Monitoring asparaginase activity in middle-income countries

Cecconello, D; Werlang, Isabel Cristina Ribas; Alegretti, Ana Paula; Hahn, Monique Cabral; Magalhães, Mariana Rodrigues; Battistel, Ana Paula; Zenatti, Priscila Pini; Yunes, José Andrés; Cabreira-Cagliari, Caroline; Rechenmacher, Ciliana; Goldani, Marcelo Zubarán; Daudt, Liane Esteves; Michalowski, Mariana Bohns

doi:10.1016/s1470-2045(18)30584-9

Cited by 28 publications

(23 citation statements)

References 6 publications

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“…In 2017, anticipating drug shortage of native asparaginase, the Ministry of Health in Brazil changed the national supplier to a foreign manufacturer that offered a new lowercost generic product (83). Concerned by the lack of published data on this new product, investigators in Brazil studied the drug's properties, and found that it was less bioactive, and contained contaminating proteins that increased the risk for immune-related side effects compared with the native asparaginase used previously (83,84). Although the nationwide distribution of this new product in Brazil was halted, this drug continues to be manufactured and distributed to other countries around world (83).…”

Section: Access To Essential Medicinesmentioning

confidence: 99%

Science and health for all children with cancer

Lam

Howard

Bouffet

et al. 2019

Science

261

190

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Each year ~429,000 children and adolescents aged 0 to 19 years are expected to develop cancer. Five-year survival rates exceed 80% for the 45,000 children with cancer in high-income countries (HICs) but are less than 30% for the 384,000 children in lower-middle-income countries (LMICs). Improved survival rates in HICs have been achieved through multidisciplinary care and research, with treatment regimens using mostly generic medicines and optimized risk stratification. Children’s outcomes in LMICs can be improved through global collaborative partnerships that help local leaders adapt effective treatments to local resources and clinical needs, as well as address common problems such as delayed diagnosis and treatment abandonment. Together, these approaches may bring within reach the global survival target recently set by the World Health Organization: 60% survival for all children with cancer by 2030.

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Section: Access To Essential Medicinesmentioning

confidence: 99%

Science and health for all children with cancer

Lam

Howard

Bouffet

et al. 2019

Science

261

190

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“…The activity of 262 samples was evaluated in our center, based on the reactions of the below-described method, which were classified according to the activity level as above or below 0.1 IU/mL 16 . The method of analysis used by all centers to determine enzyme activity was based on a technique described by Lanvers et al 10 which uses aspartic acid B-hydroxamate (AHA) as a substrate for the quantification of ASNase derived from E. coli, Erwinia chrysanthemi, and PEG ASNase in human plasma.…”

Section: Methodsmentioning

confidence: 99%

Implementation of the asparaginase activity assessment technique for clinical use: experience of a Brazilian Center

Cecconello

Rechenmacher

Werlang

et al. 2020

Sci Rep

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Acute lymphoid leukemia is a childhood cancer that in high-income countries has event-free survival rates of 80% and global survival rates of 90%. In Brazil these rates are under 70%. This difference may be due to the implementation of supportive care, including the assessment of asparaginase (ASNase) activity. ASNase may cause hypersensitivity reactions and silent drug inactivation. For this reason, ASNase activity monitoring is an essential tool to ensure an effective treatment. Our aim was to implement an ASNase activity measurement technique at a hospital setting. samples from children who were given Escherichia coli-derived ASNase were collected. The results of the analyses conducted in our laboratory Hospital de Clínicas de Porto Alegre were compared to those of two institutions: Centro Infantil Boldrini and University of Munster. 262 samples were assessed. The results of the first analyses were compared with those obtained at Centro Infantil Boldrini and showed an ICC of 0.954. Thirty samples were sent to the University of Munster and presented an ICC was 0.960. Our results, when compared to those of national and international centers, showed an excellent agreement. The study was able to implement an ASNase activity test to monitor the treatment.

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“…This kind of analysiscan help policy makers to establish the appropriate strategies to provide access to efficient treatment for all patients. 44 …”

Section: Clinical Applicationmentioning

confidence: 99%

Asparaginase: an old drug with new questions

Cecconello

Magalhães

Werlang

et al. 2020

Hematology, Transfusion and Cell Therapy

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The long-term outcome of acute lymphoblastic leukemia has improved dramatically due to the development of more effective treatment strategies. L-asparaginase (ASNase) is one of the main drugs used and causes death of leukemic cells by systematically depleting the non-essential amino acid asparagine. Three main types of ASNase have been used so far: native ASNase derived from Escherichia coli , an enzyme isolated from Erwinia chrysanthemi and a pegylated form of the native E. coli ASNase, the ASNase PEG. Hypersensitivity reactions are the main complication related to this drug. Although clinical allergies may be important, a major concern is that antibodies produced in response to ASNase may cause rapid inactivation of ASNase, leading to a worse prognosis. This reaction is commonly referred to as "silent hypersensitivity" or "silent inactivation". We are able to analyze hypersensitivity and inactivation processes by the measurement of the ASNase activity. The ability to individualize the ASNase therapy in patients, adjusting the dose or switching patients with silent inactivation to an alternate ASNase preparation may help improve outcomes in those patients. This review article aims to describe the pathophysiology of the inactivation process, how to diagnose it and finally how to manage it.

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Monitoring asparaginase activity in middle-income countries

Cited by 28 publications

References 6 publications

Science and health for all children with cancer

Science and health for all children with cancer

Implementation of the asparaginase activity assessment technique for clinical use: experience of a Brazilian Center

Asparaginase: an old drug with new questions

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