LEUKEMIAS Definition Neoplastic clonal proliferation of the haemopoetic cell lines in the bone marrow with release into

circulation of abnormal cells. Classification Based on clinical presentation Acute-Rapid onset and progression and without treatment death in few months 2-3 months. Acute leukemias have arrested maturation of the haemopoetic cells with predominance of blast cells in circulation. Chronic-Insidious onset and slow progressing and without treatment death in months to years. Mature cells and some blasts in circulation-maturation spectrum of cells. Based on cell types Lymphoid Myeloid types. ACUTE LYMPOBLASTIC LEUKEMIA Definition ALL- is a malignant (clonal) proliferation of early lymphoid precursors in the bone marrow with replacement the normal hematopoietic cells of the marrow. Pathophysiology: -The malignant cells of ALL are lymphoid precursor cells (ie, lymphoblast) that are arrested in an early stage of development. -This arrest is caused by an abnormal expression of genes, often as a result of chromosomal translocations. -The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. -The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymph nodes. Frequency: ALL is the most common type of leukemia in children. In adults, it is less common than acute myelogenous leukemia (AML) Mortality/Morbidity: Only 20-40% of adults with ALL are cured with current regimens. ALL in pediatrics is more responsive. Sex: ALL is slightly more common in men than in women. Age: ALL is more common in children than in adults

History: Patients with ALL present with either (1) Symptoms relating to direct infiltration of the marrow or other organs by leukemia cells or (2) Symptoms relating to the decreased production of normal marrow elements. -Infiltration of the marrow by massive numbers of leukemia cells frequently manifests as bone pain. This pain can be severe and is often atypical in distribution. -Uncommonly (10-20%), patients may present with left upper quadrant fullness and early satiety due to spenomegaly. -Other patients, particularly those with T-cell ALL, present with symptoms related to a large mediastinal mass, such as shortness of breath. -Symptoms of leukostasis (eg, respiratory distress, altered mental status) because of the presence of large numbers of lymphoblasts in the peripheral circulation, leukostasis is much less common in persons with ALL compared to AML and occurs only in patients with the highest WBC counts, ie, several hundred thousand per microliter. -Symptoms of anemia are common and include fatigue, dizziness, palpitations, and dyspnea upon even mild exertion. -Patients with ALL often have decreased neutrophil counts, despite an increased total WBC count have increased risk of infection. -Patients with ALL often have fever without any other evidence of infection. However, in these patients, one must assume that all fevers are from infections until proven otherwise because a failure to treat infections promptly and aggressively can be fatal. Infections are still the most common cause of death in patients undergoing treatment for ALL -Bleeding symptoms due to thrombocytopenia .The thrombocytopenia, however, tends to be less severe than that observed in patients with AML -Some may have (DIC) at the time of diagnosis, usually as a result of sepsis. Consequently, some patients may present with hemorrhagic or thrombotic complications. -Signs relating to leukostasis include respiratory distress and altered mental status

Physical: -Patients commonly have physical signs of anemia, including pallor and a cardiac flow murmur. -Fever and other signs of infection, including lung findings of pneumonia, can occur. -Thrombocytopenia usually demonstrate petechiae, particularly on the lower extremities. A large number of ecchymoses is usually an indicator of a coexistent coagulation disorder such as DIC. -Signs relating to organ infiltration with leukemia cells include hepatosplenomegaly and, to a lesser degree, lymphadenopathy. -Occasionally, patients have rashes resulting from

Procedure Bone marrow aspiration and biopsy are the definitive diagnostic tests to confirm the diagnosis of leukemia. Tests Cytochemical Staining Positive TdT- terminal deoxynucleotidyl transferase and PAS (Periodic Acid Schiff) is the hallmark of ALL. ALL is negative to myeloperoxiadase and Sudan black TdT also helps distinguish ALL from malignancies of more mature lymphocytes (ie, NHL). Immunophenotying /Flow cytometry-Cell markers Positive confirmation of lymphoid (and not myeloid) lineage by flow cytometric demonstration of lymphoid