Education

BMT Knowledge Centre

Comprehensive information about Bone Marrow Transplantation — what it is, how it works, and who needs it. Written by Dr. Suparno Chakrabarti.

Foundation

What is Bone Marrow Transplantation?

Bone Marrow Transplantation is a procedure, where healthy stem cells are transplanted into a patient's body after appropriate treatment. Healthy stem cells can be collected from the patient, when he becomes disease free after treatment. They can also be collected from fully / half HLA matched family donor, unrelated donor and cord blood. Stored stem cells of the patient / donor / cord blood are transfused into patient's blood stream, quite similar to blood transfusion.

What are Stem Cells?

Stem cells are the most primitive cells which can differentiate into various other dedicated cells, such as nerve cells, bone cells, liver cells, blood cells etc. The most primitive stem cell gets committed to organ-specific stem cells and thus forms either blood stem cells or nerve stem cells.

Sources of Blood Stem Cells

Bone Marrow: The spongy material inside large bones of adults and all bones of children is called bone marrow, which is a normal reserve for blood stem cells. Depending on body's requirement, stem cells can produce desired number of Red blood cells, white blood cells and Platelets. When a patient needs blood stem cells, they can be collected from healthy donor's hip bones under anesthesia.

Peripheral Blood: Normally, there is only an occasional blood stem cell in our circulation. However, when a blood growth factor (G-CSF) is injected, it stimulates the stem cells from the bone marrow to spill over in the circulation. If we carry out a procedure called Apheresis (similar to dialysis), stem cells can be collected from the peripheral blood.

Umbilical Cord Blood: Placenta along with the umbilical cord are waste products of pregnancy. However, in the mid-1980s, it was discovered that they are a rich source of blood stem cells. These cells can be collected after birth and stored for later use in a patient.


Types

Types of Bone Marrow Transplantation

Type 1

Allogeneic BMT

The blood stem cells are obtained from the peripheral blood or bone marrow of a donor who is suitably matched to the patient. The diseased or failing bone marrow is replaced by healthy marrow from a normal donor. This process cures the underlying disease.

Type 2

Autologous BMT

Standard dose of chemotherapy cannot always cure a cancer. High dose is often needed. However, such high doses damage the patient's bone marrow irreversibly. Patient's own blood stem cells are collected before administering high dose chemotherapy and stored. The stored blood stem cells of the patient are transfused back after Chemotherapy / Radiotherapy.


Indications

Conditions Treated with BMT

Transplantation of Bone Marrow, also termed as Stem Cell Transplant, is a complex process where the damaged or infected bone marrow is replaced by healthy ones. This process is implemented once the patient has been treated with high doses of chemotherapy and radiation treatment.

Bone marrow is a soft, spongy tissue within the bones which produces cells together with white and red blood cells along with platelets. When this bone marrow gets injured, it is no longer capable of producing these red and white blood cells. As a result, you may experience some severe consequences like infections, weakness, anemia, excessive bleeding and possibly even death.

Who Needs Bone Marrow Transplantation?

Bone Marrow is an amazing organ spread all through the body, producing millions of cells every moment of our life to keep us well and healthy. Any disease affecting the bone marrow affects our entire body. Replacing the diseased or failing bone marrow with healthy marrow stem cells is the process of Bone Marrow Transplantation.

Blood Cancers: Any blood cancer (leukemia) or lymph gland cancer (Lymphoma) which is not completely cured with chemotherapy or recurs after completion of chemotherapy (relapse), can be cured with Allogeneic or Autologous BMT in about half of the patients.
Read about: ALL · AML · CML · CLL · Hodgkin's Lymphoma · Non-Hodgkin's Lymphoma · MDS · Multiple Myeloma

Thalassemia and Other Genetic Conditions: In these conditions, the defective bone marrow cells can be killed by chemotherapy and replaced by healthy bone marrow cells from a healthy donor. This can be cured in about 90% of the patients.
Read about: Thalassemia · Sickle Cell Anemia · Inherited Metabolic Disorders

Aplastic Anaemia and Related Conditions: In these conditions, the bone marrow does not produce enough stem cells and healthy stem cells can be transplanted from a healthy donor. This is also curative in about 70-90% of patients.
Read about: Aplastic Anemia · Bone Marrow Failure · Primary Immunodeficiency · Autoimmune Diseases

Other Cancers: Many other cancers which do not arise from the bone marrow can be cured by infusing patient's own stem cells after high dose chemotherapy.
Read about: Novel Autologous BMT (IBAHCT) · All conditions we treat


The Journey

The BMT Process — Four Stages

Dr. Suparno Chakrabarti explains the four stages involved in Bone Marrow Transplantation.

1
Evaluation (Work-Up) — Usually 14–30 days before

One will undergo complete medical check-up to evaluate one's suitability to go through the BMT procedure. This involves the following:

  • Blood Tests
  • Chest X-ray and CT Scans
  • Tests to assess the condition of heart and lungs
  • Bone Marrow Tests

Patients will be counselled in detail about the procedure, the complications, the chances of success, the cost and the possible length of stay in the hospital. Patient will be encouraged to go through the educational material/booklet and discuss any queries or doubts that he/she might have.

2
Conditioning — Usually 2–10 days

High dose of chemotherapy or radiotherapy is given to destroy the diseased marrow or destroy the cancer cells and make space for the new bone marrow cells. It also suppresses the immunity of the patient so that the new bone marrow is not rejected.

The Transplant Procedure: The transplant procedure is actually fairly simple — the stem cells or bone marrow cells to be transplanted are given as a blood transfusion through the central line. This usually takes from one to several hours. Just before the infusion, the patient may be given medication to help avoid any reaction. A monitor is used to check breathing, heart rate and blood pressure during the procedure.

3
Pre-Engraftment — Usually 2–3 weeks

After high dose chemo-radiotherapy the blood stem cells are destroyed and normal blood cells are not produced. The patients need to be kept in a clean room within the BMT unit in strict isolation during this time. They also need a lot of blood and platelet transfusion. Most patients get serious infections during this period and need treatment with antibiotics.

4
Post-Engraftment — Months to Years

Early Phase (first 3 months): There are two types of white blood cells: neutrophils and lymphocytes. Once the neutrophil count is above the critical value of 500 cells per microlitre, the patient can come out of critical isolation. This is called engraftment — the first sign that the transplanted blood stem cells are functioning. There is also a risk of graft-versus-host disease (GVHD) at this stage.

Late Phase (3 months–12 months): The immunity against viruses takes a very long time to recover. Even though some immunity is restored, the patient is still at risk of infections with viruses and fungus. This is more so if they are being treated for GVHD, which can become chronic and lingering. If the patient is well, the frequency of check-ups and blood tests reduce over several months.


Major Complications

Major Complications After BMT

While BMT is carried out to cure the underlying cancer or blood disorder, it remains one of the most challenging procedures in modern medicine due to its unpredictability. The physicians and scientists involved in the field of BMT have toiled for the last five decades to understand the intricacies of this apparently simple but immunologically complex procedure. With best of efforts to understand and intervene and/or often preempt, certain complications remain unavoidable after an allogenic bone marrow transplantation which are listed below.

Graft Outcomes

Graft Failure & Dysfunction

  • Graft Failure
  • Graft Dysfunction
  • Relapse
Immune Reactions

Graft vs Host Disease (GvHD)

  • Acute Graft vs Host Disease
  • Chronic Graft vs Host Disease
Infections

Post-Transplant Infections

  • Bacterial
  • Viral
  • Fungal
Inflammatory Storms

Hemophagocytosis

  • Post Transplant Hemophagocytosis
  • Post Transplant Hemophagocytic Syndrome
Conditioning Toxicity

Organ & Endothelial

  • Conditioning-related Organ Toxicity
  • Endothelial Dysfunction
    • Veno-Occlusive Disease
    • Transplant-Associated Thrombotic Microangiopathy
Long-Term Effects

Late Sequelae

  • Secondary Malignancies
  • Reproductive Dysfunction and Infertility
  • Endocrine Dysfunction