New transplant techniques

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Israeli doctors save lives using bone marrow technique

WENDY ELLIMANSpecial to Jewish News

Dr. Tsvee Lapidot of the Weizmann Institute of Science.

Photo courtesy of Wezmann Institue of ScienceNew York lawyer was out West camping, and he "couldn't shake a draggy kind of feeling." He went to a hospital emergency room in a small Colorado town, expecting to get antibiotics. Instead, he got the news that he had chronic lymphatic leukemia."I was 36 years old. I had a wife, a daughter and a baby on the way - and I had terminal cancer," he says.He spent the next five years in and out of American hospitals, but his leukemia was stubbornly resistant, and he deteriorated steadily."My only hope was a bone marrow transplant," says , "but no one would do it because U.S. transplantation protocols are chemotherapy-based, and chemo didn't work for me."In late 1997, with time running out (his doctor had given him six months to live), came across an article in Hadassah Magazine about a bone marrow transplantation technique that relied less on chemotherapy. The following spring, he was hospitalized at the Hadassah-Hebrew University Medical Center in Jerusalem.This past September, 18 months after receiving an infusion of his sister's bone marrow, flew back to New York. He is still recovering from the treatment, but his incurable leukemia is cured."According to my U.S. doctors," he says, "the Israeli program was the only one that could have done this."Israel has been a leader in bone marrow transplantation since the technique was first developed in the 1970s. 's physician at Hadassah, Shimon Slavin, head of Israel's National Bone Marrow Transplant Center, was a key figure in developing the early protocols of the late 1970s and early 1980s, which vastly improved the outcome for patients given donated bone marrow. Among them was a way of treating donor bone marrow before transplantation, so that the patient's body will accept it. These Israeli techniques, which are now standard practice in centers around the world, were a vital stepping-stone to making bone marrow transplantation a safer treatment for patients with otherwise incurable disease.The theory of bone marrow transplantation, when first developed, was destruction of the fast-multiplying malignant cells by lethal doses of chemotherapy, followed by an infusion of healthy donated bone marrow, containing stem-cells, the body's most primitive and immature form of cell life.The stem-cells migrate into the bone marrow where they start differentiating into healthy new cells of all types. While stem-cell transplantation saves lives, it remains an imperfect and last-resort procedure. was hospitalized eight times in the 18 months after transplant, and he spent nine of those months fighting off acute graft-vs.-host disease, even though his sister was a perfectly matched donor.Matched donors, however, can't always be found, and the transplanted stem-cells, however well-matched, themselves present difficulties: they survive only a few days after transplant, and only a quarter of them ever reach the bone marrow where they can help the patient.This situation, however, is changing with Israeli research. Lapidot's team stimulated stem-cells in a test-tube to express the receptor, thus turning them into migrating cells and increasing the percentage of those reaching the bone marrow from 25 percent to more than 90 percent.Once in the bone marrow, stem-cells mature and differentiate into the different kinds of cells the body needs. A small number, however, signaled by a certain molecule, survive and renew themselves without differentiating.Undifferentiated cells like these can survive longer in the test tube, and their number can be substantially increased, thus boosting the success of bone marrow transplantation, and perhaps contributing to gene therapy research as well.That all-important signaling molecule was recently identified at Weizmann by molecular geneticists Professor Michel Revel and Dr. Judith Chebath.They developed it in a chimera recombinant form and infused the cells it signaled into mice, where they successfully repopulated the animals with healthy differentiated cells.Increasing the number of healthy stem-cells available for transplant has also been the focus of a team at the Technion - Israel Institute of Technology in Haifa, working jointly with the University of Wisconsin at Madison. Under Professor ph Itskovitz-Eldor, they have succeeded in growing human embryo stem-cells in a laboratory dish, the first time human cells have ever been cultivated in this way. Injected into mice, these cells differentiated and transformed into clusters of muscle, cartilage, bone, nerve and intestinal cells.The hope now is to establish huge banks of frozen stem-cells, and use them for repairing not only diseased blood, but also brain, heart and liver tissue.However many stem-cells there are, the problem of finding matched bone marrow donors remains, with only six in 10 patients finding a perfect match, Here, too, however, a solution seems to be close. Professor Yair Reisner led a Weizmann research team, in collaboration with Perugia University in Italy, in an approach which uses very large doses of donor marrow to overwhelm the recipient's rejection mechanism. Their method seems to eliminate the graft failure and aft-vs.-host disease that plague mismatched transplants. The method is used in several hospitals in Israel, the United States, Germany and Austria.While research in Israel and elsewhere is making stem-cell therapy safer and more effective, one investigator, at least, believes the ultimate answers may lie along a parallel track. He believes that bone marrow transplant patients are cured not by the massive chemotherapy, but by the healthy immune system transplanted along with the donor stem-cells."We know that blood and other cancers begin from a single affected cell," says Hadassah's Slavin, "and we know too that even the most massive chemo and radiation therapy fail to destroy every malignant cell. Yet stem-cell transplants, especially when the cells come from donors, cure cancer patients. This indicates that another process is at work."That other process crystallized for Slavin when he treated a 2-year-old with fatal lymphoblastic leukemia. After a failed bone marrow transplant left the child with no hope, Slavin began treating him with weekly injections of cells from the boy's older sister. The child's tumors melted away, and within six weeks, he was free of disease. He recently celebrated his bar mitzvah.What Slavin learned from this landmark case, and what he has since confirmed in other patients, in research supported by the multinational medical technology giant, Baxter International, Inc., is that normal blood cells from a healthy donor fight off cancer cells far more effectively than any conventional cancer treatment."This thinking opens a huge area of medicine," he says. "If donor cells will recognize and attack a disease that a patient's immune system fails to recognize, this approach will work not only for cancers and organ transplants, but also for autoimmune and infectious diseases.''We can lay down our chemical arms, he says, and take up biological weapons instead - and patients like , who resist chemical attack, can be saved. Elliman is a free-lance writer living in Israel. This story is part of a series on medical, scientific and technological developments in Israel, being provided to Jewish Telegraphic Agency newspaper clients by Hadassah, the Women's Zionist Organization of America; American Society for Technion; American Committee for the Weizmann Institute of Science; and American Associates of Ben-Gurion University of the Negev.=