Applicability of Western protocols in resource‐limited setting: Real‐world data of long‐term outcome of intensive treatment of adult acute myeloid leukaemia in Sri Lanka

Abstract There are no published data on long‐term survival and applicability of treatment protocols from developed countries in acute myeloid leukaemia (AML) in Sri Lanka. Eighty‐seven AML patients were reviewed; there were 56 newly diagnosed patients between 18 and 65 years. Thirty‐one out of 33 who started treatment achieved complete remission after first cycle of treatment. The induction mortality was one of 33. Twelve out of 20 patients who completed treatment are alive at the time of analysis. The estimated 5‐year overall survival rate is 0.629. Strict infection control and treatment and superior clinical experience may have contributed towards better outcome.


INTRODUCTION
Acute myeloid leukaemia (AML) is a haematological malignancy, which is almost always fatal without treatment with survival ranging from few days to a few weeks [1].
Sri Lanka is a developing country with diverse health care structure, without dedicated transplant facilities or access to novel antileukaemic agents at the time this study was started.
Sri Lanka lacks the necessary technology and expertise in performing allogeneic transplants and the cost of these in neighbouring Singapore and India are prohibitive. Crude incidence rate of 'Leukaemia' in Sri Lanka is 3.6 in males and 3.1 in females (source: Cancer Incidence Data Sri Lanka 2011; Publication by Government Cancer Control Programme).
We established Lanka Hospital Blood Cancer Centre (LHBCC) in a self-financing hospital in Sri Lanka in collaboration with colleagues in government subsidised hospitals with designated space, staff and a strategy to treat blood cancers using treatment protocols from the United Kingdom (UK). In addition, this centre was used for training purposes of first haemato-oncology trainees from government-subsidised hospitals.
The aim of the study was to analyse patient and disease characteristics and evaluate survival parameters in patients diagnosed with AML treated in line with treatment and supportive care protocols from the UK.

RESULTS
A total of 87 patients with a diagnosis of AML were reviewed; 56 newly Patient and disease characteristics are summarised in Figure 1 and Table 1; outcome data are given in Figure 2 and Table 2.

DISCUSSION
AML is a deadly disease in the West and a deadly and a costly challenge in the developing countries [2]. Several studies have demonstrated the association between the socioeconomic status and the access to and the distribution of modalities of AML treatment [3]. Sri Lanka is a developing country with a diverse health care system. Unlike in the UK, different hospitals in Sri Lanka are likely to have different approaches to the same disease and also significant heterogeneity with regards to diagnostic and treatment facilities, access to trained personnel and supportive care.

Poor compliance with treatment due to lack of insight and financial reasons
It has been shown that survival and treatment options available depend on the insurance status and country of residence, and South Asian data showed poor compliance rates compared to Western trials [4][5][6]. Our data show that 33/56 (58%) initially agreed for treatment compared to 29% reported by Philip et al., but further nine decided to stop treatment after the first cycle. Total number of patients who did not proceed with the consolidation chemotherapy was 10 (10/31) due to financial reasons. In the developed countries, the cost of AML treatment is between US $80,000 and US $150,000 per patient and regional data showed it to be around US $32,500, which may be many times of one's annual income [4,7,8]. pared to the ones who completed treatment (35% vs. 54%, p < .001) [15]. However, the reason for not continuing treatment in the West is due to delayed haematopoietic recovery compared to financial reasons in low-income countries. People who decided to stop treatment in LHBCC had a median survival of mere 1.65 months, but the median survival for the ones who continued care has not reached at the time of the analysis.

Lower induction and consolidation mortality due to strict protocols and guidelines adoption
Guidelines make health care more consistent and efficient and reduce mortality and morbidity, but there are no well-designed guidelines in developing countries [9,10]. The induction death rate was 25%, 17% and 18.4% in the following regional publications by Philip et al., Kalaiyarasi et al. and Bahl et al. [4,6,11] in the same age group. In comparison, we lost one patient (3%) during induction and another during the consolidation (5%). In the AML15 trial, CR rate of DA was 84% [15]  compared to 31/33 (93%) after course 1 of DA in our cohort. We have excluded patients outside 18-65 years range, making it difficult to do a proper comparison. Two patients died due to sepsis but in general our lower rate of treatment-related mortality was due to strict infection prevention measures and aggressive treatment, which is one of the most important parameters in AML care as published before [12]. Furthermore, it has been shown that improved survival in AML may be due to advances in supportive care and superior clinical experience [13].
We used similar antifungal and antimicrobial prophylaxis as used in the UK AML trials, and neutropenic sepsis was treated using modified Western guidelines.

Better survival figures in patients who continued treatment
Even in the countries with best facilities, 5-year OS rate in AML ranges between 25% and 40% for the group receiving intensive treatment [5,14]. However, Burnet et al. reported in AML15, an 8-year survival rate of 47% for patients who received two cycles of DA/ADE and two cycles of consolidation. The 5-year survival from diagnosis in a group of patients treated with the same protocol and with an almost identical age distribution to our patients in the AML15 study was above 40%.
We used only high-dose cytarabine consolidation as Amsacrine for other options are not available in Sri Lanka and also we believe patients are in the low-and intermediate-risk groups on the limited genetic analysis available. In addition, other consolidation options were shown to need more supportive care [15]. Subanalysis of patients who continued treatment in our cohort showed 5-year estimated OS rate of 62.9%. Comparative regional data has shown OS of 20.6 months and estimated 5-year OS rate of 35.5% [11]. Our treatment success is likely due to uniform treatment protocols, having full-time in-house clinical haematologist/haemato-oncologists, following Western protocols to treat AML and treatment-related complications and comprehensive supportive care. We acknowledge that a limitation of this study is the very small sample size, which could have resulted in some selection bias towards better outcome.

CONCLUSION
This is the only documented study related to outcome and successful applicability of Western treatment and supportive care protocols to Sri Lankan patients with AML. Though this can be considered as a small pilot study, we believe this published data will help to benchmark and in the development of the speciality of blood cancer care in the local setting.