Cancer, Leukemia, Lymphocytic, Acute (ALL)

Article Author:
Yana Puckett
Article Editor:
Onyee Chan
Updated:
10/27/2018 12:31:20 PM
PubMed Link:
Cancer, Leukemia, Lymphocytic, Acute (ALL)

Introduction

Acute Lymphocytic Leukemia (ALL) is a malignancy of B or T lymphoblasts characterized by uncontrolled proliferation of abnormal, immature lymphocytes and their progenitors which ultimately leads to the replacement of bone marrow elements and other lymphoid organs resulting in a typical disease pattern characteristic of Acute Lymphocytic Leukemia. ALL accounts for approximately 2 percent of the lymphoid neoplasms diagnosed in the United States. Acute Lymphocytic Leukemia occurs slightly more frequently in males than females, and three times as frequently in Whites as in Blacks. Patients with Acute Lymphocytic Leukemia typically present with symptoms related to anemia, thrombocytopenia, and neutropenia due to the replacement of the bone marrow with tumor. Symptoms can include fatigue, easy or spontaneous bruising/bleeding, and infections. B-symptoms, such as fever, night sweats, and unintentional weight loss are often present, but may be mild. Hepatomegaly, splenomegaly, and lymphadenopathy can be seen in up to half of adults on presentation. Central nervous system (CNS) involvement is common and can be accompanied by cranial neuropathies or symptoms, predominantly meningeal, related to increased intracranial pressure.

Etiology

The etiology of Acute Lymphocytic Leukemia is unknown. However, certain environmental factors have been implicated in the etiology of Acute Lymphocytic Leukemia such as exposure to benzene, ionizing radiation, or previous exposure to chemotherapy or radiotherapy.

Genomic studies have noted that somatic, polymorphic variants of ARD5B, IKZF1 (the gene encoding Ikaros) and CDKN2A are associated with an increased risk of ALL (odds ratio 1.3 to 1.9). Other rare germline mutations in PAX5, ETV6, and particularly p53 can also strongly predispose to the development of leukemia.

Acute lymphoblastic Leukemia is not considered a familial disease and no screening programs have been developed to test for it in childhood. 

Epidemiology

It is diagnosed in about 4000 people in the United States each year with the majority being under the age of 18. It is the most common malignancy of childhood. The peak age of diagnosis is between two and ten years of age. Acute Lymphocytic Leukemia is more common in children with Trisomy 21 (Down syndrome), neurofibromatosis type 1, Bloom syndrome, and ataxia telangiectasia. All are common in children between two and three years of age. Prognosis is diminished in children when diagnosed in infants less than one year of age and in adults. It is more favorable in children. Association of the MLL gene in children at 11q23 chromosome is associated with poor prognosis. Acute Lymphocytic Leukemia is a disease with low incidence overall in population studies. The incidence of Acute Lymphocytic Leukemia is about 3.3 cases per 100,000 children. Survival rates for ALL have improved dramatically since the 1980s, with a current five-year overall survival rate estimated at greater than 85 percent.

Pathophysiology

Acute Lymphocytic Leukemia is thought to occur after damage to DNA causes lymphoid cells to undergo uncontrolled growth and spread throughout the body. Splenomegaly and hepatomegaly occur due to sequestration of platelets and lymphocytes in the spleen and liver as the white blood cells are not typical the spleen reacts to them by trying to remove them from the blood. 

Histopathology

On peripheral blood smears of Acute Lymphocytic Leukemia patients, lymphoblasts vary in size. Various CD cytokines must be tested to evaluate for what kind of Acute Lymphocytic Leukemia the patient has.

History and Physical

The most common presenting symptoms of Acute Lymphocytic Leukemia are nonspecific and may be difficult to distinguish from common, self-limited diseases of childhood. In a meta-analysis, more than half of children with childhood leukemia had at least one of the following five features on presentation: palpable liver, palpable spleen, pallor, fever, or bruising. ALL patients typically present with symptoms of night sweats, easy bruising, skin pallor, unexplained lymphadenopathy, weakness, weight loss, hepatosplenomegaly, or difficulty breathing. Some patients may present with Superior Vena Cava Syndrome. Bone pain, mental changes, and oliguria may also be present. ALL can also present with testicular enlargement, musculoskeletal pain, mediastinal mass, and incidentally found peripheral blood cell abnormalities. 

Evaluation

Acute Lymphocytic Leukemia diagnosis should be explored initially with a laboratory evaluation consisting of a CBC, electrolyte and renal panel, LDH level. Additionally, imaging such as a chest x-ray for symptoms of shortness of breath may be obtained. If abdominal fullness, tenderness or abdominal mass are symptoms, then a CT scan of the abdomen and pelvis should be obtained. This can also help with staging of the disease.

Treatment / Management

Children who are suspected of having Acute Lymphocytic Leukemia should be referred to a pediatric center that specializes in cancer for evaluation and treatment. For children with Acute Lymphocytic Leukemia, induction therapy consists of anthracycline, vincristine, 1-asparaginase, and a corticosteroid. Maintenance therapy utilizes oral 6-mercaptopurine or methotrexate delivered once weekly or once monthly.  Successful treatment of children with Acute Lymphocytic Leukemia involves administration of a multidrug regimen that is divided into several phases (i.e., induction, consolidation, and maintenance) and includes therapy directed to the central nervous system (CNS). Most treatment protocols take two to three years to complete. Stem cell transplantation can sometimes be used as a treatment in which patient's normal source of blood cells (bone marrow) is replaced by healthy young blood cells (stem cells) from a healthy well-matched donor. Splenectomy is rarely required for Acute Lymphocytic Leukemia. Splenectomy can help boost platelet count, but does not affect the outcome of leukemia itself. Splenectomy can be performed for severe symptoms that are not amenable to chemotherapy treatment such as abdominal pain. Radiation can also be used in cases of enlarged spleen to try and reduce the size of the spleen in most cases. 

Pearls and Other Issues

Despite improvements in supportive care, death resulting from treatment toxicity remains a challenge. It is important to watch out for Tumor Lysis Syndrome which occurs when chemotherapy causes cancer cells to lyse releasing certain intracellular elements such as potassium, calcium, uric acid, and phosphorus. These elements, in large numbers, resulting in toxicity that can often lead to renal failure. Pretreatment with fluids and steroids typically prevents Tumor Lysis Syndrome. However, if it occurs, aggressive fluid therapy is the treatment. 

Even after treatment, Acute Lymphocytic Leukemia can come back (relapse). Relapses can occur as far back as 21 years. IT is important to address other issues associated cancer treatment in a young child including providing psychological support to child, parents, and family.