Treatment of Acute Lymphocytic Leukemia
Acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia is a cancer of immature white blood cells
called lymphocytes in the bone marrow.
ALL is the most common childhood cancer, although ALL is also seen in adults. This cancer tends to spread fast to other parts of the body unless treatment is provided. Modern treatment for ALL rests on the early pioneering work done to treat this condition.
In 1948, Dr. Sidney Farber, a pathologist working at The Children’s Hospital in Boston found a similarity between the immature red blood cells causing pernicious anemia as a result of vitamin B12 deficiency and the immature cells in ALL.
Since folic acid was successful in treating pernicious anemia, Farber began treating children with ALL with folic acid. Unfortunately the treatment had a disastrous clinical outcomes and he speculated that instead of killing the cells, folic acid may have stimulated more leukemic cells.
He further hypothesized that a folic acid antagonist, namely aminopterin may hold the key to the success in treating ALL patients. The treatment worked, resulting in a temporary remission for these patients. So, by 1948, the treatment came as a major breakthrough in the treatment for this dreadful disease. Researchers started looking for a better cure.
By the 1950s, the quality of survival in ALL patients had considerably improved with corticosteroids and 6-mercaptopurine, a drug discovery that led to Nobel Prize for Gertrude Elion and George Hitchings in 1950.
Methotrexate, another anti-folic acid drug was also added to the treatment regimen. These treatments also did not produce the desired survival rate of more than a year. More clinical trials for novel drug regimen combinations continued at St Judes Hospital to find a cure that could stem relapse from occurring.
Major breakthrough in the early 1970s with combinations that could aggressively treat the brain and spinal fluid with radiation and drugs that not only significantly reduced relapse, but also led to a cure rate that now stands at approximately 80%.
Over the past few decades a deeper understanding of leukemic cells and the identification of prognostic factors such as leukocytosis, age, cytogenetic and molecular abnormalities, and the early therapeutic response of leukemic cells has further increased the cure rate to up to 90% in the developed nations.
The treatment regimen for patients with ALL is determined by blood smears (elevated WBCs) and cytogenetic analysis of the bone marrow done through a biopsy.
Essentially, the chromosomes of the lymphocytes are examined for the presence (positive) or absence (negative) of the Philadelphia chromosome. Treatment is provided based on the status of the leukemia and the age of the patient.
Treatment consists of multiple components — remission induction, central-nervous-system (CNS)-directed therapy with cranial irradiation and intrathecal methotrexate, intensification (consolidation) therapy, and continuation treatment — four components that define the backbone of ALL treatments today.
The success in the transformation of an incurable cancer to a curable condition is one of the biggest success stories in oncology.