Patients with Acute Myeloid Leukemia - Essay Example

? Introduction This report will analyse cases that are regarding patients with Acute Myeloid Leukemia (AML). Included in this report is an investigation regarding a patient who presented with pulmonary infiltration. This report is important, as pulmonary infiltration is a rare presenting symptom, and, because it is, AML is often overlooked as a cause of the pulmonary infiltration. Instead, diagnoses might center around other, unrelated diseases, such as pneumonia, and the patient is left untreated for his AML. This may lead to rapid death, as was the case in the case study analyzed in this report. Other reports include promising therapies for patients who are over the age of 65, with a specific subtype of AML and promising therapies for patients under the age of 65 with other subtypes of AML. These reports are important, because they analyse the latest techniques for treating specific types of AML, and these reports have proved to be promising, with significant survival rates, especially compared to the survival rates of those with conventional therapies. Discussion 1. What is AML, How Common is It, The General Symptoms and the Subtypes Acute myeloid leukemia (AML) is considered to be the most common kinds of acute leukemia in adults. That said, its incidence is still relatively rare, accounting for just over 1% of all cancer deaths per year (Jemal et al., 2002). In 2005, the National Cancer Institute reported that there were just under 12,000 new cases of AML reported, and 10,000 deaths from the disease (Resource4Leukemia.com). The disease is rare in those under the age of 40 years old, and generally strikes those over the age of 60. It is also more common in men than in women. This cancer is signified by having an abnormal cells in the person’s bone marrow. These cells replace the healthy bone marrow tissue, as they grow so rapidly. Because of this, the bone marrow stops working correctly, and, since the bone marrow is responsible for fighting infections, the person with AML becomes more prone to infections. They also have an increased risk for bleeding, as the healthy blood cells decrease and are replaced by the abnormal cells (A.D.A.M Medical Encyclopedia, 2010). The French-American-British (FAB) classification divides AML into eight different subgroups. They are listed as follows, as well as the percentage of all AML patients who have each of the subgroups listed (Bennett et al., 1976): M0 minimally differentiated acute myeloblastic leukemia 5% M1 acute myeloblastic leukemia, without maturation 15% M2 acute myeloblastic leukemia, with granulocytic maturation t(8;21)(q22;q22), t(6;9) 25% M3 promyelocytic, or acute promyelocytic leukemia (APL) t(15;17) 10% M4 acute myelomonocytic leukemia inv(16)(p13q22), del(16q) 20% M4eo myelomonocytic together with bone marrow eosinophilia inv(16), t(16;16) 5% M5 acute monoblastic leukemia (M5a) or acute monocytic leukemia (M5b) del (11q), t(9;11), t(11;19) 10% M6 acute erythroid leukemias, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b) 5% M7 acute megakaryoblastic leukemia t(1;22) 5% 2. Misdiagnosis of AML, and the consequences of this Because AML presents with symptoms which are shared with other, more common and much less lethal, diseases, it is often misdiagnosed. The symptoms include fever, shortness of breath, fatigue, weight loss, increased bruising, bone and joint pain and persistent infections. Unfortunately, because these symptoms are the same as other diseases, such as the flu or the common cold, doctors often do not diagnose it properly unless they are specifically looking for this disease (Resource4Leukemia.com). According to Huq et al. (2005), a misdiagnosis of this disease results in increased mortality. They reported on a case of an African-American male who presented with symptoms consistent with pneumonia, including a fever, cough and back pain. His lab results showed evidence of leukocytosis and anemia, and he was treated for pneumonia with a course of azithromycin. Three months later, he presented with a progression of his symptoms, along with weight loss of 30 lbs. He was also running a fever, and had abnormal blood pressure, respiratory and pulse readings. He was treated for pulmonary infection upon this second admission to the hospital, yet continued to deteriorate. He died in the hospital (Huq et al., 2005, p. 1551). Another rare presenting symptom is jaundice. Because jaundice, like pulmonary infiltration, is rarely seen in patients who are presenting with AML, misdiagnoses may result when a patient presents with this symptom. This was the case in the case study reported by Wandroo et al. (2004). They explain that jaundice is rarely seen in presenting cases of AML, and that it is usually treatment related. However, in this case, the patient was properly treated and went into remission. Proper diagnosis techniques, including the most modern techniques Since it is crucial that patients get the proper diagnosis early in the course of their disease, as it can proceed rapidly to death if left untreated, it is equally crucial that the proper diagnostic tools are utilized by physicians. Dohner et al. (2010) describe the newest diagnostic tools that can be used when a patient presents with symptoms that might be consistent with AML. The first diagnostic tool that is used with the patient is a bone marrow biopsy. The bone marrow is examined by using the May-Grunwald-Giensa stain or the Wright-Giensa stain. The blast count must be more than 20% to diagnosis AML, and the blasts which are included in this analysis include monoblasts, myeloblasts and megakaryoblasts (p. 453). Moreover, because of the nature of AML, in that it is divided into 8 subgroups, the diagnosis must go further to identify the lineage involvement, according to Dohner et al. (2010). While some countries still rely on cytochemistry, the newest method of determining lineage involvement includes immunophenotyping. This uses three or four color flow cytometry. Immunophenotyping is necessary to establish a diagnosis of AML when there is minimal differentiation between the disease, as it does not have morphological and cytochemical evidence of myeloid differentiation, according to Dohner et al. (2010) (p. 455). Genetics testing is yet another modern procedure in diagnosing AML, according to Dohner et al. (2010). This includes cytogenetics testing, which can detect chromosomal abnormalities, as seen by 55% of the adults diagnosed with AML. It also includes molecular cytogenetics, which may detect gene rearrangements. Molecular genetics is another genetics-related procedure which is helpful in diagnosing AML properly, as this test discovers mutations in the genes (Dohner et al., 2010, p. 456). These tests are mandatory to properly treat AML, especially for patients who are receiving a treatment course other than low-dose chemotherapy or general supportive care. 3. Some promising new therapies for certain types of AML While the above represents the modern techniques in diagnosing the patient’s AML, based on the assumption that every patient will have a unique profile with regards to their individual case of AML, and the treatment should proceed accordingly, there are also new and modern treatment options for the disease. For instance, Fenaux et al., (2010) reports on modern treatment options for patients who are elderly and have a low bone marrow blast count. In their study, patients were administered 75 mgs of azacitidine, and they were compared to patients who were receiving conventional care regimens (CCR). The conventional care regimens includes intensive chemotherapy, low-dose cytarabine and best supportive care. The study conducted by Fenaux et al.. was necessary to discover new treatment options, due to the low survival rate of patients who are receiving intensive chemotherapy, with the median survival rate for these patients being between 5 and 13 months. Further, Fenaux et al. (2010) states that cytarabine is also ineffective. Therefore, their study focused upon 75 mgs Azacitidine, and they found that the patients with the low BM blast count (RAEB-t using FAB criteria) who were administered this particular regimen had significantly prolonged overall survival rates than did the patients who were administered the conventional therapies. Specifically, they found that half of the patients treated with the Azacitidine were still alive 2 years after diagnosis, compared to just 16% of the patients treated with conventional treatments. Moreover, the patients who received the best supportive care therapies had even worse outcomes than other conventional treatments, as these patients had a median survival rate of only less than six months, and only 8% of those receiving this therapy were alive two years after diagnosis (Fenaux, 2010, p. 567). Another promising modern therapy discovered for the treatment of AML is that of a protocol of Sorafenib, Idarubicin and Cytarabine in patients who are younger than age 65. They found that 75% of their patients achieved a complete remission of the disease when they were treated with this drug regimen, and that 93% of patients who present with an FMS-like Tyrosine Kinase-3 achieved a complete remission (Ravandi et al., 2010, p. 1856). 4. Why this report is important Overall, this report is helpful to medical practitioners and students, as it presents the new ways that different strains of AML are diagnosed, including diagnoses using genetic markers and immunophenotyping. These particular kinds of diagnoses are crucial, in light of the fact that AML has many different subtypes, and each diagnosis of AML will be unique from every other diagnosis. These diagnostic techniques are absolutely crucial, as the drug therapies and trials are specific for the individual diagnosis. For instance, the protocol of Sorafenib, Idarubicin and Cytarabine has shown enormous effectiveness on patients who have a certain subtype of AML, that of FMS-like Tyrosine Kinase-3. Similarly, the Azacitidine has shown effectiveness in patients who present with a specific subtype of AML, known as RAEB-t. Therefore, the traditional methods of diagnosing AML will not be effective, as the newest therapies and treatments are focused on very specific subtypes of the disease. Further, this report contributes to the body of knowledge about the disease, in that it identifies a rare presenting symptom, that of pulmonary infiltrates. As pulmonary infiltrates are often indicative of differential diagnosis from AML, including pneumonia, pulmonary infection, leukemic cell infiltration, hyperleukocytic reaction and pulmonary vascular leukostasis, and only rarely are indicative of AML, it is important that practitioners recognize that AML might be a possibility for patients who present with pulmonary infiltrates. This is particularly true when that patient also presents with anemia, leukocytosis and thrombo-cytopenia, as these symptoms should have been the tip-off of the diagnosis. Methods The cases in this report were selected by carefully analysing the research to determine what the latest therapies are for AML. During the course of the investigation, it was discovered why it is important to do detailed genetic testing for the patients with this disease, as well as the importance of immunophenotyping. It rapidly became apparent why these tests were important, as the studies that were reported specified different strains of AML, which suggests that every AML is unique, and that it is important to discover the subtype of AML before one can be properly treated. To this end, the two studies were selected for this report, as they were complementary to one another – one of the study specified treatment for those over the age of 65, which is the age that most AML cases are diagnosed. The other specified treatment for patients under the age of 65. Therefore, the two studies complemented each other, as, between the two of them, both age ranges were covered. They were also different, in that each of the studies focused upon different subtypes of the disease when describing the new treatment protocols. The other study regarding the misdiagnosis of the patient with the pulmonary infiltrations was selected because it represents a unique presenting symptom that should be properly attended to by primary physicians. Because the symptom is unusual, physicians may miss the diagnosis of AML, so this study was selected to be included in the report because it is important that health care practitioners understand this unusual presenting symptom. Summary Box 1. It is important that the proper diagnosis includes genetic testing and immunophenotyping, because a patient’s profile is unique and there are different treatment options according to what kind of AML a patient might have. 2. It is also important to understand that, in rare circumstances, a patient may present with pulmonary infiltration. If a patient does present with this, and he or she has other symptoms that are consistent with AML, then AML should be ruled out. 3. There are promising therapies for specific types of AML, both with patients above the age of 65 and patients younger than the age of 65, and these therapies are targeted towards the specific subtype of AML that the patient has. This highlights again the importance of genetic testing and immunophenotyping, as these patients may be helped with these modern therapies. Summary Box #2 – Informational Resources 1. The Mayo Clinic Website. http://www.mayoclinic.com/health/acute-myelogenous-leukemia/DS00548. This website describes treatment options for AML, along with new diagnostic procedures. It also offers resources for coping and support, as well as causes, risk factors and alternative medicine resources. 2. The Pub Med Website. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001569/. This website also offers education and information, including the causes and treatments of the disease. It also offers links to support groups, a list of symptoms of the disease, as well as a list of complications from the disease. 3. The National Cancer Institute. http://www.cancer.gov/cancertopics/pdq/treatment/adultAML/Patient/page1. This site provides general information about AML, as well as delineating risk factors that might cause the disease, including smoking. It offers a helpful “key points” box that highlights the important points that a patient might want to know, and provides links for additional information regarding these key points. Summary Box #3 – Educational Resources 1. The Cochrane Library - http://www.thecochranelibrary.com/view/0/ browse.html?cat=ccochbloodhaematologicalmalignanciesacutemyelogenousleukaemia. Provides a link to journals that describe the latest advances in the disease. 2. PubMed - http://www.ncbi.nlm.nih.gov/pubmed/. Interested readers may search the PubMed library for articles on AML, and the library provides over 2,700 articles that feature AML as a topic. To narrow it down, different search words may be used to get to articles that are regarding the specific aspect of AML that may interest the reader. Summary Box #4 – Ongoing Research Studies 1. CLAVELA is a randomised controlled phase III study comparing the survival of patients treated with elacytarabine with the survival of patients receiving the treatment(s) chosen by the investigator. The details are at http://www.clavispharma.com/clavela-clinical-study 2. Ambit Biosciences Corporation and Astellas Pharma Inc. is involved in an ongoing Phase 2 study evaluating AC220, a potent and selective FLT3 inhibitor. The study is evaluating AC220 as an oral, once-a-day, monotherapy treatment in acute myeloid leukemia (AML) in 240 patients with FLT3-ITD activating mutations who have relapsed or are refractory to other treatments, including chemotherapy and hematopoietic stem cell transplant (HSCT).http://www.ambitbio.com/press_releases/ view/pr_1313095354 Bibliography A.D.A.M. Medical Encyclopedia. [website] http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001569/ Bennett J, Catovsky D, Daniel M, Flandrin G, Galton D, Gralnick H, Sultan C. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol (1976) 33 (4): 451–8. Dohner, H., Estey, E., Amadori, S., Appelbaum, F., Buchner, T. & Burnett, A. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel. Blood (2010, January) 115(3): 453-474. Fenaux, P., Mufti, G., Hellstrom-Lindberg, E., Santini, V., Gattermann, N. & Germing, U. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. JCO (2010, February) 28 (4): 562-569 Huq, A., Flenaugh,M., Nichols, M. Hemoptysis, anemia and respiratory failure: A rare initial presentation of acute leukemia. Journal of the National Medical Association (2005, November) 97(11): 1550-1552. Jemal A, Thomas A, Murray T, Thun M. Cancer statistics 2002. CA Cancer J Clin (2002) 52 (1): 23–47. Ravandi, F., Cortes, J., Jones, D., Faderl, S. Garcia-Manero, G., Konopleva, M.,Phase I/II Study of Combination Therapy With Sorafenib, Idarubicin, and Cytarabine in Younger Patients With Acute Myeloid Leukemia. Journal of Clinical Oncology (2010) 28(11): 1856-1862. Resource4Leukemia [website] Available at: http://www.resource4leukemia.com/topics/types.html Wandroo, F., Murray, J., Mutimer, D. & Hubscher, S. Acute myeloid leukaemia presenting as cholestatic hepatitis. J Clin Pathol (2004) 57: 544–545. Read More