PATIENT INFORMATION ABOUT STEM CELL COLLECTION AND PURGING
This section is here to help answer questions that you may have about stem cells, stem cell collection and purging for neuroblastoma.
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TABLE OF CONTENTS
There are 3 types of normal blood cells circulating in the blood stream.
White blood cells -- fight infection
Red blood cells -- supply oxygen (energy source of the body) and remove waste products
Platelets -- help the blood to clot and stop bleeding
Blood cells grow from stem cells. Stem cells are the parent cells that have the ability to re-grow all the normal blood cells. Stem cells are found in the bone marrow but they can also travel (or circulate) in the blood stream (called peripheral blood stem cells).
Chemotherapy damages normal blood cells at the same time it is killing tumor cells. When this happens normal blood cell counts will be lowered for a period of time (about 7-10 days). New blood cells will grow from stem cells to take the place of the damaged blood cells and the blood counts will return to normal levels (in time to have the next chemotherapy treatment!!!)
When the blood counts are low your child is at risk for infection (low white blood cells), may be more tired or sleepy than normal (low hemoglobin or anemia) and might get bruises or bleed more easily.
Stem cell transplant is a way of treating cancers like neuroblastoma where higher doses of chemotherapy are used to kill more tumor cells. Chemotherapy given at transplant doses will damage the stem cells so that they cannot recover to produce normal blood cells. To avoid this severe side effect, stem cells that were collected and stored at an earlier time (before transplant chemotherapy is given) are given back to the patient (like a blood transfusion) to replace the stem cells that were lost. These stem cells then grow to restore normal working blood cells.
An autologous stem cell transplant uses the patient's own stem cells to replace the stem cells that are killed by the high dose transplant chemotherapy. These stem cells are collected from the patient at a time before transplant (weeks to months) and are stored until they are needed. Once the high dose chemotherapy has been given, these stem cells are infused into the patient.
The procedure of giving back the patient's own stem cells to restore normal working blood cells is called an autologous stem cell transplant. As blood cells are known as hematopoietic (means blood forming) cells, these transplants are often called autologous hematopoietic stem cell transplants, or AHSCT.
Stem cells can be collected from either the bone marrow or the peripheral blood (bloodstream).
The procedure for collecting stem cells from the blood stream or peripheral blood is called a peripheral stem cell harvest or pheresis.
The procedure for collecting stem cells from the bone marrow is called a bone marrow harvest.
Peripheral blood stem cell pheresis or PBSC pheresis:
Peripheral stem cell collection is done when the blood cell counts are beginning to recover after the patient has gotten a course of chemotherapy. (usually 10-14 days after the first day chemo was given). This is the time when the most stem cells can be found travelling in the blood stream.
A special central line or catheter with 2 lumens or ports is needed to collect peripheral blood stem cells (PBSC). A temporary catheter may need to be placed only for the PBSC harvest. Your doctor or nurse will tell you if a temporary catheter is needed to collect stem cells.
PBSCs are pheresed or collected by connecting the central line to a special machine. The central line is used to pass your child's blood through the machine that takes out the stem cells and then returns the rest of the blood to your child's body. The collected PBSCs are taken from the machine to the lab to be processed and frozen until they are needed.
Each PBSC collection takes four to six hours to complete. PBSC collections are done in the clinic but patients can be hospitalized if there are complications during the collections in the clinic.. It can take 2 to 3 days to collect enough PBSC to be used after high dose chemotherapy.
G-CSF is a drug which causes a quicker increase in the number of white blood cells seen in the blood after chemotherapy. All patients will get G-CSF as an injection under the skin once a day for several days before and during the PBSC collections, to help increase the number of stem cells in the peripheral blood. G-CSF will be stopped when the collections are finished.
Bone marrow harvest :
A bone marrow harvest is usually done after your child's blood counts have completely recovered after getting a course of chemotherapy (usually 4-5 weeks after chemo was given).
A bone marrow harvest is done in the operating room under general anesthesia and sterile conditions. Part of your child's bone marrow will be withdrawn or removed from the back of the pelvic bone (hip bone) on the right and left sides using syringes and needles. If needed, bone marrow also will be taken from the front of the pelvic bone on the right and left. The exact amount of bone marrow removed depends on your (your child's) size, but will be approximately 400 to 800 ml (2 to 4 cups). Larger children need more stem cells for transplantation and other procedures which need stem cell support. Your child would be in the hospital over night the day of the harvest. Longer hospitalization may be needed if complications occur.
PBSC collection :
Nausea, vomiting, fainting or dizziness. These symptoms are a result of the PBSC collection process. These symptoms are managed with medicines and other measures to keep your child comfortable.
BLEEDING: This is rare, but can occur from the anti-clotting medicine citrate (or heparin) mixed with your child's blood to prevent clotting in the machine during the collection.
INFECTION: This is rare, but could require treatment in the hospital with antibiotics.
ALLERGIC REACTIONS: Rarely, allergic reactions to heparin or citrate could occur which can cause rash dizziness, low blood pressure, and difficulty in breathing.
LOW CALCIUM: Citrate can cause low blood calcium with tingling and numbness, nausea and vomiting, abdominal pain, low blood pressure, and difficulty in breathing. Rarely, low calcium can cause muscle spasms, disturbances in consciousness and seizures. To prevent or minimize these side effects calcium can be given by vein or by mouth during the PBSC collection.
CENTRAL LINE PROBLEMS: The central line may clot or become infected, requiring placement of another line to perform the PBSC collections.
LOW NUMBERS OF PBSC: This can occur due to problems with the central line or low numbers of PBSC in your (your child's) blood due to the effects of chemotherapy and/or radiation on their normal production.. If there are not enough PBSC collected, additional PBSC collections could be done following another course of chemotherapy or you may have a bone marrow harvest or you may choose not to receive high dose chemotherapy. Your physician will discuss this with you if this situation occurs.
TRANSFUSIONS: A packed red blood cell transfusion (PRBC) may be needed in small children and in those individuals who have alow red blood cell count (hemoglobin) to prime the machine before the collection begins. A platelet transfusion may be needed if too many platelets are removed from blood during the pheresis process. With transfusions, there is a risk of allergic reactions (fever, chills, rash, decrease in blood pressure, rarely difficulty in breathing), and transmission of certain viruses (hepatitis viruses, and extremely rarely, the transmission of the virus that causes AIDS). The opportunity to arrange for directed donor donations of blood and platelets that can be used during the PBSC collections is available for you (your child).
Bone marrow harvest :
PAIN at the site of needle sticks is common and lasts for several days. It is usually easily controlled by pain medicines.
BLEEDING at the site of needle sticks is common, but is rarely severe.
INFECTION at the site of needle sticks may occur, but this is very unusual.
ANESTHESIA: Although reactions to anesthesia occur rarely (less than once in 3,000 procedures), they may be severe and even fatal.
TRANSFUSIONS: Red blood cell transfusions are needed during and may be needed after the bone marrow harvest. The other bone marrow cells removed will grow back in a few weeks and do not need to be replaced. With transfusion, there is a risk of allergic reaction, hepatitis, and other viral infections (including infection with the virus that causes AIDS). This would be quite unusual, but could be severe and even fatal.
While stem cells are found in the bone marrow and in the bloodstream, neuroblastoma tumor cells are also commonly found in the bone marrow and the blood. If neuroblastoma tumor cells are mixed in with the stem cells when they are collected (IE: PBSC pheresis or bone marrow harvest), they may cause tumor re-growth when the stem cells are infused into the patient.
Purging is a process that removes tumor cells from the stem cell collection, to try to decrease the risk of tumor re-growth after the stem cells are infused.
Purging will decrease the number of tumor cells that may be given to the patient with the normal stem cells. This may decrease the chance for tumor recurrence. However, there is no definite proof that purging the stem cells decreases the number of children that will have tumor re-growth.
Testing is done on all stem cell collections (purged and not purged) to see if tumor cells are present. This test must show no tumor cells before the stem cells are approved for infusion into your child. Current testing available can find one tumor cell among 100,000 normal cells. It is still possible that there may be less than one tumor cell among 100,000 normal cells present. The number of tumor cells needed to cause tumor re-growth is not known. Some stem cell collections do not show any tumor cells but they may still have rare tumor cells we cannot find with current testing available.
Stem cell purging on the COG Neuroblastoma study is done at Childrens Hospital Los Angeles (CHLA). If you do not live in Los Angeles, immediately after your (your child's) stem cells are obtained from either the peripheral blood or bone marrow, they are shipped by overnight carrier to CHLA. Your child's stem cells arrive at the CHLA Hematopoietic Stem Cell Processing Laboratory early the next day and are purged to remove tumor cells, frozen, and stored at CHLA until needed.
The purging process is described below :
PBSC Purging:
1. CARBONYL IRON FRACTIONATION : Carbonyl Iron is a non-toxic iron particle preparation, which is mixed with the stem cell collection and sticks onto some normal blood cells (monocytes, macrophages) which are not needed for the re-growth of normal blood cells. The white blood cells attached to carbonyl iron can then be removed from the other cells by passing them next to a magnet to pull them out. This step reduces the number of cells to be treated in the next step.
2. MAGNETIC BEADS WITH STANDARD MONOCLONAL ANTIBODIES : Monoclonal antibodies are special proteins that can recognize and attach to tumor cells. These antibodies are put on tiny magnetic beads, which are then mixed with the stem cells, and "lock" onto the neuroblastoma tumor cells. When the stem cells are then passed next to a magnet, the beads are pulled out along with the neuroblastoma tumor cells.
Bone Marrow Purging :
1. SEDIMENTATION : The bone marrow stem cells are mixed with a starch-like liquid called Hetastarch, which causes red blood cells to clump together, trapping neuroblastoma cells. These cell clumps can be separated by gravity from the other normal stem cells and discarded.
2. FILTRATION : The remaining bone marrow stem cells are put through a filter which traps and removes more tumor cell clumps (tumor cell clumps are too large to pass through the filter).
3. MAGNETIC BEADS WITH STANDARD MONOCLONAL ANTIBODIES : Monoclonal antibodies are special proteins that can recognize and attach to tumor cells. These antibodies are put on tiny magnetic beads, which are then mixed with the stem cells, and "lock" onto the neuroblastoma tumor cells. When the stem cells are then passed next to a magnet, the beads are pulled out along with the neuroblastoma tumor cells.
Purging also removes some normal stem cells; however stem cells from both the bone marrow and the peripheral blood have been purged using this process and they have been able to grow back all the normal blood cells.
Stem cells that have been purged at CHLA Hematopoietic Stem Cell Processing Laboratory are approved for use when the following conditions have been met :
(1), no tumor cells are found to be present after standard testing, (see benefits of purging above)
(2), there are adequate numbers of stem cells present after purging to allow for enough normal blood cells to grow back (called engraftment)
(3), there are no bacteria or fungus contaminants found in the stem cells after purging.
Failure of the stem cells to pass one or more of these tests happens in approximately 5% of patients. If this happens, the purged stem cells would not be given back to your child. It may be possible to remove more stem cells from the blood or bone marrow. If NO acceptable stem cell collection can be obtained, then you (your child) would not be able to get any kind of treatment in the future that required his/her own stem cells, and alternative treatments would be discussed with you by your child's doctor.
TUMOR CELLS ARE PRESENT IN THE PURGED STEM CELLS : This may cause tumor re-growth in your child after the stem cells are infused. After purging, the stem cells will be tested to find out if neuroblastoma tumor cells are present. Current proven methods can reliably find one neuroblastoma cell out of 100,000 normal cells. If fewer cancer cells were present, however, it is possible that they might not be found and could be given back to your child. You will be informed if tumor cells are found in the stem cells after purging. More stem cells may be collected and purged if this happens. This will be discussed with you by your child's doctor.
NOT ENOUGH NORMAL STEM CELLS ARE LEFT AFTER PURGING to give back to your child. Another stem cell collection from the blood or bone marrow may be possible if this happens.
PURGING THE STEM CELLS IN THE LABORATORY MAY INJURE THEM SO THAT THEY WILL NOT GROW WHEN GIVEN BACK TO YOUR CHILD : It is extremely unlikely that this would happen and if it did, the damage would likely be found by testing done on the stem cells before they are given to your child. Finding damaged stem cells would mean that more stem cells would need to be collected from your child. If stem cell damage were to happen and go undetected, use of those stem cells could be fatal because your child's body would not be able to make the blood cells (white blood cells, red blood cells, platelets) that are necessary to live. If purged stem cells do fail to grow in your child, extra bone marrow or PBSCs that were kept frozen (called a back-up) may be used (if available) or growth factors also may be given to try to improve blood cell growth.
(Extra back-up bone marrow or PBSCs that have not been purged may be obtained when possible in case the purged stem cells do not grow after they are given back. Back-up bone marrow or PBSCs are not required. The back-up stem cells can be tested by current methods to determine if there are tumor cells present. If the frozen back-up stem cells contain tumor cells, it is not possible to purge them before giving them to your child.)
CONTAMINATION OF THE STEM CELLS WITH INFECTIOUS AGENTS DURING PURGING COULD OCCUR : All stem cells are handled in a sterile (germ-free) manner during purging. Contamination with infectious agents (such as bacteria or fungus) could result in an infection in your child after the stem cells are infused, which would need antibiotics and could be a serious illness. The stem cells are tested (cultured) for contaminants at each step of the purging process and again before they are frozen. If contaminants are found, the stem cells could not be used and more stem cells would need to be collected from your child.
FREEZER MALFUNCTION CAUSING THE STEM CELLS TO THAW AND BE DAMAGED : Frozen purged stem cells will be stored in liquid nitrogen storage freezers in the vapor phase of liquid nitrogen (at temperatures less than 150 degrees Centigrade) at the CHLA Hematopoietic Stem Cell Processing Laboratory until they are needed. It is possible the freezer could malfunction and the stem cells could thaw and be damaged. Collecting more stem cells may be possible if this happens.
STEM CELLS COULD BE LOST OR DAMAGED IN THE SHIPPING PROCESS : Stem cells are shipped back to your child's treating institution by overnight express in a special container. The stem cells are closely tracked during shipment to CHLA for purging, storage and then when the purged stem cells are shipped back to the institution where they will be given back to your child.
EXPANDED ACCESS PURGING PROTOCOL - CONSENT AND ASSENT
2005-00051 Sample informed consent v 12-8-06
2005-00051 Sample assent v 12-8-06
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