Steroid response as prognostic factor and its correlation with molecular assessment of childhood acute lymphoblastic leukemia

  • Murti Andriastuti Department of Child Health, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta
  • Djajadiman Gatot Department of Child Health, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta
  • Riadi Wirawan Department of Clinical Pathology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta
  • Rianto Setiabudy Department of Pharmacology, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Muchtaruddin Mansyur Department of Community Medicine, Universitas Indonesia, Jakarta
  • I Dewa G. Ugrasena Department of Child Health, Faculty of Medicine, University of Airlangga, Dr. Sutomo Hospital, Surabaya
Keywords: acute lymphoblastic leukemia, molecular assessment, prognostic factor, steroid
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Abstract

Background: Survival rate of children with acute lymphoblastic leukemia (ALL) in Indonesia remains low. Risk stratification accuracy is important to improve survival. In developed countries, risk stratification is determined based on gene fusion that is known related to steroid resistency. Steroid response at day-8 correlates with prognosis. The assessment can be applied in centers that cannot perform molecular assessment. This study aims to evaluate whether steroid response correlated to molecular assessment.

Methods: A cross-sectional study was performed at Child Health Department, Cipto Mangunkusumo Hospital (January 2013-March 2014), a total of 73 patients were enrolled. Steroid was given for 7 days. Peripheral blast count at day 8 was evaluated, good response if blast count <1000 /µL and poor if ≥1000 /µL. Fusion gene detection was also performed. The data was analysed using Statistical Package for Social Sciences (SPSS) version 20.0.

Results: Fusion gene was detected in 45 patients. In 1–10 years age group, 26/32 (81%) subjects had good response, while 75% in <1 year age group and 7/9 (78%) in ≥10 years age group had poor response. 5/7 (71%) subjetcs had leukocyte count >100,000 /µL and 7/8 (88%) with T-cell showed poor response. Age, leukocyte count, and T-cell were statistically correlated with steroid response (p<0.05). E2A-PBX1 fusion gene was the most common 19/45 (42%), followed by TEL-AML1 17/45 (38%), BCR-ABL 5/45 (17%), and MLL-AF4 1/45 (3%). Four of five subjects (80%) with BCR-ABL and one subject with MLL-AF4 had poor steroid response. On the other hand, 12/19 (63%) with E2A-PBX1 and 13/17 (77%) with TEL-AML1 had good response. There was no correlation between steroid response and molecular assessment.

Conclusion: Steroid response correlates with age, leukocyte count, and T-cell but not with molecular assessment.

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References

  1. Onciu M, Pui CH. Diagnosis and classification. In: Pui CH, editor. Childhood leukemias. 2nd ed. New York: Cambridge University Press; 2006. p. 21–47. http://dx.doi.org/10.1017/CBO9780511471001.003

  2. Windiastuti E, Nency YM, Hagung P, Supriyadi E. Mulatsih S, Sjakti HA, et al. Five years evaluation of the Indonesian acute lymphoblastic leukemia: 2006 protocol of the Pediatric Hematology Oncology Working Group. In: Yeoh A, Blair S, Yen SS, editors. Malignancies in children. 7th St. Jude-Viva Forum; 2013. p. 186.

  3. Gatot D, Windiastuti E. Treatment of childhood acute lymphoblastic leukemia in Jakarta: results of modified Indonesian National Protocol 94. Paediatr Indones. 2006;46:179–88.

  4. Registered data of cancer patient Hematology Oncology Division Child Health Department Faculty of Medicine Universitas Indonesia/Cipto Mangunkusumo Hospital. Jakarta: 2014. Indonesian.

  5. Hunger SP, Sung L, Howard SC. Treatment strategies and regimens of graduated intensity for childhood acute lymphoblastic leukemia in low-income countries: a proposal. Pediatr Blood Cancer. 2009;52:559–65 http://dx.doi.org/10.1002/pbc.21889

  6. Mulatsih S, Sumadiono, Sutaryo, Purwanto. The result of treating children's acute lymphoblastic leukemia (LLA) in Dr. Sardjito Hospital with WK-LLA Protocol 1999–2002. Buletin Ilmu Kesehatan Anak FK UNAIR. 2005;17:808–19. Indonesian.

  7. Windiastuti E. Childhood acute leukemia: Cipto Mangunkusumo Hospital experiences. Presented in Perhimpunan Hematologi dan Transfusi Darah Indonesia. Medan: 2011.

  8. Donadieu J, Auclerc MF, Baruchel A, Leblanc T, Landman-Parker J, Perel Y, et al. Critical study of prognostic factors in childhood acute lymphoblastic leukaemia: differences in outcome are poorly explained by the most significant prognostic variables. Fralle group. Frech acute lymphoblactic leukaemia study group. Br J Haematol. 1998;102(3):729–39. http://dx.doi.org/10.1046/j.1365-2141.1998.00818.x

  9. Okuda T, Fisher R, Downing JR. Molecular diagnostics in pediatric acute lymphoblastic leukemia. Mol Diagn. 1996;1(12):139–51. http://dx.doi.org/10.1016/S1084-8592(96)70029-2

  10. Rubnitz JE, Downing JR, Pui CH, Shurtleff SA, Raimondi SC, Evans WE, et al. TEL gene rearrangement in acute lymphoblastic leukemia: a new genetic marker with prognostic significance. J Clin Oncol. 1997;15(3):1150–7.

  11. Raimondi SC, Behm FG, Roberson PK, Williams DL, Pui CH, Crist WM, et al. Cytogenetics of pre-B-cell acute lymphoblastic leukemia with emphasis on prognostic implications of the t(1;19). J Clin Oncol. 1990;8(8):1380–8.

  12. Gutierrez A, Armstrong SA, Look AT. Pathobiology of acute lymphoblastic leukemia. In: Hoffman R, Benz EJ, Silberstein LE, Heslop H, Weitz J, Anastasi, editors. Hematology: basic principles and practice. 6th ed. Elsevier; 2013. p. 935–50.

  13. Felice MS, Zubizarreta PA, Alfaro EM, Sackmann-Muriel F. Childhood acute lymphoblastic leukemia: prognostic value of initial peripheral blast count in good responders to prednisone. J Pediatr Hematol Oncol. 2001;23(7):411–5. http://dx.doi.org/10.1097/00043426-200110000-00004

  14. Manabe A, Ohara A, Hasegawa D, Koh K, Saito T, Kiyokawa N, et al. Significance of the complete clearance of peripheral blasts after 7 days of prednisolone treatment in children with acute lymphoblastic leukemia: the Tokyo Children's Cancer Study Grup Study L99-15. Haematologica. 2008;93(8):1155–60. http://dx.doi.org/10.3324/haematol.12365

  15. Spector LG, Ross JA, Robison LL, Bhatia S. Epidemiology and etiology. In: Pui CH, editor. Childhood leukemias. 2nd ed. New York: Cambridge University Press; 2006. p. 48–65. http://dx.doi.org/10.1017/CBO9780511471001.004

  16. Udayakumar AM, Bashir WA, Pathare AV, Wali YA, Zacharia M, Khan AA, et al. Cytogenetic profile of childhood acute lymphoblastic leukemia in Oman. Arch Med Res. 2007;38(3):305–12. http://dx.doi.org/10.1016/j.arcmed.2006.10.006

  17. Ei E, Ko Y, Thet K, Pe K, Myint T, Sein WK, et al. Clinical profile of childhood leukemia in Mandalay. St Jude Viva Forum. 2011.

  18. Yasmeen N, Ashraf S. Childhood acute lymphoblastic leukaemia; epidemiology and clinicopathological features. J Pak Med Assoc. 2009;59(3):150–3.

  19. Pui CH, Howard S. Current management and challenges of malignant disease in the CNS in pediatric leukaemia. The Lancet Oncol.2008;9:257–68. http://dx.doi.org/10.1016/S1470-2045(08)70070-6

  20. Smith M, Arthur D, Camitta B, Carroll AJ, Crist W, Gaynon P et al. Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol.1996;14:18–24.

  21. Smith M, Arthur D, Camitta B, Carroll AJ, Crist W, Gaynon P, et al. Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol. 1996;14(1):18–24.

  22. Supriyadi E, Widjajanto PH, Veerman AJ, Purwanto I, Nency YM, Gunawan S, et al. Immunophenotypic patterns of childhood acute leukemias in Indonesia. Asian Pac J Cancer Prev. 2011;12:3381–7.

  23. Meijerink, JP, den Boer ML, Pieters R. New genetic abnormalities and treatment response in acute lymphoblastic leukemia. Semin Hematol. 2009;46(1):16–23. http://dx.doi.org/10.1053/j.seminhematol.2008.09.006

  24. Borkhardt A, Cazzaniga G, Viehmann S, Valsecchi MG, Ludwig WD, Burci L, et al. Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in German and Italian multicenter therapy trials. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster Study Group. Blood.1997;90(2):571–7.

  25. Uckun FM, Pallisgaard N, Hokland P, Navara C, Narla R, Gaynon PS, et al. Expression of TEL-AML1 fusion transcripts and response to induction therapy in standard risk acute lymphoblastic leukemia. Leuk Lymphoma. 2001;42(1–2):41–56. http://dx.doi.org/10.3109/10428190109097675

Published
2015-12-31
How to Cite
1.
Andriastuti M, Gatot D, Wirawan R, Setiabudy R, Mansyur M, Ugrasena IDG. Steroid response as prognostic factor and its correlation with molecular assessment of childhood acute lymphoblastic leukemia. Med J Indones [Internet]. 2015Dec.31 [cited 2024Oct.11];24(4):215-20. Available from: http://mji.ui.ac.id/journal/index.php/mji/article/view/1177
Section
Clinical Research