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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.

SUBMITTER: Hewamana S

PROVIDER: S-EPMC9176152 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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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.

Hewamana Saman S Kandabadage Lakmali L Skandarajah Thurairajah T Pieris Natasha N Perera Eranga E Harischandra Mahesh M Wijewickrama Ananda A Wickramarathna Chandana C Somasundaram Gnani G Srinivasan Vadivelu V Somiah Surjit S Jayawardena Priyankara P Perera Mehendra M Gunasekera Dehan D Jayasinghe Chathuri C Constantine Godvin G Munasinghe Sanjeewa S De Silva Chandu C Wijesiriwardena Bandula B Balawardena Jayantha J

EJHaem 20210513 3

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 e ...[more]

PMID: 35844682

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Project description:The phenotype of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients is determined by the type of DMD gene variation, its location, effect on reading frame, and its size. The primary objective of this investigation was to determine the frequency and distribution of DMD gene variants (deletions/duplications) in Sri Lanka through the utilization of a combined approach involving multiplex polymerase chain reaction (mPCR) followed by Multiplex Ligation Dependent Probe Amplification (MLPA) and compare to the international literature. The current consensus is that MLPA is a labor efficient yet expensive technique for identifying deletions and duplications in the DMD gene. Genetic analysis was performed in a cohort of 236 clinically suspected pediatric and adult myopathy patients in Sri Lanka, using mPCR and MLPA. A comparative analysis was conducted between our findings and literature data. In the entire patient cohort (n = 236), mPCR solely was able to identify deletions in the DMD gene in 131/236 patients (DMD-120, BMD-11). In the same cohort, MLPA confirmed deletions in 149/236 patients [DMD-138, BMD -11]. These findings suggest that mPCR has a detection rate of 95% (131/138) among all patients who received a diagnosis. The distal and proximal deletion hotspots for DMD were exons 45-55 and 6-15. Exon 45-60 identified as a novel in-frame variation hotspot. Exon 45-59 was a hotspot for BMD deletions. Comparisons with the international literature show significant variations observed in deletion and duplication frequencies in DMD gene across different populations. DMD gene deletions and duplications are concentrated in exons 45-55 and 2-20 respectively, which match global variation hotspots. Disparities in deletion and duplication frequencies were observed when comparing our data to other Asian and Western populations. Identified a 95% deletion detection rate for mPCR, making it a viable initial molecular diagnostic approach for low-resource countries where MLPA could be used to evaluate negative mPCR cases and cases with ambiguous mutation borders. Our findings may have important implications in the early identification of DMD with limited resources in Sri Lanka and to develop tailored molecular diagnostic algorithms that are regional and population specific and easily implemented in resource limited settings.

Project description:BackgroundThe free antiretroviral therapy (ART) program in India still relies on the clinico-immunological monitoring for diagnosis of treatment failure. As the nucleoside reverse transcriptase inhibitor (NRTI) backbone is shared in first- and second-line regimens, accumulation of drug resistant mutations (DRMs) can compromise the efficacy of NRTI. This study was undertaken to describe the pattern of HIV DRMs following immunological monitoring and investigate its impact on the cycling of NRTI between first- and second-line ART.Methods and findingsThis cross-sectional study was performed at a state-sponsored ART clinic of Pune city in western India between January and June 2016. Consecutive adults receiving first-line ART with immunological failure (IF) were recruited for plasma viral load (PVL) estimation. Randomly selected 80 participants with PVL >1000 copies/mL underwent HIV drug resistance genotyping. Of these, 75 plasma sample were successfully genotyped. The median CD4 count and duration of ART at the time of failure were 98 (IQR: 61.60-153.50) cells/μL and 4.62 (IQR: 3.17-6.15) years, respectively. The prevalence of NRTI, non-NRTI, and major protease inhibitor resistance mutations were 89.30%, 96%, and 1.33%, respectively. Following first-line failure, sequences from 56.67% of individuals indicated low- to high-level resistance to all available NRTI. The proportion of sequences with ≥2 thymidine analogue mutations (TAMs) and ≥3 TAMs were 62.12% and 39.39%, respectively. An average of 1.98 TAMs per sequence were observed following IF as compared to 0.37 TAMs per sequence following targeted PVL monitoring at 12 months of ART from a prior study; this difference was significant (p<0.001).ConclusionThe option of cycling of NRTI analogues between first- and second-line regimens would no longer be effective if individuals are followed-up by immunological monitoring due to accumulation of mutations. Introduction of routine PVL monitoring is a priority for the long-term sustainability of free ART program in India.

Dataset Information

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.

Publications

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.

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