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Matching Made Easy: The Future of Donor Selection in Bone Marrow Transplants

A Bone Marrow Transplant (BMT) Procedure  is the transfer of haematopoietic (blood-forming) stem cells from the bone marrow of a healthy donor. A recipient is a person who is affected by blood disorders like leukaemia (cancer of white blood cells), myeloma (cancer of plasma cells), or any other condition. Blood-forming stem cells are early or immature cells that are capable of developing into:

  • Red blood cells, which carry oxygen to the cells and tissues of the body.

  • White blood cells, that are responsible for fighting infections, or 

  • Even platelets, which are essential to stop bleeding. 

When these stem cells are damaged due to cancer or as a side-effect of cancer treatment they must be replaced. They are present mostly in:

  • Bone Marrow - This is the soft gelatin that is present in the centre of most bones in the body, especially the pelvic bones and long bones.

  • Peripheral Blood - Stem cells in peripheral blood are lesser in number than in the bone marrow.

  • Cord Blood - Collected from the umbilical cord and placenta of a newborn baby.

  1. New Possibilities For Mismatched Donors.

    HLAs (Human Leukocyte Antigens) are proteins located on the surface of white blood cells and other tissues. There are 3 broad groups of HLA:

    • HLA-A

    • HLA-B

    • HLA-DR

    HLA is inherited as a set called a haplotype, consisting of these 3 groups. A child inherits one haplotype from each parent. If 2 children inherit the same HLA from the parents, they are an identical HLA match. 

    The best match is when all 6 of the major antigens are the same for both Bone Marrow Donor and recipient.

    A crossmatch test determines if the recipient has antibodies to a potential donor. Antibodies will attack the donor’s cells if they are specific to the donor’s specific HLA. A reaction or a positive crossmatch in which the recipient’s antibodies attack the donor cells is a strong contraindication against any transplant procedure.

    Previously, half-matched or haploidentical transplants were deemed impossible. But recent advances have made transplants possible even with half-matched or mismatched donors. This is done by:

    • Preparing a recipient for a transplant by giving a few days of chemotherapy, in small enough doses to suppress their immune system, and not harm any organ.

    • Immunosuppressive Drugs- Three days after a transplant, the recipient is given high doses of a drug called cyclophosphamide to reboot the immune system. The drug destroys the recipient’s immune cells but leaves the donor’s cells intact. These new cells create a new immune system that is accepted by the host. 

  2. Less Intense Conditioning.

    Conditioning is a procedure that involves chemotherapy with or without radiotherapy to prepare the body for the actual transplant.

  3. Mini-Transplant Or Ric ((Reduced-Intensity Conditioning).

    Depending on the person’s age and overall health condition, they may receive lower doses of chemotherapy or radiation. This process destroys some of the cancerous cells, (also destroying some bone marrow) and suppresses immunity. When Bone Marrow Donor stem cells are infused into the marrow, both the donor cells and the recipient’s cells co-exist for some time. Over a few months, donor cells replace the original stem cells that were present. The donor cells start functioning as normal and engage in destroying the cancer cells. This is called the ‘graft-versus-cancer’ effect. The most important result of RIC is that the pool of transplant-eligible persons has expanded.

How The Immune System Works And What Is Car-T Cell Therapy

The body’s immune system identifies foreign cells by recognizing proteins or antigens on the surface of these cells. The process continues when defense cells called T cells use their proteins called receptors that attach themselves to these antigens. This triggers other cells of the immune system to attack and destroy the foreign cells. Cancer cells also have antigens, but if the T-cell receptors are missing or unable to identify the antigens, the immune system is unable to attack cancer cells.

CAR-T cell therapy (Chimeric Antigen Receptor) - In this procedure, T cells are taken from a person’s blood and modified by adding a gene to the receptor (CAR-T), and are infused back into the person’s blood. Thus these altered T cells can attach to specific cancer cells or antigens. 

Each cancer has a different antigen, therefore CAR is developed specifically for that particular antigen. For instance, cells found in leukaemia have an antigen called CD19, and CAR-T cells are thus modified to attach to CD19 to help attack these cancer cells. These CAR-T cells wouldn’t be able to attach themselves to any cancer that does not have the CD19 antigen. 

It takes a few weeks to create a substantial amount of CAR-T cells in the lab. Affected persons are given a low dose of chemotherapy before they are infused with CAR-T cells. Once the altered T cells bind themselves to the cancer antigens, they start multiplying and getting more effective in attacking the cancer cells.

There are a few side effects with CAR-T cell therapy and persons who have received it are advised not to drive or operate heavy machinery for a few weeks. These side effects can be managed with appropriate medication.

Early Recognition Of Serious Complications Through Biomarkers

More than half of the people who receive HCT (Haematopoietic Cell Transplantation) develop GvHD. They have to be managed by immunosuppressive drugs for the rest of their lives to prevent side effects like liver or pulmonary damage and bacterial or fungal infections. 

To improve the prognosis of such recipients, biomarkers have been used to detect such complications at an early stage. Biomarkers are molecules found in blood or tissues that are signs of normal or abnormal processes or conditions. They are used to determine how well the body has responded to treatment. 

Some of the biomarkers are ST2 (Suppression of tumourigenicity) and Regenerating islet-derived 3 alpha. Elafin and calprotectin are biomarkers which have been measured when symptoms of GvHD started.

What Are The Other Indications For Bmt?

Autologous stem cell transplant is mainly used to treat:

Certain other conditions can also be treated:

  • Testicular cancer

  • Neuroblastoma

  • Systemic sclerosis

  • Multiple sclerosis

  • Systemic lupus erythematosus.

Allogeneic transplants are used to manage certain types of leukaemias and other marrow disorders like aplastic anaemia.

Other conditions include:

  • Ewing sarcoma

  • Germ cell ovarian cancer

  • Essential thrombocytosis

  • Thalassemia