Engraftment

Transplanted Blood Stem Cells Engraftment
For Aplastic Anemia

Engraftment is the process in which transplanted blood stem cells find their way to the patient's bone marrow, seat themselves, and begin producing blood cells. The actual engraftment occurs when the transplanted cells take up residency in the patient's bone marrow. The initial signs of engraftment, discussed below, are cause for great celebration; they are the first indicators that the transplant has been successfully accepted by the patient's body.

Signs and indications of engraftment

One of the most anxious periods during a bone marrow transplant is the waiting for any visible indication of engraftment. Those signs don't arrive overnight, but when they do, there is a feeling of total elation.

first indicator of engraftment

White blood cells have very short life cycles; they typically live for about 72 hours in a person's body. They are a more rapidly produced cell, and the first of the blood cells to come back after a transplant and indicate engraftment.

During the conditioning treatment prior to transplant, chemotherapy depletes the patient's bloodstream of active cells including white blood cells (WBC, also referred to as WCC or WCT) are so depleted they near zero (discussed below). The BMT unit nurses may record the white count for the patient as 100 or 10.

Since white blood cells are the first cells to come back after a bone marrow transplant, they will be the first indicator of engraftment. Engraftment at this stage is considered to be 'successful' when the white blood cell count rises.

initial white counts increase

Initially, the white blood cell count will rise slowly, typically from zero (or 10 or 100, depending upon how the counts are recorded) to 200. Within days, those counts will typically double, and continue to double until they reach near-normal levels. In most situations, the near-normal levels are not met until the patient is released from the hospital.

platelets rise next

The second type of blood cells to show signs of a successful engraftment are the platelets. They rise differently than do the white blood cells; nevertheless, they will increase, although seldom doubling their production like the white cells.

Your medical team will provide you with information about the thresholds for transfusions. Since white cells are seldom transfused due to their very short life cycles, the thresholds weren't discussed above.

An increase in platelets is necessary to maintain the patient's health and prevent medical complications such as internal bleeding. Because it takes time for the transplanted blood stem cells to begin producing a sufficient quantity of all blood cells, transfusions of platelets are common post-transplant.

Chimerism Tests

Chimerism tests are 40% accurate at best. They were originally developed to be used on thoroughbred horses to determine if they were thoroughbreds. When the first BMT's were conducted (1956), they reached out for the chimerism test (developed in 1951) to use it to determine if the cells were mixed or singular. The chimerism test worked fine to tell racehorse owners and buyers if there was even a slight hint of non-thoroughbred blood in the horse, but THEY ARE NOT reliable in determining the level of engraftment and are used only as one tool in measuring engraftment. The better tool is to put cells under a microscope and analyze them.

Refractory

It is not uncommon for a post-transplant patient to become refractory, that is resistant to transfused blood that does not match the patient's DNA. When a patient is refractory, transfusions become completely or nearly useless; the transfused cells are destroyed nearly as fast as they are infused into the patient resulting in no change in the cell count, or destroyed shortly thereafter and seen by very slight increases in cell counts.

Typically, post-transplant infusions of cells will cause a "good bump up" in the counts. If that is not the case, then the next question is whether the patient is refractory.

The typical medical treatment for a refractory patient is to transfuse with HLA-matched cells. HLA-matched cells are cells from a person whose cell proteins closely match the patient's. In almost all situations, transfusions with HLA-matched cells will result in successful retention of the transfused cells in the patient's bloodstream.

fluctuations of blood cell counts

The waiting period until the white cells show any increase can be nerve-racking; everyone is waiting for signs of engraftment. Likewise, fluctuations in counts can cause alarm because the first question is often if the engraftment is not taking as was previously thought to be the case.

Rest reassured, fluctuations in blood cell counts are often times just a normal process of the tests, normal for the blood to produce, and not a cause for alarm.

Side note on tests: while most blood cell count results are derived from a machine process, the machine may be unable to accurately detect the very few numbers of cells in a post-transplant patient, which will require that the counts be determined manually. The manual process leaves room for error, one tech may count cells differently than another, or derive a different result due to some other measure. The measurements are preformed on a small number of cells in a small sample of blood; the math alone can produce a different result.

what happened to the blood cells?

During the conditioning process prior to a transplant of blood stem cells, the patient is given a regime of drugs. Which drugs are given will depend upon the decisions of the Bone Marrow Transplant team and the patient's doctor, as not all transplant centers utilize the same drug regimes.

In Victoria's case, her conditioning process included chemotherapy and ATG treatments. There are several types of chemotherapy drugs; she was given cyclophosphamide, which is marketed under the brand name, "Cytoxan." Her immune system was suppressed by the use of anti-thymocyte globulin, which is commonly called "ATG."