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AKUT LENFOBLASTIK LÖSEMIDE KEMOTERAPÖTIK ILAÇ REJIMINE EKLENEN ASPARAJINAZ ETKINLIĞININ MINIMAL REZIDÜEL HASTALIK ÖLÇÜMÜ ILE DEĞERLENDIRILMESI

Year 2024, Volume: 52 Issue: 4, 211 - 215, 11.10.2024
https://doi.org/10.15671/hjbc.1375369

Abstract

Çocukluk çağı Akut Lenfoblastik Lösemi (ALL) hastalığının en yaygın alt tipi olan B-ALL, dünya çapında yaklaşık %85 çocuğu etkilemektedir. ALL hastalığının tedavisi devam ederken yapılan Minimal Rezidüel Hastalık (MRD) takibi, hastalığın seyri için önem taşımaktadır. Relapsın erken tespitinin, risk yüzdesi saptanmasının ve tedavinin efektifliğinin anlaşılmasını sağlayan MRD takibi Akım sitometri, qRT-PCR, NGS gibi birden fazla yöntem ile yapılabilmektedir. Asparajinaz ALL tedavisinde 1960’lı yıllardan itibaren kullanılan, asparajini amonyağa ve aspartik asite dönüştürerek serum asparajin seviyesini düşeren ve malign hücrelerin ölümüne yol açan bir enzimdir. Bu çalışmada, akım sitometri ile MRD takibi yapılan, 0-18 yaş aralığındaki 62 kişilik B-ALL hastasının, ALL IC BFM 2009 tedavi protokolüne eklenen asparajinazın hastalığa etkisi incelenmiştir. Çalışmamızda, öncelikli olarak Escherichia Coli (E.Coli.) asprajinaz, alerji gelişimi sonrası ise PEG-asparajinaz kullanılmıştır. TP1 (indüksiyon tedavi sonrası 4. hafta) noktasında ölçülen asparajin konsantrasyonu ve asparajinaz aktivitesinin, MRD düzeyleri ile birlikte değerlendirilmesi sonucu asparajinaz tedaviye olan etkisi değerlendirilmiştir. Çalışma sonucunda eklenen asparajinazın tedaviyi olumlu yönde etkilediği ve MRD düzeylerinde negatifliği arttırdığı gözlenmiştir.

References

  • T.H. Tran, & S.P. Hunger. The genomic landscape of pediatric acute lymphoblastic leukemia and precision medicine opportunities. (2022, September). In Seminars in cancer biology (Vol. 84, pp. 144-152). Academic Press.
  • S. Zahnreich, H. Schmidberger. Childhood cancer: occurrence, treatment and risk of second primary malignancies, Cancers (Basel),26 (2021) 2607.
  • SK. Tasian, SP. Hunger. Genomic characterization of paediatric acute lymphoblastic leukaemia: an opportunity for precision medicine therapeutics, Br. J. Haematol., 176 (2017) 867-882.
  • Cancer.Net Editorial Board (n.d.). Leukemia - Acute Lymphocytic - ALL: Statistics. Cancer.Net. https://www.cancer.net/cancer-types/leukemia-acute-lymphocytic-all/statistics.
  • J.D. BROOME. Evidence that the L-asparaginase of guinea pig serum is responsible for its antilymphoma effects. I. Properties of the L-asparaginase of guinea pig serum in relation to those of the antilymphoma substance, J. Exper. Ded., 118 (1963) 99–120.
  • R.A. Egler, S.P. Ahuja, & Y. Matloub. L-asparaginase in the treatment of patients with acute lymphoblastic leukemia, J. Pharmacol. Pharmacother., 7 (2016). 62-71.
  • M. Boktour, H. Hanna, S. Ansari, B. Bahna, R. Hachem, J. Tarrand, & I. Raad, Central venous catheter and Stenotrophomonas maltophilia bacteremia in cancer patients. Cancer: Interdisciplinary, International Journal of the American Cancer Society, 106 (2006) 1967-1973.
  • S. Gupta, C. Wang, E. A. Raetz, R. Schore, W. L. Salzer, E. C.Larsen,... & M. Devidas. Impact of asparaginase discontinuation on outcome in childhood acute lymphoblastic leukemia: a report from the Children’s Oncology Group, J. Clin. Oncol., 38 (2020) 1897.
  • H. van den Berg. Asparaginase revisited. Leukemia & lymphoma, 52 (2011),168-178.
  • L. Maese, & R. E. Rau. Current Use of Asparaginase in Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma, Frontiers in Pediatrics, (2022) 1030.
  • D. Campana. Minimal residual disease in acute lymphoblastic leukemia, Semin. Hematol., 46 (2009) 100-6.
  • D. Campana. Role of minimal residual disease monitoring in adult and pediatric acute lymphoblastic leukemia. Hematol. Oncol. Clin. North. Am., 23 (2009) 1083-98.
  • M.A. Pulsipher, P. Bade, T. Klingebie, L.J. Cooper. Allogeneic transplantation for pediatric acute lymphoblastic leukemia: the emerging role of peritransplantation minimal residual disease/chimerism monitoring and novel chemotherapeutic, molecular, and immune approaches aimed at preventing relapse, Biol. Blood Marrow Transplant., 15(2009) 62–71.
  • C.E. Nath, L. Dallapozza, A.E. Eslick, A. Misra, D. Carr, J.W. Earl. An isocratic fluorescence HPLC assay for the monitoring of l-asparaginase activity and l-asparagine depletion in children receiving E. colil-asparaginase for the treatment of acute lymphoblastic leukaemia, Biomed. Chromatogr., 23 (2009) 152-9.
  • T. Kalina, J. Flores-Montero, V.H.J. Van Der Velden, M. Martin-Ayuso, S. Böttcher, M. Ritgen, ... & A. Orfao. EuroFlow standardization of flow cytometer instrument settings and immunophenotyping protocols, Leukemia, 26 (2012) 1986-2010.
  • R.L. Capizzi, J.R. Bertino, R.T. Skeel, W.A. Creasey, R. Zanes, C. Olayon, R.G. Peterson, R.E. Handschumacher. L-asparaginase: clinical, biochemical, pharmacological, and immunological studies, Ann. Intern. Med., 74 (1971) 893-901.
  • I.M. Appel, K.M. Kazemier, J. Boos, C. Lanvers, J. Huijmans, A.J. Veerman, E. van Wering, M.L. den Boer, R. Pieters. Pharmacokinetic, pharmacodynamic and intracellular effects of PEG-asparaginase in newly diagnosed childhood acute lymphoblastic leukemia: results from a single agent window study, Leukemia, (2008) 1665-1679.
  • C. Lanvers-Kaminsky, Asparaginase pharmacology: challenges still to be faced, Cancer Chemother. Pharmacol., 79 (2017) 439-450.
  • L.B. Silverman, R.D. Gelber, V.K. Dalton, B.L. Asselin, R.D. Barr, L.A. Clavell, ... & S.E. Sallan. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01, Blood, 97 (2001) 1211-1218.
  • C.S. Kwok, S.K. Kham, H. Ariffin, H.P. Lin, T.C. Quah, A.E. Yeoh. Minimal residual disease (MRD) measurement as a tool to compare the efficacy of chemotherapeutic drug regimens using Escherichia Coli-asparaginase or Erwinia-asparaginase in childhood acute lymphoblastic leukemia (ALL), Pediatr. Blood Cancer, 47 (2006):299-304.

EVALUATION OF THE EFFICACY OF ASPARAGINASE ADDED TO CHEMOTHERAPEUTIC DRUG REGIMEN IN ACUTE LYMPHOBLASTIC LEUKEMIA BY MINIMAL RESIDUAL DISEASE MEASUREMENT

Year 2024, Volume: 52 Issue: 4, 211 - 215, 11.10.2024
https://doi.org/10.15671/hjbc.1375369

Abstract

B-ALL is the most common subtype of childhood Acute Lymphoblastic Leukemia (ALL), affecting approximately 85% of children worldwide. Minimal Residual Disease (MRD) monitoring during treatment of ALL is important for the prognosis of the disease. MRD monitoring, which enables early detection of relapse, determination of risk percentage and understanding the effectiveness of treatment, can be performed with multiple methods such as flow cytometry, qRT-PCR and NGS. Asparaginase is an enzyme that has been used in the treatment of ALL since the 1960s, converting asparagine to ammonia and aspartic acid, lowering serum asparagine levels and causing the death of malignant cells. In this study, we investigated the effect of asparaginase added to the ALL IC BFM 2009 treatment protocol in 62 B-ALL patients aged 0-18 years with MRD monitoring by flow cytometry. In our study, Escherichia Coli (E.Coli.) asparaginase was used primarily and PEG-asparaginase was used after allergy development. The effect of asparaginase on treatment was evaluated by evaluating asparagine concentration and asparaginase activity measured at TP1 (4th week after induction treatment) together with MRD levels. As a result of the study, it was observed that the added asparaginase positively affected the treatment and increased the negativity in MRD levels.

References

  • T.H. Tran, & S.P. Hunger. The genomic landscape of pediatric acute lymphoblastic leukemia and precision medicine opportunities. (2022, September). In Seminars in cancer biology (Vol. 84, pp. 144-152). Academic Press.
  • S. Zahnreich, H. Schmidberger. Childhood cancer: occurrence, treatment and risk of second primary malignancies, Cancers (Basel),26 (2021) 2607.
  • SK. Tasian, SP. Hunger. Genomic characterization of paediatric acute lymphoblastic leukaemia: an opportunity for precision medicine therapeutics, Br. J. Haematol., 176 (2017) 867-882.
  • Cancer.Net Editorial Board (n.d.). Leukemia - Acute Lymphocytic - ALL: Statistics. Cancer.Net. https://www.cancer.net/cancer-types/leukemia-acute-lymphocytic-all/statistics.
  • J.D. BROOME. Evidence that the L-asparaginase of guinea pig serum is responsible for its antilymphoma effects. I. Properties of the L-asparaginase of guinea pig serum in relation to those of the antilymphoma substance, J. Exper. Ded., 118 (1963) 99–120.
  • R.A. Egler, S.P. Ahuja, & Y. Matloub. L-asparaginase in the treatment of patients with acute lymphoblastic leukemia, J. Pharmacol. Pharmacother., 7 (2016). 62-71.
  • M. Boktour, H. Hanna, S. Ansari, B. Bahna, R. Hachem, J. Tarrand, & I. Raad, Central venous catheter and Stenotrophomonas maltophilia bacteremia in cancer patients. Cancer: Interdisciplinary, International Journal of the American Cancer Society, 106 (2006) 1967-1973.
  • S. Gupta, C. Wang, E. A. Raetz, R. Schore, W. L. Salzer, E. C.Larsen,... & M. Devidas. Impact of asparaginase discontinuation on outcome in childhood acute lymphoblastic leukemia: a report from the Children’s Oncology Group, J. Clin. Oncol., 38 (2020) 1897.
  • H. van den Berg. Asparaginase revisited. Leukemia & lymphoma, 52 (2011),168-178.
  • L. Maese, & R. E. Rau. Current Use of Asparaginase in Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma, Frontiers in Pediatrics, (2022) 1030.
  • D. Campana. Minimal residual disease in acute lymphoblastic leukemia, Semin. Hematol., 46 (2009) 100-6.
  • D. Campana. Role of minimal residual disease monitoring in adult and pediatric acute lymphoblastic leukemia. Hematol. Oncol. Clin. North. Am., 23 (2009) 1083-98.
  • M.A. Pulsipher, P. Bade, T. Klingebie, L.J. Cooper. Allogeneic transplantation for pediatric acute lymphoblastic leukemia: the emerging role of peritransplantation minimal residual disease/chimerism monitoring and novel chemotherapeutic, molecular, and immune approaches aimed at preventing relapse, Biol. Blood Marrow Transplant., 15(2009) 62–71.
  • C.E. Nath, L. Dallapozza, A.E. Eslick, A. Misra, D. Carr, J.W. Earl. An isocratic fluorescence HPLC assay for the monitoring of l-asparaginase activity and l-asparagine depletion in children receiving E. colil-asparaginase for the treatment of acute lymphoblastic leukaemia, Biomed. Chromatogr., 23 (2009) 152-9.
  • T. Kalina, J. Flores-Montero, V.H.J. Van Der Velden, M. Martin-Ayuso, S. Böttcher, M. Ritgen, ... & A. Orfao. EuroFlow standardization of flow cytometer instrument settings and immunophenotyping protocols, Leukemia, 26 (2012) 1986-2010.
  • R.L. Capizzi, J.R. Bertino, R.T. Skeel, W.A. Creasey, R. Zanes, C. Olayon, R.G. Peterson, R.E. Handschumacher. L-asparaginase: clinical, biochemical, pharmacological, and immunological studies, Ann. Intern. Med., 74 (1971) 893-901.
  • I.M. Appel, K.M. Kazemier, J. Boos, C. Lanvers, J. Huijmans, A.J. Veerman, E. van Wering, M.L. den Boer, R. Pieters. Pharmacokinetic, pharmacodynamic and intracellular effects of PEG-asparaginase in newly diagnosed childhood acute lymphoblastic leukemia: results from a single agent window study, Leukemia, (2008) 1665-1679.
  • C. Lanvers-Kaminsky, Asparaginase pharmacology: challenges still to be faced, Cancer Chemother. Pharmacol., 79 (2017) 439-450.
  • L.B. Silverman, R.D. Gelber, V.K. Dalton, B.L. Asselin, R.D. Barr, L.A. Clavell, ... & S.E. Sallan. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01, Blood, 97 (2001) 1211-1218.
  • C.S. Kwok, S.K. Kham, H. Ariffin, H.P. Lin, T.C. Quah, A.E. Yeoh. Minimal residual disease (MRD) measurement as a tool to compare the efficacy of chemotherapeutic drug regimens using Escherichia Coli-asparaginase or Erwinia-asparaginase in childhood acute lymphoblastic leukemia (ALL), Pediatr. Blood Cancer, 47 (2006):299-304.
There are 20 citations in total.

Details

Primary Language English
Subjects Biochemistry and Cell Biology (Other)
Journal Section Research Article
Authors

Pınar Akpınar Oktar 0000-0003-3993-4292

Merve Güneş 0000-0001-5736-6140

Rumeysa Kılıç 0000-0002-7982-1180

Gülşen Yıldırım 0000-0002-8363-3596

Deniz Yurtsever Sarıca 0000-0002-5646-1805

Serpil Taşdelen 0000-0003-2241-6907

Türkan Patiroğlu 0000-0002-5827-0068

Üstün Ezer 0000-0002-1536-7898

A. Emin Kürekci 0000-0003-3259-220X

Publication Date October 11, 2024
Submission Date November 19, 2023
Acceptance Date May 15, 2024
Published in Issue Year 2024 Volume: 52 Issue: 4

Cite

APA Akpınar Oktar, P., Güneş, M., Kılıç, R., Yıldırım, G., et al. (2024). EVALUATION OF THE EFFICACY OF ASPARAGINASE ADDED TO CHEMOTHERAPEUTIC DRUG REGIMEN IN ACUTE LYMPHOBLASTIC LEUKEMIA BY MINIMAL RESIDUAL DISEASE MEASUREMENT. Hacettepe Journal of Biology and Chemistry, 52(4), 211-215. https://doi.org/10.15671/hjbc.1375369
AMA Akpınar Oktar P, Güneş M, Kılıç R, Yıldırım G, Yurtsever Sarıca D, Taşdelen S, Patiroğlu T, Ezer Ü, Kürekci AE. EVALUATION OF THE EFFICACY OF ASPARAGINASE ADDED TO CHEMOTHERAPEUTIC DRUG REGIMEN IN ACUTE LYMPHOBLASTIC LEUKEMIA BY MINIMAL RESIDUAL DISEASE MEASUREMENT. HJBC. October 2024;52(4):211-215. doi:10.15671/hjbc.1375369
Chicago Akpınar Oktar, Pınar, Merve Güneş, Rumeysa Kılıç, Gülşen Yıldırım, Deniz Yurtsever Sarıca, Serpil Taşdelen, Türkan Patiroğlu, Üstün Ezer, and A. Emin Kürekci. “EVALUATION OF THE EFFICACY OF ASPARAGINASE ADDED TO CHEMOTHERAPEUTIC DRUG REGIMEN IN ACUTE LYMPHOBLASTIC LEUKEMIA BY MINIMAL RESIDUAL DISEASE MEASUREMENT”. Hacettepe Journal of Biology and Chemistry 52, no. 4 (October 2024): 211-15. https://doi.org/10.15671/hjbc.1375369.
EndNote Akpınar Oktar P, Güneş M, Kılıç R, Yıldırım G, Yurtsever Sarıca D, Taşdelen S, Patiroğlu T, Ezer Ü, Kürekci AE (October 1, 2024) EVALUATION OF THE EFFICACY OF ASPARAGINASE ADDED TO CHEMOTHERAPEUTIC DRUG REGIMEN IN ACUTE LYMPHOBLASTIC LEUKEMIA BY MINIMAL RESIDUAL DISEASE MEASUREMENT. Hacettepe Journal of Biology and Chemistry 52 4 211–215.
IEEE P. Akpınar Oktar, “EVALUATION OF THE EFFICACY OF ASPARAGINASE ADDED TO CHEMOTHERAPEUTIC DRUG REGIMEN IN ACUTE LYMPHOBLASTIC LEUKEMIA BY MINIMAL RESIDUAL DISEASE MEASUREMENT”, HJBC, vol. 52, no. 4, pp. 211–215, 2024, doi: 10.15671/hjbc.1375369.
ISNAD Akpınar Oktar, Pınar et al. “EVALUATION OF THE EFFICACY OF ASPARAGINASE ADDED TO CHEMOTHERAPEUTIC DRUG REGIMEN IN ACUTE LYMPHOBLASTIC LEUKEMIA BY MINIMAL RESIDUAL DISEASE MEASUREMENT”. Hacettepe Journal of Biology and Chemistry 52/4 (October 2024), 211-215. https://doi.org/10.15671/hjbc.1375369.
JAMA Akpınar Oktar P, Güneş M, Kılıç R, Yıldırım G, Yurtsever Sarıca D, Taşdelen S, Patiroğlu T, Ezer Ü, Kürekci AE. EVALUATION OF THE EFFICACY OF ASPARAGINASE ADDED TO CHEMOTHERAPEUTIC DRUG REGIMEN IN ACUTE LYMPHOBLASTIC LEUKEMIA BY MINIMAL RESIDUAL DISEASE MEASUREMENT. HJBC. 2024;52:211–215.
MLA Akpınar Oktar, Pınar et al. “EVALUATION OF THE EFFICACY OF ASPARAGINASE ADDED TO CHEMOTHERAPEUTIC DRUG REGIMEN IN ACUTE LYMPHOBLASTIC LEUKEMIA BY MINIMAL RESIDUAL DISEASE MEASUREMENT”. Hacettepe Journal of Biology and Chemistry, vol. 52, no. 4, 2024, pp. 211-5, doi:10.15671/hjbc.1375369.
Vancouver Akpınar Oktar P, Güneş M, Kılıç R, Yıldırım G, Yurtsever Sarıca D, Taşdelen S, Patiroğlu T, Ezer Ü, Kürekci AE. EVALUATION OF THE EFFICACY OF ASPARAGINASE ADDED TO CHEMOTHERAPEUTIC DRUG REGIMEN IN ACUTE LYMPHOBLASTIC LEUKEMIA BY MINIMAL RESIDUAL DISEASE MEASUREMENT. HJBC. 2024;52(4):211-5.

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