Acute Leukemia 522s

Essentials of Diagnosis     

Short duration of symptoms, including fatigue, fever, and bleeding. Cytopenias or pancytopenia. More than 20% blasts in the bone marrow. Blasts in peripheral blood in 90% of patients. Classify as acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL).

General Considerations   

Acute leukemia is a hematopoietic progenitor cell malignancy. Uncontrolled proliferation cells and replace normal bone marrow elements. Arise with no clear cause. However, radiation and some toxins (benzene) are leukemogenic. A number of chemotherapeutic agents (especially cyclophosphamide, melphalan, other alkylating agents, and etoposide) may cause leukemia.

General Considerations  Most

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of the clinical findings in acute leukemia are due to replacement of normal bone marrow elements by the malignant cell. Less common manifestations result from organ infiltration (skin, gastrointestinal tract, meninges). Acute leukemia is potentially curable with combination chemotherapy.

General Considerations 

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ALL comprises 80% of the acute leukemias of childhood. The peak incidence is between 3 and 7 years of age. It is also seen in adults, causing approximately 20% of adult acute leukemias. Acute myeloid leukemia (AML) is primarily an adult disease with a median age

Symptoms and Signs       

Bleeding (usually due to thrombocytopenia) : Skin Mucosal surfaces Ginggival bleeding Epistaxis Menorrhagia Less commonly, widespread bleeding is seen in patients with disseminated intravascular coagulation (DIC).

Symptoms and Signs 

Infection is due to neutropenia (falls below) 500/mcL. The most common pathogens are gram-negative bacteria (Escherichia coli, Klebsiella, Pseudomonas) or fungi (Candida, Aspergillus). Common presentations include cellulitis, pneumonia, and perirectal infections; death within a few hours may occur if treatment with appropriate antibiotics is delayed.

Symptoms and Signs    

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Patients may also seek medical attention : Gum hypertrophy Bone and t pain The most dramatic presentation is hyperleukocytosis, in which a markedly elevated circulating blast count (usually > 200,000/mcL) leads to impaired circulation : Headache Confusion Dyspnea

Laboratory Findings 

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The hallmark of acute leukemia is the combination of pancytopenia with circulating blasts However, blasts may be absent from the peripheral smear in as many as 10% of cases ("aleukemic leukemia"). The bone marrow is usually hypercellular and dominated by blasts. More than 20% blasts are required to make a diagnosis of acute leukemia.

Laboratory Findings      

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Hyperuricemia may be seen. If DIC is present : The fibrinogen level will be reduced The prothrombin time prolonged Fibrin degradation products or fibrin D-dimers present. Patients with ALL (especially T cell) may have a mediastinal mass visible on chest radiograph. Meningeal leukemia will have blasts present in the spinal fluid, seen in approximately 5% of cases at diagnosis; it is more common in monocytic types of AML. The Auer rod, an eosinophilic needle-like inclusion in the cytoplasm, is pathognomonic of AML

Laboratory Findings 

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AML classification by "FAB," (French, American, British) was based of morphology and histochemistry : Acute undifferentiated leukemia (M0) Acute myeloblastic leukemia (M1) Acute myeloblastic leukemia with differentiation (M2) Acute promyelocytic leukemia (APL) (M3) Acute myelomonocytic leukemia (M4) Acute monoblastic leukemia (M5) Erythroleukemia (M6) Megakaryoblastic leukemia (M7)

Differential Diagnosis        

AML must be distinguished from other myeloproliferative disorders : Chronic myeloid leukemia Myelodysplastic syndromes. ALL must be separated from other lymphoproliferative disease such as : Chronic lymphocytic leukemia Lymphomas Hairy cell leukemia. Atypical lymphocytosis of mononucleosis and pertussis.

Treatment     

The first step in treatment is to obtain complete remission : normal peripheral blood with resolution of cytopenias normal bone marrow with no excess blasts normal clinical status. The type of initial chemotherapy depends on the subtype of leukemia.

AML   

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AML are treated with a combination : anthracycline (daunorubicin or idarubicin) plus cytarabine, either alone or in combination with other agents. This therapy will produce complete remission in 80% of patients under age 60 years and in 50–60% of older patients. APL is treated differently from other forms of AML. Induction therapy should include anthracycline plus all-trans-retinoic acid. With this approach 90–95% of patients will achieve complete remission.

ALL       

Adults with ALL are treated : Daunorubicin Vincristine Prednisone Asparaginase This treatment produces complete remissions in 90% of patients. Remission induction therapy for ALL is less myelosuppressive than treatment for AML and does not necessarily produce marrow aplasia

Prognosis  

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Approximately 70–80% of adults with AML under age 60 years achieve complete remission. High-dose postremission chemotherapy leads to cure in 35–40% of these patients, and high-dose cytarabine has been shown to be superior to therapy with lower doses. Allogeneic bone marrow transplantation is curative in 50– 60% of cases. Autologous bone marrow transplantation may be superior to nonablative chemotherapy. Older adults with AML achieve complete remission in up to 50% of instances. The cure rates for older patients with AML have been very low (approximately 10–15%) even if they achieve remission and are able to receive postremission chemotherapy.