Acute Erythroblastic Leukemia

Definition

Definition of Acute Erythroblastic Leukemia
Acute erythroblastic leukemia, also called erythremic myelosis, DiGuglielmo syndrome, or erythroleukemia, results from uncontrolled proliferation of immature erythrocytes (red blood cells).

Symptoms

Symptoms of Acute Erythroblastic 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.

Causes

Causes of Acute Erythroblastic Leukemia
There are number of factors which can cause this disorder. It includes the blood disorders, chemical exposures and genetics. It also includes the ionizing radiations also. There are pre leukemic blood disorders like myelo dysplastic syndrome or myelo proliferative disease which involves the AML. The exact risk factor depends on the type of MDS or MPS. The exposure to anti cancer chemo therapy along with the alkylating agents increases the risk of this disorder . The risk is highest about 3 to 5 years after chemo therapy. There are other chemo therapy agents like epi podo phyllo toxins and anthrax cyclines. They are linked with the treatment related leukemia. They are mainly associated with the chromosomal abnormalities in the cell. The occupational chemical exposure to the benzene and other aromatic organic solvents can lead to this disorder. The benzene and its derivatives are referred as a carcinogenic. There is a link between the carcinogens and the risk associated with the occurrence of this disorder. There are radiations of ions which can lead to this disorder. The increased rate of AML is due to the atomic bombings of Hiroshima and Nagasaki. The radiologists were also exposed to the high level of radiations prior to the modern safety practices. There is a hereditary risk associated with the AML. There are many cases of the AML in a family which has a higher risk of developing by a chance alone. The increase in the chance of developing AML is many times more than in the first degree relatives as compared to the non relatives. There are many congenital conditions which have increased the chance of this disorder and the most common condition is the Down syndrome which increases the thresh hold around 20 times.

Diagnosis

Diagnosis of Acute Erythroblastic 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.

Prognosis

Prognosis of Acute Erythroblastic 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.

Treatment

Treatment of Acute Erythroblastic 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 which 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.

Prevention

Prevention of Acute Erythroblastic Leukemia
Consult with your doctor.