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New Treatments for Acute Leukemia

Acute leukemia is a hematopoietic progenitor cell malignancy. These cells proliferate in an uncontrolled fashion and ultimately replace normal bone marrow elements. Most cases arise with no clear cause. However, radiation and some toxins (benzene) are clearly leukemogenic. In addition, a number of chemotherapeutic agents (especially procarbazine, melphalan, other alkylating agents, and etoposide) may be leukemogenic.

Most of the clinical findings in acute leukemia are due to bone marrow failure, which results from replacement of normal bone marrow elements by the malignant cell. Less common manifestations include direct organ infiltration (skin, gastrointestinal tract, meninges).

Acute lymphoblastic leukemia (ALL) comprises 80% of the acute leukemias of childhood. The peak incidence is between 3 and 7 years of age. However, ALL is also seen in adults and comprises approximately 20% of adult acute leukemias. Acute myelogenous leukemia (AML; acute nonlymphocytic leukemia [ANLL]) is chiefly an adult disease.

Clinical Findings

A. Symptoms and Signs: Most patients with acute leukemia present with an acute illness and have been ill only for days or weeks. Bleeding (usually due to thrombocytopenia) is usually in the skin and mucosal surfaces, manifested as gingival bleeding, epistaxis, or menorrhagia. Less commonly, widespread severe bleeding is seen.

Treatment

Most young patients with acute leukemia are treated with the objective of effecting a cure. The first step in treatment is to obtain complete remission.

Acute myelogenous leukemia is treated initially with intensive combination chemotherapy, including daunorubicin and cytarabine. Effective treatment produces aplasia of the bone marrow, which takes 2B3 weeks to recover. During this period, intensive supportive care, including transfusion and antibiotic therapy, is required. Once complete remission has been achieved, several different types of postremission therapy are potentially curative. Options include repeated intensive chemotherapy, high-dose chemoradiotherapy with allogeneic bone marrow transplantation, and high-dose chemotherapy with autologous bone marrow transplantation. Recently, progress has been made in the treatment of acute promyelocytic leukemia (M3). The addition of all-trans retinoic acid to initial chemotherapy has improved the results of both initial treatment and long-term survival.

Acute lymphoblastic leukemia is treated initially with combination chemotherapy, including daunorubicin, vincristine, prednisone, and asparaginase. Remission induction therapy.

Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) a B lymphocyte (rarely T lymphocytes) clonal malignancy. The disease is usually indolent, with slowly progressive accumulation of long-lived small lymphocytes. These cells are immunoincompetent.

Chronic lymphocytic leukemia is manifested clinically by immunosuppression, bone marrow failure, and organ infiltration with lymphocytes. Immunosuppression, bone marrow failure, and infiltration of organs.

Clinical Findings

A. Symptoms and Signs: Chronic lymphocytic leukemia is a disease of the elderly, with 90% of cases occurring after age 50 and a median age at presentation of 65. Many patients will be incidentally discovered to have lymphocytosis.

Treatment

Most cases of early indolent chronic lymphocytic leukemia require no specific therapy. Indications for treatment include progressive fatigue, troublesome lymphadenopathy, or the development of anemia or thrombocytopenia. These patients have either symptomatic and progressive stage II disease or stage III/IV disease. Initial therapy is with chlorambucil, 0.6B1 mg orally every 3 weeks. Complications such as autoimmune hemolytic anemia or immune thrombocytopenia may be treated with high-dose prednisone but Fludarabine is a new agent which is useful in treating disease refractory to The rare young patient (age under 50) with aggressive disease may be a candidate for allogeneic bone marrow transplantation.