All you need to know about Bone Marrow Transplant in India

What is Bone Marrow?

Bone marrow is the soft, spongy, fatty tissue inside bones (spine, breastbone, skull, hips, ribs etc.) that produces blood cells. The bone marrow is responsible for the development and storage of the blood cells. It contains immature cells called stem cells (hematopoietic cells or HSC) that develop into blood. These stem cells develop into

  • Red blood cells or erythrocytes (carry oxygen and nutrients throughout the body)
  • White blood cells or leukocytes ( fights infection and aid immune system)
  • Platelets (helps in blood clotting)

Bone marrow transplant

 

Bone marrow is instrumental in production of more than 200 million blood cells per day in a human body.  Healthy bone marrow and blood cells are essential for a person to survive.When the bone marrow is damaged due to some disease, chemotherapy or radiation, it can no longer produce the stem cells. That results in anemia, weakness, infections, excessive bleeding and sometimes even death.

Bone Marrow Transplant

Bone Marrow Transplant(BMT) is the procedure involving replacement of diseased or damaged bone marrow of the patient with healthy bone marrow. BMT is sometimes the only treatment option available for a person whose bone marrow is not working efficiently.

Bone marrow transplant treats the following conditions:

Cost of Bone Marrow Transplant in India

The cost of Bone Marrow Transplant differs from country to country and depends on the hospital and registry from where the donor is identified. The Cost of Bone Marrow Transplant in India starts from 29K USD and could move upwards to 77K USD if the HLA match has to be sourced from registry.

During the Initial evaluation the doctor decides on the best conditioning regimenfor the patient. This might be either Chemotherapy or Immunotherapy. The cost of initial evaluation would be around 1500 USD

If chemotherapy is needed, then the next question would be how many cycles is required. The cost directly depends on the number of cycles advised.  Normally it is 3 to 5 cycle that is undertaken. The cost would range from 7500 to 10000 USD. Generally, there has to be a gap of minimum 3 days between each cycle. The gap could more depending on the dosage and the condition of the patient.

If doctor decides on Bone Marrow Transplant (BMT) then the price range would be:-

Procedure typeCost in USD
Autologous transplant29,000
Allogenic transplant with matching donor in family35,000
Allogenic transplant with donor from registry52,000 to 77,000*

*The cost varies based on the registry from which the donor is finalized. 

Certain cost-effective measures without compromising on the quality of the transplant outcome are followed like infection control practices to be followed strictly, to lower the transfer rates to ICU and medication to fight the infection.  Usage of WHO GMP complaint/ US FDA approved manufacturers generic drugs don’t compromise on the quality of treatment but reduces cost drastically.

Some of the hospitals have devised Outpatient Day Care BMT Program. This is mainly for treating conditions like multiple myeloma wherein autologous BMT is performed as an outpatient procedure. This helps in reducing the total cost drastically as the patient is not admitted in the hospital.

Best hospitals for Bone Marrow Transplant in India

BMT as it is a complicated treatment procedure that requires proper diagnosis, hospital with state of art technology, expert team of doctors, dedicated support team and a well-established pre and post-operative care. Thus, it is important for the patient to undergo the procedure in the hospitals that have license to perform BMT surgery and access to worldwide registries for finding suitable donors to get the best benefits of bone marrow transplant in India.

Bone marrow transplant team ideally involves BMT Physicians, Haemato-oncologists, Haemato-pathologists, Pediatric Oncologists, Trained Transplant Nurses, Medical Oncologists, Radiation Oncologists, Surgical Oncologists, Microbiologist (Infection control specialist), Research Scientist, Technicians, Clinical Coordinators, Pharmacists, Dieticians, Physiotherapist and Counsellors.

Important factors to consider while choosing the hospital are:

  • the infrastructure dedicated to the BMT unit, like the number of specialized BMT rooms following international clean room standards
  • comprehensive expertise in handling BMT for various ailments
  • standout testimonials and success stories
  • number of bone marrow transplants performed
  • counselling, language and other support services.

Further accreditations like JCI and NABH certifications are also an effective way to identify the best hospitals in India for bone marrow transplant.

Conditions curable with Bone Marrow Transplant

Bone Marrow transplant is a very effective treatment for many conditions like: –

Malignant diseases including:
  • Multiple myeloma:– A type of leukemia or lymphoma in which the plasma cells (type of white blood cells) multiplies unusually.
  • Leukemias: –
    • Acute lymphoblastic/lymphocytic leukemia (ALL): cancer in lymphoid line of blood cells in which bone marrow makes too many immature lymphocytes.
    • Chronic lymphocytic leukemia: cancer that affect lymphocytes.
    • Acute myeloid leukemia (AML): is a cancer of the myeloid line of blood cells in the bone marrow and blood and interfere with normal blood cells.

Relapsed or refractory ALL/AML can also be treated with bone marrow transplant

  • Lymphomas: –
    • Non- Hodgkin lymphoma: The type of cancer in the lymphatic system characterized by an uncontrolled growth in the number of lymphocytes (B cells or T cells).
    • Hodgkin lymphoma: The cancer in the lymphocytes caused due to genetic mutation of the lymphocytes.

BMT is the treatment for both new and relapsed version of the lymphomas

  • Neuroblastoma: A type of cancer that develops from immature nerve cells where in the Neuroblasts (immature nerve cells in babies) do not mature into nerve cells or cells of adrenal medulla.
  • Medulloblastoma: cancerous brain tumor
  • Myeloproliferative neoplasms (MPN)/myeloproliferative disorders: chronic bone marrow diseases that affect blood-forming stem cells. The bone marrow produces too many abnormal red blood cells, white blood cells or platelets which accumulates and circulates in the bloodstream.
  • Myelodysplastic Syndrome/disorder (MDS): Also known as bone marrow failure disorder. MDS is a condition where the body does not produce healthy blood cells (i.e. it produces either low number of blood cells or defective blood cells
  • Relapsed Ewing’s sarcoma: relapsed tumor in bones or soft tissue around bones
Non-malignant diseases:
  • Aplastic Anemia: The condition where the body stops producing enough new blood cells making the patient fatigued, highly susceptible to infections and uncontrolled bleeding
  • Thalassemia: It is a genetic disorder which is inherited from one of the carrier parents where the body produces abnormal form of hemoglobin. This results in excessive destruction of red blood cells that leads to anemia.
  • Sickle Cell Anemia: Caused by a genetic disorder termed as Hemoglobinopathy which affects the red blood cells.It affects the hemoglobin, the molecule in red blood cells that delivers oxygen throughout the body. People suffering from sickle cell anemia have ‘s or crescent shaped’ red blood cells. The sickle shaped red blood cells die prematurely causing acute anemia in the patient.
  • Severe auto immune diseases(such as systemic lupus erythematosus (SLE), immune thrombocytic purpura, rheumatoid arthritis (RA), insulin-dependent diabetes mellitus (IDDM), some types of non-insulin-dependent diabetes mellitus, multiple sclerosis, chronic glomerulonephritis, scleroderma etc.)
  • Severe Combined Immuno-Deficiency (SCID)disorders
  • Inherited metabolic disorder (such as congenital immune deficiencies, muco-polysaccharidosis, osteopetrosis, lipidosis, congenital lysosomal storage diseases, etc.)
  • Hurlers syndrome
  • Wiskott Aldrich syndrome: It is a rare genetic disorder where the immune system is abnormal and is characterized by reduction in number and size of platelets, (blood cell fragments that control blood clotting).
  • POEMS syndrome/ osteosclerotic myeloma: disorder of blood caused by clone of aberrant plasma cells (damages nerves)
  • Amyloidosis: abnormal protein is made in bone marrow and builds up other organs and tissues.
  • Adrenoleukodystrophy: genetic condition that damages nerve cells in the brain.

Procedure of Bone Marrow Transplant

The entire procedure of BMT, from preparation to recovery, takes more than a couple of months. The procedure involves:

Pre-procedural steps: The complete medical history of the patient is checked.Physical examination, blood tests (to evaluate the function of liver and kidneys), chest X-rays (to check if the patient has infectious diseases or lung diseases),electrocardiogram and echocardiogram (to check functioning of heart and blood vessels), CT scan (to check other organs) and biopsy ( lab testing of cancer cells) are conducted to evaluate the patients overall health.

Harvesting of stem cells: Harvesting of stem cells may be done from the patient’s (autologous transplant) or donor’s (allogeneic transplant) blood (peripheral blood stem cell collection) by a process called apheresis. In case of autologous transplant, the healthy bone marrow is harvested from the patient before the chemotherapy.

  • First, growth factor injection to increase stem cells is given to the patient for a few days. Then, the blood is drawn from vein and is circulated on a machine that separates stem cells (which is collected and frozen) and the remaining blood is returned to the body.

Usually, for BMT treatment, the bone marrow (extracted from different parts of hipbone by surgery) or cord blood (stem cells from placenta or umbilical cord of newborn baby) is used.

Conditioning regimen for BMT: Prior to the bone marrow transplant procedure, the conditioning regimen is followed in which the diseased bone marrow and other cancerous cells are removed by chemotherapy, total body irradiation, or a combination of both through two treatment techniques:

  • Ablative/myeloablative treatment: To kill cancerous cells or destroy bone marrow (in patients with other bone marrow related diseases) high dose chemotherapy, radiation or both are given to the patient. It kills the bone marrow and disables the immune system.
  • Reduced intensity treatment/ mini transplant: In older patients, low doses of chemotherapy and radiation are given before the transplant to weaken the immune system so that it accepts donor stem cells. This is called non-myeloablative conditioning.

An alternate technique of conditioning called immunotherapy is sometimes performed depending on the patient’s condition, age and severity of disease in the patient. In this conditioning technique, the patient’s own immune system is strengthened and programmed to fight and kill the cancer cells.

The conditioning regimen makes room for bone marrow from the donor stem cells to grow, removes any residual cancerous cells and helps in suppression of immune system so that the new bone marrow is not rejected by the body.

Placement of Central venous line: After the satisfactory evaluation of health status of the patient the surgeon/radiologist surgically places a needle called catheter (central venous line), or a port, in a vein in the chest or neck (transplanted stem cells, medicines and blood products are infused through it during treatment).

Transplanting of stem cells: The stem cells are infused into the patient’s bloodstream through the central venous catheter. The transplanted cells migrate to bone marrow to grow and develop. This process of recovering of bone marrow and immune system is called engraftment. Treatment of side effects and complications are taken care of by the specialized team of healthcare professionals during this phase. It takes around 10-28 days for the white blood count to increase as a mark of first sign of engraftment.

Bone marrow transplant procedure

The complete process of bone marrow transplant in India could have a duration of 60-75 days. This covers pre-procedural steps, harvesting of stem cells, conditioning regimen for BMT, and hospital stay for transplanting of stem cells.

Recovery: After engraftment the patient (treated as an outpatient) may take 3 months (in case of autologous transplant)-12 months (in case of allogeneic transplant) to recover fully. The patient is encouraged to follow up (long term follow-up) from time to time to rule out any possibility of complication.

Types of Bone Marrow Transplant

There are three ways of conducting a Bone marrow transplant:

Autologous bone marrow transplant: Stem cells are removed from the patient before giving high dose chemotherapy and radiation treatment and stored in a freezer. After the high dose chemotherapy and radiation to kill residual cancer cells the stem cells are infused into the bloodstream to make normal blood cells. It is also called rescue transplant or stem cell rescue.

Allogeneic bone marrow transplant: Stem cells are removed from other persons (donors). Selection of donors depends on various tests ( HLA typing or tissue typing) The proteins called human leukocyte antigen or HLA markers or histo-compatibility antigens of the patient are matched with that of the donor (usually,6-10 HLA matching is required depending on the patient’s condition, stage of the disease and its severity). For the treatment of fast progressing diseases like sickle cell anemia, a match of 8/10 is necessary. Members of family (close members like parents, siblings) have similar proteins (therefore, they are preferred to be a perfect match for the patient). In case, the siblings or other relatives fail to have the required HLA matching, match is tried in the worldwide registries.

For treatment of some diseases, the transplant can be done without a perfect match, but it is likely to cause reactions called graft versus host disease (GVHD). GVHD typically causes skin rashes, diarrhea, liver damage and in some cases GVHD may be severe and life threatening. Anti rejection drugs are prescribed to prevent from developing GVHD.

Umbilical cord blood transplant: It is kind of an allogeneic bone marrow transplant. Stem cells from umbilical cord immediately after the birth of the infant. These stem cells are tested, counted, typed and frozen until they are needed. Umbilical stem cells are so immature that they do not require perfect matching.

Success rate for Bone Marrow Transplant in India

Success percentage of Bone marrow transplant depends mainly on three factors:

  • Patient condition – “The younger the patient the better the outcome” is the statement after research.
  • Disease for which Bone Marrow Transplant is done – The success percentage varies drastically based on which condition is being treated for. For example, in the case of Thalassemia almost 80 % of the cases can be completely cured and the patients go back to leading a normal life. It is 70 -80% in case of Aplastic anemia where as its only 20-30% for certain badly affected blood cancers.
  • Team handling the BMT: – A BMT procedure involves the inputs from various functionalities in the team. The success of the whole procedure depends a lot on the way the team functions and the compliance with standard protocols.

Risks of Bone Marrow Transplant

There are certain risks associated with BMT before, during and after the procedure.

  • Donor: The harvesting of donor stem cells for BMT is performed under anesthesia. Thus, after the surgery the donor may experience tiredness, weakness or trouble walking. The area from where the bone marrow is extracted may feel sore. But all these symptoms wear off within a span of 2-7 days and the donor may resume his normal life.
  • Recipient: Risks of BMT range from being mild to severe. During the infusion, the patient may experience pain, chills, fever, chest pain, hives etc. After the transplant, the patient is required to stay at the hospital for some weeks and may experience certain discomforts such as being highly susceptible to infection, excessive bleeding, require blood transfusion, experience nausea, vomiting, mouth sores, diarrhea, extreme fatigue, temporary mental, emotional distress, graft failure etc.
  • After the BMT, within around 10-25 days, engraftment of new stem cells happens. Engraftment is the process by which the new stem cells reach the recipient’s bone marrow and start producing new blood cells. It may take 30 days to several months for the patient’s immune system to fully recover.

Things to take care before undertaking BMT

  • Often, the BMT treatment may require long hospital stay, the patient is to be kept in isolation as there is a high risk of having infections. The long hospital stay in isolation can be very emotionally draining for the patients hence getting involved with support groups will be helpful.
  • The patients must abstain from alcohol consumption, smoking etc. to help body withstand the strenuous course ahead.
  • The patient must talk about the problems/discomfort he’s experiencing to the medical team to get help in case the symptom is not normal in the course of recovery.
  • The patient is required to take time away from work, regular activities. It is advised to plan child care, house work and hospital visits in advance.
  • The patient is also required to understand the cost related to BMT procedure and plan management of his medical expenses.
  • The bone marrow transplant treatment may affect the fertility of the patient as the procedure may destroy healthy cells in reproductive organs. It is advisable to talk to your doctor before undergoing chemotherapy and radiation and take necessary steps of precaution. Men may collect, freeze and bank their sperm for later use. It is better to consult an infertility specialist before starting the BMT treatment. Women may be advised to harvest and freeze their eggs for later pregnancy, or they may be advised to conceive and freeze an embryo before undertaking BMT.

Complications and side effects of Bone Marrow Transplant

Bone marrow transplant may lead to certain complications depending on certain factors such as the type of BMT technique, disease requiring such transplant, age and health condition of patient, variation in tissue matching of donor and recipient etc. Possible complications are

  • Graft versus host disease (GVHD) : donor cells attack patient’s body cells
  • Graft failure: The transplanted cells don’t produce new cells
  • Infection: bacterial, viral and fungal infections.
  • Low platelets /RBC count: thrombocytopenia or anemia due to non-functioning bone marrow.
  • Diarrhea, vomiting, nausea: may be due to chemotherapy, GI irritation or irradiation
  • Damage to vital organs (heart and liver)
  • Early menopause/Infertility
  • Mucositis: inflammation and soreness in stomach, mouth and throat.

Donating bone marrow

The common belief is that donating Bone marrow is painful and dangerous to the donor. But in reality, bone marrow donation is not painful for the donor as the surgery is performed under regional or general anesthesia. The discomforts a donor may experience are only tiredness, weakness or trouble walking for a few days, soreness in the place of surgery etc. But these normally subside with time and rest.

The danger associated with donating bone marrow is similar to any other medical procedure. The possible threats of donating bone marrow are only from the side-effects of anesthesia. The donor may be discharged the same day after extraction of bone marrow but is advised to take rest after the surgery. He can return to work and resume other activities after 7-10 days.

Only 4-6 % of the total bone marrow is extracted from the hipbone of the donor during the procedure. So, it is highly unlikely that the donor’s immune system is jeopardized. The bone marrow will return to its normal levels in the donor’s body within 4-6 weeks. The bone marrow replenishes itself within a few weeks; hence a person can donate bone marrow many times during his lifetime.

Nowadays, another way of donating stem cells, called the peripheral blood stem cell (PBSC) donation is available. This method helps to avoid the side effects of bone marrow aspiration since it does not involve any anesthesia.

The donor is injected with a drug to stimulate production of white blood stem cell for 2-5 days prior to actual procedure. The blood is taken out through a needle from one arm of the donor and sent to a machine that separates white blood stem cells (which is ­­stored for transplant) from rest of the blood. The rest of the blood is returned to the other arm of the donor. It takes around 4-6 hours for the donation. The donors may experience flu like symptoms; but it subsides in a few days.

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