Bone Marrow Transplant Brings Hope to Patients with Blood Diseases

Bone marrow transplant is one of the ways to treat patients with blood cancer, blood diseases, lymphoma, or bone marrow cancer patients. If a patient’s bone marrow does not find a suitable match within immediate family members, then the patient needs to wait for a matching volunteer donor or find a suitable donor through the bone marrow bank.

Subang Jaya Medical Centre launched its first bone marrow transplant in 1999 and was the first private hospital in Malaysia to perform bone marrow transplant. As of mid-June 2022, the hospital had completed 800 bone marrow transplants, including 633 adults and 167 pediatric patients.

 According to Dr. Ng Soo Chin, Consultant Haematologist at Subang Jaya Medical Centre, “The main goal of Bone Marrow Transplant (BMT) is to use the highest dose of chemotherapy to destroy all cancer cells with or without radiation therapy. Next, pre-collected stem cells are used to restore the normal function of bone marrow hematopoiesis”.

Dr Ng Soo Chin, Consultant Haematologist at Subang Jaya Medical Centre who specialises in Bone Marrow Transplant

In recent years, bone marrow transplant has been replaced by the broader name Haematopoietic Stem Cell Transplant (HSCT), which covers other sources of haematopoietic stem cells that can be transplanted other than bone marrow, including peripheral blood stem cells and cord blood. Haematopoietic stem cells are located within the red bone marrow responsible for producing the functions of blood cells, including red blood cells, white blood cells, and platelets.

Types of Bone Marrow Transplants

Bone marrow transplant is divided into allogeneic transplant, embryonic bone marrow transplant and autologous bone marrow transplant. Allogeneic Transplants are usually donated by genetically close family members, and if the donor is not related to the patient, this condition is called "Matched Unrelated Donor" (MUD), which is suitable for patients between the ages of 60 to 65.

"Syngeneic Transplant", as the name suggests, uses stem cells from the patient's identical twin siblings; Autologous Transplant is a transplant that takes the bone marrow from a patient and re-injects it into one's own bone marrow, usually for older patients.

The advantage of receiving autologous bone marrow transplant is lower risk rate of rapid death, therefore this is suitable for older patients ages 70 to 75 years. Patients do not experience rejection of transplanted organs and do not need to undergo treatment to suppress the immune system, and the risk of infection is low.

Since the transplanted organ does not appear to be rejected, it also means that the transplanted organ does not reject the blood cancer, so the risk of blood cancer recurrence remains. In this case, if compared to allogeneic bone marrow transplant, the risk of blood cancer recurrence in autologous transplant patients will be high, because the transplanted stem cells may also be contaminated with cancer cells and are only suitable for lymphoma and multiple bone marrow cancers.

In addition, the new bone marrow transplant method, Mini Autologous Bone Marrow Transplant, can reduce the dose of chemotherapy drugs used before the transplant, and its anti-tumor efficacy is based on immune system response. Mini autologous bone marrow transplant has pushed the age group of patients down to 60 years old. For some patients who are unable to tolerate the high dose of chemotherapy before a bone marrow transplant, this mini autologous bone marrow transplant provides a life-saving opportunity for them.

Dr. Ng emphasised that the severity of "graft-versus-host disease" caused by mini-autologous bone marrow transplant is no less serious than that of traditional autologous bone marrow transplantation; therefore, mini-autologous bone marrow transplant still has its challenges.

Imagine the need to find a stem cell match among 20,000 people. Dr. Ng pointed out that even if some patients meet a stem cell match, the patient loses the opportunity for a bone marrow transplant because the donor may change his or her decision last minute or lives too far away to donate.

With the increasing advancement in modern medicine, Haploidentical Transplant (HET) is becoming the mainstream bone marrow transplant method and Subang Jaya Medical Center has adopted this technique in recent years. Usually, half of the same stem cells can be found among a patient's siblings, parents, or close relatives.

Three days after completing the Haploidentical Transplant, it is confirmed that the stem cells have entered the parent cells, followed by a high dose of immunosuppressive (PT-CY) drugs to minimize adverse reactions after transplant, with a 90% success rate.

Breakthrough in stem cells extraction in Malaysia

Stem cells are found in the bone marrow, baby's umbilical cord blood, and surrounding blood of adults. In the past, bone marrow transplant consisted of stem cells drawn from the bone marrow. In recent years, stem cells can be drawn from the bloodstream, and can proliferate in about 10 to 14 days; Stem cells extracted from the bone marrow take 3 to 4 weeks to proliferate. When doctors inject stem cells into a patient's vein, it is amazing that stem cells will flow back into the bone marrow.

“Stem cells that are usually used in bone marrow transplants are derived from the bone marrow, and in recent years, more and more doctors have adopted the method of drawing stem cells (PBSC) from peripheral blood,” adds Dr Ng.

Firstly, the stem cells are moved in the bone marrow, then the stem cells in the surrounding blood are collected using a blood cell separator. It takes 4 to 6 hours to process about 2 times the blood volume to collect enough stem cells.

Stem cells must be stored at temperatures as low as minus 196 degrees Celsius to avoid breakage

Dr Ng also mentioned, “The biggest challenge of peripheral blood stem cells is that after the stem cells are drawn from the donor's body, they must be frozen in time, and the stem cells stored at a low temperature of minus 196 degrees can be used up to 100 years. The medical team must extract enough stem cells and inject them into the patient's body so that the stem cells can proliferate”.

Due to the good effect of peripheral blood stem cell therapy, the use of peripheral blood stem cells has been expanded to treat some unique acute blood cancers and lymphomas. One of the key points of bone marrow transplant is to be sure to find stem cells that can be matched. In this way, organ rejection (stem cell proliferation) and other adverse reactions can be reduced.

Stem cell matching is called the "HLA mating system," which is the structure of the white blood cell membrane. There are 6 genes on the white blood cell membrane (Locus), if the 6 seats of both sides are the same, it is the most ideal match; If only 3 or 4 seats are the same, it can be barely used.

“In Malaysia, our understanding and willingness to donate bone marrow are still low. But I hope that we can raise the awareness and education on the importance of donating bone marrow, encourage more people to come forward and save the lives of others,” urges Dr Ng.

Before performing a bone marrow transplant, the donor's blood must be tested to see if the donor's HLA system (not the ABO blood cell system) cooperates. Hospitals must check the donor's medical records, general physical examinations, blood tests, and overall health status.

In recent years, more and more doctors have collected stem cells from surrounding blood, so it is necessary to tell patients about the process of collecting stem cells before collecting them, and sometimes it is necessary to counsel donors to eliminate their anxiety.

If the patient has identified a bone marrow transplant and has found a donor with HLA, then there are other things that should be considered, including financial arrangements and timing of the bone marrow transplant.

Patient age is the key

The younger the patient receiving a bone marrow transplant, the more effective the treatment is. Patients over the age of 60 belong to the older group, and their biggest risk when performing a bone marrow transplant is that the injected stem cells will produce "Graft Versus Host Disease" (GVHD), which seems like "fighting" in the body.

After a bone marrow transplant, these stem cells are indiscriminately proliferating and should not be misinterpreted as a rejection. The truth is that foreign stem cells do not reject after entering the patient's bone marrow. This phenomenon differs from rejection after a kidney transplant, in which the host rejects foreign kidneys.

Graft-versus-host disease is a serious latent complication in allogeneic bone marrow transplant, as bone marrow donation treats the recipient as a "foreign" and begins to attack organs such as the skin, liver, and gastrointestinal tract. Symptoms of acute transplant-versus-host (present after the first 100 days of transplant) are fever, rash on the skin, jaundice, diarrhea, and an increased risk of developing other infections.

GVHD causes skin symptoms such as erythema, papules, blisters, and even skin peeling.

Usually, the skin is the first organ to be affected, and rashes on the palms, soles of the feet, finger joints, the back of the neck, and upper body can itch or feels burn. If there is a graft-versus-host merger, the symptoms are diarrhea, a large amount of foul-smelling, excrement.

Severe graft-versus-host disease, especially those involving the intestines and lungs, can be fatal, even if properly treated. With the availability of Ruxolitinib (Jakavi) drugs, it helps to reduce the response to GVHD.

While graft-versus-host disease poses some problems, it also brings an added bonus that the immune system's response will destroy the remaining cancer cells (i.e., the organ faces a malignant cancer tumor), so patients with graft-versus-host disease have a lower recurrence rate.

Post-bone marrow transplant considerations

The road to recovery for bone marrow transplant patients is a long process. In the first month after transplant, the patient should be hospitalized for care. Because the patient must take multiple drugs during this period, the immune system is suppressed, making the patient susceptible to bacterial infections.

After discharge, it will take at least half a year to fully recover, with dietary care and putting on hold any moderate amount of exercise. If you develop a fever during your recovery, you should seek medical attention immediately.

After the patient is discharged from the hospital, close follow-ups are required for at least 3 months. This is the risk of infection rate is still high during this period. It takes about a year for the patient's immune system to fully recover from the operation. Therefore, Dr. Ng suggested that patients should not return to work, reduce going out and take extra good care of their health.

Patients with allogeneic bone marrow transplants need to be closely tracked to avoid graft-versus-host disease. Patients require intensive immune system suppression therapy, and mortality and cancer recurrence are arguably the greatest risks in the first year after transplant.

If the transplant is done after a recurrence, the recurrence rate will be higher. A recurrence can occurs within a year of bone marrow transplant. Some patients with relapses require a second transplant, but the risk is high and usually less effective than the first bone marrow transplant.

More than 100 days after transplant, about 20 to 40 percent of transplant patients will be affected by chronic diseases. It is similar to connective tissue vascular disease: skin changes, skin ulcers, Sicca syndrome, which is dry eyes and dry mouth due to dysmenorrhea of glandular manipulation, joint pain, and liver manipulation disorders.

In children's cases, bone marrow transplant can hinder their growth. At the same time, compared with ordinary people, the incidence of cancerous tumors after bone marrow transplant in children is higher. In addition, bone marrow transplant patients can also suffer from hypothyroidism and cataracts in their eyes.

Elderly transplant patients are also more likely to suffer from graft-versus-host disease, and if the patient has suffered from acute graft-versus-host disease in the past, the chance of re-occurrence will increase. Once a patient develops chronic graft-versus-host disease, their risk of infection, pathogenicity, and mortality increase.

Dr. Ng emphasised that bone marrow transplant technology has continuously improved in the past 10 years, and the success rate has also increased significantly. At the same time, bone marrow transplant is a collective effort by a team of medical professionals, including different specialists (heart, gastrointestinal and kidney), nurses, pharmacists, nutritionists and laboratory technicians, who are committed to providing an integrated and comprehensive care to patients.

Source : Sin Chew