Defusing a DNA time bomb
Sandy Ho, 31, was in the prime of her life. With a career in banking, a loving husband and a young child, her future looked rosy.
However, Ho, whose real name is withheld for reasons of patient confidentiality, was in for a shock. A regular health check revealed that she had leukocytosis, which is a high white blood cell count, and thrombocytosis, or a high blood platelet count. Leukocytosis can be caused by infections, drugs, a bone marrow disease or immune disorder.
As Ho felt healthy with no signs of infection, had a good health history and was not taking any drugs that would elevate her white blood cell count, she was referred to Dr Raymond Liang, director of the Comprehensive Oncology Centre at the Hong Kong Sanatorium and Hospital, for further investigation.
Liang found that Ho's blood had a profusion of different types of myeloid white blood cells, or cells that originate in the bone marrow. These myelocytes and metamyelocytes were in varying degrees of maturity, unlike the immature cells called myeloblasts, which multiply uncontrollably in acute leukaemia.
The doctor knew that he was looking at chronic myeloid leukaemia (CML), a blood cancer that tends to strike patients at a median age of 30 to 40 years.
To confirm his diagnosis, a genetic test was conducted on Ho's bone marrow. Liang was looking for a unique genetic abnormality called the Philadelphia chromosome, in which two chromosomes - nine and 22 - exchange material and produce an abnormal protein, tyrosine kinase, which causes white blood cells to proliferate rapidly and crowd out normal cells.
Ho tested positive for the Philadelphia chromosome and, hence, CML. Despite feeling well and being symptom-free, the young mother was handed a cancer diagnosis from out of the blue. But it was not necessarily a death sentence.
CML is one of the very few cancers triggered by a single genetic abnormality in what is termed the chronic phase. Most cancers appear with several genetic abnormalities.
During this deceptively benign chronic phase, patients will be asymptomatic. Most would know they have leukaemia only if they, like Ho, undergo regular health checks. Others might seek medical attention because their enlarged spleens might cause them discomfort in the left side of their abdomens. Yet others will have no idea they are living with a time bomb.
The disease usually accelerates after three to four years. Within 10 years, almost all untreated CML patients will undergo further genetic changes that will trigger acute leukaemia, at which point treatment is difficult and patients may not survive beyond one year.
Liang says that in the past, CML patients would be treated with an oral chemotherapy drug called hydroxyurea, which could control the white blood cell proliferation and shrink the spleen. It was effective in improving the blood count and helping the patient feel better. However, it did nothing to slow the progression of the disease into acute - and fatal - leukaemia.
Patients could opt for a cure with a bone marrow transplant, which carried a 10 per cent to 20 per cent rejection rate. But it was not easy, says Liang, to convince young, asymptomatic patients that they needed a risky operation or they could die in a few years.
Medical science then discovered that a special type of protein called interferon could help stall the transition to acute leukaemia in a very small percentage of CML patients. Unfortunately, the treatment's high toxicity, frequency of injections required and low success rate made this option less than ideal.
But more than 10 years ago, scientists had a breakthrough and created a chemical called Imatinib that could stop tyrosine kinase in its tracks, and prevent the white blood cells from proliferating. Because CML was caused by this one deviant protein, Imatinib was a powerful tool for controlling the disease, so much so that bone marrow transplants are now rarely needed to treat patients. Also, Imatinib is easy to administer in the form of a daily pill and has easily manageable side effects.
Recent research shows that patients who respond well to Imatinib have an overall survival rate of 95 per cent after eight years. Because some patients developed a resistance to Imatinib after some time, second-generation drugs such as Dasatinib and Nilotinib were developed. Much more potent than Imatinib, these new drugs cause the number of leukaemia cells to plummet very quickly.
Some doctors, including Liang, are no longer waiting for patients to develop resistance to Imatinib but are starting their patients on Dasatinib and Nilotinib. Hence, Ho was given Nilotinib, and six months after treatment first started her condition is under control. However, Ho will need long-term treatment with Nilotinib as research has shown that CML will continue to progress without continued therapy.
These new drugs are expensive, but fortunately for Ho the HK$20,000 to HK$30,000 monthly cost of Nilotinib is covered by her insurer. Patients without insurance coverage must pay on their own or seek government subsidies.
Although she has to return every quarter for a blood test, Ho's life has returned to normal. She is back at work and revelling in the joys of family and motherhood. Thanks to medical science, Ho's time bomb has been all but defused.
