Conditioning Regimen for a Bone Marrow Transplant (BMT)

During the "countdown period," usually five to 10 days before the transplant, a conditioning regimen is administered. The drugs, or chemotherapy, and/or radiation that are used vary with the underlying disease. Some children with severe immunodeficiencies may not require any chemotherapy or radiation.

The overall goals of the conditioning regimen are to:

Suppress the immune system so that the patient will not reject the new bone marrow
Make room in the bone marrow for the donor marrow stem cells to grow
Destroy any residual cancer cells

Chemotherapy Agents

There are various chemotherapy agents that your child may receive in preparation for a bone marrow transplant. Not all of the potential side effects may occur and the negative side effects vary greatly from patient to patient.

It is important to know that most of the drugs used in the conditioning regimen contribute to the following negative side effects:

Nausea and Vomiting
Hair loss
Organ damage, in particular to the liver and kidney
Risk of infertility, short stature, developmental delay, abnormal teeth and another cancer

Your child's doctor will go over all of the early and late side effects with you and explain which are most frequent as well as and those that are rare.

ATG (Anti-Thymocyte Globulin)
What it does:	Decreases the body's ability to reject new bone marrow. May also be used to treat graft vs. host disease. Made in horses or rabbits.
How it is given:	Administered IV over 4-10 hours. The recipient will be pre-medicated with Tylenol, Benadryl, and Decadron to help prevent reactions.
Potential side effects:	Fever Chills Hives or other skin rashes Severe allergic reaction (rare)

BCNU (Carmustine)
What it does:	Destroys cancer cells.
How it is given:	IV.
Potential side effects:	Nausea, vomiting, and diarrhea Scarring of the lungs Lowers the blood counts Liver damage Flushing of the skin

Busulfan
What it does:	Destroys cancer cells and/or makes room for new bone marrow to grow.
How it is given:	Taken by mouth or through a tube which is inserted through the nose into the stomach. A new preparation is now available which is injected intravenously.
Potential side effects:	Nausea and vomiting Scarring of the lungs Lowers the blood counts Hair loss Irritation of the tongue Clouding of the lens in the eye (rare) Seizures

Carboplatin (CBDCA)
What it does:	Destroys cancer cells and makes room for new bone marrow to grow.
How is it given:	IV (sometimes as a continuous infusion).
Potential side effects:	Lowers blood counts Nausea and vomiting Damage to the liver and the kidney Abnormal function of the nerves to the arms and legs Damage to the ears that can affect normal hearing

Cyclosporin A
What it does:	Helps prevent and/or treat Graft vs. Host disease.
How is it given:	While in the transplant unit is it given IV. When beginning the process of discharge it is changed to an oral medicine.
Potential side effects:	Damage to the liver and kidney Elevated blood pressure Hair growth on all areas of the body Shakiness or tremors Seizures

Cytoxan (Cyclophosphamide)
What it does:	Destroys cancer cells and/or prevents the transplanted marrow from being rejected by the recipient.
How it is given:	Administered IV. Additional IV fluids are started the night before the 1st dose and continued for 24 hours after the last dose to minimize irritation of the bladder or kidneys. Also, a drug called Mesna is given to help minimize irritation to the bladder.
Potential side effects:	Irritation and damage to the bladder. This may result in mild to severe bleeding and/or pain Nausea and vomiting Low blood counts Mouth ulcers Abnormal taste and smell Hair loss Damage to the liver, lungs and heart Abnormal retention of water in the body

Etoposide (VP-16)
What it does:	Destroys cancer cells.
How is it given:	Administered IV either as a continuous infusion or as a single dose once or twice a day.
Potential side effects:	Low or high blood pressure Nausea, vomiting, diarrhea Sores in the mouth and intestines, and on the skin Fatigue, headache, confusion Lowers blood counts Hair loss Liver damage

Fludarabine
What it does:	Destroys cancer cells and prevents rejection by destroying T cell immunity.
How is it given:	Administered IV as a single dose once a day.
Potential side effects:	Immunodeficiency and increased infections Nerve damage Nausea and vomiting

GM-CSF OR G-CSF (Neupogen)
What it does:	Stimulates bone marrow cells to grow and mature into neutrophils and causes some stem cells in the bone marrow to temporarily move into the circulating blood.
How is it given:	Administered intravenously or subcutaneously (under the skin).
Potential side effects:	Fever Flu-like symptoms Bone pain Nausea and vomiting Abnormal taste in mouth

Melphalan
What it does:	Destroys cancer cells.
How is it given:	Administered IV. Additional IV fluids are started the night before the 1st dose and continued for 24 hours after the last dose to minimize irritation of the bladder or kidneys.
Potential side effects:	Lowers blood counts Hair loss Skin rash Bladder irritation Mouth sores Lung and liver damage Low blood pressure Allergic reaction

Methotrexate
What it does:	Destroys cancer cells and/or helps prevent graft vs. host disease.
How is it given:	Administered IV over a few minutes. It is given post-transplant on days 1, 3, 6, and 11. In addition, some children will get methotrexate weekly for the first 100 days post transplant.
Potential side effects:	Nausea, vomiting and diarrhea Lowers blood counts Hair loss Irritation and sores in the mouth and intestinal tract Damage to the liver Drowsiness blurred vision May sensitize the skin to sunlight

Tacrolimus (FK506)
What it does:	Helps prevent and/or treat graft vs. host disease. Used for patients who have not responded to or are unable to take cyclosporin A.
How is it given:	IV or by mouth.
Potential side effects:	Damage to the liver and kidney Elevated blood pressure Hair growth on all areas of the body Shakiness or tremors Seizures

Thiotepa
What it does:	Destroys cancer cells.
How is it given:	Administered IV.
Potential side effects:	Lowers blood counts Nausea, vomiting Irritation and sores in the mouth and intestinal tract Hair loss Rash, itchy skin Irritation and damage to the bladder (rare) Headache, dizziness Bronzing and peeling of the skin. The skin may blister especially in areas of previous radiation therapy

Topotecan
What it does:	Destroys cancer cells.
How is it given:	Administered IV.
Potential side effects:	Nausea, vomiting, diarrhea Sores in the mouth and intestines, and on the skin Fatigue, headache, confusion Lowers blood counts Hair loss Liver damage

Total Body Irradiation

The purpose of radiation therapy is to destroy residual cancer cells and/or further depress the immune system to improve acceptance of the new bone marrow. The radiation is given to the entire body, called total body irradiation (TBI). The total dose of radiation usually is given over several days just prior to transplant in the Radiation Oncology Department. Typically the patient receives a total of 1200 to 1300 centigray (dose of radiation) given over three to four days. The daily dose is split in two so that the patient will make two trips to the Radiation Oncology Department each day.

All doctors, nurses and technicians take isolation precautions. The patient wears a mask when out of the BMT room and is covered as much as possible. Each radiation treatment will take approximately 20 to 30 minutes to administer. It takes some additional time to adjust the patient in just the right position so that the proper dose of radiation is administered. Some children may need to be sedated so they can hold still throughout the procedure. For young children, a general anesthetic will be administered so that the child is asleep during the radiation treatment. Only the child can be in the room during the treatment. There is a TV camera and intercom so everyone can watch and talk to the child.

The immediate side effects of radiation therapy, which occur within the first few hours and days, may include diarrhea, nausea, vomiting and tiredness. Mouth sores also can be a problem due to the combination effect of chemotherapy and radiation. Many children complain of a dryness of the mouth, sore throat and thickened saliva. Starting several days after radiation therapy, hair loss, sunburning and dryness of the skin may be experienced. Much rarer side effects include swelling (like mumps) of the glands in the cheeks and fever. Radiation therapy also destroys the cells of the bone marrow and, most importantly, cancer cells.

Potential long-term effects of chemotherapy and radiation, which will be discussed by your child's doctors, include cataracts (clouding of the lens in the eye), delayed growth and development, sterility and the possible development of a second cancer.

UCSF Benioff Children's Hospitals medical specialists have reviewed this information. It is for educational purposes only and is not intended to replace the advice of your child's doctor or other health care provider. We encourage you to discuss any questions or concerns you may have with your child's provider.