Oncology | Acute Myelogenous Leukemia (AML)

Hi everyone, welcome back to the Metabullets Step 2 in 3 podcast. In today's episode, we cover the topic of acute myelogenous leukemia or AML found under the oncology section at metabullets.com. Let's begin with a clinical snapshot. A 63-year-old man presents with fever, increasing fatigue, and actively bleeding gums. Physical exam also reveals several oral mucosal petechiae.

His CBC reveals decreased platelets and hemoglobin. His PT and PTT are elevated with low fibrinogen. Peripheral blood smear demonstrates blasts and schistocytes. His D-dimer level is elevated. He is diagnosed with DIC and given fresh frozen plasma. He is referred to a hematologist oncologist. Let's continue with an introduction to acute myelogenous leukemia or AML. There are different subtypes of AML.

These may include M3, aka acute promyelocytic leukemia, or APL. This is due to a translocation on chromosomes 15 to 17. and results in a disruption of retinoic acid receptor, which is required for myeloblast maturation. This subtype is associated with DIC, and it demonstrates the presence of hour rods, which should peroxidase positive cytoplasmic inclusions.

There is acute megakaryoblastic leukemia, which is associated with Down syndrome in patients less than 5 years old, and recall that leukemia and Down syndrome occurring in patients greater than 5 years old typically represents ALL. There is also acute monocytic leukemia, which results in infiltration of the gums. In terms of the epidemiology, the median onset of age is 65 years old. Risk factors include alkylating chemotherapy,

radiation, myeloproliferative disorders, Down syndrome, and smoking. Moving on to the presentation. Symptoms of pancytopenia, which include a high white blood cell count, but white blood cells that are dysfunctional. include fatigue, dyspnea, infection due to dysfunctional blasts, and bleeding. On exam, one may note lymphadenopathy, which is an infiltration of leukemia, hepatosplenomegaly, which is due to infiltration of leukemia.

fever, and swollen gums, which is also due to infiltration of the leukemia. In terms of further studies, the best initial test is a peripheral blood smear. It will demonstrate greater than 20% blasts in a blood smear. The most accurate test is flow cytometry. One may also perform a bone marrow biopsy with cytogenetics. This may demonstrate myeloblast with hour rods in APL, and it will be myeloperoxidase positive in APL.

but negative in other subtypes. Other labs to perform include a CBC which will demonstrate a decrease in RBCs, a decrease in mature white blood cells, and a decrease in platelets. In terms of the differential,

make sure to think about ALL, myelodysplastic syndrome, CML blast crisis, and leukemoid reaction. In terms of treatment, the initial treatment is with chemotherapy. This is in order to induce remission. and the specific drug that may be used includes citerabine. Another option is bone marrow transplant after remission. This is especially helpful for cytogenetics revealing high chance of relapse. Another option is all transretinoic acid.

for those patients with M3 or APL. Complications related to AML include febrile neutropenia, DIC, especially with APL, gout, and tumor lysis syndrome. And lastly, with regards to prognosis, Remember that the best prognostic indicator is cytogenetics. 90% will have complete response rate from initial chemotherapy in those with good cytogenetics, and the relapse rate is greater than 50% with a median survival of 3 to 12 months.

Now that we've discussed the major points relating to acute myelogenous leukemia, let's walk through some questions to apply what we've learned and get a sense of how the topic might be tested. For the first question, consider the following clinical scenario. A 55-year-old woman with no significant past medical history presents to her primary care doctor with fever, fatigue, and bleeding gums for the past three days. She denies any sick contacts.

Her temperature is 101 degrees Fahrenheit or 38.3 degrees Celsius. Blood pressure is 110 over 70. Pulse is 96 beats per minute and respirations are 15 breaths per minute.

Physical exam reveals several oral mucosal petechiae, bleeding gums, bilateral submandibular lymphadenopathy, and hepatosplenomegaly. Initial laboratory workup demonstrates a leukocyte count of 6,600 per millimeter cubed, 60% segmented neutrophils, 20% bands, 9% eosinophils, 1% basophils, 0% lymphocytes, 10% monocytes, a platelet count of 99,000 per millimeter cubed, hemoglobin is 8.1 grams per deciliter, hematocrit is 25%, prothrombin time is 25 seconds.

partial thromboplastin time is 50 seconds, an international normalized ratio of 1.6, D-dimer is 2,000 micrograms per milliliter, and fibrinogen is 99 milligrams per deciliter. A bone marrow biopsy demonstrates 34% myeloblast with hour rods that are myeloperoxidase positive. What is the best treatment option? And the answer choices are choice one, ascorbic acid. Choice two. cryoprecipitate. Choice three, fresh frozen plasma. Choice four, retinoic acid. Or choice five, zoledronic acid.

The best answer to this question is choice four, retinoic acid. This vignette describes a patient with acute promyelocytic leukemia, or APML, with disseminated intravascular coagulopathy. The treatment of choice is chemotherapy, including tretinoin or all-transretinoic acid. APML results from a chromosomal 15-17 translocation that produces a disruption in the retinoic acid receptor

required for myeloblast maturation, which produces the fusion gene PML-RAR-alpha. Proliferation of myeloblast results in a decrease of mature leukocytes as it crowds out the bone marrow and leads to bone marrow failure. APML typically occurs in the fifth to sixth decade of life. DIC can occur when dying leukemic promyelocytes release their granule components. To minimize mortality from DIC, modern chemotherapy employs tretinoin.

an oral drug that promotes maturation of white blood cells along with intravenous anthracycline therapy such as doxorubicin. Tretinoin has not proven to produce durable remission when used alone. Let's also discuss why the other choices are incorrect. Choice one, ascorbic acid or vitamin C is useful for management of scurvy, which can also present with bleeding gums.

It is not used as a primary drug for cancer therapy. Choices 2 and 3. Cryoprecipitate and fresh frozen plasma are reasonable for management of DIC, but it is not the best ultimate treatment option for APML. Choice 5. Zoledronic acid is an intravenous bisphosphonate used for oncological pain secondary to bone metastases. Finally, a bullet summary.

All transretinoic acid is a major component of treatment for acute promyelocytic leukemia. For the second question, consider the following clinical scenario. A 52-year-old man presents to his primary care physician. The man has been feeling very tired lately and thinks that he looks more pale. The physician orders a complete blood count, which demonstrates a hemoglobin of 8.5 grams per deciliter, white blood cell count,

of 1,200 per microliter, platelets of 70,000 per microliter. The patient is referred for bone marrow biopsy, which demonstrates cells with hour rods. Which of the following is the correct diagnosis? And the answer choices are choice one, acute lymphoblastic leukemia. Choice two, acute myelogenous leukemia. Choice three, chronic lymphocytic leukemia. Choice four, chronic myelogenous leukemia.

or choice five, multiple myeloma. The best answer to this question is choice two, acute myelogenous leukemia. This patient has clinical findings of fatigue and pallor, laboratory findings of pancytopenia, and biopsy findings of myeloblasts with hour rods in keeping with the diagnosis of acute myelogenous leukemia.

AML is caused by a neoplastic proliferation of myoblasts in the bone marrow. The neoplastic myeloblasts are not able to mature normally, eventually leading to crowding out of normal hematopoiesis. AML is most commonly seen in adults in the fifth to sixth decades of life. Three major subtypes of AML are acute promyelocytic leukemia, acute megakaryoblastic leukemia, and acute monocytic leukemia.

The publication by Davis et al. reviews acute leukemia in adults. AML accounts for 80% of all cases of acute leukemia in adults. As compared with chronic leukemias, Acute leukemias present with sudden onset symptoms and are more likely to present with significant constitutional symptoms such as fever or weight loss. Abnormal bleeding and infections are also common. Complete blood count and AML will vary.

depending on the subtype, but generally shows pancytopenia. The publication by Yu et al. discusses the detection of hour rods. Hour rods, which are crystallized aggregates of myeloperoxidase, are important in the rapid diagnosis of acute promyelocytic leukemia, which is a subtype of AML. The authors compared two different histological staining techniques, Wright-GM-sustained versus Lewis-stained.

The authors used both stains on cells taken from known APL patients and found a significantly higher rate of detectable hour rods with loose stain, thereby suggesting loose stain is more sensitive for rapidly diagnosing APL. Let's also discuss why the other choices are incorrect. Choice 1. Acute lymphoblastic leukemia would not have hour rods on histology. Choices 3 and 4.

Chronic leukemias do not typically present with acute symptoms, as seen in this patient. Choice 5. Multiple myeloma is a monoclonal plasma cell disorder, which usually presents in older patients. with an average age of diagnosis at 70. That's all for this review about acute myelogenous leukemia. We hope that was helpful. This is the MedBullets Step 2 in 3 podcast, a daily audio review session for MedBullets.

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