A bone marrow transplant often is the last hope for survival for those living with blood disorders such as AIDS, sickle cell anemia, and thalassemia, but the procedure requires patients to endure a grueling and sometimes lethal regimen of chemotherapy and radiation to first knock out the bad stem cells.

Now, Harvard scientists in collaboration with researchers at three renown Boston hospitals have developed a safer, non-toxic transplant procedure that’s as effective as chemotherapy and radiation in targeting blood stem cells.

The new procedure uses antibodies rather than chemo and radiation. In tests on mice, results showed that the treatment removed more than 98% of blood stem cells.

Harvard Stem Cell Institute scientists Rahul Palchaudhuri, left, and Dr. David Scadden. Their treatment uses antibodies, rather than conventional toxic chemicals and radiation, to prepare for bone marrow transplants. Source: HSCI by BD ColenSpecifically, researchers armed CD45-targeting antibodies with a payload that destroys only existing blood cells, in contrast to conventional treatments.

“Antibodies are remarkably specific in what they target,” said researcher Rahul Palchaudhuri, a chemist with a background in cancer research. “We can direct them to CD45, a cell marker which is exclusively expressed in the blood system. That way we avoid toxicities to non-blood tissues.”

Unlike chemotherapy and radiation, which indiscriminately damage healthy cells and tissues, the CD45-targeting antibodies leave unharmed the thymus and bone marrow, which are critical to the formation of T cells and innate immune cells. Animals receiving the antibody treatment were able to withstand infection that was lethal to mice treated with radiation.

Infections after transplant are common and about one in ten patients do not survive transplantation following standard treatments. Those who do may suffer a variety of maladies from stunted growth and intellectual development to infertility and damaged DNA. Because of these outcomes, many families and doctors shrink from transplant options, especially when treating children.

In the animal study, mice suffering from sickle cell anemia were successfully transplanted using the antibody method and cured of their anemia. Should the same hold true for humans, researchers say that what amounts to months of recovery in a hospital may be replaced by an outpatient procedure; and a failed transplant would not be fatal.

Scientists are now trying to identify antibodies that would be effective in humans, and a company has been formed to advance the research and determine which models are most useful in a preclinical setting.