School Papers

The high, almost 6 out of 10 (55%)

The Risks and Benefits of Chemotherapy in Elderly Patients with
Acute Myeloid Leukaemia

Acute Myeloid Leukaemia (AML) is
a type of blood cancer affecting the white blood cells specifically granulocytes
or monocytes in the bone marrow. In 2014, 3,100 new cases of AML were diagnosed
in the UK. That is approximately 8 cases each day which accounts for less than
1% of all news cases in the UK. Over the past 10 years, prevalence of AML in
the UK increased by 8%. While affecting all age groups, incidence rates of AML
are high, almost 6 out of 10 (55%) in people aged 70 and over but it is highest
in elderly people aged 85 and above from 2012-2014 (Cancer Research UK,
2014).  Blood cancers are usually treated with chemotherapy, which uses drugs to
kill cancer cells. Intensive chemotherapy means having high doses of
chemotherapy (NICE, 2016).  Systemic
Anti-Cancer Therapy (SACT) is the delivery of cytotoxic chemicals to the body
that kills rapidly dividing cells, both cancer and non-cancer. It can be given
via different routes such as intravenous, oral, subcutaneous, intramuscular,
intrathecal, arterial, intra-vesical, intra-pleural and topical (London Cancer
Alliance, 2011). This paper aims to discuss and critically analyse the
advantages and disadvantages of   receiving chemotherapy by elderly patient with
Acute Myeloid Leukaemia.

Having said that AML mostly affects elderly people, treatment of AML
remains a big challenge for haematologists and oncologists. Despite of
evidences of better survival for patients undergoing treatment in this patient
population, it is not readily offered to all patients. Assessing patients that
are fit to receive chemotherapy still remains a struggle. There is a need for a
complete geriatric valuation in able to decide better for the patients (Rao AV,
2016). Over the past several decades, the prognosis of AML in elderly patients
remains bleak as nearly 70% of patients with AML 65 years and older eventually
succumbing to their disease.  This is
also caused by disease-related and patient-related factors resulting in poor
outcome. The disease biology is significantly different in elderly population
as well (Mamdani et al, 2016).

There are several reasons that are causing poor results for treating AML
in elderly people. Advanced age is often accompanied by frailty and
comorbidities. These factors have very important impact on patient’s tolerance
of intensive treatment. There are lower rates of remission in the elderly,
40-50% versus 60-70% in the young. This is associated with elderly patients’
clinical features, the cytogenetic profile of older adults with AML differ from
younger patients, presenting greater occurrence of multiple chromosomal
abnormalities. The probabilities of developing several diseases increase with
chronological age giving elderly patients risks of notwithstanding intensive
chemotherapy regime. In these cases, a comprehensive geriatric assessment with
specific guidelines to help doctors choose the best option for the patient is
necessary. There are several screening tools developed ranging from simple to
complex, such as the Short Physical Performance Battery, Gait Speed, as well as
the Modified Mini-Mental Score or the Short Portable Mental Status
Questionnaire. However, some are not always readily available. Still, careful
evaluation of both patient and disease is required to support the doctors in
deciding whether the treatment will be appropriate with patient (Almeida and
Ramos, 2016).

Despite the recent developments in the management of patients with
haematologic malignancies, the progress of emerging novel targeted therapies
and enhancement of supportive care measures, the overall outcome for elderly
patients with AML remains poor (Nazha and Ravandi, 2014). The 5-year overall
survival is less than 5% in patients 70 years and older and less than 1% in
patients older than 80 years. Poor outcomes is being linked to multiple reasons
including concomitant comorbidities, inferior responses to chemotherapy and
differences in biology of the disease that are related to the incidence of high
risk features such as complex karyotype and secondary AML (Juliusson et al,
2012).

Many oncologists are reluctant to offer intensive chemotherapy to
elderly patients because increased comorbidities lead to higher morbidity and
mortality. A retrospective cohort study has been conducted wherein 5,480
patients with Acute Myeloid Leukaemia (median age being 78 years with range
65-93 years), 38.6% received leukaemia therapy within three months after being
diagnosed (treated group). Median survival was six months in the treated group
compared to just two months in the untreated group. The most marked
improvements were seen in patients aged 65-69 years with 10 months survival
versus 4months and 70-74 years with 8 moths versus 3 months. The results of the
study show that therapy for leukaemia improves overall survival in older acute
myeloid leukaemia patients. Putting into consideration the patients’
comorbidities, most patients up to 80 years of age should still be considered
for treatment. New therapies including hypomethylating agents and allogeneic
cell transplantation are promising but must still be compared with other
chemotherapy regimens (Oran and Weisdorf, 2012).

Another aspect to be considered in the treatment decision in elderly
patients with AML is the judgment of treating physicians, and the factors that
determine their decision relating to whether the patient is unfit to receive intensive
chemotherapy as well as the patient’s expectations for the treatment. In a
retrospective analysis of 1672 elderly patients with AML from six separate
health regions in the Swedish Leukaemia Registry database, the percentage of
patients who were deemed to be fit to receive intensive chemotherapy varied
significantly between the various geographic regions. Remarkably, the overall survival
was better in areas where patient were more likely to receive treatment with
standard chemotherapy compared to palliative approach only. Moreover, early death
rate was low in patients who underwent intensive therapy compared to those
patients who had palliation alone, even among those with poor performance
status. Similar conclusions have also been reported by several other studies
that have compared intensive or non-intensive chemotherapy to palliative care
(Billstrom et al, 2006).

Age has always been considered as a strong independent prognostic marker
for overall survival in patients with AML, with a worse result as age increases.
In a retrospective analysis from German AML cooperative group, the 4 –year
overall survival for patients above 60years old was considerably lower than for
patients younger than 60 years (16% vs 37%). 
In a retrospective analysis of 968 patients with AML included in five
Southwest Oncology Group (SWOG) clinical trials, it showed that as the
patient’s increasing age is related to less favourable cytogenetics, poorer
performance status at presentation, lower white blood cell counts and lower
percentage of marrow blasts. Furthermore, advancing age was also linked with a
lower response rate (only 33% responded to induction chemotherapy among older
patients older than 75). A higher rate of early mortality during induction
therapy and shorter survival (median overall survival was 3 and a half months
among patients older than 75). More prominently, lower performance status at
diagnosis was connected with higher induction mortality rates more so in
elderly patients, signifying that the presence of other comorbidities has a
significant impact the overall outcome of these patients (Applebaum et al,
2006).

Treatment of elderly patients with AML is challenging and difficult, and
the choice of best treatment strategy for most patients is still under debate.
These challenges are related to several factors, including: empirically, most
of the trials conducted in AML focused mainly on younger patients, making it
hard to apply their results to the elderly population, there is some
disinclination by physicians and patients to use intensive chemotherapy regimes
in elderly patients; this is because chemotherapeutic regimens used for AML are
considered more intensive than those used for other tumours, and usually, the
majority of trial conducted in elderly AML does not include patients with poor
performance status and comorbid medical conditions, making it difficult to
apply results of these trials to routine practice (Nazha and Ravandi, 2014).

The selection of treatment options for elderly AML patients can be based
on four main factors: patient’s clinical condition, disease characteristics,
patient’s wishes and social support. Hence, the most fragile and oldest among
the oldest will have the least net benefit from chemotherapy, even if they
receive the best available treatment, while the fittest and the youngest
patients will benefit most. Considering the aforementioned factors, it can be
said that the relative prognosis of elderly AML patient will depend on our
capability to choose and administer an effective treatment, and that the
benefits must outweigh the risks before subjecting a patient to intensive
chemotherapy and must be based not only on the predicted toxicity of the
regimen, but also on the possibility of response, where cytogenetics play a
very big role. In current practice, the physician’s goal should be to offer
patients with conventional intensive chemotherapy followed by hematopoietic
transplantation whenever this is feasible taking into considerations the
factors that can affect treatment such as disease-related, patient-related and
transplantation-related prognostic factors. Chemotherapy is still considered as
the best option for treating leukaemia. Supportive therapy should be avoided as
much as possible. All effort and means to treat patients with AML should be
exhausted including administering low-intensity chemotherapy prior to
considering supportive therapy alone (Almeida and Ramos, 2016).

In my experience as a haemato-oncology nurse, I have witnessed the
prevalence of AML in our ward. Though it affects different people from all
walks of life, most of our patients our elderly patients. This can be very
challenging to deal with as most of the elderly people are very fragile and
weak. Though some of the patients from the ageing population were able to
maintain fitness, most of the elderly patients can still be considered at risk
of more complications if an intensive chemotherapy regime will be given. In
practice, various tests and procedures are being done by the team prior to
deciding which treatment will best cater the patient’s needs. It is very
important that patients feels supported throughout the treatment process and
the team should be acting based on the best interest of the patient. Elderly
patients receiving chemotherapy in the ward have experienced more side effects
and more complications compared to younger patients. In conclusion based on
what I have read and what I have experienced, chemotherapy is still the best
treatment option for the elderly patients. However, certain factors such as
comorbidities and disease biology should be carefully considered. Being the
ones in the receiving end, patients should have a say on what treatment they
want as well, the physicians should make sure that all details of treatment has
been thoroughly explained to the patients. Age remains a very big factor on
decision making for elderly patients with AML. It is very helpful to the
practice that recently, a lot of trials are being done, which includes more age
group towards the development of treatment for blood malignancies such as AML.
Having these studies will greatly benefit the practice in the future as
physicians will have more evidence-based options to choose from to treat AML.
This will mean higher chances of giving the best treatment for elderly patients
rather than resorting to supportive therapy right away.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

References

Cancer Research UK (2014) Acute Myeloid Leukaemia. Available at: http://www.cancerresearchuk.org/about-cancer/acute-myeloid-leukaemia-aml?_ga=2.15877749.2127976463.1509464065-407095418.1509464065
accessed: 10 September 2017

London Cancer Alliance (2011) Pan London Guidelines for the Safe
Prescribing, Handling and Administration of Systemic Anti Cancer Treatment
Drugs. Available at: http://www.londoncanceralliance.nhs.uk/media/42575/panlondoncytopolicy_final_v1_01.pdf
accessed: 10 September 2017

Rao, AV (2016) ‘Fitness in the
elderly: how to make decisions regarding acute myeloid leukaemia induction’, American Society of Hematology,
EducationProgram, 2016(1), pp. 339-347

Mamdani, H., Dos Santos, C.,
Konig, H. (2016) ‘Treatment of Acute Myeloid Leukaemia in Elderly Patients – A
Therapeutic Dilemma’, JAMDA, 17(2016),
pp. 581-587

Almeida, A. and Ramos, F. (2016)
‘Acute myeloid leukemia in the older adults’, Leukemia Research Reports, 6(2016) pp. 1 -7

Nazha,A. and Ravandi, F. (2014)
‘Acute myeloid leukemia in the elderly: do we know who should be treated and
how?’ Informa Healthcare, 55(5), pp.
979-987

Juliusson, G., Lazarevic V.,
Horstedt AS, et al. Acute myeloid leukemia in the real world: why
population-based registries are needed. Blood 2012; 119: pp 3890-3899

Oran, B. and Weisdorf, D. (2012)
‘ Survival for older patients with acute myeloid leukemia: a population-based
study’ University of Minnesota
Hematology, Oncology and Transplantation, 97(12) pp.1916-1924

Billstrom, R., Juliusson, G.,
Gruber, A., et al. Attitude towards remission induction for elderly patients
with acute myeloid leukemia influences survival. Lekemia 2006;20: pp 42-47

Appelbaum,  FR., Gundacker, H., Head, DR., et al. Age and
acute myeloid leukemia. Blood 2006; 107: pp 3481-3485