What is Bone Marrow Transplant?
As we explained above, the main limitation to giving higher dose chemotherapy or moderate dose Total Body Irradiation to kill cancer is Bone Marrow Suppression. Patients who get chemotherapy often have a significant LOWERING of their blood counts; the lowest counts (called the “nadir” ) are usually about 18 days after each “cycle” is given. Then we (hopefully) expect a brisk recovery over the next 7 days, so that by 30 days after administration of a chemotherapy cycle blood counts should return to [near] normal. This is why conventional chemotherapy is usually given in cycles ONE MONTH apart, to allow for Bone Marrow Recovery. Sometimes, the marrow does not recover well, and this explains why oncologists are so adamant about getting a “Complete Blood Count” (“CBC”) prior to giving more chemotherapy. We are particularly interested in whether the Red Blood Cell count is at least 10.0 grams of hemoglobin per deciliter, the Platelet Count is above 100,000 and the “Absolute Neutrophil Count” or “ANC”– (a type of White Blood Cell) is over 1,000. If not, further chemotherapy will commonly be suspended until the “counts”recover. While the fast majority of patients will have a complete bone marrow recovery with conventional doses of modern chemotherapy, some will have a “delayed recovery” lasting month or even years– a consequence of killing some Stem Cells in the marrow. Very rarely, some patients will apparently have all their Stem Cells killed and go on to total “aplasia” — no new blood cells being formed whatsover. This will obviously be fatal if the bone marrow cannot be replaced (“reconstituted”) using someone else’s(“donor”) bone marrow.
It became apparent, in the 1970′s, that we could give more chemotherapy, and possibly cure the patient, if only we could get around the problem of bone marrow damage. We could also give higher doses of radiation to the whole body– about twice as much (12 Gray versus 5 Gray) if we could replace the bone marrow. It had been known for about 20 years that some patients could survive bone marrow failure from other causes (i.e. a drug side effect or virus) if they got a “Transplant” with another person’s healthy marrow. However, in the early studies, most patients did NOT do well getting someone else’s marrow (unless they were an identical twin) since it did not match the marrow they had lost . As transplant of other organs (i.e. kidneys, livers) developed, new drugs became available to “dampen” the immune response against them, called“rejection” . This re-awoke interest in being able to give a cancer patient very“high dose chemotherapy” — enough to actually kill their cancer, but also enough to kill all their Stem Cells. If the patient’s destroyed (“ablated”) marrow could be replaced by someone else’s after the chemotherapy, it might take(“engraft”) and re-establish new blood cell formation. This was especially appropriate for cancers in which we really wanted to destroy the patient’s native marrow anyway– that is when it was contaminated with cancer cells! Thus the first attempts with “High Dose Chemotherapy Followed by Bone Marrow Transplant for Rescue” were done on patients with leukemias, lymphomas and myelomas which dwelt in the bone marrow. Although some patients were cured (~20%) in the 1970′s and 80′s, the main problem for getting higher cure rates and extending the use of Bone Marrow Transplant to other cancers was two-fold. The first problems was that some cancer cells might persist in the body even after high dose chemotherapy– especially for cancers that had already been exposed to chemotherapy and developed a resistance to it. The second was a problem of“rejecting” the transplant, called “Graft Versus Host” (“GVH”) Disease . This was a unique form of rejection, since the patient’s native immune system had been destroyed by ablating their bone marrow. Instead of their body rejecting the transplanted bone marrow, in Graft Versus Host Disease THE NEW MARROW REJECTS THE BODY IT WAS TRANSPLANTED INTO! Every cell in the body has particular protein markers(“antigens”) on its surface to identify it as a member of that unique body, and not someone else’s body or an animal or vegetable. This is what normally stimulates to immune system to recognize and destroy foreign tissue. With Bone Marrow Transplant from another Donor, the patient’s native immune system is dead– they have lost “immunocompetence” . Instead, the immune capability resides in the Transplanted Marrow, which identifies THE BODY as foreign and seeks to destroy it. As will be discussed, newer drugs to“immunosuppress” the transplanted marrow can usually alleviate Graft Versus Host Disease, and allow patients who would previously have died of it to survive.
Besides giving higher doses of chemotherapy, we could also give higher doses of “systemic” (whole body)radiation if we could get around the“dose limiting toxicity” — that is bone marrow destruction. With particular cancers (i.e. lymphoma, myeloma) some cancer cells often will spread to areas where there is poor blood supply or protective membranes exclude chemotherapy. These areas (i.e. brain, spinal cord, skin, testicles) are called “sanctuary sites” . Putting enough drug into the bloodstream to properly diffuse into these sanctuary sites would cause other serious toxicities (i.e. to lung, liver and heart) which still limit the amount of chemotherapy that can be safely given– even with a Bone Marrow Transplant. Gamma Radiation(“photons”) of high energy (i.e. over 10 Megavolts) travels right through the body, killing cancer cells in all the sanctuary sites. Thus, givingTotal Body Irradiation (“TBI”) complements high dose chemotherapy; both kill cancer cells and destroy the bone marrow (which may itself be infested with cancer). If we successfully replace the Bone Marrow Stem Cells, and they start growing (“engraft”) on the bony spicules inside the marrow cavities of bone, they will produce new blood cells. We will then have been able to give higher doses of cancer cell killing(“cytotoxic”) therapy– and have a better chance at curing the patient . Importantly, to “Transplant” Bone Marrow or the Stem Cells which reconsitute it, we DO NOT NEED TO STICK THE NEW MARROW INTO THE PATIENT’s (recipient’s) BONES. Instead, we need only inject it into an an arm vein and the Stem Cells WILL FIND THEIR OWN WAY BACK INTO THE BONES TO RE-ESTABLISH THEMSELVES . Thus “High Dose Chemotherapy” (and possibly Total Body Irradiation ) followed by a “rescue” with“Bone Marrow Transplant” has become the“Latest Effective Therapy” to cure a variety of cancers.
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Your blog is so informative … keep up the good work!!!!
Nice post! GA is also my biggest earning. However, it’s not a much.
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