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Bone Marrow Transplant for Sickle cell disease

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Bone Marrow Transplant for Sickle cell disease

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Bone marrow transplant is the only promising procedure with a potential for curing sickle cell disease in young symptomatic patients. Sickle cell disease is the most common inherited blood disorder which is characterized by sickle shaped red blood cells due to the presence of abnormal hemoglobin (Hb-S) subsequently resulting in rigid, fragile RBCs, frequent hemolysis and micro vascular occlusion (clog small blood vessels). Bone marrow transplant weakens and destroys cells or tissues that are responsible for causing blood disorders and replace them with healthy blood cells derived from the stem cells of the donor. This restores the normal healthy blood. BMT is, however, recommended for patients with severe SCD accompanied with symptoms such as frequent pain episodes, acute chest syndrome and stroke.

 

If you are searching for a reliable hospital that can provide the best bone marrow transplant in India, then come directly to us. At HealthcaretripIndia, we are engaged in providing excellent bone marrow transplant treatment to the patients, from best hospitals of India. The treatment is conducted by some of the highly qualified surgeons. Our hematologists are globally trained from USA and UK. They have carried out several bone marrow transplant procedures with high success rate. So, contact us anytime.

Q1 What is sickle cell disease?

 

A1 Sickle cell disease is the most common inherited blood disorder which is characterized by sickle shaped red cells due to the presence of abnormal hemoglobin(Hb-S) subsequently resulting in rigid RBC, frequent hemolysis and microvascular occlusion.

 

Q2 What is Hematopoiesis?

 

A2 Hematopoiesis is derived from Greek word that literally means"to make blood". It refers to the formation of blood cells. All blood cells are produced from Hematopoietic stem cells.

 

Q3 What are Hematopoietic stem cells?

 

A3 The stem cells, primitive, immature and undifferentiated cells that have a unique ability to produce all types of mature blood cells by way of hematopoiesis are referred to as HSC(Hematopoietic stem cells) or hemocytoblasts. They are found in adult bone marrow especially in femur(thigh bone), sternum(breast bone) or pelvis. They are also present in umbilical cord blood and in very small numbers in peripheral blood.  

 

Q4 What is bone marrow?

 

A4 Soft, Spongy gelatinous tissue inside the hollow centre of some bones such as hip and thigh bone with abundant supply of stem cells is referred to as Bone marrow. It is responsible for the production of blood cells circulating in your body. Bone marrow constitutes 4% of the total body weight.

 

Q5 What does Bone marrow transplant involve?

 

A5 Extraction of the stem cells from the donor. Prior to BMT, patient's defective bone marrow is weakened and destroyed through high dose chemotherapy along with or without radiation therapy,so as to prevent the rejection of the stem cells from the donor. Subsequently, patient's bone marrow is replaced with blood forming stem cells from the donor. Replaced bone marrow produces healthy blood cells.This is carried out similar to a blood transfusion through IV tube.

Stem cells are infused in the blood stream of the patient and eventually they find their way into the bone marrow and start producing healthy blood cells such as RBCs,WBCs and platelets.

The patient is kept in BMT unit under strictly hygienic environment in isolation from the time his/ her defective bone marrow cells are destroyed with the high dose chemotherapy and/or radiotherapy till the time transplanted stem cells start producing healthy blood cells. All this while the patient needs blood and platelet transfusion. Once the count of the blood cells restores to normalcy and clinical condition of the patient improves, he/she can be discharged. However, the patient needs regular follow ups to detect any conditions such as graft verses host reactions, any complication or infection that call for medical attention.

 

The whole process starting from chemotherapy and /or radiotherapy till discharge from the hospital may take weeks or 1 to 2 months followed by few more months of recovery.

 

Q6 What is the relationship between sickle cell disease and gall stone formation?

 

A6 Patients with sickle cell disease are more vulnerable to the develpment of Gall stones, 30% to 70% increased risk due to chronic hemolysis.

 

Q7 Who can be a donor for BMT?

 

A7 A donor should not have sickle cell disease. He should have normal hemoglobin or can have sickle cell trait.

Donor can be:

Matched and Related:Sibling with same bone marrow type and have the same mother and father. Siblings are matched through special tests such as HLA typing.

Matched and Unrelated:Persons who are not related to the patient and have same bone marrow type. National organizations play a key role in matching the bone marrow of the patient and the donor.

Haploidentical:In contrast to near complete HLA match, this donor need to be only a 50% match to the recipient. 

 

Q8 What is Haploidentical transplant?

 

A8 A modified and an advanced form of stem cell transplant, a relatively new procedure, developed to widen the horizon of potential donors which comprises of a donor who is a healthy first degree relative such as a parent, a sibling or a child of the recipient. In contrast to near complete HLA match, this donor need to be only a 50% match to the recipient.

Earlier, it was imperative to have a closely matched tissue types for the donor and the recepient. Proteins on the surface of the body cells, HLA(Human Leucocyte antigens) determines the tissue type. They regulate the human immune system and help it to differentiate between body's own protein or foreign protein that needs to be eradicated. Doctors always seek donors that have the closest match of the tisue type to reduce the risk of attack on healthy, normal tissue.

 

Q9 What are the benefits of Haploidentical transplant over conventional transplant?

 

A9 Haploidentical transplant have several advantages over the conventional bone marrow transplant as mentioned below:

  • Easy availability of a suitable donor.
  • Prompt execution of the procedure unlike traditional unrelated donor.
  • Relatives can donate on a short notice unlike for unrelated donors especially if they belong to another country.

Haploidentical transplant procedure is more or less the same as that of standard allogeneic transplant. The only major difference is that the recipient has to be given high dose of chemotherapy drug post transplant, to sharply decrease active T cells which are instrumental in the development of a potential side effect of the transplant i.e., GVHD.

 

Q10 What is GVHD(Graft verses host disease)?

 

A10 GVHD is a potential complication that may arise after the bone marrow or stem cell transplant from a genetically different person, wherein the donated blood marrow or peripheral blood stem cells perceive the recipient's body as stranger and attack the recipient's body. GVHD can be acute or chronic.

In acute GVHD, signs and symptoms happen within 100 days f the transplant whereas in Chronic GVHD the sign and symptoms will arise after 100 days of transplant.

Your team of specialists will guide you to watch out for the GVHD associated signs and symptoms so that they can be addressed timely to prevent serious complications later.

 

Q11 What can be the potential risks associated with BMT?

 

A11 The following are the potential risks that may be associated with BMT

  • Infection
  • GVHD (Graft Verses host disease)
  • Graft failure
  • VOD (Veno-occlusive disease)
  • Nutrition related problems such as diarrhea, naurea, vomiting and even lack of appetite.
  • Decreased blood counts
  • Infertility issues
  • Social and emotional concerns due to lengthy hospital stay of around 4 to 6 weeks and being away from home, family and friends.

Q12 Is BMT the only treatment for sickle cell disease?

 

A12 BMT is not the only treatment for sickle cell disease. There are other treatments like use of medicines like hydroxyurea and chronic blood transfusions that helps manage the disease well. However, BMT is the only treatment that has the potential to cure sickle cell disease for good. Several studies have suggested that BMT from matched related donor offers 85% chances to cure the sickle cell disease.

 

Q13 What are the other diseases for which BMT offers treatment?

 

A13 Your specialist advises you to undergo bone marrow transplant if you are suffereing from cancer or any other disease affecting your blood such as 

  • Blood Cancer (malignancy)
    • Acute or Chronic Leukemia
    • Hodgkin's Lymphoma and Non Hodgkin's lymphoma
    • Multiple Myeloma
    • Myeloproliferative syndromes and Myelodysplasia
    • Renal cell carcinoma
    • Myelofibrosis
  • Non malignant or non cancerous blood disorders
    • Aplastic anemia
    • Hemoglobinopathies such as in case of sickle cell disease
    • Inborn errors of metabolism
    • Autoimmune diseases such as Multiple sclerosis and scleroderma
    • Immune deficiency disorders

 

Q14 What are the different types of bone marrow transplant?

 

A14 There are mainly three kinds of Bone marrow transplant depending upon who is the donor, such as:

  • Autologous BMT
    • Also reffered to as rescue transplant. "Auto" means self. In this type of transplant the stem cells from the patient's bone marrow are extracted prior to chemotherapy or radiation therapy and then replaced back.

​​

  • Allogeneic BMT
    • "Allo" means other. Here, the immature bone marrow cells or stem cells are extracted from the donor. Allogeneic means from a genetically different individual from the same species and hence immunologically incompatible.

​​

  • Syngeneic BMT
    • Donor is healthy identical twin of the recipient.

 

Q15 What type of BMT is recommended in patients with sickle cell disease?

 

A15 Allogenic Bone Marrow Transplant is done in patients with symptomatic SCD. In this transplant, stem cells are procured from matched and related donor (usually brother or sister), unrelated donor or Umbilical cord blood.

 

Q16 Is BMT right for me?

 

A16 Your specialist(Hematologist) and his team will determine whether BMT is a right choice of treatment for you or your child. Your age, extent of organ damage and severity and frequency of symptoms are some factors they will take into consideration to take decision. Your specialist will weigh the risk and benefits of the BMT in your case.

Usually it is recommended in young patients with severe SCD symptoms such as stroke, acute chest syndrome, frequent painful crisis and an availability of a suitable donor with matching bone marrow. The risk of BMT increase with growing age and/ or development of organ damage. Therefore, in adults with SCD, it is not considered a viable treatment option.

 

Q17. What is the source of stem cells?

 

A17. Stem cells can be procured from 3 sources namely,

  • Bone Marrow

  • Peripheral blood 

  • Umbilical cord blood from new borns.

​Bone marrow or the peripheral blood can be the recipient's himself or herself or from the donor.

 

Q18 What is the relationship between Sickle Cell Anemia and Malaria resistance?

 

A18 Sickle cell Anemia is a genetic disease with impaired Hemoglobin structure, the protein that carries oxygen in the blood, to the tissues.

 

Distorted Hemoglobin in sickle cell anemia, once de-oxygenated in tissues(not carrying oxygen), clumps together with other de-oxygenated hemoglobin and form long chains rendering sickle shape to the RBC instead of their normal smooth disc shape. These distorted RBCs block the blood vessels and thereby the flow of blood to the vital organs of the patient’s body leading to several complications.

 

The Normal (N) or sickle cell(S) hemoglobin tend to deoxygenate due to a physiological principle named"Bohr effect" taken after the name of the scientist who discovered it. According to this principle,  if N or S Hemoglobin is placed in an acidic or High CO2 environment, the hemoglobin will deoxygenate or release oxygen.

 

RBCs(whether with normal or sickle cell hemoglobin) containing malarial parasites are induced by the parasite to produce acidic environment as they metabolize food and form CO2 as waste product which in turn in RBCs aqueous environment produces acidic environment which by way of Bohr effect causes deorxygenation of hemoglobin, its clumping, forming long chains resulting in sickle shapd RBCs.

 

The genetic change that causes Sickle cell anemia, renders protection against malaria at the same time.

 

Sickle cell anemia patients are endowed with one protection amongst many setbacks, which is “Protection against Malaria”. It happens because of the following two reasons:

 

  1. The body of Sickle cell anemia patients sense the distorted RBC and tries to eliminate them as many as possible, through spleen. If the distorted RBcs are inhabited by the malarial parasite then they are too destroyed.
  2. Once sickle shaped, the RBC cell membrane tends to stretch far too much thereby making its membrane porous. It results in leakage of nutrients such as Potassium from the cells which are essential for the survival of the malarial parasites. 

​In nutshell, since Sickle shaped RBC are poor host to the malarial parasite and the parasites die in sickle shaped RBCs. Patients with sickle cell hemoglobin are resistant to Malaria.

 

Q19 What are the signs and symptoms of Sickle cell disease?

 

A19 The signs and symptoms may differ from person to person and even time of their onset also vary. 

Early signs and symptoms can be listed as follows:

  • Irritability caused due to anemia
  • Fatigue
  • Pain and swelling in hands and feet , referred to as Dactylitis in medical parlance.
  • Due to breakdown of astronomically huge number of red blood cells, Jaundice is caused.

​It is important to note that most of the signs and symptoms of SCD happen as a result of its associated complications. The complications of sickle cell disease and their associated symptoms can be summarized as follows:

  • Acute pain crisis, also referred to as Vaso Occlusive crisis

    • ​Sudden, sharp and intense pain develops in any or multiple part/s of the body due to blockage of the blood vessels supplying blood to them, by sickle shaped RBCs and thereby depriving them of the oxygen supply. There may be certain triggers initiating such crisis such as stress, sickness, dehydration and so on, however, the exact trigger is often poorly identified. 

  • Chronic pain

  • Acute chest syndrome

    • ​Manifested by symptoms such as shortness of breath, cough, chest pain, fever and fast breathing. The symptoms develop as a result of blockage of blood vessels supplying oxygen rich blood to the lungs, by the sickle shaped red blood cells. The lung function is compromised as part/s of it get damaged.   It is often associated with lung infection as well.

  • Stroke 

    • ​When the blood supply to the brain is blocked due to sickle shaped RBC, it may cause nerve cells to die leading to the stroke. Stroke may be clinically apparent(clinical stroke) or silent wherein no clinical symptoms are visible, although part/s of the brain has been damaged or died. The signs and symptoms depend upon the area of the brain which has been damaged leading to its compromised functions.

    • Normally clinically apparent symptoms are weakness in one side of the body, difficulty in speech, gait disturbance, difficulty in comprehension, intense headache and balance disorder whereas silent stroke is associated with thinking problem, difficulty in decision making.

  • Severe anemia

    • ​Usually  the intensity of anemia is mild to moderate, however, it may be severe sometimes which may be fatal. Anemia is manifested by the following symptoms such as shortness of breath, fatigue, pale skin and so on.

  • Pulmonary hypertension

  • Heart disorders such as enlargement of the heart. Repeated blood transfusion may also cause heart damage due to iron overload.

  • Kidney disease associated with symptoms such as frequent urination, nocturia(the person wakes up at night to pass urine), blood in urine, protein loss through urine and compromised kidney function due to kidney damage.

  • Liver disease due to iron overload as a result from repeated blood transfusion or liver may get damaged eventually leading to liver failure due to its blocked blood supply.

  • Gall bladder stones formed as a result of breaking of RBC(hemolysis); release of hemoglobin and thereby bilirubin, high proportion of which contributes in the formation of gall bladder stones. The stones get obstructed causing symptoms such as pain in the upper right side of the abdomen, nausea and vomiting. The gall stones may remain asymptomatic for years.

  • Painful and prolonged erections in males, often referred to as Priapism in medical terminology. It may eventually lead to impotence.

  • Ulcers in  legs

  • Delayed growth and puberty, due to anemia.

  • Avascular or aseptic necrosis of the joint especially hip joint leading to joint problems.

  • Eye disorders when blood supply to eyes is affected leading to impairment or loss of vision.

  • Infections

    • ​Caused due to damaged spleen. Spleen when functions normally, helps in preventing infections in a person by conferring protection against them, however, when damaged due to SCD, may result in occurrence of gamut of serious infections, possibly fatal.

  • ​Depression

 

Benefits of Bone Marrow Transplant in India

 

  • High quality Bone marrow transplant at fraction of cost of what you may have to pay in US or UK for the comparable treatment.

  • World class hospitals with state of the art infrastructure.

  • No waiting period

  • USA, UK trained Hematologists who are highly experienced in carrying out the procedure with competence and ease.

  • Great ambience

  • Compassionate staff to look after

  • Hospitals accredited with international organizations such as JCI(Joint commission International) for quality standards.

  • Language no barrier. English speaking people and if required, translators are available for your convenience

  • Most economical accommodation available at a walking distance from the hospital. Wide range of options starting from guest house, service apartments to five star hotels, best suited to your budget and choice.

  • Good flight connectivity

  • India has a diverse and rich cultural heritage. You can witness its beauty and uniqueness. It offers most conducive environment for recuperation.

Dr Ashok Vaid

MBBS, MD(Internal Medicine), DM(Medical Oncology)

Chairman, Division of Medical and Pediatric Oncology,Hematology

Bone marrow/Stem cell transplant

Medanta-The Medicity, Gurgaon, Delhi-NCR

Dr Rahul Naithani

MBBS, MD(Pediatrics), DM(Clinical Hematology)

Senior Consultant, Bone Marrow/stem cell Transplantation and Clinical Hematology

Max Super Speciality Hospital, Saket, Delhi

 

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