Veteran TV personality Huang Wenyong was 60 when he died on April 20 of lymphoma, cancer of the lymphocytes, a type of white blood cell that fights infection.
The cancer occurs mostly in the lymph nodes - small, bean-shaped organs throughout the body - but sometimes in other organs, including the spleen, stomach or intestines.
The type of blood cancer that killed the veteran entertainer was similar to what Prime Minister Lee Hsien Loong was diagnosed with, at the age of 40, in 1992 and recovered from.
It was also what a 49-year-old woman who works in the finance sector, and wants to be known only as Amy, suffered from in 2009.
Amy, who is now in remission, recalled: "It was devastating as I am a mother of three young kids whose ages ranged from seven to 13 at that time. But I am very thankful I had good care."
All three had fast-growing lymphoma that was potentially curable, but Mind Your Body understands the late actor had a very rare form which was relatively resistant to treatment.
Whether it is a rare form or not, more people here are contracting lymphoma.
But the good news is that fewer are dying from it, statistics from the Ministry of Health show.
In the five-year period from 2006 to 2010, the incidence for men stood at 15.2 out of 100,000 people, up from 12.9 in the previous five years. The rate was even lower at 11.8 in the period from 1996 to 2000.
These figures, for Singapore residents aged 15 and above, were age-standardised, meaning the influence of age was eliminated, as cancer risks rise with age. This means that this increase in the proportion of men here who developed lymphoma is not due to the larger proportion of older people in the population now.
Fewer women than men have lymphoma but the figure for female patients is also rising, with 9.5 out of 100,000 women getting the disease between 2006 and 2010, up from 8.6 per 100,000 in the earlier five-year period, said the Ministry of Health.
Between 1996 and 2000, the rate was at 7.6 women out of 100,000 people, it said.
The five-year survival rates for women have risen to 54.9 per cent between 2006 and 2010, up from 46.6 per cent between 2001 and 2005.
Men are also doing better, with a 47.6 per cent survival rate between 2006 and 2010, up from 37.8per cent in the earlier five-year period and just 31.4 per cent between 1996 and 2000.
In Singapore, lymphoma is now ranked as the fifth most common cancer among men and the seventh most frequent cancer for women, based on the Singapore Cancer Registry interim report for 2007 to 2011.
No known reason for the rise
Lymphoma starts in the lymphocytes and manifests as a solid tumour of lymphoid cells.
Lymphocytes move throughout the body in a clear fluid called lymph via a network of vessels that make up the lymphatic system, part of the immune system.
Along the network are lymph nodes. These small, bean-shaped organs filter lymph as it flows through them, trapping harmful substances, which are then destroyed by lymphocytes.
The incidence of lymphoma is rising but oncologists cannot pinpoint reasons for it.
"We don't even know what causes it. It's a bit of a black box," said Dr Wong Seng Weng, the medical director of Singapore Medical Group's The Cancer Centre.
Dr Lim Soon Thye, the deputy head and senior consultant at the department of medical oncology at the National Cancer Centre Singapore, said: "We don't really know what causes this trend but it is also an observation made worldwide. The incidences seem to rise as countries become more developed.
"A possibility is that it might be related to viruses and infections. For example, patients with human immunodeficiency (HIV) infections are at a higher risk of developing lymphoma. Patients on long-term immunosuppressive drugs are also at an increased risk."
Added Dr Ang Peng Tiam, the medical director of Parkway Cancer Centre: "We do know that patients with HIV infection have a higher risk of developing lymphoma but the large majority of our patients with lymphoma do not have HIV infection.
"Since HIV impairs the patient's immune system, the theory is that the rise in lymphoma may be due to an impairment of the patient's immune system."
Associate Professor Chng Wee Joo, the head and senior consultant at the division of haematology at the department of haematology-oncology at the National University Cancer Institute, Singapore, said the higher incidence rates may be related to better diagnosis, better awareness and an ageing population, but no one knows for sure.
It is also not clear whether stress is a factor.
Smart drug raises survival rates
Because the causes for lymphoma are unclear, the only known reason for the higher survival rate would be the improvement in its treatment, experts said.
"Patients are surviving longer and cure rates are better because we have better treatment now," said Prof Chng.
In most other types of cancer, surgery would be performed to remove the cancerous growth.
But as lymphocytes travel throughout the body, lymphoma can start in and can spread to any part of the body where there is a lymph node or possibly other organs such as the spleen, stomach or even the breast.
Imagine the white blood cells as trains while the lymph nodes and related immune system organs are the MRT stations, Dr Wong said.
Lymphoma occurs in the trains while they are at a station, and is not isolated to one station as the trains are constantly on the move. Any abnormal white blood cells would almost invariably have travelled to the next station, he said.
This is why the mainstay of therapy for lymphoma is chemotherapy, not surgery. Radiation therapy is sometimes added.
In the last 10 years, patients who have relapses can be given transplants of stem cells, which are immature cells that give rise to all blood cells.
Such patients are given very high chemotherapy doses to kill the lymphoma cells, which are more resistant to treatment. But these doses will kill healthy cells in the bone marrow too.
So stem cells are taken from the bone marrow before chemotherapy and then put back into the body after that so they can restore the bone marrow and build healthy new blood cells.
"Lymphoma is one of the few cases where stem cell transplant is proven to work. In almost every other type of cancer, stem cell transplant treatment is a myth," said Dr Wong.
But the most significant improvement in treatment has been the artificially created antibody Rituximab, which appeared in the market around a decade ago, he said.
This drug, given through an injection, acts like a "smart bomb" targeting lymphoma, he said. It can zoom in on the lymphoma cells, leaving the normal cells alone. In comparison, in chemotherapy, the normal cells get affected in varying degrees, he said.
Prior to this, there had been no breakthrough for decades. "Rituximab was 'wow' and it will be decades before another breakthrough like this comes," Dr Wong said.
The drug has helped to improve the cure rate in fast-growing lymphoma and to sustain the remissions in frequently relapsing forms of slow-growing lymphoma, he said.
Lymphoma can be broadly divided into Hodgkin's lymphoma and non-Hodgkin's lymphoma.
Hodgkin's lymphoma, which accounts for about 10 per cent of lymphoma cases, is fast-growing and highly curable.
The risks are higher with non-Hodgkin's lymphoma, which can be broadly classified as B-cell lymphoma or T-cell lymphoma. B-cells and T-cells are different types of lymphocytes.
These two types can then be further divided into high-grade or fast-growing lymphoma and low-grade or slow-growing lymphoma.
High-grade lymphoma, if left untreated, typically causes death in a few weeks to a few months.
On the other hand, low-grade lymphoma may take years to develop and become life-threatening.
"What is rather counter-intuitive about lymphoma is that fast-growing high-grade lymphoma is more likely to be cured than its slow-growing low-grade cousin," said Dr Wong.
Fast-growing lymphoma responds very well to chemotherapy, unlike slow-growing lymphoma, he said. It is thus hard to get rid of slow-growing lymphoma totally and permanently, he said.
Even if it were to respond to treatment initially, it tends to relapse down the road.
That is the key difference between the lymphoma suffered by PM Lee and the one diagnosed in former president and deputy prime minister Ong Teng Cheong. Both were diagnosed in 1992.
PM Lee underwent chemotherapy not long after and recovered. The late Mr Ong did not undergo treatment immediately. He was advised to wait and see as his lymphoma was slow-growing. He later had treatment and eventually succumbed to the cancer at the age of 66 in 2002.
Dr Wong said: "While slow-growing lymphoma is not usually curable in the permanent sort of way, with appropriate treatment, it is not uncommon to be able to control the disease and achieve survival of up to 10 years and beyond."
In contrast, high-grade lymphoma can be totally cured, though it is very difficult to detect early as it can take a few weeks to a few months to become fairly explosive, he said.
However, there is hope as "fast-growing lymphoma is potentially curable even at the most advanced stage (stage 4, which is when the cancer has spread widely through the body)," he said.
Other types of cancer are usually incurable at an advanced stage. Dr Ang said: "The most common type of malignant lymphoma is high-grade lymphoma of the B-cell diffuse large cells type. Even with stage 4 disease, 60 to 70 per cent of patients can still be cured. This is attributed to better supportive care during treatment, the availability of very effective chemotherapy drugs and the monoclonal antibody called Rituximab."
What to watch out for
Lymphoma commonly appears as a painless lump that persists or increases in size.
If one has a swollen lymph node in the neck which does not go away and is not painful when pressed, one should seek medical attention, doctors said.
But if it starts in a non-sensitive part of the body, it may not be felt. In fact, most lymph nodes cannot be felt. So it is hard to screen for the cancer.
Dr Lim said: "Generally, the warning symptoms are unexplained weight loss, a recurrent fever that won't go away and unexplained night sweats."
But these symptoms may not appear either.
Amy said she had no symptoms.
She found out about the tumour in her lungs accidentally, when she went to check out a persistent pain in her chest, which turned out to be gastric reflux and unrelated to the cancer.
She recalled: "I thought it was a lack of exercise and my heart wasn't functioning well, so I went for an electrocardiogram (ECG)."
The result of the test of the heart's electrical activity was normal. But she went for a chest X-ray three weeks later as the pain was still present and she felt that something was just not right.
She said: "The chest specialist took a look at the X-ray and said: 'It's a tumour. What are you waiting for?' I got a shock. He ordered a scan and a biopsy. It turned out to be lymphoma."
Further tests were done to zoom in on the type she had - stage 2 high-grade Hodgkin's lymphoma.
She took medical leave to go through four cycles of chemotherapy over a three-month period, which was followed by a one-month rest period and three weeks of daily radiation.
"A positive attitude is very important. You also need to be cautious. In my case, I refused to see any visitors because of the possible germs they may bring. My immunity was low."
She added: "It's important to listen to your body. If you don't feel well in any way and if any pain persists, you should have it checked out."
At the end of the day, one should know that lymphoma is a treatable disease, "often curable in many cases or controllable for extended periods in others", Dr Wong said.
Dr Ang added: "One must never give up hope when one is struck with this cancer as the chances of a cure are good."
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