Annals of Oncology 15:839-840, 2004
© 2004 European Society for Medical Oncology
Use of red blood cell transfusion in palliative care services: is it still up to date or is cancer-related anaemia controlled better with erythropoietic agents?
Fondazione ANT Italia, Via Curiel 7, 40134 Bologna, Italy
*E-mail: stephan.tanneberger@antitalia.org
Randomised clinical trials of erythropoietin have shown a statistically significant substantial reduction in blood transfusions overall, even though the response rate definitions include an increase in haemoglobin by 2 g, which is only achieved in 
60% of patients. Increases in haemoglobin <2 g are achievable in more patients. The review by Cella et al. [1] strongly recommends ‘the use of erythropoietic agents in anemic cancer patients as a means of raising their haemoglobin levels and consequently improving their quality of life’. Anaemia is defined as a ‘a multi-symptom syndrome with fatigue being the primary symptom’, characterized by ‘a haemoglobin level of <12 g/dl’.
However, not all groups of anaemic cancer patients may be appropriate candidates for erythropoietin treatment. Disadvantages of recombinant human erythropoietin include its cost, its efficacy in only some patients and the 4–8 week delay before maximum benefit is achieved [2]. Careful consideration of the advantages and disadvantages of the major treatment forms of anaemia (transfusion and erythropoietin) will help avoid ineffective, costly interventions [3]. Certainly this was reason for the editors of Annals of Oncology [4] to classify the discussion on anaemia in elderly cancer patients as a ‘highlight’ of the Seventh International Conference on Geriatric Oncology.
Advanced cancer patients receiving palliative care represent a large group of anaemic patients. Cella et al.’s review raises the question of whether these patients could be candidates for treatment with erythropoietic agents. Palliative care is defined as the combination of active and compassionate therapies intended to comfort and support individuals and families who are living with or dying from a progressive, life-threatening illness. Of course, one can treat advanced cancer patients having a haemoglobin <12 g/dl with erythropoietin, assuming that the number of necessary blood transfusions will eventually decrease. However, palliative care follows specific rules. Knowing when it is ‘worthwhile’ to palliate a symptom means being able to estimate the possible burden of side-effects and the time delay until the treatment works compared with the actual prognosis, as well as the economic consequences for the patient and the clinic [5]. Unfortunately, there is a noticeable lack of evidence base, in the strict sense of randomised clinical trials, in palliative care of anaemia. Monti et al. [6] studied 246 terminally ill patients admitted for end-of-life care in a palliative care unit (60% died during the same hospitalisation, a median of 49 days after transfusion) and reported improved subjective well-being after blood transfusion in 51.4% of cases without significant relationship to pre-transfusion haemoglobin levels or performance status. The influence of blood transfusion was not related to the severity of dyspnoea or fatigue. We would like to add our data to this discussion.
Between 1985 and June 2003, a total of 41 398 patients, frequently affected by anaemia, were admitted to the hospital-at-home programme of ANT Italia [7]. Anaemia is defined as an abnormally low haematocrit or haemoglobin concentration in the peripheral blood. Fifty per cent of our patients showed haemoglobin levels 
12 g/dl, and 15% 8 g/dl. In cases of anaemia-related symptoms, patients were treated by blood transfusion. There was no use of erythropoietin. We studied in detail, from 2000 to 2002, the effect of blood transfusion in symptom control in 112 advanced cancer patients presenting with a mean haemoglobin value of 7.1 g/dl [95% confidence interval (CI) 7.0–7.3] and receiving a median number of 3.7 units (95% CI 3.0–4.4) of blood. All transfusions were administered out-of-hospital at patients’ homes. The mean difference between the baseline haemoglobin value and the value after the first unit of blood was +1.75 g/dl (95% CI 1.61–1.95), and after the second unit was +1.43 g/dl (95% CI 1.18–1.68). Control of symptoms was achieved for a mean duration of response of 18.5 days (95% CI 14.8–22.2) after each transfusion. The median survival of patients was 3 months (95% CI 2.43–4.93). As shown in Table 1, 1 week after transfusion there was excellent control of symptoms regarding quality of life.
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We conclude that transfusion does offer prompt symptom relief and improvement of well-being in anaemic patients with terminal malignant disease. Neither in the review by Cella et al. [1] nor in the Medline-registered literature do data exist which show that erythropoietic agents offer comparable results with respect to response rate, and time to onset and duration of response. Based on 1473 home blood transfusions performed in the city of Bologna between 25 August 1997 and 8 August 2003, we did not experience the ‘many real and perceived risks, such as infections and haemolytic reactions which patients often prefer to avoid’ described by Cella et al. [1]. There was no case of serious haemolytic reaction. Only slight immunologically mediated reactions, such as flushing and itching, were observed in 5.9% of patients. Concerning the risks of virus infections, we would like to point out that these have been drastically minimised by recent technological advances in blood preparation.
There is no doubt that research into finding alternatives to blood transfusion deserves great attention, and that this research should include the development of erythropoietic compounds. In parallel, we need to define correctly the strategic use of blood transfusion and erythropoietic agents to meet better the varying clinical, psychological and ethical needs of the heterogeneous group of anemic cancer patients. The goal of anaemia treatment tailored to an individual cancer patient has to be made at the bedside by an experienced medical oncologist in conjunction with the patient’s preferences and values [8]. Otherwise, we treat the anaemia but not the patient.
Acknowledgements
The following individuals also participated in this study: Drs R. Mellone, G. Agnani, S. Coppola, G. Farabegoli and M. Mineo. We thank the medical staff of Fondazione ANT Italia for caring for the patients in this trial, and Drs Lucia Gualandi, Gordana Jovic and Enrico Aiello from ‘Master of Biostatistics’ of the University of Bologna for their help with the statistical analysis. Dr N. Kolazek provided us with editorial assistance.
REFERENCES
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