Major hospitals in India have oncology units comprising surgical oncology, medical and radiation therapy as well as the crucial Bone Marrow Transplantation (BMT). The BMT unit with high pressure hipa filters has helped achieve a very high success rate in the various types of transplantation.

Beginning in early 1983, bone marrow transplantation (BMT) facilities in India have undergone slow but steady growth. With about 50% disease-free survival in acute myeloid leukaemia and aplastic anaemia and 90% survival in thalassemia major, the results are encouraging. However, the outcome in chronic myeloid leukemia so far has been poor.

Cord Blood Transplant and Mismatched Allogeneic Stem Cell Transplant have been performed successfully in India, a feat that is remarkable and significant, considering the fact that the treatment costs one-tenth of what it does in the west. Special surgeons are available for individual organs. Plastic surgeons of repute provide treatment for head and neck cancer, breast cancer and other malignancies. Facilities offered include tele-therapy which includes simulation work stations to ensure high precision and safety during treatment at the 18 MV linear accelerator or telecobalt machines, brachy therapy and 3-D planning systems. In orthopedics, the Ilizarov technique is practiced for the treatment of limb deformities, limb shortening and disfiguration.

Hospitals in India treating Bone Marrow Transplants are; Manipal Hospital (Bangalore), Apollo Hospitals (Chennai) and Indraprastha Apollo Hospital (New Delhi). In Israel Shemer Medical Hospitals have been leading in mismatched Bone Marrow Transplants and patients can be referred to superior BMT facility available in Israel if such treatments in India are not available by Mediescapes.

What is DEFINITION of Bone Marrow?

The bone marrow-the sponge-like tissue found in the center of certain bones-contains stem cells that are the precursors of white blood cells, red blood cells, and platelets. These blood cells are vital for normal body functions, such as oxygen transport, defense against infection and disease, and clotting. Blood cells have a limited lifespan and are constantly being replaced; therefore, healthy stem cells are vital.

In association with certain diseases, stem cells may produce too many, too few, or otherwise abnormal blood cells. Also, medical treatments may destroy stem cells or alter blood cell production. The resultant blood cell abnormalities can be life threatening.

Bone marrow transplantation involves extracting bone marrow containing normal stem cells from a healthy donor, and transferring it to a recipient whose body cannot manufacture proper quantities of normal blood cells. The goal of the transplant is to rebuild the recipient's blood cells and immune system and hopefully cure the underlying ailment.

What is the PURPOSE of Bone Marrow?

A person's red blood cells, white blood cells, and platelets may be destroyed or may be abnormal due to disease. Also, certain medical therapies, particularly chemotherapy or radiation treatment, may destroy a person's stem cells. The consequence to a person's health is severe. Under normal circumstances, red blood cells carry oxygen throughout the body and remove carbon dioxide from the body's tissues. White blood cells form the cornerstone of the body's immune system and defend it against infection. Platelets limit bleeding by enabling the blood to clot if a blood vessel is damaged.

A bone marrow transplant is used to rebuild the body's capacity to produce these blood cells and bring their numbers to normal levels. Illnesses that may be treated with a bone marrow transplant include both cancerous and noncancerous diseases.

Cancerous diseases may or may not specifically involve blood cells; but, cancer treatment can destroy the body's ability to manufacture new blood cells. Bone marrow transplantation may be used in conjunction with additional treatments, such as chemotherapy, for various types of leukemia, Hodgkin's disease, lymphoma, breast and ovarian cancer, and other cancers. Noncancerous diseases for which bone marrow transplantation can be a treatment option include aplastic anemia, sickle cell disease, thalassemia, and severe immunodeficiency.

What is the PRECAUTIONS of Bone Marrow Transplantation?

Bone marrow transplants are not for everyone. Transplants are accompanied by a risk of infection, transplant rejection by the recipient's immune system, and other complications. The procedure has a lower success rate the greater the recipient's age. Complications are exacerbated for people whose health is already seriously impaired as in late-stage cancers. Therefore, a person's age or state of health may prohibit use of a bone marrow transplant. The typical cut-off age for a transplant ranges from 40 to 55 years; however, a person's general health is usually the more important factor.

Even in the absence of complications, the transplant and associated treatments are hard on the recipient. Bone marrow transplants are debilitating. A person's ability to withstand the rigors of the transplant is a key consideration in deciding to use this treatment.

TYPES of Bone Marrow Transplantation;

Autologous and Allogeneic Transplants
Two important requirements for a bone marrow transplant are the donor and the recipient. Sometimes, the donor and the recipient may be the same person. This type of transplant is called an autologous transplant. It is typically used in cases in which a person's bone marrow is generally healthy but will be destroyed due to medical treatment for diseases such as breast cancer and Hodgkin's disease. Most bone marrow transplants are autologous. If a person's bone marrow is unsuitable for an autologous transplant, the bone marrow must be derived from another person in an allogeneic transplant.

Allogeneic transplants are more complicated because of proteins called human lymphocyte antigens (HLA) that are on the surface of bone marrow cells. If the donor and the recipient have very dissimilar antigens, the recipient's immune system regards the donor's bone marrow cells as invaders and launches a destructive attack against them. Such an attack negates any benefits offered by the transplant.

What is HLA MATCHING?
 
There are only five major HLA classes or types-designated HLA-A,-B, -C,-D, and class III-but much variation within the groupings. For example, HLA-A from one individual may be similar to, but not the same as, HLA-A in another individual; such a situation can render a transplant from one to the other impossible.

HLA matching is more likely if the donor and recipient are related, particularly if they are siblings; however, an unrelated donor may be a potential match. Only in rare cases is matching HLA types between two people not an issue: if the recipient has an identical twin. Identical twins carry the same genes; therefore, the same antigens. A bone marrow transplant between identical twins is called a syngeneic transplant.

NEW ADVANCEMENTS in Bone Marrow Transplantation

Haploidentical Allogeneic BMT for patients without donors
Haploidentical Allogeneic peripheral blood stem cell transplant offers an innovative option for patients who cannot be suitably matched with a family member, or who do not have an unrelated donor readily available for transplant.

This technique makes it possible to use partially matched family members as donors.

In this new procedure, peripheral blood stem cells are collected from the donor, and depleted of T cell lymphocytes known to cause graft-versus-host disease. The first treatment phase for the patient includes chemotherapy, immunosuppressive drugs, and radiation. Transplant specialists can then infuse the prepared cells from the donor into the patient's body. This transplant method allows physicians to select a partially matched donor from the patient's family whose white blood cells will act as natural killer cells against the leukemic cells of the patient.

Clinical researchers in hematology and bone marrow transplant at Shemer Medical Centre, Israel have been in the forefront in  this new type of transplant in Israel. Italian physicians developed the original procedure and in Israel it was practiced off late with encouraging results. At present, patients 30 or younger can participate in a research protocol that uses this technique. A new study is in development for treatment of older adults as well. One can always check with Mediescapes for further details provided all current medical records of the patients are sent to Mediescapes.

Peripheral blood stem cell transplants
A relatively recent development in stem cell transplantation is the use of peripheral blood cells instead of stem cells from bone marrow. Peripheral blood stem cells (PBSCs) are obtained from circulating blood rather than from bone marrow, but the amount of stem cells found in the peripheral blood is much smaller than the amount of stem cells found in the bone marrow. Peripheral blood stem cells can be used in either autologous or allogeneic transplants. The majority of PBSC transplants are autologous. However, recent clinical studies indicate that PBSCs are being used more frequently than bone marrow for allogeneic bone marrow transplantation.

The advantages of PBSC transplants when compared to bone marrow transplants are: in allogeneic transplantation, haematopoietic and immune recovery are faster with PBSCs which reduces the potential for disease recurrence, primarily graft-versus-host-disease. In autologous transplantation, the use of PBSCs can result in faster blood count recoveries. Also, some medical conditions exist in which the recipient cannot accept bone marrow stem cell transplants, but can accept PBSC transplants. Some possible disadvantages to PBSC transplant versus bone marrow transplantation are: so much more fluid volume is necessary to collect enough PBSCs that, at the time of infusing the new stem cells into the recipient, the fluid can collect in the lungs or cause temporary kidney problems. Also, the time commitment for the donor for a PBSC transplant is considerable. When the PBSCs are being collected, several outpatient sessions are needed and each session lasts approximately two-four hours.

Know about the TRANSPLANT PROCEDURE in BONE MARROW TRANSPLANTATION

The bone marrow extraction, or harvest, is the same whether for an autologous or allogeneic transplant. Harvesting is done under general anesthesia (i.e., the donor sleeps through the procedure), and discomfort is usually minimal afterwards. Bone marrow is drawn from the iliac crest (the part of the hip bone to either side of the lower back) with a special needle and a syringe. Several punctures are usually necessary to collect the needed amount of bone marrow, approximately 1-2 quarts (0.9-1.91). (This amount is only a small percentage of the total bone marrow and is typically replaced within four weeks.) The donor remains at the hospital for 24-48 hours and can resume normal activities within a few days.

If the bone marrow is meant for an autologous transplant, it is stored at -112 to -320°F (-80 to -196°C) until it is needed. Bone marrow for an allogeneic transplant is sometimes treated to remove the donor's T cells (a type of white blood cell) or to remove ABO (blood type) antigens; otherwise, it is transplanted without modification.

The bone marrow is administered to the recipient via a catheter (a narrow, flexible tube) inserted into a large vein in the chest. From the bloodstream, it migrates to the cavities within the bones where bone marrow is normally stored. If the transplant is successful, the bone marrow begins to produce normal blood cells once it is in place, or engrafted.

Know about the TRANSPLANT PROCEDURE in PERIPHERAL BLOOD STEM CELL TRANSPLANTATION

Before collection for a PBSC transplant, donors receive daily four injections of the drug G-CSF, or filgrastim. (Patients can give it to themselves at home if need be.) These pretreatments stimulate the body to release stem cells into the blood. After these pretreatments, the donors' experience is similar to that of a whole blood donor's experience- PBSC donors' blood is collected at a clinic or hospital as an outpatient procedure. The differences are that several sessions will be needed over days or weeks and the blood is collected in a process called apheresis. The blood travels from one arm into a blood cell separator that removes only the stem cells, and the rest of the blood is returned back to the donor, in the other arm. The cells are then frozen for later use.

The PBSCs are administered to the recipient using the same methods as those used in bone marrow transplantation. As stated, the amount of fluid with PBSCs infused into the recipient's body can be an issue.

COST implication in Bone Marrow Transplantation
Bone marrow transplantation is an expensive procedure. (Bone marrow donors are volunteers and do not pay for any part of the procedure.) Insurance companies and health maintenance organizations (HMOs) may not cover the costs.

HOW PREPARATION in Bone Marrow Transplantation done?

A bone marrow transplant recipient can expect to spend four to eight weeks in the hospital. In preparation for receiving the transplant, the recipient undergoes "conditioning"-a preparative regimen in which the bone marrow and abnormal cells are destroyed. Conditioning rids the body of diseased cells and makes room for the marrow to be transplanted. It typically involves chemotherapy and/or radiation treatment, depending on the disease being treated. Unfortunately, this treatment also destroys healthy cells and has many side effects such as extreme weakness, nausea, vomiting, and diarrhea. These side effects may continue for several weeks.

AFTERCARE necessary in Bone Marrow Transplantation

A two- to four-week waiting period follows the marrow transplant before its success can begin to be judged. The marrow recipient is kept in isolation during this time to minimize potential infections. The recipient also receives antibiotic medications and blood and platelet transfusions to help fight off infection and prevent excessive bleeding. Further side effects, such as nausea and vomiting, can be treated with other medications. Once blood counts are normal and the side effects of the transplant abate, the recipient is taken off antibiotics and usually no longer needs blood and platelet transfusions.

Following discharge from the hospital, the recipient is monitored through home visits by nurses or out-patient visits for up to a year. For the first several months out of the hospital, the recipient needs to be careful in avoiding potential infections. For example, contact with other people who may be ill should be avoided or kept to a minimum. Further blood transfusions and medications may be necessary, but barring complications, the recipient can return to normal activities about 6-8 months after the transplant.

What are the RISKS in Bone Marrow Transplantation?

Bone marrow transplants are accompanied by serious and life-threatening risks. Furthermore, they are not always an absolute assurance of a cure for the underlying ailment; a disease may recur in the future. Approximately 30% of people receiving allogeneic transplants do not survive. Autologous transplants have a much better survival rate-nearly 90%-but are not appropriate for all types of ailments requiring a bone marrow transplant. Furthermore, they have a higher failure rate with certain diseases, specifically leukemia.

In the short term, there is the danger of pneumonia or other infectious disease, excessive bleeding, or liver disorder caused by blocked blood vessels. The transplant may be rejected by the recipient's immune system, or the donor bone marrow may launch an immune-mediated attack against the recipient's tissues. This complication is called acute graft versus host disease, and it can be a life-threatening condition. Characteristic signs of the disease include fever, rash, diarrhea, liver problems, and a compromised immune system.

Approximately 25-50% of bone marrow transplant recipients develop long-term complications. Chronic graft versus host disease symptoms include skin changes such as dryness, altered pigmentation, and thickening; abnormal liver function tests; dry mouth and eyes; infections; and weight loss. Other long-term complications include cataracts (due to radiation treatment), abnormal lung function, hormonal abnormalities resulting in reduced growth or hypothyroidism, secondary cancers, and infertility.

What can be NORMAL RESULTS in Bone Marrow Transplantation?

In a successful bone marrow transplant, the donor's marrow migrates to the cavities in the recipient's bones and produces normal numbers of healthy blood cells. Bone marrow transplants can extend a person's life, improve quality of life, and may aid in curing the underlying ailment.

An easy guide to some of the scientific terminology.

Allogeneic transplant
When stem cells are donated from one person and transplanted into another person to be used as a treatment for certain illnesses and conditions

Autologous transplant
When stem cells are taken from a person and then transplanted into the same person to be used as a treatment for certain illnesses and conditions

Cell expansion technology
This allows doctors to increase the number of stem cells in a unit in a controllable way. Many future treatments rely on cell expansion technology as these treatments need a larger supply of stem cells than can be obtained from a single cord blood unit. Cell expansion technology research is progressing well and the first patented processes are expected to be in place by 2010.

Haematopoeitic
This relates to the creation of blood in the body. A haematopoietic stem cell is one that can divide and produce blood cells.

Human Leukocyte Antigen (HLA)
Tests performed on the cord blood stem cell unit that identifies tissue types. Tissue types are similar to blood types. For a person to receive a transplant of cells or tissue from someone else, they must have the closest possible tissue type 'match'. Our tissue type is determined by our DNA. There are millions of possible tissue types, so a large bank of stem cells increases the chance of finding a matched unit when one is needed

Leukaemia
Is a cancer of the blood forming system, the blood forming system is found in the bone marrow. In leukaemia, some blood cells do not grow properly, but remain within the bone marrow and continue to reproduce in an uncontrolled way. These cells fill up the bone marrow and prevent it from making healthy white blood cells. This means the body is less able to fight off infections. There are many different kinds of leukaemia.

Match / Matched
Refers to a tissue typing match, the scientific term for this is HLA-type match. Tissue types must be matched as closely as possible between the person donating stem cells and the person receiving them to reduce the risk of rejection.

Peripheral blood
This is the blood that circulates around the arteries and veins of the body.

Processing
The way in which the stem cells found in umbilical cord blood are extracted from the blood, counted, tested and frozen ready for long-term storage.

Regenerative medicine
This is about treatments in development that, in the future, may be able to treat diseases and injuries by using stem cells to repair or regenerate damaged cells and tissues in the body.

Stem cell
A special kind of cell that can divide many times to make exact copies of itself, or to make specialised cells that do a particular task in the body for example a blood cell, bone cell or liver cell. Some people call stem cells ‘master’ cells or ‘blank’ cells because they can change into so many different types of cell.

Tissue type / typing
Tissue types are similar to blood types. For a person to receive a transplant of cells or tissue from someone else, they must have the closest possible tissue type 'match'. Our tissue type is determined by our DNA. There are millions of possible tissue types, so a large bank of stem cells increases the chance of finding a close match when one is needed.

Transplantation
Taking cells, tissues, or organs and placing them into the same person or a different person to treat disease.

Unit
Stems cells collected from the umbilical cord are properly described as a ‘cord blood stem cell unit’.

Breast Cancer
A tumour (lump) can be benign or malignant. Benign tumours do not spread to any other part of the body. A malignant tumour is a true cancer because it has the ability to spread beyond the original site via blood stream or lymphatic system. Dislodged cells reach a new site where they have to overcome resistance offered by your immune system and then form a colony to establish 'metastasis' or 'secondary tumour'.

Oncology (Cancer) & Chemotherapy
The most common cancers are Head & Neck (30%), Gynecological (30%, largely cervical), and Breast (about 14%). Luckily, all three are amenable to prevention by simple modifications in personal lifestyle and tobacco and food habits, by education and awareness programmes and counseling. They can be detected early through mass screening exercises, preventive clinics and simple self-examinations
Oncology is a medical specialty, which includes diagnosis, treatment and preventive measures of cancers. Chemotherapy is the practice of using drugs and medicines to treat cancer. These drugs are often referred to as "anti-cancer drugs". Depending on the type of cancer and its stage, one or more drugs are used. Cancer occurs due to uncontrolled and uncoordinated multiplication and /or growth of cells. Chemotherapy can slow or completely stop this process, resulting in the partial or total resolution of cancerous process. Some times hormones are also used to treat some specific types of cancer.

HPV Testing and Cervical Cancer
A HPV is a virus recognized as a risk factor for development of cervical cancer. It is one of the most common sexually transmitted infections. There are over 70 known types of HPV. Thirteen of these types are called high-risk viruses because they are cancer-related. In almost all cases, a healthy immune system will suppress or clear the virus (make the virus go away or will control the virus from causing any damage), including the cancer-related types. Most women with HPV will not develop cervical cancer. However, if HPV infection remains over many years, there is a greater chance of developing cell changes that may lead to cervical cancer.

BMT EMOTIONAL Aspects

Family members often wish they could be at the hospital, at home and at work all at once. Arguments may arise over what other family members are doing (or not doing). Family members may feel guilty or blame each other. Love, anger, vulnerability and faith may all be felt together.

Separation from part of your family can be hard. Sometimes it may be easy, and at other times it may be hard to deal with staying in the isolation room. Complying with the treatment regimen can be difficult, and privacy is difficult to maintain since medical care depends on knowing intimate details of everything that happens. We will try to respect your privacy as much as possible.

Siblings and donors ROLE in Bone Marrow Transplantation

Brothers and sisters often feel left out and hurt, so it is important to set aside special time for them. It helps to involve siblings in planning, telephoning, and visiting the patient. Often, donors feel ambivalent about donating. They want to donate yet at the same time feel apprehensive about the procedure. Many donors worry unnecessarily that their bone marrow might not be "good enough" or that they may be permanently harmed by the donation. Donors may also feel they are only partially appreciated by their family and the staff for undergoing surgery to give their bone marrow. It is important to show much recognition and appreciation for donors.

Coping strategies for patients and family members

Planning ahead seems to help. You may want to talk with staff about your own expectations, concerns, and worries. Please tell us how you and your child learn best, and what works best at times which are difficult for you. Tell us how much detail you like to know regarding medical information and doctors concerns. Some people like to anticipate all possibilities while others like to wait to find out when changes occur. It will be important to talk to the staff about your child's reactions to medicines, both physical and emotional, so we can know how to help.

Remember how your child normally handles boredom, fatigue, and frustration. Help him/her to use these coping methods or to find new ones. And remember that you will have similar feelings. You might want to plan ahead on how you will relax while at the hospital. You will be asked if you want to talk with other families who are involved with bone marrow transplantation. You may choose to do so at times or find kindred spirits on your own. Conserving your energy and resources is a challenge. When friends and family want to help you, remind them that hospitalization is only the beginning of transplantation and you may need their support even more when you return home.

The bottom line is that there is no "right way" to act or feel. Let us know your way, so we can help.

Issues relating to BMT Donor
There are several different types of donors including relatives (usually siblings or parents) and unrelated volunteers. In general all donors feel proud to make such a valuable life-saving contribution. Often they feel frightened of the unknown and feel better after discussing their thoughts and fears. Information about donation is discussed at an "age appropriate" level. Children who are donors meet with the child life specialist and are given a chance to use puppets and other forms of play.

Depending on a number of factors, the donor may either undergo a bone marrow harvest or a peripheral blood stem cell collection.

Bone marrow harvest
During the bone marrow harvest, which usually occurs on the day of the transplant, a small portion of bone marrow is collected from the anesthetized donor in the hospital. Because a significant amount of blood is taken with the marrow, the adult donor may be asked to donate 1-2 units of his or her own blood (auto-donation) approximately 1-2 weeks prior to the harvest. The nurse coordinator or the clinical nurse specialist will make these arrangements. Following the marrow harvest, the donor's blood is then infused back into the donor. This approach is intended to minimize the chances of the marrow donor having to receive a blood transfusion from another individual.

One to two weeks prior to the transplant day, the adult donor is seen by an internist for a screening history and physical, and the sibling donor is seen by the attending transplant physician. On the day before the transplant, the consent for anesthesia and surgery is signed with the transplant attending and the donor is evaluated by the anesthesiologist in the Pre-Sep department near the Admissions Department. Paperwork and additional blood tests are a part of the pre-admission process.

After midnight, the donor cannot eat or drink anything. On the morning of the bone marrow harvest or collection, the donor is admitted to the pre-op area on the designated floor. There will be doctors, nurses and other patients in this area, including the transplant physician who will be performing the bone marrow harvest. The operation usually begins early in the morning.

In the operating room the anesthesiologist will "put the donor to sleep." The physicians will then collect a small portion of bone marrow from the upper part of the pelvic bones. This process usually takes 2-4 hours, but may take longer depending on the amount of marrow needed.

The donor will wake up in the recovery room before being taken to his / her hospital room. A large bandage will cover the area from where the bone marrow was taken. Between 1-6 needle marks will be visible on the donor's skin. The donor will be sore following donation and will have some bruising. The amount of pain varies from donor to donor, and can last from a few days to several weeks. Medications will be given to help relieve the pain. The nurses will be checking the dressings for drainage at the needle sites and change the dressings as needed. An IV will be in place following surgery in order to administer routine antibiotics to minimize infection. Adult donors are admitted to one of the adult medical units. Sibling donors are admitted to room. The adult donor usually leaves the hospital one day after surgery. The sibling donor may be able to leave on the evening of surgery.

For unrelated donor marrow transplants, the same procedure occurs but at a donor center nearest to the donor's home / place of stay. The marrow is then brought to the BMT Hospital for further processing and / or administration to the recipient.

Peripheral blood stem cell (PBSC) collection
The PBSC collection is done mostly as an out - patient basis. Beginning five days prior to transplant, the donor receives 1-2 daily injections under the skin of a drug, granulocyte colony stimulating factor (G-CSF), which stimulates recruitment of bone marrow stem cells into the circulating blood. Common side effects include headaches and bone pain, which are relieved with Tylenol and / or ibuprofen.

The donor is admitted on the morning of the fifth day (the day of transplant) to the Leukapheresis Unit as an out-patient. For most adult donors, special catheters are placed under local anesthesia in the veins in each arm. For the young sibling donor, a double lumen catheter is placed under local or general anesthesia either in a vein in the neck or in the groin. This may be done in the operating room by one of the Pediatric Surgeons using general anesthesia or in the Leukapheresis Unit or the Cardiac Cath Unit by one of the Pediatric Cardiologists using local anesthesia. The catheters are necessary in order to carry blood to the apheresis machine where the stem cells are collected, and to return the residual blood back to the donor.

The PBSC collection takes 4-5 hours during which the donor can sleep, read, or watch TV. Typically, only a single collection is necessary, following which the catheter(s) are removed and the donor is able to go home. The PBSC are either administered directly to the recipient or taken to the BMT Laboratory for further processing prior to transplant. When a second donation is necessary, the donor will need to receive another injection of G-CSF and may need to stay in the hospital overnight.

For Detailed Dossier on Bone Marrow Transplantation, please write to us at  mktg@mediescapes.com