieving a remission. There are three stages in chemotherapy. A remission induction, B intensification, and C maintenance therapy. A Remission Induction. The major goals are 1 Rapidly kill all the tumor cells and restore normal hematopoiesis, 2 Reduce blast cells in the bone marrow to 5 and eliminate tumor cells from blood, 3 Cause absence of other symptoms of the disease. The following drugs are used in combination steroids like dexamethasone, vincristine, asparaginase etc Hoffbrand et al 2013 38. B Intensification High doses of chemotherapy is helpful in removing the tumor burden.
Typical protocol use the following drugs in different combination depending on the patient's risk category, cyclophosphamide, etoposide, vincristine, thioguanine, mercaptopurine, cytarabine. National Cancer Institute 39. The central nervous system prophylaxis is given during induction and intensification via ommaya reservoir or lumbar puncture. It can also be achieved by craniospinal irradiation, liposomal irradiation, liposomal cytarabine drug or cytarabine methotrexate Jabbour et al 2010 40. Relapse in the central nervous system is treated with intrathecal administration of drugs like hydrocortisone, cytarabine and methotrexate. C Maintenance therapy. Any blast cells that are not killed by remission induction and intensification are killed by maintenance therapy. If these cells are not eradicated they will cause relapse, hence maintenance is necessary. The typical protocol includes. A daily oral dose of mercaptopurine, weekly oral dose of methotrexate, a monthly five-day course of oral corticosteroids and intravenous vincristine. National Cancer Institute 39. Chemotherapy treatment also depends upon subtypes of ALL i e B cell ALL and T cell ALL B cell ALL is generally associated with cytogenetic abnormalities, which requires aggressive therapy, which includes brief high-intensity regimes. T cell ALL generally responds to cyclophosphamide containing agents the most National Cancer Institute 39.
Males usually need a longer course of treatment as compared to females as the testicles can act as a cancer reservoir. Radiation therapy. Radiation therapy is generally used for painful bony areas in high disease burdens. Radiation was used for central nervous system prophylaxis in the form of whole-brain radiation to prevent the occurrence and or relapse of leukemia in the brain, but CNS chemotherapy provides better results with side effects, hence radiation therapy is not used anymore Paul et al 2016 4. Biological therapy. Biological targets can be selected on the basis of their combinational effects on the leukemia lymphoblasts, it can be helpful in improving ALL treatment with the help of clinical trials Lambrou et al 2012 42. Patients suffering from BCR ABL 1 ALL are treated with Tyrosine Kinase Inhibitors TKIs like Imatinib mesylate which is the first example of targeted drug therapy for cancer Druker et al 2001 43. Imatinib inhibits the kinase activity by binding to the ATP binding site in the kinase domain of BCR ABL which leads to inactivation of BCR ABL hence ATP cannot bind to it. Therefore subsequent phosphorylation and activation of downstream signal pathway is inhibited and hence uncontrolled proliferation is arrested, thus restoring normal cellular processes.
More TKIs including dasatinib ponatinib and nilotinib have been developed to treat leukemia. A CD19 CD3 bispecific monoclonal murine antibody Blinatumomab is promising as a novel pharmacotherapy. By engaging the CD3 T cell with the C19 receptor on B cells it triggers a response that induces the release of cytokines and proliferation of T cell to kill CD19 B cells National Cancer Institute 39. Gene therapy Chimeric antigen receptors CARs have emerged as new gene therapy for ALL. It uses a single-chain variable fragment scFv which is designed to recognize the cell surface marker CD19 to treat ALL Tisagenlecleucel Kymriah which is the first autologous chimeric antigen receptor CAR T cell therapy was approved in August 2017 for the first time it was used in patients aged 25 years or younger with B cell precursor. ALL that is refractory or in second or later relapse www fda gov 2017 44 Autologous. T cells are collected from peripheral blood and genetically engineered to express a CAR that targets a specific molecule on cancer cells. The modified T cells are then expanded and reinfused into the patient. 2 14 days after completing lymphodepletion with conditioning chemotherapy. Because of the risk of potentially fatal adverse effects use of tisagenlecleucel is limited to hospitals and clinics with special certification in risk evaluation and mitigation.
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