الفهرس 
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Abstract
Acute lymphoblastic leukemia (ALL) also known as acute lymphocytic leukemia is a malignant (clonal) neoplasm of the bone marrow in which lymphocyte precursor cells or lymphoblasts have exaggerated and uncontrolled growth, fail to mount a normal immune response, and cause a DROP in production of normal bone marrow cells that leads to a deficiency of circulating red cells (anemia), platelets (thrombocytopenia), and white cells other than lymphocytes (especially neutrophils, or neutropenia). Both T-cell and B-cell precursors can give rise to ALL; B-cell ALL represents about 75% of all cases (Pui C. 1996).
ALL occurs at all ages but displays a bimodal distribution of incidence, with one peak in early childhood and a second in patients older than 50 years. (Faderl et al. 2003). For adult ALL, the yearly incidence is 2 per 100,000, with 75% of the cases being B lineage and the remainder of T cell origin. (Rodriguez et al. 2007). For pediatric ALL, the yearly incidence is 3 to 4 cases per 100,000 (Shu et al. 2002).
ALL represents approximately less than 1% of adult cancers, and 25% of all childhood cancers. In the United States of America (USA) among all ages, it represents less than 0.4% of all cancers, 13.6% of all leukemias, and 29.6% of all lymphocytic leukemias. (Groves et al. 1995).
ALL represents less than 1.1% of total US cancer related deaths and 28.9% of all leukemia deaths. In US children, however, ALL represents almost 16% of total cancer mortality and 50% of all leukemia deaths. (Ries et al. 2006).
The clinical presentation of ALL may range from nonspecific symptoms such as progressive malaise, fever, and fatigue to severe life-threatening manifestations, requiring immediate medical intervention such as acute tumor lysis syndrome (ATLS). Symptoms may appear insidiously or acutely. The presenting features generally reflect the degree of marrow failure and the extent of extramedullary spread. Among the frequently evident findings are pallor, petechiae, and ecchymosis in the skin and mucous membranes and bone tenderness as a result of leukemic infiltration or hemorrhage that stretches the periosteum. Liver, spleen, and lymph nodes are the most common sites of extramedullary involvement, and the degree of organomegaly is more pronounced in children than in adults. Very rarely, ALL produces no signs or symptoms and is detected during routine examination (Chessells et al. 1998).
The diagnosis of acute lymphoblastic leukemia (ALL) is dependent on the identification and characterization of blast cells in peripheral blood or bone marrow. (Weinkauff et al. 1999).
Diagnosis and classification are generally based on the morphologic, cytochemical, and immunologic features of the blasts. However, cytogenetic and molecular studies are frequently needed to confirm the diagnosis, predict clinical behavior, and stratify patients for therapy (Pui et al. 2004).
The French, American, and British (FAB) classification of ALL, which recognizes three subclasses of ALL (L1, L2, and L3), is based strictly on blast morphology and cytochemistry, (Bennett et al. 1981) whereas the World Health Organization (WHO)classification scheme also incorporates immunophenotyping and cytogenetics. (Harris et al. 2000 ).
Remarkable progress has been made in the treatment and outcome of adult acute lymphoblastic leukemia over the past 3 decades. This progress is the result of an accumulation of a mosaic of knowledge and experience, which have led to a more profound understanding of the biology of the disease, and at the same time the development of new drugs and treatment strategies. The combination of further cytogenetic-molecular dissection of ALL subtypes with the emergence of new and targeted therapies will thus continue to constitute the fundament upon which further progress will hopefully occur in adult ALL (Kantarjian H. 2000)
Most of the initial therapeutic advances in adult ALL have arisen from successful adaptation of ALL treatment strategies in children. ALL therapy incorporates multiple drugs into regimen-specific sequences of dose and time intensity and is divided into several phases: (i) induction; (ii) a sequence of intensified consolidation; (iii) a prolonged maintenance phase; and (iv) CNS prophylaxis. Intensive combination therapy in ALL following this pattern has resulted in complete remission (CR) rates of 80% to 90% and leukemia-free survival rates of between 30% and 40%. (Gِkbuget et al. 2002).
The backbone of induction therapy consists of vincristine, steroids, and anthracyclines to which various other drugs such as L-asparaginase, cyclophosphamide, or cytarabine have been added. Dexamethasone has replaced prednisone for better antileukemia activity and achievement of higher levels in the CSF. (Bostrom et al. 2003).
Consolidation strategies include repetition of a modified induction regimen, use of rotational consolidation programs frequently involving high doses of cytarabine, methotrexate, cyclophosphamide, or L-asparaginase, and stem cell transplant. There is evidence that some of these components may contribute to subset specific improvements in outcome. For example, high dose methotrexate may be especially effective in low risk B-lineage ALL and T-ALL, whereas cyclophosphamide and L-asparaginase have led to improved outcome in T-lineage ALL patients. (Thomas et al. 1999).
Early use of stem cell transplantation (SCT) remains disputed. Although recommended for patients with poor-prognosis ALL (Philadelphia-chromosome-positive, 11q23 translocations), the benefit of SCT for standard-risk patients in first CR is not established. The Eastern Cooperative Oncology Group (ECOG) together with the Medical Research Council of the United Kingdom (MRC UK) is investigating early matched-related allogeneic SCT for those CR patients less than 50 years who have a histocompatible donor, whereas all other patients are randomized between autologous SCT and consolidation therapy followed by maintenance for 2.5 years. In the standard risk group, the 5-year EFS rates were 66% with allogeneic SCT and 45% for the randomized group whereas the rates were 44% and 26% for high-risk patients. (Song K. et al. 2007)
The backbone of maintenance therapy has remained fairly constant throughout the various ALL regimens and consists of vincristine, prednisone, 6-mercaptopurine and methotrexate for the duration of 2–3 years. Although maintenance therapy is proven to be beneficial in ALL, there is so far no evidence that intensification of maintenance provides any additional benefit. (Mandelli et al. 1996).
Several novel agents are being investigated in ALL The two groups of agents that have the potential to make the biggest impact currently are the tyrosine kinase inhibitors (imatinib) and the monoclonal antibodies (rituximab, alemtuzumab) CD20 is expressed in around 35% of ALL patients with higher expression found in Philadelphia chromosome-positive ALL and mature B-cell ALL. In addition, it was found that presence of CD20 on ALL blasts is associated with worse outcome (Thomas et al. 2000). Thus, including rituximab as part of the induction/consolidation part of therapy may improve the prognosis of ALL patients further. ALL blasts also show high expression of the CD52 antigen. Unlike CD20, CD52 is also expressed on cells of T lineage and use of the anti-CD 52 monoclonal antibody alemtuzumab may therefore provide additional benefit to patients with particularly T-cell leukemias (Thomas et al. 2001).
A number of other novel agents are investigated in relapsed in refractory disease states and include new nucleoside analogs (clofarabine, nelarabine), liposomal agents (liposomal vincristine), or hypomethylating agents (decitabine). (Deangelo et al. 2007).