Despite the fact that acute myeloid leukemia (AML) accounts for less than 1.5% of all cancer cases in the United States, deaths due to complications associated with AML account for a disproportionately high number of deaths annually when compared to the fraction of the population diagnosed with the disease. A rare but aggressive cancer of the bone marrow, AML is primarily characterized by the improper proliferation and differentiation of abnormal white blood cells other than lymphocytes. Lymphocytes are a particular type of white blood cell involved in the production of antibodies and the destruction of cancerous cells, whereas the other white blood cells, like neutrophils, eosinophils, basophils, and monocytes, help mediate immune responses by engulfing foreign bodies and destroying them.  In AML patients, abnormal white blood cells continue to differentiate without regulation, impairing the production of normal white blood cells, red blood cells, and megakaryocytes, which are bone marrow cells that manufacture platelets1. Due to this disruption of proper complete blood cell count, AML can rapidly induce threatening physiological complications. Furthermore, because metastases from the afflicted bone marrow have been demonstrated to rapidly spread and affect cerebrospinal fluid and liver function, AML can rapidly progress and result in death (2). For all patients treated for AML, the 5 year survival rate is around 26%3.  The combination of AML’s aggressive rate of progression and potential to induce fatal complications has prompted researchers to resolve the particular problems presented by this rapidly advancing leukemia.

Patients with AML typically present with symptoms including shortness of breath, easy bruising of the skin, fever, fatigue, unusual bleeding, or unusual frequency of infection. However, a proper diagnosis of AML is confirmed through a combination of blood tests and bone marrow biopsies, both of which show the relative amount of normal white blood cells, abnormal white blood cells, and red blood cells (3). Following an affirmative diagnosis, treatment is dependent on how far the leukemia has progressed. Typically, chemotherapy is the primary course of action for most patients, with the exception of the very elderly. Since most forms of AML progress so rapidly, most patients undergo chemotherapy in a comparatively compressed time period. Chemotherapeutic drugs, like anthracyclines and corticosteroids, are effective at eliminating the number of abnormal blood cells in the bone marrow, but negatively impact healthy blood cells as well (3). These drugs adversely affect normal platelets, red, and white blood cells, and thus leave the patient less capable of controlling bleeding, circulating oxygen, and fighting infection.

Thus, a major complication associated with the use of chemotherapy to treat AML is the susceptibility of patients to infection, which is the primary cause of the septic shock and subsequent death that is so prevalent in AML patients (4). To improve the prognosis of AML patients undergoing chemotherapy, oncologists have adapted hematopoietic stem cell transplantation (HSCT) as a supplemental technique to mitigate susceptibility to infection by introducing cells capable of producing healthy platelets, white, and red blood cells.

Typically, transplanted hematopoietic stem cells come from a donor in an allogeneic transplantation, which comes with a considerable risk of rejection by the recipient’s immune system.Even if the transplant is successful, the combination of chemotherapy and HSCT is still not sufficient to completely eliminate the possibility of relapse, which occurs in about 75% of patients over the age of 60 (3).

The propensity of AML relapse, even in spite of chemotherapy coupled with HSCT, has inspired researchers to explore other possibilities for combating this aggressive cancer. One such possibility is the implementation of immunotherapy. Immunotherapy takes advantage of the ability of T cells, produced in the thymus gland, to mediate an immune response against a variety of pathogens and cancer cells. In this treatment technique, T cells localized to an area known to be the origin of malignant cells are isolated. After their isolation, these T cells are genetically modified so that they are able to more effectively target and eliminate the malignant cells specific to that individual. In a 2017 study, Felix Lichtenegger of the University of Munich evaluated the potential of immunotherapy to treat AML. He and his research team determined that adaptation of immunotherapy to fight AML is complicated by the fact that leukemic growths located in tissues away from the bone marrow do not display the typical target antigen of immunotherapy.  Because these growths do not contain the antigen target that prompts an immune response, they are more difficult to control.  However, he was able to conclude that the sequencing of mutations characteristic of AML gives genetically modified T cells a more specific target, which improves the potential of the T cells to combat the malignant cells in the patient’s bone marrow (7).

Almost 50 million dollars is allocated annually to the research of techniques to combat various subtypes of leukemic cancers (1). Despite its rarity, acute myeloid leukemia is one of the deadliest cancers, and the distribution of resources toward the development and perfection of immunotherapeutic techniques could prove to save innumerable lives as scientists continue the battle against cancer. While immunotherapeutic treatment of AML does have imperfections in its specificity and overall effectiveness, laboratory trials have indicated that immunotherapy does have the potential to be applied to patients on an individualized basis, and does have the potential to supplement or even supplant chemotherapy and HSCT as the predominant courses of care for patients afflicted with this disease.


REFERENCES

  1. American Cancer Society. “What is Acute Myeloid Leukemia?.” American Cancer Society. February 2016.
  2. Brinch, Lorentz MD. “Metastatic Patterns of Leukemia.” Oncology Encyclopedia. January 2010.
  3. Nall, Rachel RN. “Survival Rates and Outlook for Acute Myeloid Leukemia.” University of Illinois-Chicago School of Medicine. October 2016.
  4. American Cancer Society. “Chemotherapy for Acute Myeloid Leukemia.” American Cancer Society. February 2016.
  5. Gupta A, et al. “Infections in acute myeloid leukemia: an analysis of 383 febrile Episodes.” Med Oncol. December 2010.
  6. Park, Bokyung et al. “Hematopoietic stem cell expansion and generation: the ways to make a breakthrough.” Blood res. December 2015.
  7. Lichtenegger, Felix, et al. “Recent developments in immunotherapy of acute myeloid leukemia.” Journal of Hematology and Oncology. 2017.

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