Bone Marrow Transplant – All you need to know

Overview

Bone marrow transplant (BMT) is a special procedure for patients with certain cancers or other life-threatening diseases. BMT involves taking stem cells that are usually found in the bone marrow, filtering these cells, and giving them back to either the patient they were taken from or to any other person. The objective of BMT is to infuse healthy bone marrow cells into an individual after his/her own unhealthy bone marrow has been removed. 

Bone Marrow Transplant: What is Bone Marrow?

Bone Marrow is a spongy tissue found in the center of bones such as the back of hips and breastbone (the sternum) which produces blood cells. Bone Marrow produces three different types of blood cells called red cells, white cells and platelets. Like all other Cells they have limited life span hence need for continuous production.

• Red cells- carry oxygen, if low one get tired easily (Anemia)
• White cells- help us fight infections
• Platelets- help to prevent or stop bleeding or bruising
• Without normal blood cell production, you can become tired, susceptible to infections and bruise easily.
• Specific terms are used to describe low numbers in all three groups and you may hear these terms mentioned frequently.
• Neutropenia– when one type of white cells is low
• Thrombocytopenia– when platelet numbers are low
• Anemia– low hemoglobin (many synonymously use as low blood)

These stem cells are of prime importance in Bone Marrow Transplantations.

Other sources of stem cells have gained popularity in the last decade, as their harvesting is better tolerated by patients while delivering almost identical success rates when compared to bone marrow transplants. These include peripheral blood stem cells and cord blood stem cells.

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Where do stem cells come from?

There are two categories of transplants. One is called Autograft where patients own stem cells are re infused after high dose chemotherapy. Second is called Allograft where bone marrow cells derived from donor- who could be sibling, unrelated, family donor and cord. If sibling is used we call it Sib Allo transplant. If unrelated donor is used we call it Matched unrelated donor transplant (MUD)

If Father, Mother, Son or Daughter are used who would be at least  half match we call that transplant as Half match Transplant or Haplo Bone Marrow Transplant.

What conditions require Bone Marrow Transplant?

The conditions which necessitate a BMT can be broadly classified into 2 groups:

Cancerous Conditions

• Acute Myeloid and Lymphoblastic Leukemia
• Chronic Myeloid and Lymphoblastic Leukemia
• Hodgkin’s and Non-Hodgkin’s Lymphoma
• Myelodysplastic Syndrome
• Myeloproliferative Neoplasms, Primary Myelofibrosis, etc.
• Multiple Myeloma

Non-Cancerous Conditions

• Aplastic Anemia
• Haemoglobinopathies like Sickle Cell Anemia
• Immuno-deficiency disorders
• Congenital errors of metabolism
• Congenital storage disorders
• Thalassemia – In India there are estimated 10,000 -12,000 new Thalassemia cases diagnosed every year. Thalassemia is an inherited Genetic condition of Hemoglobin abnormality. The most common types are:
  • Thalassemia Trait or Thalassemia Minor:  means you carry the defective gene but can still make enough red blood cells. Its asymptomatic unless some blood tests( CBC) are done . Many times these patients are wrongly treated as Iron deficiency with Iron supplements.
  • Symptomatic Thalassemia or Thalassemia Major There is more than one gene abnormality and most of the Hemoglobin produced is faulty and they become severely anemic by 6 months of age and will need frequent blood transfusions

What are the stages of a Bone Marrow Transplant?

Undergoing a Bone Marrow Transplant is a five-stage process.

1. Physical examination – to assess the recipient’s health status
2. Harvesting: the process of procuring stem cells to be used in the transplant
3. Conditioning – preparing the body for transplant
4. Transplanting the stem cells
5. Recovery period 

Physical Examination

Routine diagnostic tests such as complete Haemogram, X-ray, and urinalysis are performed. In addition, HLA (Human Leukocyte Antigen) typing and blood grouping are done to evaluate recipient/donor compatibility. This compatibility evaluation is most vital to reduce the risk of transplant rejection.

Harvesting the Cells from the Donor

• Autologous Bone Marrow Transplant: The donor is the patient himself. Stem cells are procured from the patient by either bone marrow harvest or apheresis (a process to collect peripheral blood stem cells), frozen, and later given back to the patient after a thorough treatment.

• Allogeneic Bone Marrow Transplant: The donor shares the same HLA type as the patient. Stem cells are procured by either bone marrow harvest or by apheresis from a genetically matched donor, generally a sister or brother.

Other donors for allogeneic bone marrow transplantations may include:

• A parent/relative: A haplo-identical match is when the donor is a parent and the genetic match is at least half identical to the recipient
• Unrelated bone marrow transplants. The stem cells or marrow are from an unrelated donor. For unrelated donors, national bone marrow registries are surfed.
• Peripheral Blood Stem Cell Transplant: This is routinely performed compared to the bone marrow harvest method as this procedure is easy to perform and less invasive. Some research studies even suggest that the stem cell yield by this method is higher when compared to bone marrow harvest. The process takes 4-6 hours after administering the necessary medication for 4 days.

Donors are injected with Granulocyte Colony Stimulating Factor (GCSF) for a duration of 4 days to stimulate stem cell proliferation.

The stem cells from the donor are collected using a process called apheresis and administered intravenously to the patient. The stem cells of the donor have the property of stem cell homing whereby they migrate to the bone marrow of the patient and override his/her defective stem cells. This restores the ability of bone marrow of the patient to produce normal blood elements.

• Umbilical Cord Blood Transplant: Umbilical cord blood is a very rich stem cell source. After delivery or birth of the infant, cord blood can be collected from the umbilical cord (which is a waste by-product of child birth) and preserved for later use. Cord blood has a higher concentration of stem cells compared to adult blood. About 80 to 100 ml cord blood is collected and such stem cells are perfectly suitable for transplants in children. The cord blood stem cells are typed, counted as well as tested before storage and preservation. Cord blood cells are frozen until required for transplant.

Bone Marrow Transplant: Conditioning of the Patient

The conditioning procedure involves radiation (sometimes) and high doses of chemotherapy. It is carried out for three reasons:

• Destroying the existing bone marrow cells in order to make room for the transplanted stem cells
• Destruction of any existing cancer cells
• Suppression of activity of the immune system to decrease chances of rejection of donor stem cells

Transplanting the Stem Cells

The Bone Marrow Transplant process does not involve the insertion of the marrow stem cells physically into the marrow of the recipient but is more of a delicate and intricate blood transfusion method. The stem cells that are harvested are administered through a central venous catheter into the bloodstream. From there these harvested stem cells find their way to the marrow by a property of stem cells known as stem cell homing.

5. Recovery: The patient is monitored continuously to ascertain the success of the transplant. But, the procedure involves a few risks including:
6. Graft versus host disease (GvHD): In this disease, the transplanted stem cells (“graft”) attack the recipient’s cells (‘host’) as they are considered alien to the body.

There are two types of GvHD:

1. Acute GvHD – This occurs during the first three months after the transplant.
2. Chronic GvHD – Develops from acute GvHD and can cause symptoms for many years.
3. Infections as a consequence of chemotherapy and bone marrow suppression, the body is transiently unable to produce cells to combat infections.

10 Things You Didn’t Know about Bone Marrow Transplant

1. Bone marrow transplant is not a surgery, it is a complicated medical treatment.
2. Bone marrow donor donates cells as day care for few hours.
   1. No sedation
   2. No operation
   3. No procedure to donor
   4. Donor donates stem cells quite similar to platelet donation.
3. Bone marrow transplant is a cure for many blood disorders.
4. Bone marrow donor is chosen on the basis of blood test called HLA typing which should be fully matched that is 10 out of 10. First priority is matched sibling, next comes matched unrelated donor, if no match available third option would be half match from parents, children or siblings.
5. Generally patients have lots of tests to assess suitability for transplant.
6. Patients have in-patient stay for three weeks in special transplant ward with all safety precautions.
7. Patients need to have regular doctor visits for three months after the transplant to look for any infections.
8. Patients generally can resume their work after 6-12months post-transplant.
9. There are lot of things specialist takes into consideration before transplant, blood group match is not mandatory.
10. Half match transplant allows every patient to have a donor.

Conclusion

As with any surgery/procedure like Bone Marrow Transplantation (BMT), prognosis and long-term survival may vary significantly from patient to patient. The number of transplantations being performed for an increasing number of diseases and ongoing medical developments has improved and the outcome for BMT in adults and children too.

Constant follow-up care is necessary for the patient after a BMT. New procedures and methods to improve treatment therapies and reduce complications and side effects of transplantation are constantly being discovered.

FAQ

How the donor is selected for Bone Marrow Transplant?

Once we identify there is need for Bone marrow transplant, we will perform a Blood test called HLA testing on patient and look for similar HLA type or close match from the donor.

If there are siblings they are tested as 1 out of every four siblings will be a full match. If no siblings we check on the bone marrow donor registry database to identify suitable match. If no suitable donor available then we would recommend half match transplant from parent/children/half match sibling.

Who is the preferred donor?

Younger and healthier donor is an acceptable match. (20-30 yr age is preferred)

What is HLA (Human Leucocyte Antigen) Tissue typing?

HLA are proteins or markers found on most cells in your body. Your immune system uses these markers to recognize which cells belong in your body and which do not. HLA typing is the testing used to determine a person’s tissue type.

Can we find Acceptable match for every patient for Bone Marrow Transplant?

No. Sometimes we cannot get perfect match for patient from donor registry. The new research has enabled us to use father/Mother or sibling who would be biologically half match. So called half match transplants are giving more hope for patient without fully matched donor.

https://www.youtube.com/watch?v=tIGVoSSfvOk 

Doctor Profile:

Doctor Name – Dr Padmaja Lokireddy

Qualification -MBBS, MD (Internal Medicine), MRCP, FRCPath (Haematology) CCT

Experience – 8+ years