Acute Lymphoblastic Leukemia: Miracles for Millions and the People Who Created Them

 

According to a recent article in MedicalXpress, the story begins fifty years ago with the grim statistics that a child with acute lymphoblastic leukemia (ALL) would not survive longer than three months.

The disease took control of their spleens, livers, nervous systems, and lymph nodes.

Now those numbers are reversed. Ninety percent of children with ALL are cured. And this is only one part of a phenomenal success story that transformed cancer therapy for millions.

The Chronology of a Cure

Boston’s Dana-Farber Cancer Institute was named for the esteemed Sidney Farber, a pediatric pathologist known as the father of modern chemotherapy. In addition to his contributions to medicine, he was considerably talented at fund-raising.

Dr. Farber’s search to find a cure for children with ALL began in the 1940s. He based his initial research on studies conducted during the Second World War.

He noted that the essential vitamin, folic acid, could cure anemias which were the result of a low red blood cell count. In leukemia, immature white blood cells (lymphoblasts) in the bone marrow are out of control.

Dr. Farber’s first attempt at treating children with folic acid failed as their condition appeared to worsen. He turned his theory around and reasoned that the folic acid may actually stimulate the bone marrow, creating blasts (cancers).

Following that theory, he decided on a folic acid blocker that could potentially stop cancer’s growth.

At about the same time, 1947, Lederle pharmaceutical began to test a folic acid antagonist. It was called aminopterin and had dangerous adverse reactions.

Nevertheless, since it acted just as Dr. Farber had hoped, he administered the drug to sixteen children. Ten of the sixteen children showed dramatic improvements but only for a short period of time.

A Breakthrough in 1950

In 1950, two scientists received the Nobel Prize for development of the drug 6-MP (mercaptopurine).  It is a drug that prevents the growth of cancer cells by substituting DNA and RNA building blocks.

The drug 6-MP is also effective against ulcerative colitis and adult leukemias. During this time methotrexate, a corticosteroid that fights inflammation, was added to the roster against ALL.

For a time this arsenal was effective, but then the lymphoblasts developed a resistance to the therapy, sending the children spiraling back down into the grip of the disease.

Danny Thomas and St. Jude Hospital

St. Jude Children’s Research Hospital in Memphis, Tennessee opened to children and their parents in 1962. The hospital is proud to say that parents may stay with their children at the hospital yet never be billed for treatment or housing.

Danny Thomas, the well-known comedian, and devout Catholic promised St. Jude, his patron saint, that if he could just get a job to support his family he will build a hospital for children. His wish was fulfilled and he made good on his promise.

A dedicated oncologist, Dr. Donald Pinkel, was determined to find a cure for ALL. He became the CEO and director at St. Jude’s. Dr. Pinkel’s team had several obstacles to overcome.

The first was drug resistance; then it was drug toxicity and the relapse of the central nervous system. The general consensus among the medical world was that there was no cure for ALL.

Undaunted, Dr. Pinkel and his team worked with several medical centers. Their clinical trials involved combining radiation with multiple drugs. They called it “Total Therapy”.

The Total Therapy Cure

Total Therapy is a major factor in the current protocol. It involves chemotherapy administered over a period of three years. It is broken down into four segments:

  • to bring about remission (no blasts)
  • eliminate minimal residual disease (MRD) or undetectable cancer
  • put the patient on a maintenance regimen to prevent relapse
  • Wipeout cancer in the central nervous system

By the end of the 1960s, about fifty percent of children who were treated with the full four-year regimen of Total Therapy were cured.

This year at age 92 Dr. Pinkel will be able to add the Giants of Cancer Care award to his other honors.

The Philadelphia Chromosome

Within the community of children diagnosed with ALL, there was a subset that still received standard chemotherapy and could not be cured. These children had a genetic defect called the Philadelphia chromosome.

Two scientists at the University of Pennsylvania’s Cancer Center identified the chromosome in 1959. Through what could be considered a “chain reaction”, targeted, personalized treatments were eventually developed to treat cancers.

The discovery of the Philadelphia chromosome laid the groundwork for a class of “tyrosine kinase inhibitors” that disrupt cell growth signals. As a result of these inhibitors, seventy percent of children with ALL are now cured.

Doctor Brian Druker and Gleevec

In 2001, Gleevec (imatinib) was the first in this class of inhibitors to be approved for adult leukemia. In 2013 Gleevec had expanded to treat ALL.

According to The National Cancer Institute, Gleevec was instrumental in transforming cancer research and leukemia treatment. Gleevec’s platform was the starting point for fifty other precision (targeted) therapies for various types of cancer.

Dr. Brian Druker, Director of the Knight Cancer Institute, was said to revolutionize cancer treatment with the first drug that targeted the molecular defect of cancer without harming healthy cells. His discovery, Gleevec®, turned ALL that was once fatal into a condition that could be controlled.

Time magazine featured Gleevec on its cover and Dr. Druker became a pioneer in precision medicine. Follow-up studies, including a study of 500 CML patients who take Gleevec daily, found that eighty-three percent were still alive at the ten-year mark. There were no new signs of safety risks. Gleevec patients could enjoy a life expectancy similar to that of the general public.

The Principles of Precision Medicine in Early Detection

Currently, Dr. Druker is focusing on the principles that govern precision medicine and early detection. A $1 billion philanthropic fund allows Dr. Druker and his team to work towards increasing cancer survival rates.

Emily’s Miracle

It was spring of 2012 when six-year-old Emily Whitehead entered the Children’s Hospital of Philadelphia as an ALL patient with only days to live. Emily had relapsed twice during two years of relentless chemotherapy treatments. She was too frail to undergo a stem cell transplant (SCT) that replaces immune system blood cells with a donor’s cells.

The doctors believed that they had a chance to save Emily’s life with an experimental therapy that had only been tried on six adults with cancers other than ALL. However two of the six patients exhibited solid remissions.

The therapy Emily received was problematic. Emily went into organ failure due to the engineered T cells causing an immune system overreaction. Her doctors attempted an emergency procedure. They used a new immune-moderating drug that saved her. The drug has since become an important part of the immunotherapy protocol.

Emily’s cancer was gone within eight days. Emily is now fourteen years old and is still cancer free. Her parents have set up a foundation to raise money for cancer research.

An article published in the American Society of Hematology declared that curing these children who have ALL is probably the “greatest success story” in cancer treatment history.

 


Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia four years ago. He was treated with a methylating agent While he was being treated with a hypomethylating agent, Rose researched investigational drugs being developed to treat relapsed/refractory AML.

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