THE fight against cancer has been a long journey, with many experts in the field pushing the envelope to find ways to help their patients.
According to haematologist Datuk Dr Chang Kian Meng, stem cell treatment started in the 1970s as a result of radiation sickness and bone marrow failure.
Since then, it has extended to bone marrow cancers, lymphomas and myelomas.
“Following that, stem cell treatment has also been done with patients with solid organ tumours which are chemotherapy responsive such as germ cell tumour and immune-related bone marrow disorders.
“But the majority of stem cell transplant was still done for blood cancers, largely for leukaemia and myelodysplastic syndrome (MDS),” says the consultant haematologist at Sunway Medical Centre, Sunway City.
What’s more, patients who are healthy and fit with good major organ function are able to go through stem cell transplantation without age being a barrier.
“We have done it for patients who are in their 70s. So age is never a barrier as long as they are medically fit.
“In our fight against cancer, the first treatment ought to be the best treatment.
“When they first see their haematologist they should have a clearly laid out plan that is the most effective therapy albeit targeted treatment or chemotherapy, the number of cycles, and the best means for a cure or remission.
“If they need a stem cell transplant as a form of consolidation, they should go for it,” he says.
There are a myriad of methods to help the process along especially when it comes to the battle against treating blood cancers including leukaemia, lymphoma and multiple myeloma.
Aside from chemotherapy, there are now targeted therapies, immunotherapies, monoclonal antibodies, genetically engineered cell therapy (CAR-T) and stem cell transplantation.
Dr Chang adds that the elderly benefit most from these effective therapies and haematopoietic stem cell transplantation (HSCT).
How HSC is harvested
Stem cell transplantation has come a long way over the decades in terms of its safety and risks as well as the donation process.
“When I started stem cell transplantation training in the 90s, we used to go to the operating theatre where we would extract haematopoietic stem cells (HSC) from the bone marrow.
“The donor would have to undergo general anaesthesia, where they would lie face down and we would insert needles into their pelvic bones to extract their bone marrow stem cells,” he says.
Since then, he adds, stem cells are derived from peripheral blood where doctors can mobilise and encourage bone marrow stem cells into the blood where it can be harvested from the blood.
“In the 80s we used to derive stem cells from the umbilical cord from mothers who just delivered and placentas that are full of umbilical blood stem cells.
“Nowadays, haematopoietic stem cells are mainly derived from peripheral blood where donors undergo a process known as apheresis, whereby blood is circulated into the stem cell collection machine and is then returned to the donor immediately.
“While the blood is in the machine, the machine separates out the stem cell and here is where we collect the stem cells we need.
“This process eases the process of collecting stem cells and also increases the safety of the donors.
“Most of these stem cells are derived from an allogeneic donor who is usually human leukocyte antigens (HLA) matched.
“This donor may be a sibling, a blood relative, an offspring or an internationally sourced unrelated donor from another country.
“The intention is to replace old stem cells with new stem cells which are normal,” he says.
HSC transplantation process
Stem cell transplantation is performed for two reasons – to eradicate cancer cells and for immunological impact.
“If we want to cure patients with stem cell therapy or transplantation, they need to be in fairly good remission.
“Patients would usually need to undergo some form of chemotherapy to achieve that stage of remission.
“Before beginning transplantation, we also need to prepare the patients to accept the new stem cells, which involves creating some space inside the bone marrow as well as getting rid of the cancer cells.
“Patients have to undergo a preparative regimen which comprises immunosuppressive therapy and chemotherapy, and sometimes radiation,” he says.
Dr Chang adds that many forget that stem cell transplant is a form of immunotherapy where the donor’s immune system is harnessed to enhance the fight against leukaemia – graft versus malignancy effect.
“We began with matched transplants where we had to match HLA antigens but as families get smaller, the chances of finding a match among siblings is getting lower and the chances are about 25% at best.
“Therefore exploration has been made on (the impact of) half-matched donors (haplo-match) where stem cells are derived from offspring or parents.
“Moreover, since the majority of siblings may also be half-matched, this increases the donor pool,” he says.
Genetically engineered cells
Over the past decade, he says, immune effector cells that are our own T-cells and natural killer (NK) cells have been found to be effective against cancer.
“Sometimes, these T-cells are ineffective in eradicating leukaemia or cancers for many reasons.
“Now we are able to genetically engineer our own T-cells where we place an inactivated viral DNA to arm the T-cells with a bullet to seek, identify and kill off cancer cells.
“T-cells are harvested from the patient and sent to the lab to genetically engineer the cells. These are CAR-T cells.
“In certain conditions where patients are not completely responsive towards chemotherapy, we would use CAR-T cells to improve the response,” he says.
Dr Chang opines that certain diseases do well with chemotherapy or targeted therapies and do not need to undergo stem cell transplantation.
“An accurate diagnosis including cytogenetic and molecular diagnostics are extremely critical in order to risk stratify the patients.
“If you are treating bone marrow failure, the success rate of stem cell transplantation can be up to 90%.
“For most leukaemia that we treat, the success rate is 50%-70% depending on the stage,” he says.
Currently, stem cell transplantation is still the most effective strategy in curing acute leukaemia, according to Dr Chang.
In the past, he adds, doctors used to treat chronic leukaemia with transplantation but now with very good targeted drugs, HSCT is reserved for patients who are not responsive to targeted treatments.
“Then there are lymphoma and multiple myeloma which need autologous transplant.
“In some solid organ transplants, HSCT is used as a rescue for high dose chemotherapy,” he says.