As chemotherapy dosages rise, the body system that gives out long before any other is the bone marrow, where blood cells are made. The red cells and platelets can be replaced somewhat with blood transfusions, but what cannot be transfused are the white cells, which protect the body from infection. Oncologists can now give relatively high dose chemotherapy and then add granulocyte colony stimulating factors (G-CSF, Neupogen) to stimulate the bone marrow to put more white cells into the circulation quickly. But G-CSF is not enough to rescue the bone marrow from massive (and theoretically curative) doses of chemotherapy for women who either have distant metastasis or are at very high risk for it.

That is where the autologous bone marrow transplant (ABMT) and the peripheral stem (or progenitor) cell transplant come in. These processes keep the woman's bone marrow or stem cells in reserve for a "rescue." This means the oncologist can administer huge doses of chemotherapy, which have the side effect of destroying the bone marrow, knowing they can replace these vital cells when they need to. While transplants are becoming somewhat easier and less expensive, they are still grueling, costly, and potentially dangerous.

Nor do they offer a sure or even a likely cure for the woman with metastatic breast cancer, although many women have complete remissions (no sign of cancer) and a small percentage continue to be healthy five years later. The results are much better in women without known distant metastasis but at very high risk for it because of many positive lymph nodes or a very aggressive tumor, most of whom are doing well five years posttransplant. Many women with metastasis or at high risk for it see very high dose chemotherapy followed by bone marrow or stem cell support as their only real chance for survival; a few women with advanced ovarian cancer have also received transplants.

The first step involves several cycles of conventional doses of chemotherapy to see whether the cancer is sensitive to the drugs. This is the time to assess whether any lesser treatments might work, such as relatively high dose conventional chemotherapy followed by G-CSF.

If a woman and her oncologist decide to use the highest dose chemotherapy, the rescue agent is either bone marrow or special stem blood cells from the woman's own body, harvested and then stored for later use. The procedure is autologous because the transplant comes from the woman's own body. This avoids problems of donor mismatch and possible transplant rejection, which can happen when the transplant is from another person. Because the bone marrow comes from a woman with cancer, however, it could have some stray cancer cells in it, so any marrow cells are checked carefully.

For a bone marrow harvest, the woman is put to sleep with a general anesthetic. Needles are inserted into large bones, typically the pelvic bones, and one to two pints of the marrow -- a fluid -- is withdrawn into syringes. Because many needle insertions are necessary, the harvest area can ache for several days. The marrow is then specially prepared so that it can be stored until needed.

Instead of using bone marrow, the oncologist may use stem, or progenitor, cells, "baby" white blood cells that could mature into one of several types of white blood cell but are not "committed" yet. Stem cells are usually found in the bone marrow, but G-CSF can mobilize large numbers of them out of the marrow and into the peripheral circulation, the bloodstream. These work well to repopulate the bone marrow, and using stem cells lessens the problem of possible contamination with cancer cells.

Pheresis, the process of obtaining stem cells, is like a long and complicated blood donation. The blood is drawn off into a special machine that separates out the stem cells and recycles the rest of the blood back into the woman. The process is repeated many times over two to four hours to gather a good supply of stem cells.

As the woman learns about and prepares for the transplant process, the transplant team learns about her, including her psychological readiness for a stressful procedure. What happens next depends on the institution and the protocol -- and has changed dramatically in many hospitals over the last few years.

Typically, the woman receives her very high dose chemotherapy, which may cause severe symptoms, such as vomiting, mouth sores, and fatigue, some of which can be treated with medication. She receives G-CSF or GM-CSF (another white blood cell stimulator), red blood cell and platelet transfusions, and often antibiotics. The chemotherapy and other fluids are given through a long-term catheter tube threaded through the skin into a large vein in her chest.

Meanwhile, her blood counts are monitored for the dramatic drop in white blood cells several days after chemotherapy which indicates that it is time for rescue by the stored stem cells or bone marrow. At that point, the stem cells or marrow are transfused back into the woman like any other blood transfusion. This is probably the most undramatic part of the transplant procedure, although the woman will require careful monitoring for a brief time, as with any transfusion. (With stem cell transplants, women tend to react with nausea and vomiting to the strong odor of the solution that chills and protects the cells.)

It takes several days to two or more weeks for the transplant to "take" and to start producing enough blood cells to protect her. Until this happens, the woman is extremely vulnerable to infection -- but then her blood count will show an occasional white blood cell, and then a few more, and then a wonderful surge as her new bone marrow becomes functional. She can stop thinking of herself as nothing but a profoundly interesting blood count, stop wondering why she ever got into this.

A few years ago everyone undergoing a transplant spent a month or more in a special isolation "bubble" room with all care given through heavy plastic walls. Now, although at some institutions women still stay in the hospital throughout the transplant procedure, more and more often women are going through most of the procedure as outpatients. They may come to the hospital or clinic during the day for chemotherapy, transfusions, and other medications and then go home or to a nearby apartment or hotel at night; sometimes they even receive much of the treatment at "home" from a specially trained visiting nurse, with medical backup on call 24 hours a day for questions or complications.

Shortening hospital stays cuts the transplant costs in half, without sacrificing safety. How often people with low white blood cell counts develop infections (and how serious the infections are) depends less on how low the WBC count falls than on how long it stays low. This means that G-CSF and GM-CSF, which shorten and lessen the WBC dip, have been key players in making transplants safer. The "bubble" rooms have almost disappeared as transplant teams realized that the infection threat comes more from the patient's own normal bacteria than from any outside source.

Getting a transplant is far from easy, but powerful antibiotics, a red blood cell stimulating factor, and new methods of controlling distressing symptoms after very high dose chemotherapy have made it more tolerable. There is still a possibility of death from the treatment itself, although that risk decreases every year.

To increase success rates, transplant researchers experiment with chemotherapy drugs, combinations, dosages, and timing. For instance, serial transplants are a potential technique, with high-dose chemotherapy followed by stem cell transplant, and the whole process repeated another time or two. Researchers are using new technology to clear ("purge") the bone marrow or stem cells of cancer cells so that cancer does not reenter the body along with the transplant. Of course, any effective biological therapy would be most welcome.

Some oncologists consider ABMT state-of-the-art treatment for breast cancer while others believe it is both unproven for this disease and unnecessary for most women. Many insurance companies balk at paying for what they consider experimental therapy, but some have been forced by the courts to pay for the procedure. In fact, the National Cancer Institute is currently sponsoring several studies comparing the results of high-dose chemotherapy followed by transplant with standard-dose chemotherapy in patients with advanced breast cancer or at high risk to find out whether it really makes a difference.

The woman who is interested in stem cell or bone marrow transplants can get information from her doctor, a transplant center, NCI's Cancer Information Service, and by a literature search. Centers that perform many transplants in breast cancer patients tend to have -- by far -- the best safety and long-term survival records. It also helps if she can talk to at least one woman who is a veteran of the procedure.