Acute Lymphoblastic Leukemia Treatments

 Acute Lymphoblastic Leukemia is a type of cancer that arises in the lymphoid kind of blood cells in bones.¹ In this type of cancer, there are a large number of immature lymphocytes, which are the early version of white blood cells in the bone marrow. Leukemia cells spread in the body rapidly and travel to various other parts of the body including lymph nodes, spleen, liver, and central nervous system such as the brain and spinal cord. For males, the testicles could also be affected by the spreading of leukemia cells.¹ The term “acute” implies that this form of leukemia spreads quite quickly and can become fatal in only a few months. Because of this, it is very important that it be diagnosed and treated immediately. Oftentimes, bodies reject typical chemotherapy and radiation treatments for this form of cancer. In these cases, medicines are often used as a supplement or replacement for treatment to chemotherapy. Generally, these medications aren’t considered until the cancer is found to not go into remission after other treatments or the cancer returns. More and more medications and treatment variations are being approved for the treatment of Acute Lymphoblastic Leukemia every year. In this paper I will focus on newer and more well-known treatments for Acute Lymphoblastic Leukemia (ALL).

Newer Medicinal Treatments for ALL

Nelarabine is a drug that is used to treat T-cell Acute Lymphoblastic Leukemia cancer but can only be used after patients haven’t responded to or relapsed after treatments with at least two chemotherapy regimens. Its molecular formula is C₁₁H₁₅N₅O₅ and it is only slightly soluble in water which generally isn’t the best for medications since it can make it harder for the medicine to travel throughout the body. When nelarabine was tested on patients in relapse, it was very successful.² The patients that were in the trial received a combination of nelarabine and escalating-dose methotrexate and it had significant results. This group had a 4-year disease-free survival rate of 91%.² Considering the fact that Acute Lymphoblastic Leukemia is a very deadly cancer, these results were spectacular. There was another study conducted for those that had failed to go into remission. These patients were treated with high-dose methotrexate and nelarabine after their ALL failed to go into remission after 29 days.² After four years of treatment, these patients had a disease-free survival rate of 55%.² Patients in many other studies that hadn’t utilized nelarabine had a disease-free survival rate of 19%.² This indicates that nelarabine is obviously a very effective drug for increasing the survival rate of Acute Lymphoblastic Leukemia patients after having been either in relapse or having failed to go into remission in the first place after having been treated by either chemotherapy multiple times before.

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 Cytarabine is another medication that is used to treat ALL. The main function of this medicine is to utilize the medicine to cease DNA replication.³ By doing this, mitosis is slowed down since the S phase of the cell cycle is inhibited by the lack of DNA replication that would occur. This would cause cells to divide at a much slower rate which in turn decreases the chance of cancer cells replicating and cancer spreading further throughout the body. In ALL it is very common for the cancer to spread much further than the bone marrow, so any decreasing the rate of cancer cell division is beneficial. Cytarabine also inhibits DNA polymerase which helps to cease or decrease the DNA replication and repair at the same time.³ This inhibits the growth of cancer cells in the body as well. The molecular formula of Cytarabine is C₉H₁₄ClN₃O₅. It is an antimetabolite analogue of cytidine with arabinose instead of ribose.³ An antimetabolite is any substance that interferes with the metabolic processes of cells. This medication is very soluble in water and is diluted with water for treatment since the medicine contains hydrochloric acid which isn’t good for human consumption.

 Tisagenlecleucel injection is another treatment used to treat ALL. It is used in relatively young people (twenty-five years old or younger) that are either unresponsive to other treatments or the cancer returned after having already been treated using another form of treatment such as conventional chemotherapy.⁴ Tisagenlecleucel injection is also used to treat non-Hodgkin’s lymphoma which begins in the white blood cells that help to fight infections. This cancer is similar to Acute Lymphoblastic Leukemia in the type of cells that the cancer targets. In this case, tisagenlecleucel injection is also a medicine that is used after multiple other treatments. For non-Hodgkin’s lymphoma, for example, the other treatments are two other medications.⁴ Tisagenlecleucel injection is classified as an autologous cellular immunotherapy which means that it is prepared by using white blood cells from the patient in order to train these cells to attack the cancer cells that are present. So, this medication is prepared by using cells from the patient’s own blood.⁴ Tisagenlecleucel injection works by causing the body’s immune system (cells, tissues, and organs) to fight the cancer cells in the body.³ This medicine is very different from nelarabine and cytarabine in the way that it operates. They use organic compounds to target the killing of cancer cells and inhibiting the growth of cancer cells. Tisagenlecleucel injection uses a patient’s own cells to kill the cancer cells which is rather unique. Therefore, the chemical composition of Tisagenlecleucel injection varies by person. It is an extremely new development for the treatment of ALL, as the European Commission just approved Novartis’ Tisagenlecleucel injection Kymriah for the treatment of ALL in August of 2018 and the United States Food and Drug Administration approved it in May of 2018.

Older Treatments for ALL

Doxorubicin injection is a drug used to treat ALL in combination with other medicines in chemotherapy. It is in a class of medications called anthracyclines which indicates that it works by either slowing down or halting all together the growth of cancer cells in a patient’s body.⁵ This medication is an anti-tumor medication that interferes with the cell cycle as do many other medicines that treat ALL. Doxorubicin is a powder that is then mixed with a liquid so that the aqueous solution can then be injected into the vein.⁵ The equation for doxorubicin is C₂₇H₂₉NO₁₁. doxorubicin alone is very bad at which cells it targets, it often kills many healthy cells in the process of killing the quickly dividing cancerous cells.⁶ It was found more recently that this could be helped significantly by injecting doxorubicin by nanodelivery.  Nanodelivery makes targeted delivery of drugs much easier as well as reducing side-effects to chemotherapy treatments at the same time. This was achieved by encapsulating doxorubicin polymeric nanoparticles that can be delivered in a CD19 way and can target the killing of specifically leukemia cells.⁶

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 Another form of traditional treatment for Acute Lymphoblastic Leukemia is radiation therapy. It is a type of cancer treatment that utilizes a high dose of radiation to target the killing of cancer cells and the shrinking of cancerous tumors.⁷ The amount of radiation used to try to kill cancerous cells is a much greater amount than the amount used for x-ray screening to see broken bones, for instance. This is why radiation therapy for cancer can be very harmful for a patient’s body. There are two main types of radiation therapy: external beam and internal beam. External beam radiation is focused on one portion of the body and is used if the cancer is localized and hasn’t traveled throughout.⁶ On the other hand, internal beam radiation is put inside of the body and is used if the cancer has spread throughout. Radiation therapy can be used to help Acute Lymphoblastic Leukemia by increasing the survival rate and lowering the rapid spreading of cancer cells.⁷ There are limits to the amount of radiation a part of the body can receive and that is one of the many reasons it is generally used in combination with other treatments, it also just generally works best if combined with other forms of treatment.⁷ Just like chemotherapy, radiation kills healthy cells while killing cancer cells which can cause damage to the body; these damages can show up immediately or even years down the road.⁷

 Acute Lymphoblastic Leukemia is a very severe cancer that attacks the lymphoid line of blood cells in bones. There are many forms of treatment approved for this kind of cancer and many more are being approved each year. The survival rate of ALL is still relatively low compared to other forms of cancer, but by combining different forms of treatment it can be improved. A couple of the many factors that inhibit the growth of cancer cells and kill cancer cells are radiation therapy and chemotherapy. Radiation therapy utilizes high-energy subatomic particles to kill cancer cells and chemotherapy uses organic compounds to kill cancer cells. Both of these forms of treatment can harm healthy cells. New medications can be used in addition to traditional forms of cancer treatment to target the cancer cells more directly. These newer medicinal treatments are composed of the same elements as classic chemotherapy treatments. Nelarabine, cytarabine, and doxorubicin all are composed of carbon, hydrogen, nitrogen, and oxygen in different ratios. The effects of these treatments are more about how targeted the treatment is to only killing the cancer cells present in the body rather than the actual composition of the treatments.

References

1. American Cancer Society. What Is Acute Lymphocytic Leukemia (ALL)? | Acute Lymphocytic Leukemia (ALL). https://www.cancer.org/cancer/acute-lymphocytic-leukemia/about/what-is-all.html (accessed Nov 14, 2018).
2. National Cancer Institute. Nelarabine Improves Survival in Young Patients with T-Cell ALL.    https://www.cancer.gov/news-events/cancer-currents-blog/2018/leukemia-nelarabine-improves-survival (accessed Nov 14, 2018).
3. National Institutes of Health. Cytarabine. https://medlineplus.gov/druginfo/meds/a682222.html (accessed Nov 14, 2018)
4. The American Society of Health-System Pharmacists. Tisagenlecleucel Injection: MedlinePlus Drug Information. https://medlineplus.gov/druginfo/meds/a617053.html (accessed Nov 14, 2018).
5. National Institutes of Health. Doxorubicin. https://medlineplus.gov/druginfo/meds/a682221.html (accessed Nov 16, 2018)
6. Vinu Krishnan, Xian Xu, Dakota Kelly, Adam Snook, Scott A. Waldman, Robert W. Mason, Xinqiao Jia, and Ayyappan K. Rajasekaran. CD19-Targeted Nanodelivery of Doxorubicin Enhances Therapeutic Efficacy in B-Cell Acute Lymphoblastic Leukemia. Molecular Pharmaceutics 2015. 12. https://pubs-acs-org.proxy1.nku.edu (accessed Nov 18, 2018)
7. National Institutes of Health. Radiation Therapy to Treat Cancer. https://www.cancer.gov/about-cancer/treatment/types/radiation-therapy (accessed Nov 18, 2018)