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Matthew's New Marrow

Matthew's New Marrow

HLA and Bone Marrow Transplantation

Magazine article

By: Matt Clark

Date: May 10, 1976

Source: Newsweek.

About the Author: Based in New York, the magazine Newsweek is known for its coverage of global issues in politics, economics, medicine, science, and the arts. Founded by Thomas J. C. Martyn, former foreign editor of Time, the first News-Week, as it was then called, appeared on February 17, 1933, and cost ten cents. Today, Newsweek has a worldwide circulation of more than four million and has won many prestigious awards for its journalism. Matt Clark was born in Chicago, Illinois, in 1930. He was the medical editor of Newsweek when he wrote "Matthew's New Marrow." Clark has received a number of awards for science journalism including the Albert Lasker Medical Journalism Award (1964, 1967) and the American Heart Association's Howard W. Blakeslee Award (1965, 1968, 1973, 1983).

INTRODUCTION

Bone marrow transplant (BMT) involves the infusion of bone marrow into a person whose lymphocytes (white blood cells) are deficient or absent. The bone marrow is the source of these cells, and a transplant is potentially life-saving for people with leukemia, immune deficiency disorders, and other conditions arising from lymphocyte dysfunction.

Doctors knew the role of bone marrow in leukemia and anemia as long ago as the nineteenth century and tried giving bone marrow by mouth to affected patients. Such experiments failed, but research in animals suggested BMT could be a real therapeutic possibility. In 1958, French researcher Jean Dausset (1916–) made a major advance when he described human leukocyte antigens (HLAs), proteins on the surfaces of all cells in the body that allow the immune system to distinguish foreign from non-foreign cells. That is, because invading bacteria, viruses, and even organ transplants have different HLAs on their surfaces, the immune system will reject them. In the context of BMT, it is important that the HLAs of the recipient match the HLAs of the bone marrow donor. Dausset was awarded the 1980 Nobel Prize for Physiology or Medicine in recognition of this work.

Ideally, therefore, the donor should be an identical twin of the recipient. Since identical twins are genetically identical, they have the same HLAs. In 1956, Dr. E. Donnall Thomas (1920–) of Cooperstown, New York, performed the first successful BMT on a patient with leukemia, using an identical twin as donor. Along with Dr. Joseph E. Murray (1919–), Thomas went on to win the Nobel Prize for Physiology or Medicine in 1990 for work on organ and cell transplantation.

In 1968, the first bone marrow transplant for severe combined immune deficiency (SCID) was performed on a four-month-old boy at the University of Minnesota. SCID is a rare inherited disorder that leaves a child completely vulnerable to infection, since the patient's immune system lacks lymphocytes and cannot make antibodies against invading organisms. To survive, affected children must live in a sealed environment—hence the name "bubble boy" given to this young patient. The donor was the boy's sister; the extended family had already lost eleven children to SCID. The BMT was successful and the boy is now grown-up, fully employed, and a father himself.

However, only a minority of those who could benefit from BMT have an identical twin or a suitable sibling as donor. Doctors wanted to make BMT more widely available by finding unrelated donors with HLAs that matched those of the potential recipients. Matthew Ruffer's case, described here, is the first in which a non-related donor took part in a successful BMT. Matthew was found at birth to have SCID and the BMT was carried out at Memorial Sloan-Kettering Cancer Center in New York, using bone marrow from a donor in Sweden. Matthew had already lost a sister to SCID after doctors had tried a BMT using their father as a donor.

PRIMARY SOURCE

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SIGNIFICANCE

Matthew Ruffer's bone marrow transplant was far from simple. He received multiple infusions of bone marrow and, in fact, needed seven in all before his blood count became normal. He also suffered various complications, including graft-versus-host disease (GVH), where the transplanted bone marrow reacts against the host and produces potentially fatal responses, including liver failure. Matthew's eventually successful procedure opened the door to more widespread BMT, especially as doctors began to understand more of the HLA system—that three specific HLAs, i.e. HLA-A, HLA-B, and HLA-DR, were the most important in determining a match between donor and recipient. GVH continues to be an issue in BMT and is a very active area of research.

The next major development in bone marrow transplantation was the creation of a database of HLA-type volunteers who could act as donors. This was driven by researchers at the Fred Hutchinson Cancer Research Center, an early pioneer in BMT, who searched for a donor for a young girl with leukemia in 1979. The operation was successful, but she died later from a recurrence of her disease. Her family campaigned for the creation of HLA-typed databases of volunteers and these were established in several U.S. cities over the next few years. In 1984, the U.S. Congress passed the National Organ Transplant Act, which set the scene for the establishment of the National Bone Marrow Donor Program (NMDP). In 1987, the first donor was identified and gave two years of extra life to a girl with acute leukemia. By 1996, there were two million potential donors participating in the NMDP and 5,000 transplants had taken place. By then, peripheral and umbilical cord blood were also being used as sources of lymphocytes for transplant. The NMDP is now global and 40 percent of BMTs involve a U.S. patient receiving cells from an international donor or vice versa.

FURTHER RESOURCES

Books

Carrier, Ewa. 100 Q&A About Bone Marrow and Stem Cell Transplantation. Boston: Jones and Bartlett, 2003.

Web sites

Seattle Cancer Care Alliance. "What is a Bone Marrow Transplant." 〈http://www.seattlecca.org/patientsandfamilies/adultCare/transplant/WhatIsBoneMarrowTransplant.htm〉 (accessed November 5, 2005).

National Marrow Donor Program. "The History of Marrow and Blood Cell Transplants." 〈http://www.marrow.org/NMDP/history_of_transplants.html〉 (accessed November 5, 2005).

University of Minnesota Cancer Center. "Transplant Biology & Therapy. Historical Overview." 〈http://www.cancer.umn.edu/page/research/trsplant/bmthist.html〉 (accessed November 5, 2005).

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