Explained: Why Boy with Rare Genetic Disorder Struggles for Treatment

In India, one in every 2,500 people or 0.04% of the population has registered as potential stem cell donors, experts say. Similarly, the global figure is 0.05%, but, unlike other countries, India does not even have a national registry to record data of donors.

The World Marrow Donor Association (WMDA) has recorded more than 39.71 million registered donors across the world. In India, three organisations — DATRI Blood Stem Cell Donors Registry, DKMS BMST Foundation India, and Marrow Donor Registry (MDRI) — maintain the stem cell donors' registry. DATRI and DKMS BMST Foundation have together recorded over 5.1 lakh potential donors, and they say the total donors in the country are not over 6 lakh currently.

There's a wide gap in the demand and supply of stem cells and that's mainly due to fear and lack of awareness about the transplantation, its impact on patients with cancer and other fatal diseases, experts from DATRI and DKMS told FactChecker. So, let's understand what is the rare disease Vijayendra has been diagnosed with, what is stem cell transplantation and why are there so few donors.

What is BENTA

BENTA or B-cell expansion with NF-jB and T-cell anergy, is a rare genetic disorder of the immune system caused by mutations in the gene CARD11, according to National Institute of Allergy and Infectious Diseases, United States of America (NIAID). Expansion of B-cell, which is a type of immune cell from the bone marrow, means that the number of cells is greater than normal. NF-jB is a protein complex involved in gene expression, or the degree to which certain genes are turned on or off. T-cell is a type of immune cell that matures in the thymus and anergy refers to a "less-than-normal" (T cell) immune reaction to foreign substances.

Every person has two copies of the CARD11 gene, one inherited from each parent and it takes one of the two copies to be abnormal for a person to have the disease.

"Children of a parent who carries a CARD11 mutation have a 50% chance of inheriting the mutation. In a family, each child's risk of inheriting a mutated copy of the CARD11 gene is independent of whether his or her siblings inherited the mutation," according to NIAID.

Children who do not inherit the mutation will not develop the disease or pass on the mutation to their offspring. "BENTA involves an increased risk of infection and symptoms such as enlarged lymph nodes and spleen," Dr Girish VB, Senior Consultant Haematology, Haemato-Oncology & Bone Marrow Transplant at Fortis Cancer Institute, Bengaluru, told FactChecker. "The stem cell transplant is the only cure for a patient, otherwise the disease will have to be treated symptomatically," he added.

Stem Cells and Transplant

What are stem cells? Stem cells or hematopoietic stem cells are the immature, raw or unspecialised cells, from which other cells with specialised functions, such as blood cells, brain cells, heart muscle cells or bone cells, are generated. Its main functions are to make red and white blood cells and platelets.

These cells are located and make new blood cells in the bone marrow (the spongy centre of certain bones). Once the blood cells mature, they leave the bone marrow and enter the bloodstream.

Stem cell transplants are required mostly for blood cancers that affect the bone marrow. In fact, transplants are mainly needed when the bone marrow cells are affected by cancer or when it is destroyed during chemotherapy or radiation, said Dr Girish.

Transplant process: There are two ways of extracting stem cells from a donor: peripheral blood apheresis and bone marrow harvest. Peripheral blood cell donation does not require anaesthetic or admission to hospital. "Stem cells are taken directly from the bloodstream and are similar to a blood platelet donation," Patrick Paul, CEO of DKMS BMST Foundation India, told FactChecker.

For peripheral blood apheresis, a sterile needle is placed into a vein in each arm and blood is drawn through one vein and passed through a filter machine that collects stem cells. After the cells are collected, the rest of the blood is injected back into the body through the other arm.

On the other hand, in the bone marrow harvest method, stem cells are extracted directly from the bone marrow. Here, the donor undergoes general anaesthesia while the doctor extracts the bone marrow from the back of the pelvic bone. Both procedures take up to four hours.

Finding Donors

"Looking for a matching stem cell donor is like looking for a needle in a haystack," said Paul. While the organisation has 50,000 registered donors, only 41 donations have been possible.

The first step is to conduct a Human Leukocyte Antigens typing test for the patient's family members because they tend to be possible matches.

"If someone has four siblings, there is a 25% chance that they will match," said Dr Girish. The smaller the family, the slimmer the chances in finding a match, he added. "The chances to find a match are less than 10% for single children or patients with one sibling," the oncologist explained. A person's blood group acts only as a bonus factor and what really matters is a 100% match between the tissue characteristics from the donor and patient, said Paul.

Patients lose lives if a donor couldn't be found or if the doctor didn't register with one of the three organisations. "There are far more patients in India who or their doctors have not registered with us due to not being aware of our registry," said Sumati Misra, Head, Counseling & Transplant Centre Management, DATRI Blood Stem Cell Donors Registry. There are 2,700 patients waiting to find a match, she added.

Dearth of Donors

Lack of awareness about stem cell donation is one of the leading reasons behind scarcity of donors in the country. "People are unaware of bone marrow transplant and hence do not register as donors. Illiteracy and myths are an added hurdle that we face when we conduct awareness drives. Some people feel that they can donate later, not realizing that the patient may not have time," said Misra.

Paul echoed Misra's concern when he said, "People are unaware of the chances of survival when cells are donated," said Paul.

Misconceptions such as the permanent loss of stem cells once donated is common. "This is not true. The body reproduces stem cells within two weeks," said Paul. Some are even concerned about their safety during the donation process and many think that donating stem cells is expensive.

Since India is highly diverse, there is a lack of donors from various communities. "The chances of finding an unrelated donor as a match is 1:10,000 to 1 in a million. If the patient is a Punjabi, there are high chances that the potential donor will be from the same community," said Misra.

Moreover, northern and north-eastern states have the least number of donors, while southern states fare much better. "Kerala and Tamil Nadu have a good representation in registered donors and in states such as Bihar, Odisha and Uttar Pradesh representation is pretty low," said Misra.

The COVID-19 pandemic has had an impact on donor registration too — due to a halt in face-to-face awareness campaigns registrations have dramatically reduced. Registering organisations have come across instances of family members being hesitant in sending donors due to COVID-related safety issues. "All these things have become speed breakers in helping a patient get a second chance of life," Misra concluded.