Transplant Information

Tomorrow I will write of tales of Ethan and the last few days. Today I can only manage to write about TRANSPLANT DETAILS, and our meeting today with the transplant doc…

We met with Dr. Jennifer Clark for the first time today. Dr. Clark is the Director of the Stem Cell Transplantation Unit and will be Ethan’s primary doctor going forward. She’s very bright, has so much knowledge, was very informative about the entire process Ethan would be entering very shortly, and answered almost all 40 of my prepared questions without me even asking them. Yancy and I were very impressed to say the least. In this post I will try to inform those that are interested and answer any questions you may have, I will layout the basics of a bone marrow transplant, and how it will pertain to Ethan, and Eliot:

What is a bone marrow transplantation?

Bone marrow transplantation (BMT) is a special therapy for patients with cancer or other diseases which affect the bone marrow. A bone marrow transplant involves taking cells that are normally found in the bone marrow (stem cells), filtering those cells, and giving them back either to the patient or to another person. The goal of BMT is to transfuse healthy bone marrow cells into a person after their own unhealthy bone marrow has been eliminated.

Why does Ethan need a bone marrow transplant?

Ethan is receiving a bone marrow transplant for two primary reasons: 1) His type of leukemia, AML, is harder to treat, and when there is a sibling that matches an AML patient, a bone marrow transplant is preferable, than to continue with chemotherapy alone; 2) His leukemia cells have abnormal chromosomes, there is only 1 #7 chromosome, there should be two of these. This condition, called Monosomy 7, puts Ethan in a high risk category. It is preferred that AML kids in a high risk category have a bone marrow transplant. These two factors make Ethan a prime candidate for a bone marrow transplant: Matched sibling donor, and Monosomy 7 (high risk).

What is bone marrow?

The bone marrow is a soft, spongy tissue found inside the bones. The bone marrow in the hips, breast bone, spine, ribs, and skull contain cells that produce the body’s blood cells. The bone marrow is responsible for the development and storage of about 95 percent of the body’s blood cells. The three main types of blood cells produced in the bone marrow include:

red blood cells (erythrocytes) – carry oxygen to the tissues in the body.
white blood cells (leukocytes) – help fight infections and to aid in the immune system
platelets – help with blood clotting.

What are stem cells?

Every type of blood cell in the bone marrow begins as a stem cell. Stem cells are immature cells that are able to produce other blood cells that mature and function as needed.
Stem cells are the most important cells needed in a bone marrow transplant. Stem cells, when transplanted, find their way to the recipient’s marrow and begin to differentiate and produce all types of blood cells that are needed by the body.

Why is a bone marrow transplant needed?

The goal of a bone marrow transplant is to cure many diseases and types of cancer. When a child’s bone marrow has been damaged or destroyed due to a disease or intense treatments of radiation or chemotherapy for cancer, a marrow transplant may be needed. A bone marrow transplant can be used to replace diseased, non-functioning bone marrow with healthy functioning bone marrow (for conditions such as leukemia).

Bone marrow transplantation has risks involved, some of which are life threatening. The risks and benefits must be weighed in a thorough discussion with the bone marrow transplant team prior to the procedure.

What are the different types of bone marrow transplants?

There are different types of bone marrow transplants depending on who the donor is. Ethan is receiving an allogeneic bone marrow transplant: The donor shares the same genetic type as the child. Stem cells are taken either by bone marrow harvest or apheresis (peripheral blood stem cells) from a genetically-matched donor, usually a brother or sister.

Once a match for a child needing a bone marrow transplant is found, then stem cells will be collected either by a bone marrow harvest (collection of stem cells with a needle placed into the soft center of the bone marrow).

How are a donor and recipient matched?

Matching involves typing human leukocyte antigen (HLA) tissue. The antigens on the surface of these special white blood cells determine the genetic make-up of a person’s immune system. There are at least 100 HLA antigens, however, it is believed that there are a few major antigens that determine whether a donor and recipient match. Medical research is still investigating the role all antigens play in the process of a bone marrow transplant. The more antigens that match, the better the engraftment of donated marrow. Engraftment of the stem cells occurs when the donated cells make their way to the marrow and begin reproducing new blood cells. Eliot and Ethan appear to be a “perfect” match, as far as can be tested.

How are the stem cells collected?

A bone marrow transplant is done by transferring stem cells from one person to another. Stem cells can either be collected from the circulating cells in the blood (the peripheral system) or from the bone marrow.

Bone marrow harvesting involves collecting stem cells with a needle placed into the soft center of the bone, the marrow. Most sites used for bone marrow harvesting are located in the hip bones and the sternum. The procedure takes place in the operating room. The donor will be anesthetized during the harvest and will not feel the needle. Eliot’s bone marrow will be harvested from his hip bones. While they will only puncture the skin in two different spots, they will penetrate the bone 50 times, to do 50 draws of bone marrow. In recovery, the donor may experience some pain in the areas where the needle was inserted.

The bone marrow transplant procedure:

The preparations for a bone marrow transplant vary depending on the type of transplant. Ethan’s will include the following preparations:

High doses of chemotherapy and/or radiation are included in the preparations. This intense therapy is required to effectively treat the malignancy and make room in the bone marrow for the new cells to grow. This therapy is often called ablative, or myeloablative, because of the effect on the bone marrow. The bone marrow produces all the blood cells in our body. Ablative therapy prevents this process of cell production and the marrow becomes empty. An empty marrow is needed to make room for the new stem cells to grow and establish a new production system.

After 2 days of chemotherapy and 4 days of radiation, twice a day, the marrow transplant is given through Ethan’s central venous catheter into the bloodstream. It is not a surgical procedure to place the marrow into the bone, but is similar to receiving a blood transfusion. The stem cells find their way into the bone marrow and begin reproducing and establishing new, healthy blood cells.

Supportive care is given to prevent and treat infections, side effects of treatments, and complications. This includes frequent blood tests, close monitoring of vital signs, strict measurement of input and output, weighing Ethan daily (or twice daily), and providing a protected and sterile environment.

The days before transplant are counted as minus days. The day of transplant is considered day zero. Engraftment and recovery following the transplant are counted as plus days. For example, our tentative plan is that Ethan will enter the hospital on day -7 (Friday, July 6, 2007) for preparative regimen. (There is a strong possibility he could be home for a few days prior to going to transplant.) Day -6 and Day -5 (Saturday, July 7 and Sunday, July 8 ) will be chemo days. Days -4, -3, -2 and -1 (Monday through Thursday) will be radiation days. The day of transplant is usually numbered as day 0, potentially Friday, July 13 (let’s ignore that date, shall we?). Days +1, +2, etc. will follow. There are specific events, complications, and risks associated with each day before, during, and after transplant. The days are numbered to help the child and family understand where they are in terms of risks and discharge planning.

After infusion, Ethan will spend several weeks in the hospital, be very susceptible to infection, have blood transfusions, be confined to a sterile environment, take multiple antibiotics and other medications, be given medication to prevent graft-versus-host disease (if the transplant was allogeneic). The transplanted new cells (the graft), tend to attack the child’s tissues (the host), even though the donor is a relative, such as a brother, sister, or parent. He will undergo continual laboratory testing, experience nausea, vomiting, diarrhea, mouth sores, and extreme weakness.

When does engraftment occur?

Engraftment of the stem cells occurs when the donated cells make their way to the marrow and begin reproducing new blood cells. Depending on the type of transplant and the disease being treated, engraftment usually occurs around day +15 or +30. Blood counts will be performed frequently during the days following transplant to evaluate initiation and progress of engraftment. Platelets are generally the last blood cell to recover.
Engraftment can be delayed because of infection, medications, low donated stem cell count, or graft failure. Although the new bone marrow may begin making cells in the first 30 days following transplant, it may take months, even years, for the entire immune system to fully recover.

What complications and side effects may occur following BMT?
The following are complications that may occur with a bone marrow transplantation. However, each child may experience symptoms differently. Complications may vary depending on the following:

type of marrow transplant
type of disease requiring transplant
preparative regimen (excellent)
age and overall health of the recipient (excellent)
variance of tissue matching between donor and recipient (Eliot and Ethan are a perfect match)
presence of severe complications

Possible complications may include the following. These complications may also occur alone, or in combination:

infections – Infections are likely in the child with severe bone marrow suppression. Bacterial infections are the most common. Viral and fungal infections can be life threatening. Any infection can cause an extended hospital stay, prevent or delay engraftment, and/or cause permanent organ damage. Antibiotics, anti-fungal medications, and anti-viral medications are often given to prevent serious infection in the immuno-suppressed child. Preventative measures for common sources of infection are also a part of transplant. This may include any, or all, of the following:
specially filtered rooms
diet restrictions
isolation requirements
restriction of visitors
strict hygiene regimen
frequent linen changes
blood tests are performed to prevent, detect, and treat infections. Often, multiple antibiotics are started if an infection is suspected.

low platelets and low red blood cells

Pain – Pain related to mouth sores and gastrointestinal (GI) irritation is common. High doses of chemotherapy and radiation can cause severe mucositis (inflammation of the mouth and GI tract). Without the normal immune system functioning, your child is unable to heal these irritations quickly. Often, pain medication is required. Mouth care is needed to prevent infection and injury when mucositis is expected. Diarrhea, nausea, and vomiting may occur with chemotherapy, radiation, and/or GI irritation. Calories and proteins may be given through an intravenous (IV) line until your child is able to eat again and the diarrhea has resolved.

Fluid overload – Fluid overload is a complication that can lead to pneumonia, liver damage, and high blood pressure. The primary reason for fluid overload is because the kidneys cannot keep up with the large amount of fluid being given in the form of medications, intravenous (IV) and nutrition, and blood products. The kidneys may also be damaged from disease, infection, chemotherapy, radiation, or antibiotics. During transplant and recovery, Ethan will be assessed for signs and symptoms of fluid overload. He may be weighed at least daily, often twice or three times daily, and blood chemistries and input and output will be measured frequently. Medications that help kidney function and elimination of excess fluid may be given.

Respiratory distress – Respiratory status is an important function that may be compromised during transplant. Infection, inflammation of the airway, fluid overload, graft-versus-host disease, and bleeding are all potential life-threatening complications that may occur in the lungs and pulmonary system.

Organ damage – The liver and heart are important organs that may be damaged during the transplantation process. Temporary or permanent damage to the liver and heart may be caused by infection, graft-versus-host disease, high doses of chemotherapy and radiation, or fluid overload. Close monitoring of Ethan’s blood work and vital signs is important in minimizing and detecting any organ damage that has occurred.

Graft failure is a potential complication. Graft failure may occur as a result of infection, recurrent disease, or if the stem cell count of the donated marrow was insufficient to cause engraftment. Graft failure may be treated with an additional marrow transplant if a source is available.

Graft-versus-host disease – GVHD can be a serious and life-threatening complication of a bone marrow transplant. GVHD occurs when the donor’s immune system reacts against the recipient’s tissue. The new cells do not recognize the tissues and organs of the recipient’s body. The most common sites for GVHD are GI tract, liver, skin, and lungs. GVHD is graded from I to IV and can be acute (occurs suddenly) or chronic (occurs over a period of time). Ethan will be monitored closely for signs and symptoms of GVHD. Diarrhea, fever, rash, skin changes, abdominal pain, respiratory complications, and decreased liver function may be present with GVHD. Medications will be given prior to transplant to reduce the risk of this complication.

When will Ethan be discharged?

Ethan could be discharged 4 – 5 weeks from Day 0. When Ethan is discharged, he will go home, knowing we will have frequent, multiple times/week, visits to the Jimmy Fund Clinic, where he will be treated after being discharged. Ethan will also be “house bound”, for about 1 year: no school, no stores, no public places, no visiting other houses. We will not be allowed to have anyone in our house for this period either. Ethan is allowed outside…outside is good for him, just no crowds. So, we will be able to meet up with one or two people at a time outside.

The frequent visits to the Jimmy Fund Clinic will help determine the effectiveness of treatment, detect complications, detect recurrent disease, and to manage the late effects associated with a bone marrow transplant.

Long-term outlook for a bone marrow transplantation:

Prognosis greatly depends on the following:

type of marrow transplant
type and extent of the disease being treated
disease response to treatment
genetics
age and overall health of the child
your child’s tolerance of specific medications, procedures, or therapies
severity of complications

As with any procedure such as bone marrow transplant, prognosis, and long-term survival can vary greatly from child to child. The amount of transplants occurring for an increased number of diseases and medical developments has greatly improved the outcome for bone marrow transplant in children and adults. Continuous follow-up care is essential for the child following a bone marrow transplant. New methods to improve treatment and to decrease complications and side effects of a bone marrow transplant are continually being discovered.