Treatment of Acute Myeloid Leukemia

As a person ages, his/her prospect of contracting Acute Myeloid Leukemia (AML)

increases. Children and adults of any ages, however, may develop AML This qualitative study asserts that the potential for development of significant improvement of therapies for AML depends on continuing studies such as the three which this qualitative case study investigates.

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Context of the Problem

Organization of the Study

TREATMENT of ACUTE MYELOID LEUKEMIA

"The overall cure rate for childhood [acute lymphocytic leukemia] ALL

is now approximately 75-80%; however, for [acute myelogenous leukemia] AML

the cure rate is between 40 and 45%"

(Belson, Kingsley, and Holmes, para. 6)

Context of the Problem

Acute Myeloid Leukemia (AML)

Leukemia currently maintains the status of being one of the 10 leading causes of cancer deaths in the United States. Although chemotherapy or allogeneic bone marrow transplantation, may contribute to a durable survival for a number of leukemia patients, adults with relapsed and/or refractory leukemias do not hold a satisfactory survival record. The number of Americans projected to be diagnosed with acute myelogenous leukemia (AML), a cancer of the blood and bone marrow, in the United States (U.S.) during 2008 was approximately 13,290. The prospect of contracting AML increases as a person ages, albeit children and adults of any age may develop AML (Detailed Guide: Leukemia). This thesis asserts that the potential for development of significant improvement of therapies for AML depends on continuing studies such as the three which this qualitative case study investigates.

In adults and children, AML typically worsens rapidly when not treated. In adults, whether the reason is due to their older age, the absence of a donor, or the refractory/progressive disease, the majority of leukemia patients may not have the option for allogeneic bone marrow, Ken Shiozawa, Takeo Nakanishi, Ming Tan, Hong-Bin Fang, Wen-chyi Wang, Martin J. Edelman, David Carlton, Ivana Gojo, Edward a. Sausville and Douglas D. Ross report in "Preclinical Studies of Vorinostat (Suberoylanilide Hydroxamic Acid) Combined with Cytosine Arabinoside and Etoposide for Treatment of Acute Leukemias," Study I, one of the three studies this thesis examines.

In Study II, "Nuclear Factor- B Modulation in Patients Undergoing Induction Chemotherapy for Acute Myelogenous Leukemia," the second study this thesis explores, Roger K. Strair, Mecide Gharibo, Dale Schaar, Arnold Rubin, Jonathan Harrison, Joseph Aisner, Hsin-Ching Lin5, Yong Lin, Lauri Goodell, Monika Anand, Binaifer Balsara, Liesel Dudek, Arnold Rabson and Daniel J. Medina investigated whether standard anti-inflammatory agents modulate AML cell nuclear NF-B when administered in conjunction with induction chemotherapy. Results from the study by Strair, et al. indicate the need warrants more follow-up study for determining the effects of NF-B modulation on clinical end points.

The researcher notes that in Study III, the third study this study explores, "Preclinical Studies of Vorinostat (Suberoylanilide Hydroxamic Acid) Combined with Cytosine Arabinoside and Etoposide for Treatment of Acute Leukemias," that the authors, Ken Shiozawa, Takeo Nakanishi, Ming Tan, Hong-Bin Fang, Wen-chyi Wang, Martin J. Edelman, David Carlton, Ivana Gojo, Edward a. Sausville and Douglas D. Ross, utilized an experimental design. Shiozawa, et al. appraised "combining cytosine arabinoside [1-?-D-arabinofuranosylcytosine (ara-C)] and/or etoposide with vorinostat for use in the treatment of acute leukemias" (Abstract). The assessment of drug combination effects by Shiozawa, et al. ultimately proffered a preclinical rationale for phase I trials of the sequential combination of vorinostat followed by ara-C and etoposide in patients evidencing advanced or refractory leukemias.

Statement of the Problem

While approximately one in five children with leukemia has AML, according to the Leukemia & Lymphoma Society (LLS), adult AML constitutes the most common type of acute leukemia in adults. The Leukemia & Lymphoma Society stresses it to be vital that acute leukemia be treated right away. At this time, no "cure" exists. The prognosis for the AML patient, as well as his/her treatment options depend on, but may not be limited to:

The age of the patient.

The subtype of AML.

Whether the patient received chemotherapy in the past to treat a different cancer.

Whether there is a history of a blood disorder such as myelodysplastic syndrome.

Whether the cancer has spread to the central nervous system.

Whether the cancer has been treated before or recurred (come back).

(Lukemia & Lymphoma…)

Significance of the Study

The fact that the overall cure rate for AML totals only 40 and 45%, approximately half, the rate for ALL (Belson, Kingsley, and Holmes), the researcher asserts, contributes to this study's claim to merit a "significant" status. In addition, as leukemia currently maintains the status of being one of the 10 leading causes of cancer deaths in the United States, the researcher contends that this thesis which explores the potential for development of significant improvement of therapies for AML, proves significant as it contributes to the understanding of possible advancements toward improved treatments.

The American Cancer Society notes the following key statistics regarding AML:

About 44,270 new cases of leukemia will be diagnosed in the United States during 2008.

About 8,820 deaths from AML will occur in the United States during 2008, and almost all will be in adults.

Acute myeloid leukemia is generally a disease of older people and is rare before the age of 40. The average age of a patient with AML is about 67 years.

AML is slightly more common among men than among women. The lifetime risk of getting AML for the average man is about 1 in 225; for the average woman the risk is about 1 in 300. (Detailed Guide: Leukemia).

Study Rationale

Current clinical concerns regarding AML, particularly regarding the low overall cure rate, along with the disease's high rate of new cases and deaths, noted in the previous section, factor into the researcher's rationale for choosing to focus on this disease. During the course of this thesis, the researcher relates a number of findings from examining three contemporary clinical studies related to AML. In turn, the researcher, as well as readers will increase understanding of this disease. Ultimately, the researcher contends, this research effort will serve as a source for consideration as a credible resource by other researchers and encourage even more research relating to treatment of AML.

Research Questions

For this study's research questions, the researcher drew/adapted the following three questions from the three studies explored during this thesis. These three questions double as the research questions for this study effort.

1. Does C/EBP mRNA serve as a target for miRNA-124? (Hackanson, et al.).

2. Do standard anti-inflammatory agents modulate AML cell nuclear NF-B when administered in conjunction with induction chemotherapy? (Strair, et al.).

3. How affective is the practice of "combining cytosine arabinoside [1-?-D-arabinofuranosylcytosine (ara-C)] and/or etoposide with vorinostat for use in the treatment of acute leukemias"? (Shiozawa Abstract).

Research Design and Methodology

Case Studies (2008) asserts that a case study research design, a form of qualitative descriptive research, provides the researcher with a blueprint for him/her to utilize to build his/her study. As the study examines "an individual or small participant pool, it draws conclusions only about that participant or group and only in that specific context" (Case Studies 2008, Introduction and Definition section). To complement this thesis which investigates treatment for AML, the researcher examined three clinical studies related to AML.

Organization of the Study

Chapter I: Introduction

This study's first chapter, Chapter I presents the background of the phenomenon, AML and introduces the focus for the thesis. Chapter I also denotes s the three clinical studies being expounded during this study effort.

Chapter II: Review of the Literature

Chapter II, the literature review relates the three studies the researcher chose to foucs on during this thesis. This chapter also presents additional information the researcher accessed for this study. The researcher subscribed to the American Association for Cancer Research Web site (http://cancerres.aacrjournals.org/) to access the three primary studies utilized as the foundation for this study's focus.

Chapter III: Methodology

Chapter III of this thesis mirrors the methodology the researcher used to implement this particular qualitative case study focusing on AML.

Chapter IV: Analysis

Chapter IV of this thesis relates numerous findings the researcher dissects from the three clinical studies. Chapter V: Discussion, Conclusion and Recommendations

Chapter V reviews the study scenario, recounts a number of the findings from the clinical studies, and reiterates relevant points addressing the three research questions regarding AML treatments. At the end of this study/chapter, the researcher proffers several recommendations, relating to the treatment of AML, for future researchers to consider for further research projects. The researcher also notes any experiences that could serve as lessons for future study opportunities.

Aims and Objectives

The primary aim for the study is to examine three clinical studies, noted earlier in this study, relating to the treatment of AML.

Objective 1

Access three specific clinical studies relating the treatment of AML.

Objective 2

Access additional literature which relates credible information relating to the treatment of AML.

Objective 3

Utilize the data accessed from the three studies to compile with informatio retrieved from the other sources to…