A step forward in the treatment of acute myeloid leukaemia

Cristina G. Pedraz/DICYT Acute myeloid leukaemia (AML) is the commonest type of acute leukaemia in adults. Normally bone marrow produces cells known as myeloids which after maturing become granulocytes, the cells in charge of defending the organism against infection. In AML the myeloids proliferate abnormally to progressively invade the bone marrow and interfere with the production of normal blood cells.

A group of researchers of the Haematology Service of the Hospital of León, as part of the activities of the Biomedicine Institute of the University of León (Ibiomed) and with the collaboration of the Haematology and Haemotherapy Foundation of Castilla-León and the sponsorship of the pharmaceutical company Celgene, has taken a step forward in the treatment of this disease.

As part of a study known as ALMA (Azacitidina en la Leucemia Mieloblástica Aguda or Azacitidine in Acute Myeloid Leukaemia), the researchers have designed and validated a tool capable of predicting the response of patients to azacitidine, one of the drugs suitable for treating this disease.

As is explained to us by Fernando Ramos, the Head of the Clinical Haematology Section of the Hospital of León and the researcher of the Ibiomed in charge of the study, azacitidine “is a drug that acts by reactivating various genes that have been silenced as a consequence of their methylation (a chemical process that stifles the expression of normal genes)”. Therefore “it is a modifying agent of tumour epigenetics and acts on both ribonucleic acid (RNA) and DNA”.

The study, which was published in the journal Leukemia research, describes the application of the drug in practice, what effect it has on the disease, what problems may be expected from it, and above all which patients may benefit most from the treatment. In the first place the response to treatment and the survival of 110 patients from various Spanish hospitals to whom the drug was administered have been assessed. This information has been used to develop a tool that allows the prediction of both the response to treatment and the survival rate of the patients receiving the drug.

The tool has been validated and refined with the information obtained from 261 other patients treated with azacitidine in France, Italy, and Austria. “We have included direct social services, which complements formal clinic trials. Only patients who are not so ill take part in the latter, which limits the extrapolation of their results to those suffering from the disease as a whole”, Ramos adds.

As for the implications of the study, the researcher points out that it would allow improves use of resources and would avoid “the unnecessary suffering of both those who do not respond to other treatment and who do respond to azacitidine and of those to whom azacitidine is applied and will probably not respond”. In short, “it would enable us to work with more common sense and to offer a solution to people who owing to their age, associated diseases, or the characteristics of their disease cannot receive very demanding treatment that is intended to cure them. Azacitidine does not cure the disease for the moment, but it extends survival and improves quality of life”, he reminds us.

A critical disease

Acute myeloid leukaemia is a serious threat to the lives of its sufferers and without medical treatment death may occur very quickly. Its annual incidence is some 2-4 cases per 100,000 inhabitants and in about two thirds of these cases patients are aged over 65 at the time of diagnosis. With intensive chemotherapy and a possible haematopoietic transplantation some 40 per cent of adults and 10-20 per cent of those aged over 60 can be cured.

The researchers of the Haematology Service of the Hospital of León and the Ibiomed have been working on acute myeloid leukemia since 1995 and on the clinical use of azacitidine since 2008. The ALMA study was designed in 2010 and work began in Spanish hospitals in October 2011. The research has benefitted from the collaboration of Violeta Martínez-Robles of the Haematology Service of the Hospital of León, which is directed by José Antonio Rodríguez García.

Subsequent work along these lines will concentrate on improving the predictive capacity of this tool by means of the inclusion of molecular data. Since 2013 the researchers have been collaborating with the Oncological Cytogenetic Unit of the Hospital Universitario de Salamanca, with Doctor Hernández-Rivas, in a pharmacogenomic study with this objective.

	Bibliographical reference:
	Ramos, F., Thépot, S., Pleyer, L., Maurillo, L., Itzykson, R., Bargay, J. et al. (2015). “Azacitidine frontline therapy for unfit acute myeloid leukemia patients: Clinical use and outcome prediction”. Leukemia research, 39, 3, 296–306