Assignment task: Acute Lymphocytic (Lymphoblastic) Leukemia
It's called the children's ward. For two teenagers who have been recently diagnosed with leukemia, it seems insulting to have their lives hijacked by doctors and nurses with stuffed animals clipped to their stethoscopes.
Laura is a forward on her school soccer team and leads the league in scoring. For the last four months, she has been really tired, but nothing seemed really wrong until her legs became covered with bruises. Just pressing her fingers on her skin was practically enough to make a bruise. It didn't seem real when her doctor, Jane Ryder, diagnosed her with Acute Lymphocytic (or Lymphoblastic) Leukemia (ALL), or when she told her that ALL is the most common malignant (spreading) cancer found in children. She's 14 years old; she's not a child!
Beth is 13 and looks remarkably like Laura. Both have straight dark hair, large brown eyes, and tall slender builds. Beth has never been that athletic; she prefers reading and theater. She's hoping to be part of the drama team next year when she goes to high school, even though she'll only be a freshman. But she's been missing a lot of school because of one virus after another, lots of fevers and night sweats, then that rash in the fall. Now she's in a hospital, and it seems like the only people she sees are her parents, Dr. Ryder, and the nurses.
Laura and Beth both have ALL, which arises from the uncontrolled growth of immature lymphocytes (a type of white blood cell, or leukocyte). These cells, which are "stuck" in an early stage of development, become so numerous that they crowd out normal blood cells. Each year about 30 cases occur per million people, and most of those cases are in children aged 2-5 years. The cause of ALL remains largely unknown, although a small number of cases are associated with inherited genetic syndromes.† Both girls are suffering from anemia (low blood cell levels), fevers, bleeding, and are pale and thin. Dr. Ryder has decided to treat them as in-patients, keeping them in the hospital while treating them with a "thiopurine" drug called 6-mercaptopurine (6-MP) known to be highly effective in treating leukemia. Thiopurines are very similar to the regular purine nitrogen bases such as adenine and guanine that make up DNA and RNA. The only difference is that thiopurines have an extra sulfur group attached to them. They are similar enough to a regular purine base that our cells convert them to nucleotides (with the addition of a deoxyribose sugar and phosphate). These modified thioguanine nucleotides (TGN) are then incorporated into DNA.
The TGN nucleotides interfere with DNA replication and stop rapidly growing cells like cancer cells from further growth. Unfortunately, they also block the growth of other fast growing cells needed for good health, like the cells in the bone marrow that develop into erythrocytes (red blood cells) and leukocytes. As with many drugs given as chemotherapy, it is important to give a high enough dosage to prevent cancer cells from replicating, while avoiding damage to the normal tissues. Too high a drug dose can be very toxic. Dr. Ryder knows that drugs are processed in various ways in the body. They must be absorbed by the blood, distributed throughout the body's tissues, converted or transformed into forms that are easier to eliminate, and then removed from the body. Dr. Ryder gives both girls the same dosage of the drug before leaving the hospital for the night.
While making her rounds over the next few days, Dr. Ryder sees Laura's vital signs plummet. Her anemia has worsened; her erythrocyte count is so low that her heart function could be compromised. Her fevers are spiking, and her breathing is becoming shallow and labored. She is not eating and is being hydrated intravenously. Her condition is life-threatening. In contrast, Beth's anemia has decreased, she is free of fever, and is actually showing signs of an appetite and boredom, good indicators of improved health. Dr. Ryder had not anticipated that the drug could act so differently in two individuals. Even as she looks at Beth's chart, she can picture Laura's body struggling to hold its own just two private rooms away. Dr. Ryder knows she must find out why her patients are responding so differently. But where should she start, and will she find an answer in time to help Laura?
1. Summarize the conditions of the two girls introduced in Part I of the case study and what their response is to the treatment with 6-MP.
2. Why are the two girls responding differently to the drug and what tests might Dr. Ryder order to determine why the girls are reacting as they are to the drug?