What is bone marrow ?
Bone marrow is the spongy tissue found inside your large bones. It is responsible for making blood cells including red blood cells, white blood cells and platelets. It is also home to the immune system.

What are stem cells ?
Blood cells grow in the same way as other human cells. They are developed in the bone marrow from a parent cell known as a “stem cell.” These stem cells begin to divide and mature until they are fully developed, forming all the different types of blood cells: white blood cells, platelets and red blood cells.

Stem cells usually are found inside the bone marrow spaces of large bones, however, they can travel from one bone to the other by way of the blood system. A very small percentage of the white blood cells circulating through your veins are stem cells.

What is a bone marrow transplant ?
Bone marrow transplant is actually a transfusion of bone marrow stem cells or blood stem cells (collected from either a donor or the patient), which are used as a “rescue” for the patient after high doses of chemotherapy. There are several types of bone marrow transplantation. Each transplantation process is made up of two parts:

a) Collection / harvesting
b) Infusion / the actual "transplant"

The infusion or “transplant” is done very much like a blood transfusion. If you are receiving stem cells from a donor (an Allogenic transplant), the infusion is given to you soon after the stem cells are collected. The “transplant” is given through your IV catheter much as other blood transfusions.

If you receive your own stem cells (an Autologous transplant), a blood bank technologist will bring the frozen product to your room for thawing immediately before infusion.

How are bone marrow stem cells or blood stem cells collected ?
Bone marrow stem cells are collected from either the patient or a donor depending on the type of transplant being done. The process of collecting these cells is called “harvesting.” Stem cells usually are found inside the bone marrow spaces of large bones, however, they can travel from one bone to the other by way of the blood system. Therefore, stem cells can be harvested from either the bone marrow or the blood.

The procedure is performed in the operating room. The patient/donor can be given general anesthesia so he or she is not awake and won’t feel anything during the procedure. The patient/donor may also select spinal anesthesia. Once in the operating room, the patient/donor is positioned on his or her stomach. The doctors place needles into the hip bone (pelvis) and pull out the marrow with syringes. The needles are placed through the skin three to five times over each hip bone. For each puncture in the skin there are many punctures into the bone.

Once collected, the marrow is filtered and placed into blood bags. If an Autologous transplant is to be done, the marrow is processed and stored frozen until later. If the marrow is donated for an Allogenic transplant, it is brought to the patient for transfusion soon after the harvesting is completed. When the marrow is donated from an unrelated donor, it is collected where the donor lives and brought by courier to the patient within hours of collection.

The entire harvesting procedure takes one to two hours. The patient may receive a blood transfusion during the collection to replace the blood removed with the bone marrow. Once completed, the patient/ donor is taken to the recovery room with a large bandage across the hips that remains in place for 24 hours. Discharge from the hospital is generally the same day. There is soreness from the harvesting, but pain medication is given as needed. Soreness can vary from person to person, but normal activity is usually resumed within three to four days and complete recovery within approximately two weeks.

What are the types of blood and marrow transplantation ?
There are different types of transplants depending on who donates the bone marrow or blood stem cells. The most common are:

++ Allogenic Transplant - stem cells are donated from a genetically matched family member (usually a brother or sister). Genetic matching, called HLA matching, is done from blood samples.

++  Matched Unrelated Transplant - another type of Allogenic transplant, but the stem cells are donated by someone other than a family member. This donor is found in one of the worldwide donor registries.

++ Syngeneic Transplant - the person donating the stem cells is an identical twin.

++  Autologous Transplant - the patient donates his or her own stem cells prior to treatment for infusion later.

Your doctor will discuss what type of transplant is available for you.
++  “Peripheral Blood” Stem Cell Harvesting (Aphaeresis)

Stem cells also can be collected from the circulating blood system for transplant. This method of collection is called “peripheral stem cell aphaeresis.” Aphaeresis is performed as an outpatient procedure and usually takes two to three hours per procedure. Most patients or their donors will have one to three procedures done to collect the required number of stem cells. For several days prior to the procedure, a drug called “growth factor” is taken in injection form to produce a greater number of stem cells, which are released into the blood.

Aphaeresis is done by inserting a needle into one arm and connecting attached tubing to a machine where the peripheral stem cells are separated and collected. The remaining blood components (white cells, red cells and platelets) are returned to you through a needle in your other arm. The only discomfort you may feel is when the needles are inserted. In some cases, an IV catheter is inserted in the neck or groin if the veins in the arms are not strong enough for the procedure.

What happens after blood or marrow transplantation ?
Approximately two to four weeks after your transplant you can expect to see signs of your bone marrow “engrafting” or beginning to grow. The first sign of this is the production of white blood cells. Platelets often take a little longer to begin developing. Once you have engrafted and your condition is stable, you will be discharged from the hospital.

What are types of Donors fro BMT?
One of the first evaluations done for patients who are being considered for a BMT involves special blood studies on the patient and his or her entire family in order to decide who is the best donor. The standard test is called tissue typing (also referred to as HLA or histocompatibility typing). A second test, which has recently been developed, is called high resolution DNA typing. These tests gauge how much the donor and recipient cells will recognize one another as the same or different. The greater the differences in the HLA typing, the greater the chance that either the donor's cells will not grow in the recipient (rejection or graft failure) or they will attack the recipient and cause a reaction called graft vs. host disease (GVHD).

The optimal donor: HLA matched
The optimal donor is an HLA matched (histocompatible) relative who is usually a sibling or, in rare cases, a parent or grandparent with identical HLA tissue typing. HLA matched (histocompatible) donor-recipient pairs are always identical by high resolution DNA typing.

Everyone inherits two sets of chromosomes containing HLA genes (4 genes per set), one set from their father and one from their mother (a total of 8 genes). There is a one in four (25%) chance that any brother or sister will have inherited the same two sets of HLA genes as the patient. For a parent to be "matched" with his or her child, both parents must by chance have some HLA genes in common with each other. It is very unlikely (1 in a million) for two unrelated individuals to have the same HLA genes in common, and there is only a 1 in 200 chance that a parent and child will be HLA matched.

Partially-matched (haplocompatible) relative
A biologic parent is always half matched (i.e., haplocompatible,or 4 out of 8 HLA match) with his or her child since each child inherits half of the HLA genes from each parent. There is a 50% chance that any sibling will be haplocompatible with any other sibling. In order for a haplocompatible bone marrow transplant to work without resulting in a fatal GVHD reaction, the stem cells must be specially treated after they are collected from the donor and before they are transplanted into the patient. This treatment depletes them of the donor T lymphocytes that cause GVHD (T cell depletion).

There are advantages and disadvantages to T cell depletion. The technique that is used at individual BMT treatment hospital may vary as per their protocols and the aim her eto follow is that these Programs significantly reduces the risk of GVHD both in terms of its chances of occurring, as well as its severity if it does occur. However, there is an added risk that the marrow might not engraft. In order to improve the chances for successful engraftment (>95%), additional treatment with radiation and chemotherapy) must be added to the conditioning regimen in most cases (except for children with severe combined immunodeficiency disease or SCID). Also, there may be a delay in the recovery of the immune system (the body's defense against infection) resulting in a higher risk of infections after transplant. T cell depleted bone marrow stem cells from a parent or sibling may be considered for children who do not have an HLA matched related or unrelated donor.

Autologous donor
For some types of cancers (for example, brain tumors, neuroblastoma, lymphomas, sarcomas, Wilm’s tumor, and PNET) it is possible to use the patient's own (autologous) marrow stem cells (bone marrow or peripheral blood) for the transplant.

If bone marrow stem cells are going to be used, prior to admission for the transplant (a few days to many months), a portion of the patient's marrow is harvested in the operating room under general anesthesia and frozen in liquid nitrogen in the Bone Marrow Transplant Laboratory. Prior to freezing, the marrow may need to be treated to remove cancer cells that may still be present. Following the conditioning period, the stored marrow is thawed and transfused into the patient. While one advantage to this type of transplant is the absence of GVHD, a potential disadvantage is the greater risk that the cancer will recur.

If possible,  peripheral blood stem cells are now used for autologous transplants.  Prior to admission for the transplant, the patient’s stem cells are collected using a special process called leukapheresis. During this procedure the patient’s blood is passed through a machine which collects the portion of white cells containing bone marrow stem cells. The remaining white cells, red cells, and platelets are given back to the patient. Placement of a special intravenous line, (double lumen pheresis catheter), may be necessary for this procedure. In preparation for the leukapheresis, the patient receives a drug or cytokine called G-CSF for 3-4 days to encourage stem cells to leave the marrow and enter the blood. Occasionally, after many cycles of chemotherapy and / or local radiation therapy G-CSF is inadequate to "mobilize" a sufficient number of bone marrow stem cells into the blood. Some hospital specialists are currently evaluating a new approach using a combination of cytokines.

Unrelated donor
When a matched relative is unavailable and there is time to conduct a search, an unrelated donor is usually considered. The chances of any 2 unrelated individuals being matched for all 8 HLA genes is 1 in a million. The chances of finding a matched donor vary from 20-60% depending on the patient's ethnic background. It may take 6 months (or longer) to identify a donor, however, and the added cost of using an unrelated donor may be as much as US$ 35,000. Finally, even with a perfectly matched donor there is a significant chance that GVHD will occur and that it will be more severe than with a matched relative.

Umbilical cord blood
If a matched unrelated marrow stem cell donor is unavailable, another source of unrelated donor bone marrow stem cells, umbilical cord blood (UCB), may be considered. There are over three dozen UCB registries worldwide which process and store cord blood collections from healthy babies. The cord blood, which is normally thrown away after a baby is born, contains a relatively large number of bone marrow stem cells. One potential advantage of using cord blood is that it does not need to be a perfect tissue match with the recipient. Disadvantages include the limited number of cells in a collection and relative delay in the recovery of marrow function post-transplant.

Discharge from Hospital ?
Although each person varies in how long he or she takes to recover, the following are general criteria used for discharge:

++ no evidence of an emerging infection or graft versus host disease

++ able to tolerate oral medications, food and fluids

++ active enough to function outside the hospital

++ discharge teaching completed for you and your caregiver.

     Some additional insight on BMT in India

Que. 1 : What particular medical records your oncologists team require for searching a suitable Donor from regional / international registry?
Ans. : Full details on patient's name, age, date of birth, Dx, HLA class I and II and High Resolution typing. 

Que. 2 : How much time does it take to search a suitable Donor from the regional / international registry ?
Ans. : Three months to more than one year through NMDP, USA.

Que. 3 : Where are the regional / International registry located in relations to India from where Donor samples comes?
Ans. : None

Que. 4 : Does any of the Hospital in India maintain a regional Donor registry database?
Ans. : No

Que. 5 : What are the cost implications for searching a Donor match from a registry ?
Ans. : As per NMDP rates. 

Que. 6 : How much percentage of Recipient vs. Donor match is termed as acceptable when no one on family is found to be near match ?
Ans. :  Eight out of Eight  or Seven out of Eight - High Resolution match.

Que. 7 : What are the cost implications of transport of blood and marrow products to India to your hospital, suppose a non - resident  patient is invited to come to your hospital for further treatment.  
Ans.: Whoever provides the graft (NMDP),  set the rate, plus the transplant charges approximately US Dollar 55,000/- (U S Dollar Fifty Five Thousand) onwards for eight weeks stay in hospital and extra. 

Que. 8 : Does the registries send "donor in person" to outside its territory if all expenses of physical traveling of Donor are born by the Recipient ?
Ans. : We are not aware of such arrangements if carried out by Registries.