The inaugural scientific meeting of the ASEAN Federation of Haematology (AFH)/Malaysian Society of Haematology (MSH) was held at the Shangri-La Hotel in Kuala Lumpur, Malaysia from 22 to 24 April 2010.
Chronic myeloid leukaemia – Clinical practice guidelines in a developing country
Despite available clinical practice guidelines (CPGs) for chronic myeloid leukaemia (CML), there is still a need to develop customised guidelines in developing countries such as Malaysia, Dr Ng Soo Chin shared at the AFH/MSH scientific meeting.
“There are daunting challenges to overcome to provide state-of-the-art care to our people,” said Dr Ng, who is the incumbent president of both the MSH and the AFH, and was the co-organising chairman of the inaugural AFH/MSH scientific meeting. By addressing these challenges through customised CPGs, appropriate recommendations are formulated based on the available resources of a developing country.
Among the CML management issues identified by Dr Ng in Malaysia include financial constraints, a relatively younger CML population, the shortage of medical personnel trained in haematology/haematopoetic stem cell transplant, and the lack of infrastructure necessary to provide both the diagnostic services and therapeutic care. The delivery of healthcare to CML patients is further complicated by the geographical divide of East and West Malaysia.
CML is the first human cancer whereby a consistent chromosomal abnormality linked to a specific type of leukaemia was discovered. The demonstration of the translocation [t(8;22)] in the Philadelphia chromosome in the 1960s (Science 1960;132:1497), has led to a better understanding of cancer biology as well as to the development of imatinib, the first molecularly targeted cancer treatment.
Prior to imatinib, allogeneic stem cell transplantation and interferon-alfa provided much of the groundwork for CML frontline treatment. Back then, CML was considered to have a poor prognosis, with the mean survival ranging from 3 to 6 years only (Ann Intern Med 1999;131:207–19). The discovery of imatinib ushered in the era of targeted cancer therapy, and the availability of these tyrosine kinase inhibitors (TKIs) has transformed the landscape of treating CML patients. The disease now has an excellent prognosis, with patients having a mean survival of over 25 years (N Engl J Med 2001;344:1031–37).
Much of the currently available CPG for CML treatment and management are based on the results of the International Randomized Study of Interferon and STI571 (i.e. imatinib) or IRIS trial. The 6-year update results of this trial underscore the efficacy and safety of imatinib as first-line therapy for CML patients (Leukemia 2009;23:1054–61).
Current CML CPGs such as the European LeukemiaNet (ELN) (J Clin Oncol 2009;27:604–51) recommend that CML patients receive an initial treatment of 400 mg of imatinib daily, and should be continued indefinitely in optimal responders. Suboptimal responders may benefit from continued imatinib use at the same or higher dose, or may be eligible for investigational therapy with second-generation TKIs. In instances of imatinib failure, second-generation TKIs are recommended, followed by allogeneic haematopoietic stem cell transplantation only in instances of failure and, sometimes, suboptimal response, depending on transplantation risk.
The recent Asian Consensus Statement for CML released by the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (V.1.2009) has recommendations similar with that of most available CML CPGs regarding imatinib.
“Unfortunately, the main shortcoming of the NCCN guidelines for CML is that cost was not considered as an issue when the recommendations were formulated,” said Dr Ng, who is also a panel member of this consensus statement. According to Dr Ng, excluding financial considerations from these guidelines is not practical in the actual clinical setting, and is one of the crucial issues encountered in Malaysia.
“Majority of Malaysian CML patients cannot afford imatinib, especially on a long-term basis,” added Dr Ng. Fortunately, the proven benefits of imatinib have been enjoyed by many Malaysian CML patients largely due to the assisted patient programme run by The Max Foundation, a US-based non-profit cancer organisation that aims to help patients diagnosed with blood and rare cancers by facilitating access to treatment and providing care and support for those who have limited access to resources.
On the other hand, hardly any patients can afford the second generation TKIs because there are currently no assistance programmes for these drugs. Also, care for bone marrow transplant patients is very expensive. Thus, Dr Ng stressed the need to examine a sustainable government subsidy scheme to make these treatments available as viable second-line or alternative options.
Aside from financial constraints, Dr Ng believes that the need for customised CPG in Malaysia is driven by the following factors: age, manpower and infrastructure.
“I think that most Asian CML patients are younger than Western CML patients,” commented Dr Ng. In Malaysia, the mean age of CML patients was shown to be 35 years, while their Western counterparts have a mean age of 44 years (Malays J Pathol 1990;12:111).
Due to the relatively younger Malaysian CML population, customised CPGs need to address other issues that may complicate treatment in this population, such as pregnancy, long-term treatment, compliance problems, and the possibility of more transplant options.
Customised CPG recommendations also need to consider the shortage of infrastructures and manpower needed to provide state-of-the-art healthcare for CML patients in Malaysia.
Delivery of optimum care to patients is further complicated by Malaysia’s geography. According to Dr Ng, outside the major towns, diagnostic, medical and supportive facilities are still lacking, especially in the inland parts of East Malaysia.
The number of haematopoetic stem cell and bone marrow transplant facilities is still relatively low in Malaysia. However, Dr Ng reported that there has been steady improvement in the delivery of healthcare to CML patients in Malaysia. Recently, the number of haematology departments has increased, and there are currently about 30 haematologists available to the 28 million Malaysians.
In summary, Dr Ng emphasised that in developing countries such as Malaysia, a customised CPG for CML management needs to address the issue of how best to manage CML patients with the limited resources in the face of an evolving treatment landscape.
Dr Ng Soo Chin is a consultant haematologist at the Sime Darby Medical Centre Subang Jaya in Malaysia. He is also the current president of the Malaysian Society of Haematology and the ASEAN Federation of Haematology.
