Cancer Information

Home Common Types of Cancers Acute Lymphocytic Leukemia Symptoms & Prognostic Indicators Diagnosis & Treatment Diagnosis and Treatment - Acute Lymphocytic Leukemia  Diagnosis Peripheral blood smear examination Bone marrow examination Cerebrospinal fluid examination, X-ray chest and other test are required to assess the extent of the disease and immunophenotyping of the cells. Immunophenotype of ALL  1. B-precursor ALL: B-cell precursor (or B-lineage) ALL, defined by the expression of CD19, HLA-DR, CD10 (cALLa), and other B-cell associated antigens, represents 80% to 85% of childhood ALL. Approximately 80% of B-precursor ALL express the cALLa, CD10 antigen. The lack of cALLa expression has also been shown in some series to be associated with a worse prognosis. For example, CD10 negativity is observed in a higher proportion of infants with B-precursor ALL and is associated with poor outcome. There are 3 major subtypes of B-precursor ALL Early pre-B (no surface or cytoplasmic immunoglobulin)- Approximately 75% of patients with B-precursor ALL have the early pre-B phenotype and have the best prognosis. Pre-B (presence of cytoplasmic immunoglobulin)- The leukemic cells of patients with pre-B ALL contain cytoplasmic immunoglobulin (cIg), an intermediate stage of B-cell differentiation. Twenty-five percent of patients with pre-B ALL have the t(1;19) translocation.  Approximately 3% of patients have transitional pre-B ALL expression of surface immunoglobulin heavy chain without light chain, without C-MYC gene involvement or L3 morphology. Patients with this phenotype respond well to therapy used for B-cell precursor ALL. B-cell (presence of surface immunoglobulin) - Approximately 2% of patients present with B-cell ALL (surface Ig expression, generally with FAB L3 morphology and C-MYC gene translocation). B-cell ALL is a systemic manifestation of Burkitt?s and Burkitt?s-like non-Hodgkin?s lymphoma, and its treatment is completely different from that for other forms of childhood ALL. Rare cases of ALL that express surface Ig but lack C-MYC gene translocations are appropriately treated as B-precursor ALL rather than B-cell ALL. 2. T-cell ALL: T-ALL is defined by the leukemic cell expression of the T-cell-associated antigens CD2, CD7, CD5, or CD3. Approximately 12% of children with newly diagnosed ALL have the T-cell phenotype.  Common clinical features for T-cell ALL include -Male sex -Older age -Leukocytosis -Mediastinal mass. With appropriately intensive therapy, however, children with T-cell ALL have an outcome similar to that for children with B-precursor ALL. 3. Myeloid antigen expression: About 33% of childhood ALL cases have leukemia cells that express myeloid-associated surface antigens. There is no independent adverse prognostic significance for myeloid-surface antigen expression. Cytogenetics of Acute Lymphocytic Leukemia: Chromosome number - Hyperdiploidy: Hyperdiploidy (>50 chromosomes per cell or DNA index >1.16) is the presence of additional copies of whole chromosomes and occurs in 20% to 25% of cases of B-precursor ALL. Hyperdiploidy generally occurs in cases with favorable prognostic factors and is itself associated with favorable prognosis. Trisomies -Children with trisomies of chromosomes 4, 10 and 17 have better prognosis. Hypodiploidy-Approximately 1% of children with ALL have leukemia cells showing hypodiploidy with less than 45 chromosomes. These patients are at high risk for treatment failure. Chromosomal translocations- The Philadelphia chromosome t(9;22) is present in approximately 3% of pediatric ALL patients and confers an unfavorable prognosis. TEL-AML1 (t(12;21) cryptic translocation): is present in 20% to 25% of cases of B-precursor ALL. Patients with the TEL-AML1 fusion have an excellent outcome. Translocations involving the MLL (11q23) gene occur in approximately 8% of childhood ALL cases, and are generally associated with increased risk for treatment failure. The t(1;19) translocation occurs in 5% to 6% of childhood ALL, and involves fusion of the E2A gene on chromosome 19 to the PBX1 gene on chromosome 1. Patients with this translocation usually have a relatively inferior prognosis. Treatment for Acute lymphocytic leukemia : Chemotherapy Blood Stem Cell Transplant Successful treatment of children with ALL requires the control of systemic disease (marrow, liver and spleen, lymph nodes, etc.) as well as the treatment (or prevention) of extramedullary disease particularly in the central nervous system (CNS). Only 3% of patients have detectable CNS involvement by conventional criteria at diagnosis (≥5 WBC/μL with lymphoblast cells present), however, unless specific therapy is directed toward the CNS, 50% to 70% or more of children will eventually develop overt CNS leukemia. Therefore all children with ALL should receive systemic combination chemotherapy together with some form of CNS prophylaxis. At present, most groups treat patients with documented CNS leukemia at diagnosis with intrathecal therapy followed by cranial irradiation with or without concurrent spinal radiation. Chemotherapy for children with ALL is divided into stages: -Remission induction: Three-drug induction therapy using vincristine, Prednisone/dexamethasone, plus L-asparaginase in conjunction with intrathecal therapy (IT), results in complete remission rates of greater than 95%. High risk patients generally receive induction therapy that includes an anthracycline (e.g., daunomycin) along with the other three drugs. -Consolidation or intensification -Maintenance (continuation) therapy -CNS sanctuary therapy generally provided in each stage - Every patient with ALL receives intrathecal chemotherapy with methotrexate alone or methotrexate with cytarabine plus hydrocortisone. Children with ALL who present with CNS disease at diagnosis (defined as ≥5 white cells/μL in cerebral spinal fluid (CSF) with lymphoblasts present) generally receive cranial radiation (1,200-1,800 cGy) in addition to appropriate systemic and intrathecal chemotherapy. The intensity of both induction therapy and postinduction therapy is determined by the clinical and biologic prognostic factors utilized for risk-based treatment assignment and some type of early response assessment (day 7 and/or day 14 marrow blast percentage, day 7 peripheral blood blast count, end induction minimal residual disease burden as measured by polymerase chain reaction [PCR], and/or flow cytometry). The average duration of maintenance therapy for children with ALL ranges between 2 and 3 years. Blood Stem Cell Transplant Until recently, blood stem cell transplants were known as bone marrow transplants, because marrow was the only source of blood stem cells used to treat diseases. The three sources of stem cells now being used for transplants are marrow, circulating blood (also known as peripheral blood) and umbilical cord blood. In a blood stem cell transplant, the patient is first given a pre-transplant treatment of chemotherapy and/or radiation therapy to destroy the patient's leukemia cells and immune system. Blood stem cells are then put into the patient's blood to restore the patient's immune system and blood production. There are two types of blood stem cell transplants that can be used to treat ALL patients: Autologous blood stem cell transplants use the patient's own blood stem cells. Allogeneic blood stem cell transplants use the blood stem cells of a donor, either someone from the patient's family or an unrelated donor. Prognosis for Acute Lymphocytic Leukemia - 75% to 80% of children with ALL attain remission and survive free of leukemia recurrence at least 5 years from diagnosis with current treatments that incorporate systemic therapy (e.g., combination chemotherapy) and specific central nervous system (CNS) preventive therapy (i.e., intrathecal chemotherapy with or without cranial irradiation).