DOI QR코드

DOI QR Code

Prognostic significance of minimal residual disease detected by a simplified flow cytometric assay during remission induction chemotherapy in children with acute lymphoblastic leukemia

  • Koh, Kyung-Nam (Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Park, Mee-Rim (Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Bo-Eun (Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Im, Ho-Joon (Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Park, Chan-Jeoung (Division of Pediatric Hematology/Oncology, Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Jang, Seong-Soo (Division of Pediatric Hematology/Oncology, Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Chi, Hyun-Sook (Division of Pediatric Hematology/Oncology, Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Seo, Jong-Jin (Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine)
  • Received : 2010.06.23
  • Accepted : 2010.09.13
  • Published : 2010.11.15

Abstract

Purpose: Our study attempted to determine the prognostic significance of minimal residual disease (MRD) detected by a simplified flow cytometric assay during induction chemotherapy in children with B-cell acute lymphoblastic leukemia (B-ALL). Methods: A total of 98 patients were newly diagnosed with precursor B-ALL from June 2004 to December 2008 at the Asan Medical Center (Seoul, Korea). Of those, 37 were eligible for flow cytometric MRD study analysis on day 14 of their induction treatment. The flow cytometric MRD assay was based on the expression intensity of CD19/CD10/CD34 or aberrant expression of myeloid antigens by bone marrow nucleated cells. Results: Thirty-five patients (94.6%) had CD19-positive leukemic cells that also expressed CD10 and/or CD34, and 18 (48.6%) had leukemic cells with aberrant expression of myeloid antigens. Seven patients with ${\geq}1%$ leukemic cells on day 14 had a significantly lower relapse-free survival (RFS) compared to the 30 patients with lower levels (42.9 % [18.7%] vs. 92.0% [5.4%], $P$=0.004). Stratification into 3 MRD groups (${\geq}1%$, 0.1-1%, and <0.1%) also showed a statistically significant difference in RFS (42.9% [18.7%] vs. 86.9% [8.7%] vs. 100%, $P$=0.013). However, the MRD status had no significant influence on overall survival. Multivariate analysis demonstrated that the MRD level on day 14 was an independent prognostic factor with borderline significance. Conclusion: An MRD assay using simplified flow cytometry during induction chemotherapy may help to identify patients with B-ALL who have an excellent outcome and patients who are at higher risk for relapse.

Keywords

References

  1. Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet 2008;371:1030-43. https://doi.org/10.1016/S0140-6736(08)60457-2
  2. Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study. Blood 2008;111:5477-85. https://doi.org/10.1182/blood-2008-01-132837
  3. Cave H, van der Werff ten Bosch J, Suciu S, Guidal C, Waterkeyn C, Otten J, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia. European Organization for Research and Treatment of Cancer-- Childhood Leukemia Cooperative Group. N Engl J Med 1998;339:591-8. https://doi.org/10.1056/NEJM199808273390904
  4. Coustan-Smith E, Sancho J, Hancock ML, Boyett JM, Behm FG, Raimondi SC, et al. Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia. Blood 2000;96:2691-6.
  5. van Dongen JJ, Seriu T, Panzer-Grumayer ER, Biondi A, Pongers-Willemse MJ, Corral L, et al. Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood. Lancet 1998;352:1731-8. https://doi.org/10.1016/S0140-6736(98)04058-6
  6. Stow P, Key L, Cjen X, Pan Q, Neale GA, Coustan-Smith E, et al. Clinical significance of low levels of minimal residual disease at the end of remission induction therapy in childhood acute lymphoblastic leukemia. Blood 2010;115:4657-63. https://doi.org/10.1182/blood-2009-11-253435
  7. Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grumayer R, Moricke A, et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood 2010;115:3206-14. https://doi.org/10.1182/blood-2009-10-248146
  8. Szczepanski T, Orfao A, van der Velden VH, San Miguel JF, van Dongen JJ. Minimal residual disease in leukaemia patients. Lancet Oncol 2001;2:409-17. https://doi.org/10.1016/S1470-2045(00)00418-6
  9. Campana D. Determination of minimal residual disease in leukaemia patients. Br J Haematol 2003;121:823-38. https://doi.org/10.1046/j.1365-2141.2003.04393.x
  10. Scrideli CA, de Paula Queiroz R, Bernardes JE, Defavery R, Valera ET, Tone LG. Use of simplified strategies to evaluate early treatment response in childhood acute lymphoblastic leukemia. Leuk Res 2006;30:1049-52. https://doi.org/10.1016/j.leukres.2005.11.021
  11. Scrideli CA, Assumpcao JG, Ganazza MA, Araujo M, Toledo SR, Lee ML, et al. A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups. Haematologica 2009;94:781-9. https://doi.org/10.3324/haematol.2008.003137
  12. Coustan-Smith E, Ribeiro RC, Stow P, Zhou Y, Pui CH, Rivera GK, et al. A simplified flow cytometric assay identifies children with acute lymphoblastic leukemia who have a superior clinical outcome. Blood 2006;108:97-102. https://doi.org/10.1182/blood-2006-01-0066
  13. Gaynon PS, Angiolillo AL, Carroll WL, Nachman JB, Trigg ME, Sather HN, et al. Long-term results of the children's cancer group studies for childhood acute lymphoblastic leukemia 1983-2002: a Children's Oncology Group Report. Leukemia 2010;24:285-97. https://doi.org/10.1038/leu.2009.262
  14. McKenna RW, Asplund SL, Kroft SH. Immunophenotypic analysis of hematogones (B-lymphocyte precursors) and neoplastic lymphoblasts by 4-color flow cytometry. Leuk Lymphoma 2004;45:277-85. https://doi.org/10.1080/1042819031000151950
  15. Ito S, Ishida Y, Murai K, Kuriya S. Flow cytometric analysis of aberrant antigen expression of blasts using CD45 blast gating for minimal residual disease in acute leukemia and high-risk myelodysplastic syndrome. Leuk Res 2001;25:205-11. https://doi.org/10.1016/S0145-2126(00)00127-2
  16. Campana D. Minimal residual disease in acute lymphoblastic leukemia. Semin Hematol 2009;46:100-6. https://doi.org/10.1053/j.seminhematol.2008.09.001
  17. Basso G, Veltroni M, Valsecchi MG, Dworzak MN, Ratei R, Silvestri D, et al. Risk of relapse of childhood acute lymphoblastic leukemia is predicted by flow cytometric measurement of residual disease on day 15 bone marrow. J Clin Oncol 2009;27:5168-74. https://doi.org/10.1200/JCO.2008.20.8934
  18. Pui CH, Campana D. New definition of remission in childhood acute lymphoblastic leukemia. Leukemia 2000;14:783-5. https://doi.org/10.1038/sj.leu.2401780
  19. Cazzaniga G, Biondi A. Molecular monitoring of childhood acute lymphoblastic leukemia using antigen receptor gene rearrangements and quantitative polymerase chain reaction technology. Haematologica 2005;90:382-90.
  20. Coustan-Smith E, Sancho J, Behm FG, Hancock ML, Razzouk BI, Ribeiro RC, et al. Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood lymphoblastic leukemia. Blood 2002;100:52-8. https://doi.org/10.1182/blood-2002-01-0006
  21. Campana D, Coustan-Smith E. Detection of minimal residual disease in acute leukemia by flow cytometry. Cytometry 1999;38:139-52. https://doi.org/10.1002/(SICI)1097-0320(19990815)38:4<139::AID-CYTO1>3.0.CO;2-H
  22. Babusikova O, Zeleznikova T, Kirschnerova G, Kankuri E. Hematogones in acute leukemia during and after therapy. Leuk Lymphoma 2008;49:1935-44. https://doi.org/10.1080/10428190701817274
  23. Park CJ, Kim MC, Moon AR, Seo EJ, Chi HS, Seo JJ, et al. Detection of minimal residual disease by IgH gene rearragnement-PCR in childhood acute lymphoblastic leukemia. Korean J Clin Pathol 1999;19:163-71.
  24. Cui L, Li Z, Wu M, Li W, Gao C, Deng G. Combined analysis of minimal residual disease at two time points and its value for risk stratification in childhood B-lineage acute lymphoblastic leukemia. Leuk Res 2010;34:1314-9. https://doi.org/10.1016/j.leukres.2009.11.031
  25. Sutton R, Venn NC, Tolisano J, Bahar AY, Giles JE, Ashton LJ, et al. Clinical significance of minimal residual disease at day 15 and at the end of therapy in childhood acute lymphoblastic leukaemia. Br J Haematol 2009;146:292-9. https://doi.org/10.1111/j.1365-2141.2009.07744.x

Cited by

  1. Monitoring MRD with flow cytometry: an effective method to predict relapse for ALL patients after allogeneic hematopoietic stem cell transplantation vol.91, pp.2, 2010, https://doi.org/10.1007/s00277-011-1285-1
  2. Minimal residual disease monitoring in childhood acute lymphoblastic leukemia vol.19, pp.4, 2012, https://doi.org/10.1097/moh.0b013e3283543d5c
  3. Measurements of treatment response in childhood acute leukemia vol.47, pp.4, 2010, https://doi.org/10.5045/kjh.2012.47.4.245
  4. Measurements of treatment response in childhood acute leukemia vol.47, pp.4, 2010, https://doi.org/10.5045/kjh.2012.47.4.245
  5. Outcome of Reinduction Chemotherapy with a Modified Dose of Idarubicin for Children with Marrow-Relapsed Acute Lymphoblastic Leukemia: Results of the Childhood Acute Lymphoblastic Leukemia (CALL)-0603 vol.32, pp.4, 2010, https://doi.org/10.3346/jkms.2017.32.4.642
  6. Implementation of a simplified flow cytometric assays for minimal residual disease monitoring in childhood acute lymphoblastic leukemia vol.94, pp.1, 2010, https://doi.org/10.1002/cyto.b.21394
  7. Bone marrow recovery of hematopoietic stem cells and microenvironment after chemotherapy in childhood acute lymphoblastic leukemia: consecutive observations according to chemotherapy schedule vol.36, pp.4, 2010, https://doi.org/10.1080/08880018.2019.1623354
  8. A High‐Sensitivity 10‐Color Flow Cytometric Minimal Residual Disease Assay in B‐Lymphoblastic Leukemia/Lymphoma Can Easily Achieve the Sensitivity of 2‐in‐106 vol.98, pp.1, 2010, https://doi.org/10.1002/cyto.b.21831
  9. Immunophenotypic modulation in pediatric B lymphoblastic leukemia and its implications in MRD detection vol.61, pp.8, 2010, https://doi.org/10.1080/10428194.2020.1742902
  10. Toward the Cure of Acute Lymphoblastic Leukemia in Children in China vol.7, pp.None, 2010, https://doi.org/10.1200/go.21.00049