Acute Lymphoblastic Leukemia Research Paper

ACUTE LYMPHOBLASTIC LEUKEMIA

BACKGROUND

Acute lymphocytic or lymphoblastic leukemia (ALL) is an aggressive cancer of the bone marrow, specifically affecting the immature lymphocytes that is fatal within weeks if left untreated. Leukemia cells are aggressive, rapidly reproducing, and do not mature appropriately. There are two types of ALL based on the affected lymphocytes, B lymphocytes or T lymphocytes. B lymphocytes are important to the immune system as they protect the body from invaders (e.g., viruses, bacteria, fungi) and make antibodies that tag these intruders and trigger the immune system to destroy them. T lymphocytes can directly destroy invades but some types also boost or slow the immune system depending on their specific subtype.

This risk then decreases until the mid-20s and begins to increase again after the age of 50. About 40% of cases are in adults, males are at a slightly higher risk than females, and it is more common in whites than African Americans. Even though only 40% of cases are in adults, about 80% of deaths due to ALL occurs in adults.12 There are risk factors for ALL but the majority of patients diagnosed with ALL have no risk factors at all. Risk factors include high levels of radiation exposure, chemical exposure (e.g., chemotherapy, benzene), inherited syndromes (Down syndrome, Klinefelter syndrome, Fanconi anemia, Bloom syndrome, ataxia-telangiectasia, and neurofibromatosis), white ethnicity, male gender, and an identical twin with ALL. What causes ALL is still unknown but scientists do know that translocations are the most common form of mutation in ALL although deletions and inversions can also occur. The Philadelphia chromosome (Ph+), t(9;22), is an exchange of DNA between chromosomes 9 and 22 and is the most common translocation in ALL occurring in about 25% of adult ALL cases. Other translocations that occur in ALL but are less common are t(4;11) and

B-cell ALL is divided into common ALL (50%), early pre-B ALL (10%), pre-B ALL (10%) and mature B-cell or Burkitt’s leukemia (4%).12 T-cell ALL consists of mature T-cell ALL (15-20%) and pre-T cell ALL (5-10%). There are several prognostic factors that can affect outcomes. Patients diagnosed with ALL under the age of 50 tend to have better outcomes than those over the age of 60. Initial white blood cell count (WBC) is also critical to prognosis. For B-cell ALL, a WBC less than 30,000 is a better prognosis and for those with T-cell ALL a white blood cell count less than 100,000 at diagnosis a better prognostic indicator. The subtype also plays an important role in prognosis. Generally, mature B-cell ALL is the poorest prognosis while T-cell ALL has a better prognosis and all the other types are somewhere in the middle. Chromosome abnormalities are also important as t(4;11), trisomy 8, or deletion 7 are poor prognostic indicators. The Philadelphia chromosome used to be thought of as a poor prognostic indicator but now there are targeted drugs (e.g., tyrosine kinase inhibitors) that can improve the overall prognosis. The response to initial chemotherapy also impacts prognosis as those who go into CR (e.g., less than 5% blasts in the marrow and normal blood counts) within 4-5 weeks have better prognosis while those that do not go into CR have a