STEP 41. Acute Lymphoblastic Leukemia ( ALL) is a malignancy of lymphoid precursor cells , the blood cells will differentiate into T lymphocytes and B lymphocytes LLA is more common in children ie 75 % , while the rest occurred in adults . More than 80 % of the cases of malignancy of the LLA is the occurrence of T cells , and the rest is a malignancy of B cells Incident 1 : 60,000 / year and dominated by children aged < 15 years , with the highest incidence at 3-5 years of age .EtiologyUntil now, the cause is unknown LLA , aka idiopathic . However, the researchers have proposed several theories of possible causes of this LLA . There are two theories , namely genetic and environmental .

Genetic , such as those with Down syndrome and Wiskott Aldrich who also had leukemia .

Environment , ie, there are some things that underlie this theory , among others : ( 1 ) ionic radiation , such as post - Nagasaki bombing Hiroshima in Japan , the incidence of leukemia increased sharply ; ( 2 ) chemicals , such as benzene , (3 ) smoking habits ; ( 4 ) chemotherapeutic drugs ; ( 5 ) viral infections such as EBV , and others.

Pathogenesis and PathophysiologyOn a proliferation of LLA patients pathological young lymphoid cells in the bone marrow . He will urge other normal haemopoietic system , such as erythropoietic , thrombopoietic and granulopoietik , so the bone marrow blast cells dominated and leukemia cells until they spread ( infiltrate ) to the peripheral blood and other organs .

Cytogenetic abnormalities are often found , teruatama in adult patients is : t ( 9 ; 22 ) / translocation of chromosomes 9 and 22 / fusion gene BCR - ABL / philadelphia chromosome ( CML ) , or t ( 4 ; 11 ) / translocation of chromosomes 4 and 11 / ALL1 - AF4 . If there is a translocation of this kind it will activate proliferation and cell growth pathways abnormally resulting in leukemia . Other abnormalities in the karyotype can hipdiploid and t ( 10 ; 14 ) , or due to loss or inaktivnya tumor suppressor genes p16 and p15 such , Rb and p53 .

ClassificationSystem based on French - American - British ( FAB ) , LLA divided into 3 types :

L1 , characterized by small -sized blast cells , homogeneous ( relatively equal ) , with little cell cytoplasm and nucleoli ( child core ) vague / unclear . L1 is the most common LLA compared to other types of LLA , and generally occurs in children .

L2 , characterized by blast cells are larger, heterogeneous ( non-uniform ) , and the apparent nukleolinya nucleus - cytoplasm ratio is low . Usually this type of LLA occurred in adults .

L3 , characterized by a large blast cells , cytoplasm bervakuol , and looks concentrated ( basophilic ) . The prognosis is poor but the incidence is only slightlyClinical Overview

In patients LLA will visible signs of anemia such as pale , tired , lethargic , then anorexia , osteoarthritis due to infiltration of bone marrow cells leukemi , fever , infections due to decreased activity of the immune system as a result of abnormal lymphocytes , bleeding skin , gums , hematuria , gastrointestinal bleeding , bleeding to the brain . In addition it was found also hepatomegaly , splenomegaly , lymphadenopathy , and mediastinal mass .

A child with LLA

Diagnosis and Differential DiagnosisTo make a diagnosis LLA , still made history, physical examination and laboratory tests which include : complete blood count , peripheral blood smear , fibrinogen levels , blood chemistry , blood group and HLA ( human leukocyte antigen ) . Can also performed radiographic examination , lumbar puncture and bone marrow aspiration and biopsy for the diagnosis of course .

As for diagnosis , LLA should be differentiated from pure lymphocytosis , lymphadenopathy , hepatosplenomegaly due to infection , and aplastic anemia .Laboratory PreviewFor a complete blood count and peripheral blood smear , usually found drastically increased levels of leukocytes , but can also be normal and even decreased . Hemoglobin and platelets dropped to below normal , and there are blast cells in the peripheral blood varied , ranging from 0-100 % .

Llimfoblast sightings on peripheral blood smear

For bone marrow aspiration and biopsy , found a picture hypercellular with increased limfoblas . Test results will be negative cytochemistry on Sudan Black staining and myeloperoxidase ( compound used for coloring granules , in order to distinguish between cells and myeloblasts limfoblas whose structure is similar , but not limfoblas granulated cells so that the result is negative ) . To distinguish whether the ferocity found on B cells or T cells , can be examined with a compound of acid phosphatase ( positive in malignant T cells ) , or Periodic Acid Schiff ( PAS ) ( Positive on malignant B cells ) . Besides it can also imunofenotip and cytogenetic examination to determine whether the severity occur in T cells or B cells

TherapyFor its management , first to note some of the following conditions :

metabolic conditions , need to be considered also in the case of LLA patients hyperuricemia , hyperphosphatemia or hypocalcemia secondary that previously had to be treated first with intravenous hydration , alkalinization of urine or alupurionol administration to prevent the accumulation of uric acid .

infection , due to immunosuppression . It should be given to the prevention of dangerous infectious agents such as herpes viruses , pneumonia , etc. .

hematologic conditions , where there is anemia and thrombocytopenia . It should be also given a transfusion if the conditions are very bad , except in patients who hiperleukositosis ( leukocytes > 100.000/mm3 ) because it can increase blood viscosity and precipitate sudden leukostasis .

The main therapy for LLA there are 4 :

Remission induction therapy . Useful to eliminate / eradicate leukemia cells that could be detected morphologically in the blood and bone marrow , then in order to return to normal hematopoiesis . Can be used medications such as prednisone , vincristine , daunorubicin and others.

Consolidation or intensification therapy . Pointless to completely crush depleted leukemic cells remaining after induction therapy , in order to avoid relapse .

Central nervous system prophylaxis , to prevent relapse .

Maintenance / long-term maintenance . Can the preparations 6 -mercaptopurine and methotrexate every day of every week for 2-3 years .

Fourth above the main therapeutic use of drugs that can be tailored to the protocol used . There are several treatment protocols are available , such as OPAL Protocol , Hyper - CVAD , LALA 87 , CALGB , and others .

Other treatments that can be given is supportive therapy , such as anti-infective , given adequate nutrition , psychological support , and condition monitoring of blood components regularly. Then there is also the cytostatic therapies such as radiation but not used anymore . Another way is with a bone marrow transplant in patients at high risk for relapse , for example patients with Philadelphia chromosome , changes in the composition of the MLL gene (a type of genes involved in the maintenance of epigenetic transcriptional memory ) hiperleukositosis , and failed to achieve complete remission within 4 weeks .PrognosisLLA prognosis for adult patients is usually worse than the younger . For the 15-20 year old good prognosis and can be cured with chemotherapy if accompanied by a good prognostic factor . But the actual adult patients LLA also depends on intensive therapy given , such as bone marrow transplantation . For age > 60 years the prognosis is rather poor , because the survival rate is usually only 10 % after complete remission .2. pathophysiology

In normal circumstances , the white blood cells serve as our defense to infection . These cells normally develop in accordance with the command , can be controlled according to the needs of our bodies . Leukemia increases the production of white blood cells in the bone marrow that is more than normal . They look different from normal blood cells and do not function as usual . Leukemia cells to block the production of normal white blood cells , impairing the ability of the body to infection . Leukemia cells also destroy other blood cell production in the bone marrow , including red blood cells where the cell 's function is to supply oxygen to the tissues.

According to Smeltzer and Bare (2001 ) cytogenetic analysis produces a lot of knowledge about the chromosomal aberrations found in patients with leukemia , . Chromosomal changes may include changes in the numbers , which adds or removes an entire chromosome , or a change in the structure , which includes this translocation , two or more chromosomes alter the genetic material , with the development of altered gene thought to cause the onset of abnormal cell proliferation .

Leukemia occurs when the process of maturation of stem cells into white blood cells susceptible to interference and produce a change in the direction of malignancy . Such changes often involve the rearrangement of parts of chromosomes ( genetic material of the cell complex ) . Chromosome rearrangement ( translocation chromosome ) disrupt the normal control of cell division , so that cells divide uncontrollably and become malignant . Eventually these cells dominate and displace the bone marrow cells that produce blood cells are normal . This cancer can also infiltrate into other organs , including the liver , spleen , lymph nodes , kidneys and brain.Weakness, fatigue , fever is not too high ( 38.5 C axillary ) , and seem less nutrition . Caused by hypermetabolism that occurs due to the proliferative activity of leukemia cells . All the body's energy reserves used by the activity of leukemic cells are malignant , so the longer the reserve of fat in adipose tissue decreased, consequently the patient seem less nutrition , weakness, and fatigue . Other possible causes of decline in the nutritional status of the patient is anemic and impaired tissue oxygenation . Increased cellular activity that has resulted in an increase in core temperature , resulting in body temperature regulation mechanism are resulting in fever . Another possibility is the presence of fever due to infection . Although the cells are leukocytes that play a role in increasing the immune system , but not undifferentiated cells formed by the immune cells of any kind , so it is not functional in keeping the immune system . This phenomenon is called the functional leukopenia .

Bleeding through the nose and thrombocytopenia ( platelets 67 x 103/mm3 [ normal 1.5-3 x 105/mm3 ] ) . As a result of the suppression of bone marrow hematopoiesis in the other , then decreased platelet production . In fact , platelets play an important role in primary hemostasis system . If platelets is reduced , there will be bleeding time is longer than if the conditions and the amount of normal platelet count . Capillaries in normal circumstances is often ruptured , but this can be quickly solved by a system of primary hemostasis , ie platelets . In the event of thrombocytopenia then one of the symptoms is nasal bleeding due to rupture of the capillary wall .Tachycardia ( 108x/menit [ normal 60-100/menit ] ) , conjunctival pallor , optic disc atrophy of the tongue , and anemia ( Hb 7.5 g / dl [ normal 12-16 g / dl ] ) . Similar to thrombocytopenia , anemia arising caused by hematopoietic suppression by leukemic cells in the bone marrow . As a result, the typical clinical manifestations of anemia as above . Tachycardia arising from the hard work of the heart to meet the oxygen needs of tissues due to the quantity of hemoglobin ( Hb ) is low with the mechanism of accelerated blood flow . Quantity of low Hb central pallor resulting pale erythrocytes . It is then represented by the various tissues of the body , such as the conjunctiva , nail beds , palms , and oral mucous membranes . Tongue atrophy of the optic disc may occur due to injury papilla cells due to lack of oxygen caused by anemia suffered by the patient .Cervical lymphadenopathy . Lymph node hyperplasia caused by excessive work in producing lymphocytes . So that the lymph node cells causing excessive pain ( pathy ) .

Hepatomegaly . Can occur due to three related things : 1 ) infection , 2) due to hemolytic anemia , or 3 ) as a result of infiltration . However , in this case , the link is most likely hepatomegaly caused by infiltration of leukemic cells into the liver tissue .

Splenomegaly . Splenomegaly can occur due to three related things : 1 ) infiltration , 2) infections , or 3 ) obstruction / interruption of blood flow . However , in this case , likely that most of splenomegaly caused by infiltration of leukemic cells into the spleen / spleenpathogenesis

Acute leukemia is a disease with malignant transformation and expansion of clones of hematopoietic cells is inhibited at the level of differentiation and can not develop into a more mature form . Blood cells derived from pluripotent stem cells hematopoesis which then differentiate into lymphoid stem and myeloid stem ( non- lymphoid ) multipotent . Lymphoid stem cells will form T cells and B cells , myeloid stem cells will differentiate into cells of erythrocytes , granulocytes - monocytes and megakaryocytes . At each stage of differentiation may occur changes into a leukemic clone of unknown cause. When this happens maturation can be interrupted , so that the young will increase the number of cells and suppress the formation of normal blood cells in the bone marrow . The leukemic cells can enter the blood circulation which then infiltrate organs , causing disruption of cell metabolism and organ function . Mortality in patients with acute leukemia is generally caused rapid bone marrow suppression and severe , but can also be caused by the infiltration of leukemic cells into the patient's body organs . Keep in mind that the leukemia cells undergo recycling time is slower than normal cells . The process of maturation or incomplete maturation and slow running and survive longer than similar cells are normal .On a proliferation of LLA patients pathological young lymphoid cells in the bone marrow . He will urge other normal haemopoietic system , such as erythropoietic , thrombopoietic and granulopoietik , so the bone marrow blast cells dominated and leukemia cells until they spread ( infiltrate ) to the peripheral blood and other organs .

Cytogenetic abnormalities are often found , teruatama in adult patients is : t ( 9 ; 22 ) / translocation of chromosomes 9 and 22 / fusion gene BCR - ABL / philadelphia chromosome ( CML ) , or t ( 4 ; 11 ) / translocation of chromosomes 4 and 11 / ALL1 - AF4 . If there is a translocation of this kind it will activate proliferation and cell growth pathways abnormally resulting in leukemia . Other abnormalities in the karyotype can hipdiploid and t ( 10 ; 14 ) , or due to loss or inaktivnya tumor suppressor genes p16 and p15 such , Rb and p53 .3. Several laboratory tests required for diagnostic confirmation LLA , prognostic classification and planning of appropriate therapies :

1 . A complete blood count and peripheral blood smear

Leukocyte count may be normal , increased , or lower at the time of diagnosis . Hiperleukositosis ( > 100.000/mm3 ) occurs in approximately 15 % of patients and may exceed 200.000/mm3 . In general, anemia and thrombocytopenia . The proportion of blast cells in the leukocyte count varied from 0-100 % . Approximately one third of patients had a platelet count of less than 25.000/mm3 .

2 . Bone marrow aspiration and biopsy

Specimens obtained should be examined for histological analysis , cytogenetic and immunophenotyping . Bone marrow appears hypercellular smear with limfoblas very much , more than 90% of nucleated cells in the adult LLA . If the bone marrow is replaced entirely by leukemia cells , the bone marrow aspirate can not succeed , so the biopsy touch imprint of jarinngan important for the evaluation of cytology picture .

3 . Cytochemical

In the LLA , Sudan black and myeloperoxidase staining will give negative results . Myeloperoxidase is a cytoplasmic enzyme that is found in the primary granules of granulocytic precursors , which can be detected in blast cells LMA . Cytochemical also useful to distinguish B and B - precursor ALL from T - ALL . Staining of acid phosphatase will be positive in the malignant T lymphocytes , whereas B cells can give positive results on periodic acid Schiff staining ( PAS ) . TdT is expressed by limfoblas can be detected by flow cytometry staining or imunoperoksidase .

4 . Imunofenotip ( with flow cytometry / flow cytometry )

This examination is useful in the diagnosis and classification of LLA . In about 15-54 % of adults obtained LLA myeloid antigen expression . Common myeloid antigen was detected CD13 , CD15 , and CD33 . Concurrent expression of lymphoid and myeloid antigens can be found on bifenotip acute leukemia . These cases are rare, and the course of their illness worse .

5 . Cytogenetics

Cytogenetic analysis is very useful because some cytogenetic abnormalities associated with specific subtypes of LLA , and may provide prognostic information .

6 . molecular Biology

Molecular techniques performed when routine cytogenetic analysis failed to detect that and not detectable with standard cytogenetic . This technique should also be performed to detect gene BCR - ABL that have a poor prognosis .

7 . other tests

Coagulation parameters are usually normal and rare disseminated intravascular coagulation . Metabolic disorders such as hyperuricaemia may occur especially in patients with leukemia cells that rapidly divide and high tumor burden . A lumbar puncture was performed at the time of diagnosis to examine the cerebrospinal fluid . Whether or not an action is performed on patients with the number of circulating blast cells is still controversial . Definition of central nervous system involvement ( SPP ) is when it is found more than 5 leukocytes / mL of CSF with blast cells in the specimen morphology of cells were centrifuged .4. Definition

Acute myeloblastic leukemia (LMA) is a disease characterized by impaired differentiation of neoplastic transformation and progenitor cells of the myeloid series.When left untreated, the disease will rapidly lead to death within a few weeks to months after diagnosis.Prior to the 1960 LMA chiefly palliative treatment, but since about 40 years ago the treatment of this disease develops rapidly and today many patients can be cured of the LMA illness.LMA treatment progress is achieved with a better chemotherapy regimens, high-dose chemotherapy with bone marrow transplant support and better supportive therapy as a new generation of antibiotics and transfusion of blood components to cope with the side effects of treatment.

Etiology

In most cases, the etiology of the LMA is unknown.Nevertheless there are several factors that are known to cause or at least be a factor in certain populations prediposisi LMA.Benzene, a chemical compound that is widely used in leather tanning incidence in developing countries, is a substance known leukomogenik for LMA.Besides ionic radiation is also known to cause the LMA.It is known from research about the high incidence of leukemia cases, including the LMA, the people who survived the atomic bomb on Hiroshima and Nagasaki in 1945.Leukomogenik effects of exposure to ionic radiation began to appear since 1.5 years after the bombing and peaked 6 or 7 years after the bombing.Other factors known to predispose to the LMA is a trisomy of chromosome 21 is found in hereditary diseases down syndrome.Down Syndrome Patientswith trisommi chromosome 21 have a risk 10 to 18 times higher for leukemia, especially LMA type M7.Besides genetic syndromes in some patients such as bloom syndrome and Fanconi anemia is also known to have a much higher risk than the normal population to suffer LMA.

Another factor that can trigger the LMA is treatment with cytotoxic chemotherapy in patients with solid tumors.LMA due to therapy is a serious long-term complications of treatment of lymphoma, multiple myeloma, breast cancer, ovarian cancer, and testicular cancer.This type of therapy is most often trigger the onset of the LMA are a class of alkylating agents and topoisomerase II inhibitors.

Pathogenesis

LMA is the main pathogenesis of maturity blockade causes cells differentiated myeloid series halted in young cells (blast) with the result of the accumulation of blasts in the bone marrow.Blast accumulation in the bone marrow will cause disruption of normal hematopoesis and in turn will result in bone marrow failure syndromes (bone marrow failure syndrome) is characterized by the presence of cytopenia (anemia, leukopeni, thrombocytopenia).The presence of anemia will cause the patient to be tired and in more severe cases will be shortness of breath, presence of thrombocytopenia will cause signs of bleeding, while the presence of leukopenia will cause the patient susceptible to infections, opportunistic infections termausk of normal flora bacteria in the human body.In addition, blast cells are formed also have the ability to migrate out of the bone marrow and infiltrate into other organs such as skin, bone, soft tissue and central nervous system and damage organs such with all its consequences.

Malignant cells in the AML myeloblasts.In normal hematopoiesis, myeloblasts an immature precursor of myeloid white blood cells, a normal myeloblasts will gradually grow into mature white blood cells.However, in AML, a single myeloblasts accumulation of genetic changes which "freeze" in immature cells and prevent diferensiasi.Seperti mutation alone does not cause leukemia, but when such a "differentiation arrest" is combined with other mutations that disrupt genes controlling proliferation, the result is growth not restrained from immature clone of cells, which leads to the clinical entity of AML.Most of the diversity and heterogeneity of AML stems from the fact that leukemic transformation can occur in a number of different steps along the differentiation pathway.Modern classification schemes for AML acknowledges that the characteristics and behavior of leukemic cells (and leukemia) may depend on the stage at which differentiation was stopped.Specific cytogenetic abnormalities can be found in many patients with AML, a type of chromosomal abnormalities often have prognostic significance.The chromosomal translocations encode abnormal fusion proteins, usually transcription factors that can lead to change the nature of "differentiation arrest."For example, in acute promyelocytic leukemia, t (15; 17) translocation generating the PML-RAR fusion protein that binds to retinoic acid receptor element in the promoters of myeloid-specific genes and inhibits myeloid differentiation.Clinical signs and symptoms of AML result from the fact that, as the leukemic clone of cells grows, it tends to replace or interfere with the development of normal blood cells in the bone marrow.This leads to neutropenia, anemia, and thrombocytopenia.Clinical symptoms

In contrast to the common assumption has been, in patients LMA is not always found leukocytosis.Leukocytosis occurs in about 50% cases of the LMA, while 15% of patientshave normal leukocyte numbers and about 35% had neutropenia.However, blast cells in significant numbers in the peripheral blood will be found in 85% of cases the LMA.It is therefore very important to check the details of types of cells in the peripheral blood leukocytes as the initial examination, to avoid misdiagnosis in people suspected of having the LMA.

Signs and symptoms of the LMA is the main fatigue, bleeding and infections caused by bone marrow failure syndrome as already mentioned above.Bleeding usually occurs in the form of purpura or petechiae are often found in the lower extremities or in the form of epistaxis, bleeding gums and retina.Heavier bleeding rarely occurs except in cases accompanied by DIC.The DIC cases pling is often found in cases of type M3 LMA.Infection often occurs in the throat, lungs, skin and fairy rektl areas, so that these organs should be examined carefully in patients with fever LMA.

In patients with very high leukocyte numbers (more than 100 ribu/mm3), frequent leukocytosis, namely leukocyte clots that block the flow of the veins and arteries.Leukocytosis Symptoms vary widely, depending on the location of the blockage.Symptoms are often encountered is a disorder of consciousness, shortness of breath, chest pain and priapism.

Infiltration of blast cells will cause the signs / symptoms varies depending on the organ infiltration.Infiltration of blast cells in the skin will cause leukemia cutis in the form of lumps that are not pigmented and without pain, moderate infiltration of blast cells in the soft tissue will cause nodules under the skin (kloroma).Infiltration of blast cells in the bone will meninbulkan bone pain spontaneously or with mild stimulation.Swelling of the gums is often found as a manifestation infiltration of blast cells in the gums.Although rare, the LMA can also be found infiltration of blast cells to the area menings and necessary for the diagnosis of cytologic examination of cerebrovascular spinal fluid taken by lumbar puncture procedure.

Diagnosis

In the classic LMA diagnosis is made based on physical examination, cell morphology and cytochemistry staining.As already mentioned, since about two decades years ago developing two (2) most recent inspection techniques: immunophenotyping and cytogenetic analysis.Based on the examination of cell morphology and cytochemistry painting, combined hematologist America, France and Britain in 1976 set the LMA classification consisting of 8 subtypes (M0 to M7).This classification is known as the FAB classification (French American British).FAB classification to this day remains a basic diagnosis of the LMA.Painting cytochemistry important for patients LMA is Sudan Black B (SSB) and myeloperoxidase (MPO).Both painting cytochemistry will give positive results in patients with type LMA M1, M2, M3, M4, and M6.

First, blood tests are done to count the number of each different type of blood cell and see if they are within normal limits.In AML, the red blood cell levels may be low, causing anemia, platelet levels may be low, causing bleeding and bruising, and white blood cell levels may be low, causing an infection.A bone marrow biopsy or aspiration (suction) from the bone marrow may be done if the abnormal blood test results.During a bone marrow biopsy, a hollow needle is inserted into the hip bone to remove a small amount of bone marrow and for testing under a microscope.In bone marrow aspiration, a small sample of bone marrow fluid withdrawn through injection.Lumbar puncture, or spinal tap, may be done to see if the disease has spread into the cerebrospinal fluid, which surrounds the central nervous system or the central nervous system (CNS) - the brain and cord

spine.Diagnostic tests may include other important flow cytometry (in which cells pass through a laser beam for analysis), immunohistochemistry (using antibodies to distinguish between types of cancer cells), cytogenetics (to determine changes in the chromosomes in a cell), and molecular genetic studies (DNA testing and RNA from cancer cells).

Leukemia can be confirmed by several tests, such as; biopsies, blood tests {complete blood count (CBC)}, CT or CAT scans, magnetic resonance imaging (MRI), X-ray, Ultrasound, Spinal tap / lumbar puncture.

Haematological abnormalities

Anemia with decreased red cell count is approximately 1-3 x 106/ mm3.

Leukocytosis with leukocyte counts between 50-100 x 103/ mm3.Leukocytes in peripheral blood is most myeloblas.

Decreased number of platelets.Myeloblasts that appeared occasionally contain "Auer bodies" a disorder pathogonomis for LMA.

Hypercellular bone marrow because they contain massive myeloblasts, while megakaryocytes and pronormoblas very rarely encountered.The bone marrow disorders will already be clear though myeloblas not appear in the peripheral blood.So sometimes found in cases with peripheral pancytopenia but it was clear hypercellular bone marrow infiltration due to myeloblas.Kadan-sometimes found "Auer body" in myeloblasts.Sometimes the first manifestation as eritroleukemia (eritroblas proliferation and myeloblasts in the bone marrow) that lasts a few months / years before it becomes clear fambaran mieloblastiknya true.

Dignosis appeal

Acute myeloblastic leukemia diagnoses should be made and all acute leukemia and aplastic anemia.If found "Auer body" then diagnosabandin g is not difficult to enforce, because these abnormalities patogonomis for acute myeloblastic leukemia.

If not found Auer body then it should be done where the peroxidase reaction will be positive pereksidase myeloblasts.

Aplastic anemia with acute myeloblastic alekemik differentiated on the basis of bone marrow examination.Clinically similar bacterial endocarditis due myeloblastic leukemia akaut febrile, anemia, splenomegaly, and ptechiae.Surely there's a history of heart disease, splenomegaly greater and no abnormalities in the gums can distinguish these two conditions.

Komplikasi

Two kinds of complications are often fatal cerebellar hemorrhage and infection.Is a rare complication of complaints caused by the pressure of a tumor leukemia.

TheraphyFix common circumstances are: anemia with blood transfusion given PCR (Packed red cells) or whole blood.Threatening thrombocytopenia resolved with platelet transfusion konsetrat.What if there is an infection that is adequately given antibiotics.Specific therapies such as leukemia therapy usually begins with an induction phase with: doxorubicin 40 mg / mm2weight 1-5 days.Continued denagan Ara C 100 mg IV every 12 hours days 1-7.For patients aged over 50 years with a reduced dose of Adriamycin only 3 days and Ara C 5 days.Replacement drug Adriamycin is Farmorubicin.Clinical and haematological evaluation.Bone marrow examination at the end of the third mimggu.If there is no remission or remission merely parsiil the therapeutic regimen should be replaced with another.

In the event of complete remission (clinical and haematological) then begin consolidation phase.At this stage given doxorubicin 40 mg / mm2days 1-2 and Ara C 1-5.This Refimen given 2 times at intervals of 4 weeks.

If at all possible then given a bone marrow transplant at the time of complete remission.Therapy is the standard induction chemotherapy with cytarabine and daunorubicin regimen with cytarabine 100 mg/m2 protocol given a continuous infusion for 7 days and daunorubicin 45-60 mg/m2/day iv for 3 days.Approximately 30-40% of patients experienced a complete remission with cytarabine therapy and dounorubisin given as a single agent, whereas when administered as a drug combination achieved complete remission by more than 60% of patients.

Prognosis

With aggressive therapy, 40 -50% of patients who achieve remission will live a long time (30-40% overall success rate).Penderit who relapse after receiving chemotherapy or autologous transplantation can be treated with CST allogenetik as salvage therapy.Some morphological or genetic subtypes have a better prognosis LMA.5. Treatment

a. Special treatment and should be performed in a hospital . Various treatment regimens vary , because many treatment trials are still ongoing to determine the optimum treatment .

b . Combination of drugs is better than a single treatment .

c . If possible , the treatment should be sought with outpatient treatment .

d . Patient endurance decreases because the leukemia cells , as well as drugs , and thus infection by a particular organism may be a problem , for example septicemia . The organisms are often found is staphylococcal , pneumocystis carinii , fungi and cytomegalovirus .

Therapy

Therapy for acute leukemia can be classified into two general categories :

1 . Specific therapy : in the form of chemotherapy

Chemotherapy has stages of treatment are:

a. Induction of Remission .

Many drugs can make remission in acute lymphocytic leukemia . At the time of remission , the patient is free of symptoms , peripheral blood and bone marrow cytological normal , and organ enlargement disappeared . Remission can be induced with drugs whose effects are great but limited . Remission can be maintained by giving other drugs that have the capacity to maintain the patient free of this disease .

Form of intensive chemotherapy to achieve remission , ie a state in which the clinical symptoms disappeared , accompanied by bone marrow blasts less than 5 % . With morfolik examination can not be found leukemia cells in the bone marrow and peripheral blood . ( Bakta , I Made , 2007: 131-133 )

Usually 3 or more drugs given to granting sequentially depending on the regimen or protocol applicable . Some induction plans include : prednisone , vincristine ( Oncovin ) , daunorubicin ( daunomycin ) , and L - asparaginase ( Elspar ) . Other drugs that may be included in the initial treatment is 6 - mercaptopurine ( Purinethol ) and Methotrexate ( Mexate ) . Allopurinol administered orally in combination with chemotherapy to prevent hyperuricemia and potential kidney damage . After 4 weeks of treatment , 85-90 % of children and more than 50 % of adults with ALL in complete remission . Teniposude ( VM - 26 ) and cytosine arabinoside ( Ara - C ) may be used to induce remission Juka initial regimen fail .

a. The drugs used consist of :

Vincristine ( VCR ) 1.5 mg/m2/minggu , iv

Predison ( Pred ) 6 mg/m2/day , orally

L Asparaginase ( L asp ) 10,000 U/m2

Daunorubicin 25 mg/m2/minggu-4 week

b . Regimens used for ALL with standard risk consists of :

Pred + VCR

Pred + VCR + L asp

c . ALL regimens for high risk premises or ALL in adults include:

Pred + VCR + DNR with or tanap L asp

The G ! MEMA of Italy gives DNR + VCR + Pred + L asp with or without cyclophosphamide .b . Phase Postremisi

A phase of treatment to maintain remission as long as possible , which in turn will lead to a cure . This is achieved by :

a. Continued chemotherapy , consisting of :

Consolidation therapy

Maintenance therapy (maintenance )

Late intensification

b . Bone marrow transplantation : a consolidation therapy that provides a permanent cure that part of patients , especially patients aged under 40 years .

Therapy postremisi

a. Therapy for sanctuary phase ( eradicate leukemia cells hide in the CNS and testes )

Triple IT consisting of : intrathecal methotrexate ( MTX ) , Ara C ( cytosine arabinoside ) , and dexamenthason

b . Therapy iontensifikasi / consolidation : noncrossresistant regimens against remission induction regimens .

c . Maintenance therapy (maintenance ) : generally used 6 mercaptopurine ( 6 MP ) and MTX orally every week . Given for 2-3 years interspersed premises or intesifikasi consolidation therapy .

2 . Supportive therapy

This therapy aims to address the failure of the bone marrow , either due to the leukemia itself or as a result of therapy .

Supportive therapy in patients with leukemia is not as important as the specific therapy because it will determine the success rate of therapy . Intensive chemotherapy should be supported by intensive supportive therapy as well , otherwise this is then the patient may die from the side effects of the drug , an iatrogenic death . Supportive therapy serves to overcome the effects caused by leukemia itself and also to overcome the side effects of the drug . Supportive therapy is given ;

1 . Therapies to treat anemia

PRC transfusion to maintain hemoglobin around 9-10 g / dl . For prospective bone marrow transplant , blood transfusion should be avoided .

2 . Therapies to treat the infection , the same as the case of aplastic anemia consists of :

a. adequate antibiotic

b . Transfusion of granulocyte concentrates

c . Special treatment ( isolation )

d . Hemopoitic growth factor ( G - CSF or GM - CSF )

3 . Therapies to treat bleeding consists of :

a. Platelet transfusions to maintain platelet concentrates minimum of 10 x 106/ml , ideally above 20 x 106/ml

b . At M3 given heparin for DIC overcome

4 . Therapy to address other things that :

a. Management leukostasis : performed with intravenous hydration and leukapheresis . Immediately do the induction of remission to decrease the number of leukocytes

b . Management of tumor lysis syndrome : with adequate hydration , allopurinol and alkalinization award of urine .Results of treatment

The results of treatment depends on the following:

1 . Types of leukemia : ALL generally have a better prognosis compared with AML

2 . Characteristics of patients with prognostic factors

3 . Type of drug regimen given

6. Leukocyte is another name for white blood cells . Leukocyte function defend the body against disease by eating ( phagocytosis ) of the disease . That is why leukocytes also called phagocytes . Leukocytes have different shapes with erythrocytes .The shape is varied and has a rounded or concave cell nucleus .His movements such as Amoeba and can penetrate the capillary wall .

Based on the presence / absence of granules in the plasma , leukocytes are divided into :

1 . Granular leukocytes ( granulocytes )

a. neutrophils

b . eosinophils

c . basophils

2 . Not granular leukocytes ( agranulosit )

a. lymphocytes

b . monocytes

a . neutrophils

Plasma is neutral , numerous cell nuclei with a variety of forms . Neutrophil phagocytosis of the erythrocytes ( red blood cells ) , bacteria , and dead tissue .

b . eosinophils

Plasma acidic . That is why eosinophils to dark red when spilled eosin . Eosinophils are also phagocytes and the number will increase if the body is exposed to infection .

c . basophils

Plasma alkaline . That is why plasma is blue if spilled alkaline solution . The white blood cells will amount to much if exposed to infection . Basophils are also phagocytes . In addition , basophils contain anti- caking chemicals , namely heparin .

d . lymphocytes

Lymphocytes are not able to move and core one . The size is great and there is nothing small . Lymphocyte function to form antibodies .e . Monocytes Monocytes can move like Amoeba and the core has a round / elliptical . Monocytes are produced in lymph tissue and are phagocytes .

Sometimes a foreign object or unwanted microbes entering the body . When that happens the body will treat it as an object entering a foreign body or antigen . What happens to these antigens ?

Antigen into the body would be considered as foreign . As a result of the body through the white blood cells ( leukocytes ) produce antibodies to destroy the antigen . Glycoprotein that is present in our hearts can be an antigen for others if the glycoprotein is injected to others . This proves that a material can be considered as an antigen for others but not necessarily as an antigen for us . This also applies to the opposite situation .

Leukocytes that play an important role on the immune system there are 2 kinds , namely phagocytes and lymphocytes .

Phagocytic cells to destroy the foreign object by means of swallowing ( phagocytosis ) .

Phagocytes consists of two kinds of cells , namely :

1 . Neutrophils , present in the blood .

2 . Macrophages , can leave the blood circulation to enter into tissues or body cavities .

Lymphocytes consist of :

1 . T lymphocytes ( T cells ) , which moves to the thymus glands ( lymph glands at the base of the neck ) .

2 . B lymphocytes ( B cells ) .

Both are produced by the bone marrow and circulate throughout the body via the blood vessels , produce antibodies tailored to that antigen enters the body . Often the virus enters the body through the blood vessels but not through the skin and mucous membranes to avoid leukocytes . However, the body's cells do not remain silent . The cells of the body will produce interferon is a protein substance that can produce barrier formation of new viruses ( replication ) .

STEP 51. explain the approach taken in AML disease? 2. explain how pathogenesis, patofisologi, clinical manifestations, laboratory results, diagnosis, therapy in CML disease? 3. explain how pathogenesis, patofisologi, clinical manifestations, laboratory results, diagnosis, therapy in CLL disease? 4. explain how pathogenesis, patofisologi, clinical manifestations, laboratory results, diagnosis, therapy in Hodgkin lymphoma and non-Hodgkin? 5. how aspects of the submission of laboratory tests?STEP 6

(Independent Learning)

STEP 7