There are more chronic myelogenous leukaemia (CML) sufferers in Hong Kong than ever. But that's a good thing because it means patients are living longer, according to experts. Once an almost inevitable death sentence, the blood cell cancer has transformed into a nearly always treatable condition in the past decade or so, thanks to targeted drugs known as tyrosine kinase inhibitors (TKIs). "The prognosis [for CML patients] is now very good," says Dr Herman Liu Sung-yu, a specialist in haematology and haematological oncology. "So we've seen a cumulative increase in patients." The incidence of CML in Hong Kong is about 0.8 to 1 per 100,000 people, says Liu. About 50 to 70 new cases are diagnosed each year. CML - one of five types of leukaemia - can occur at any age, but it most commonly affects middle-aged and older people. Tyrosine kinases are proteins on leukaemia cells that act as on-off switches. TKIs shut down these proteins, in particular a mutant gene known as BCR-ABL, which causes the disease to flourish. BCR-ABL occurs when two chromosomes swap portions of their genetic material from the BCR and ABL genes during cell division. This abnormal gene is called the Philadelphia chromosome. The resultant fusion protein drives the overproduction of white blood cells and immature stem cells, called blasts, which crowd out red blood cells and platelets. Before 2000, fewer than half of CML patients survived seven years after diagnosis; now nearly 90 per cent do so. Imatinib was the targeted drug that turned things around: it received approval from the US Food and Drug Administration (FDA) in 2001, and in the same month made the cover of Time magazine as the "magic bullet" to cure cancer. However, patients eventually become resistant to imatinib, and this has prompted the development of newer generation inhibitors. Last month, the FDA approved the drug ponatinib, which will "drastically improve the outcome of most patients" who are resistant or intolerant to prior inhibitors, says Dr Jorge Cortes, professor and deputy chair at the University of Texas MD Anderson Cancer Centre Department of Leukaemia. Ponatinib is the third drug approved by the FDA for CML in the past four months. "It's important to have as many therapies against cancer as we can, because rarely does one drug or combination succeed for all patients," says Cortes. Dr Raymond Wong Siu-ming, honorary clinical associate professor at the department of medicine and therapeutics at Chinese University, says a phase III clinical trial for ponatinib, involving patients worldwide, including a number in Hong Kong, will begin in a couple of months. For now, patients in the territory have three treatment options approved by the Hospital Authority: dasatinib, imatinib and nilotinib. All three have been included in the Samaritan Fund as self-financed drugs with a safety net - meaning the government subsidises the drugs for patients who need them but have financial difficulties. "Imatinib is a terrific drug; but 30 to 40 per cent of CML patients become resistant to it," says Cortes. "Nilotinib and dasatinib work for 40 to 50 per cent of these patients." Dasatinib, the newest drug on the list, was approved in Hong Kong as a first-line therapy for newly diagnosed CML in the chronic phase (about 85 per cent are diagnosed at this phase) in July last year. A landmark study, published last year in the American Society of Haematology journal Blood , compared the effectiveness of dasatinib with imatinib. It showed that dasatinib has superior efficacy, as well as faster and deeper responses. The drug also gave patients better control of the disease and a higher overall survival rate. Furthermore, dasatinib is unique in its simple treatment schedule - once daily, either in the morning or evening, with or without a meal. Liu says this improves compliance among patients. "Continuous, effective dosing is important for optimal outcomes," he says. Madam Ho, 51, was prescribed dasatinib daily in July last year. After five months, her BCR-ABL reached undetectable levels. However, Ho has to take the drug continuously, which costs about HK$17,000 to HK$18,000 a month, says Liu. If she stops, the disease is likely to relapse. "TKIs don't eliminate leukaemia stem cells, which remain a potential source of cancer recurrence," says Dr Ravi Bhatia from the City of Hope National Medical Centre in Duarte, California. For now, patients have to take TKIs indefinitely, which Bhatia says carries "a significant risk of toxicity, lack of compliance, drug resistance, relapse and associated expense". Fortunately, in Hong Kong, despite the growing pool of CML patients, Wong says the government has been very supportive. Hospital Authority figures show that in the past two financial years, all who applied to the Samaritan Fund for imatinib or dasatinib were successful. That's 441 applications, or about HK$67 million in subsidies, for imatinib, and 40 applications, or HK$9.4 million, for dasatinib. "We haven't encountered any problems in getting support for these patients," says Wong. "And we're thankful for that."