What is an Acute Myelocytic Leukemia?

March 08 00:00 2019 Print This Article

It is defined as a disorder in which there is a cancer of the myeloid line of blood cells. In this there is a rapid growth of the abnormal white blood cells which get accumulated in the bone marrow. It is also known as the AML. It refers to acute myelogenous leukemia. They interfere with the production of normal blood cells. It is the most common and acute form of leukemia. It affects adults and its incidence increases with the age.

The AML is a rare disease which accounts for 1.2 percent of the deaths caused by cancer. Its incidence is going to increase with the age. The symptoms of the disease are caused due to the replacement of bone marrow with the leukemic cells which decreases the red blood cells, platelets and normal white blood cells. It leads to fatigue, shortness of the breath, easy bruising and bleeding. There is also an increased chance of infection. There are many risk factors which can increase the AML but the exact cause is still not clear. It progresses rapidly and it may lead to the death of the individual within few months or weeks if not treated properly. It has different sub types and in which the treatments are different.

Their prognosis varies and the five year survival rate varies from 15 to 70 percent. The relapse rate varies from 33 to 78 percent. It is treated initially with the chemo therapy which induces a remission. The patient may also receive an additional chemo therapy which is also known as the hematopoietic stem cell transplant. There are many researches which have shown that the genetics of AML has developed tests that tell how long a patient is likely to survive and to determine whether the drug is effective or not.

What are the signs and symptoms of Acute myelocytic leukemia?

The symptoms of the disease are caused due to the replacement of bone marrow with the leukemic cells which decreases the red blood cells, platelets and normal white blood cells. It leads to fatigue, shortness of the breath, easy bruising and bleeding. There is also an increased chance of infection. There are many risk factors which can increase the AML but the exact cause is still not clear. It progresses rapidly and it may lead to the death of the individual within few months or weeks if not treated properly. The absence of platelets may lead to the bleeding or bruising. The early signs of this disorder are vague and non specific. They are similar to influenza.

It includes the fever, anemia, fatigue and the weight loss. There is also a loss of apetite and formation of petechiae which are flat and pin head size spots which are formed under the skin due to bleeding. It may also cause bone and joint pain and persistent infections. One can also observe the enlargement of spleen which can be asymptomatic and mild. One can hardly see the lymph node enlargement as it is seen in the ALL. The involvement of the skin is around 10 percent and it occurs in the case of leukemia cutis. Sometimes one can see the presence of sweet syndrome which is the para neoplastic inflammation of the skin.

One can also experience the swelling of gums as a result of the infiltration of leukemic cells into the gum tissue. The first sign of leukemia rarely occurs by the development of a solid leukemic mass or a tumor outside the bone marrow. It is referred as a chloroma. The person may show no symptoms accordingly and leukemia can be discovered by a routine blood test.

What is the diagnosis of Acute myelocytic leukemia?

It is mainly done with the help of complete blood cell count. In this there are more number of white blood cells which is a common finding and leads to the leukemic blast. There is a decrease in the platelets and red blood cell count. One can also see a decrease in the white blood cell count. It is referred as a leucopenia. The diagnosis can also be done by the blood smear count which can show the circulating leukemic blasts. It is a definite diagnosis and requires a bone marrow aspiration along with the biopsy.

The blood is examined with the help of light microscopy. The flow cytometry is also helpful and it differentiates between the AML and leukemia. It classifies the sub types of disease. The sample of marrow is helpful to know about the chromosomal translocations. It is a done with the help of cyto genetics or fluorescent in situ hybridization. There are genetic studies which help us to look for specific mutation in different genes. It influences the outcome of disease.

The cyto chemical stains on blood and bone marrow are helped to distinguish the AML from ALL. It also sub classifies the AML. The combination of esterase and myelo peroxidase is very helpful in the identification of AML and differentiating from the ALL. There are nonspecific esterase stain which are used to identify the monocytic component in AML and to differentiate the monoblastic leukemia from ALL. The diagnosis and classification of this disorder is controversial and can be challenged. It must be done by the hemato pathologist or hematologist.

The presence of certain features like auer rods or a specific flow cytometry which can differentiate the AML from other leukemia. If there are no such features the diagnosis may be very difficult. As per the WHO criteria the diagnosis of AML is established by the involvement of more than 20 percent of the cells of blood and marrow. It occurs by leukemic myeloblasts.

The AML can be differentiated from the pre leukemic conditions by myelo dysplastic or myelo proliferative syndromes. They are treated differently. The highest curability is seen in the APL which is referred as the acute pro myelocytic leukemia. It requires a unique treatment and it is important to exclude the diagnosis of sub type of leukemia. A fluorescent in situ hybridization is performed on blood and is used for this purpose. It identifies the chromosomal translocation which characterizes the APL.

What is the patho physiology of Acute myelocytic leukemia?

The cells which cause malignancy are the myeloblats. In the normal process of hematopoiesis the myeloid precursor cells are the cells which form the myeloblasts. The normal myelo blast can form the mature white blood cells. In the case of AML a single myeloblast can accumulate the genetic changes which freeze the cell in the immature form and prevent the differentiation. It is not the sole factor which gives rise to leukemia. It is combined with the other mutations and disturbs the proliferation of gene which results in the uncontrolled growth of the immature clone of cells which lead to the clinical entity of AML.

The diversity of the AML is due to the leukemic transformation which can occur at a number of different steps along the differentiation path. The different classification systems can identify the characters and behavior of leukemic cells which depend on he stage at which the differentiation was stopped. The clinical signs of this disorder occur as a result of the leukemic clones of cell. They affect the normal development of the blood cells in the bone marrow. There are cyto genetic abnormalities seen in the patients with AML. They have a great prognostic significance.

The trans location of the chromosome encodes abnormal fusion proteins. It involves the transcription factors whose altered properties can cause arrest in the differentiation. In the case of pro myelocytic leukemia the process of translocation forms a fusion protein. It binds to the retinoic acid receptor element in the promoters of many myeloid specific genes which inhibit the differentiation. The symptoms of AML are due to the low number of normal blood elements. In few cases patient can develop a solid tumor of the cells which are present outside the marrow and can lead to many symptoms. It depends on the location.

What is the prognosis of Acute myelocytic leukemia?

This disorder is curable and it depends on the multiple prognostic factors. The single most important prognostic factor in AML is the cyto genetics. It tells us about the chromosomal structure of the cell. Some of them are associated with a good outcome. In the case of trans location in acute pro myelocytic leukemia. Around 50 percent of the patients have normal cyto genetics and they come under intermediate risk group. The other cyto genetic abnormalities are linked with the poor prognosis and have a high risk of relapse.

The first publication which addresses the cyto genetics and prognosis was published in the year 1998 by a MRC trial. In the favorable risk category the 5 year survival rate is 70 percent and the relapse rate is 33 percent. In the intermediate risk category the 5 year survival rate is 48 percent and the relapse rate is 50 percent. In the adverse risk category the 5 year survival rate is 15 percent and the relapse rate is 78 percent. After some time the different oncology groups and leukemia groups published the overlapping lists of cyto genetic prognostication in leukemia.

The AML may arise from the myelo proliferative disorder or the pre existing myelo dysplastic syndrome. These are also known as the secondary AML and have a worse prognosis. They also have a high rate of unfavorable cyto genetic abnormalities. The other prognostic markers include the elevated levels of lactate dehydrogenase which were present in the individuals age 60 and above and have a poorer outcome. The general physical condition and the activity level of the patient play a very crucial role in it.

FLT3 internal tandem duplication play a role in the poorer prognosis of AML. The long term survival cannot be reached by the treatment of patients with the aggressive therapy like stem cell transplantation. It is not of clinical significance. One can also see its association with the leukostasis. The researchers are investigating the clinical significance of c KIT mutations in AML. These are prevalent and significant clinically as the availability of tyrosine kinase inhibitors can block the activity of c KIT.

The other genes being investigated as the prognostic factors include the BAALC and ERG. The cure rates in the clinical trials have been less than 50 percent. It includes mainly the younger patients which can bear the aggressive therapy. In the elderly patients the cure is going to be lower and the cure rates for pro myelocytic leukemia can be as high as 98 percent.

What is the classification of Acute myelocytic leukemia?

There are many classifications which are linked to this disorder. It includes the world health organization classification, French American British classification and un common phenotypes of acute myeloid leukemia. In the world health organization classification the acute myeloid leukemia is more useful clinically and produces a good prognosis than the other classifications.

The WHO contains many sub categories of interest to the hemato pathologist and oncologist. It is mainly done by the categorization into different sub types. They have divided AML as AML with the genetic abnormalities and AML with the multi lineage dysplasia, AML and MDS therapy related and not categorized AML. The AML with the genetic abnormalities includes the trans locations between different chromosomes. It includes the chromosome 8 and 21. There are inversions seen in the different chromosomes 16. There are trans locations between chromosome 15 and 17.

The patients with this disorder have a high rate of remission and have a better prognosis. The multi lineage dysplasia, AML and MDS with the myelo proliferatve disease can be transformed into the AML. It occurs in the elderly patient and has a worst prognosis. In the case of AML and MDS therapy the patients had prior chemo therapy or radiation and develop AML or MDS. They have a worst prognosis and have specific chromosomal abnormalities. In the non categorized types one includes all the left AML types.

The acute leukemia’s of ambiguous lineage which is also known as the mixed phenotype or bi phenotypic acute leukemia. It occurs when the leukemic cells cannot be classified as a myeloid or lymphoid cells. Both type of cells are present. The French American British classification divided AML into 8 different sub types. They range from M0 to M7. They are divided on the basis of cells from which the leukemia develops and its degree of maturity. It is done with the help of examining the cells by the use of light microscope and cyto genetics. This system is widely used but the WHO system is more successful.

The examination of cells helps us to know about the chromosomal abnormalities. The different sub types have different prognosis and their response to the therapy. The M1 is also known as the acute myeloblastic leukemia without maturation. The M0 is also known as the minimal differentiated acute myeloblastic leukemia. The M2 is also known as the acute myeloblastic leukemia with granulocytic maturation. The M3 is also known as the acute pro myelocytic leukemia. The M4 is also known as the acute myelo monocytic leukemia. The M4eo is also known as the myelo monocytic leukemia along with the bone marrow eosinophilia. The M5 is also known as the acute monoblastic leukemia or acute monocytic leukemia. The M6 is also known as the acute erythroid leukemia which includes the erythro leukemia or very rare pure erythroid leukemia. The M7 is also known as the acute myelo mega karyoblastic leukemia. The M8 is also known as the acute basophilic leukemia. In the un common phenotypes there are rare types of AML which are not included under the other classification systems.

However, most of them are included under the WHO system except acute myeloid dendritic cells. It includes the acute basophilic leukemia and acute eosinophilic leukemia. The mast cell leukemia and myeloid sarcoma are also included under it. The acute myeloid dendritic cell leukemia and acute panmyelosis are also included under it.

What is the epidemiology of Acute myelocytic leukemia?

It is relatively a rare cancer. In the US alone one can see around 10 thousand new cases per year. The incidence rate has been stable from the year 1995 to 2005. It accounts for 1.2 percent of all the deaths in the United States. Its incidence increases with the age. The median survival age at diagnosis is 63 years. The AML constitute 90 percent of the all acute leukemia and is rare in the children. The rate of therapy related AML is rising and it accounts for 10 to 20 percent of the cases of AML. It is more common in the men as compared o the women. The male female ratio is 1.3 to 1. There are the geographic variations in the incidence of AML. In adults one can see the highest rate in North America, Europe and Oceania but in the case of adult AML it is rarer in the Asia and America. The childhood AML is not so common in the North America and India as compared to the other parts of Asia. The difference is due to the population genetics, environmental factors and a combination of above factors.

What is the treatment of Acute myelocytic leukemia?

There are many ways by which this disorder can be treated. It involves the use of chemotherapy which is divided into two phases involving the induction and post remission. The induction therapy helps to achieve the complete remission. It reduces the amount of leukemic cells by the undetectable levels and the consolidation therapy aim is to remove the residual undetectable disease and help in a cure. The induction therapy involves the sub types of FAB except the M3 which is usually given induction chemotherapy with cytarabine and anthrax cycline. It is also known as the 7 plus 3. In this scenario cytarabine is given for consecutive 7 days and the anthra cycline is given for consecutive 3 days. It is an intra venous push. Normally, more than two third of the patient achieve a remission with this protocol.

The other alternative induction regimen includes the high dose cytarabine alone or along with the investigational agents. There are toxic effects of therapy which include the myelo suppression and there is an increased risk of infection. It should not be given to the elder people. They must be given less intense chemotherapy or they must be offered a palliative care. The M3 is also known as the acute pro myelocytic leukemia. It is treated with the help of ATRA which is referred as a all trans retinoic acid. It is given in addition to the induction chemotherapy. One must prevent the DIC which can complicate the acute pro myelocytic leukemia treatment.DIC refers to disseminated intra vascular coagulation. The pro myelocytes release the content of their granules into the peripheral circulation. The acute pro myelocytic leukemia can be cured with the well documented treatment protocols.

The goal of induction phase is to reach a complete remission. It does not mean that the disease has been cured but it tells that no disease can be diagnosed with available methods. Normally, more than two third of the patient achieve a complete remission. It depends on the prognostic factors. The length of remission depends on the prognostic features of the leukemia. If there is no consolidation therapy it will lead to the failure of all remissions. After complete remission is achieved leukemic cells are so small in number that it is very hard or impossible to detect them with the help of diagnostic techniques which are used now days. If no further therapy is given the patient relapse so more therapy is required to eliminate the non detectable diseases and prevent the relapse.

There is a specific type of post remission therapy in which the patients prognostic factors and general health is taken into the account. For the good prognosis the patient undergoes additional 3 to 5 day courses of the intensive chemotherapy which is known as the consolidated chemotherapy. In the patients who have a high degree of relapse one can go for the allogenic stem cell transplantation. It is given when the patient can tolerate a transplant and has a suitable donor.

The best post remission therapy for intermediate risk AML is less clear and depends on the age, overall health, patient personal value etc. The patients who are not suitable for the stem cell transplant they are given immune therapy along with the histamine and inter leukin. It occurs after the completion of consolidation has reduced the risk of relapse by14 percent and changing into the 50 percent risk of maintained remission.

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