Upping cell counts: on clinical trial.

Upping cell counts: On clinical trial

"Too little, too late' can be the unhappy ending of a patient's medical history if he or she has too few white blood cells. Normally, growth factors made by the body stimulate the adequate production of white cells like granulocytes and macrophages. But white-cell production, which is part of the immune system's arsenal against infection, often drops after exposure to anticancer drugs or to infectious agents like the AIDS virus. Researchers say that injecting more of a particular growth factor might "artificially' boost cell numbers and fight infection. Granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) are two such factors currently being tested.

Biotechnology, companies now can manufacture human GM-CSF and G-CSF in yeast or bacteria, and researchers have begun testing the usefulness of these two recombinant growth factors in various medical conditions, including AIDS (SN: 9/12/87, p.165). The factors might be used as, among other things, a supportive therapy for cancer patients undergoing chemotherapy or radiation. Current cancer treatments can suppress the bone marrow's production of needed cells, necessitating that physicians wait until cell numbers increase before beginning another cycle of treatment.

At the meeting, several groups reported on early clinical trials using one of the factors in cancer patients. At the Sloan-Kettering Cancer Center in New York City, 18 patients with a cancer called transitional-cell carcinoma were given G-CSF after a standard chemotherapy regimen that depletes cell numbers. Traditionally, 70 percent of patients receiving this chemotherapy have too few white cells to withstand the next cycle of chemotherapy, usually scheduled two weeks after the previous cycle, says Sloan-Kettering's Janice Gabrilove. All 18 patients treated with G-CSF, however, were able to receive chemotherapy on shcedule, and their white blood cell counts at the end of the first therapy cycle increased three-fold over those not receiving G-CSF. Other preliminary clinical trials of GM-CSF suggest that it also may be useful in cancer patients.

Results of an unusual "clinical trial' involving GM-CSF agree with the promising findings of more formal studies, says Robert P. Gale of the University of California at Los Angeles. In September, two men in Goiania, Brazil, took a lump of cesium-137 from an abandoned radiation therapy facility. Intrigued by the radioactive material's blue glow, several people broke open the cesium and showed it to friends, some of whom ate part of the grainy material. By the time health officials realized what had happened, about 250 individuals had been exposed. Isolating the most seriously ill became "both a scientific and a political nightmare,' says Gale, one of an international team of scientists who treated the patients. Because radiation can kill bone marrow, infection is a major concern following such an accident. Gale gave GM-CSF to eight patients; he reports that seven responded to GM-CSF with increased cell counts. Four of those patients later died, two from infections present before the GM-CSF treatments.

How much and when GM-CSF should be given after a radiation accident remains unclear, Gale says. He adds that it is also unclear how often a patient will need GM-CSF infusions.

Other studies of GM-CSF in custom-designed mice have also indicated that excessive stimulation of cell production could cause problems (SN: 12/12/87, p.375), and some researchers question whether overproduction could lead to leukemia. But data from the various human clinical studies indicate that toxicity is "uniformly mild,' says Joseph H. Antin of Brigham and Women's Hospital in Boston. Thus far, he and other scientists have seen no evidence that using the factors could lead to leukemia. But, Antin says, "the range of patients likely to benefit from this therapy remains to be established.'