Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

Characteristics and outcome of t(8;21)-positive childhood acute myeloid leukemia: a single institution's experience

Abstract

To elucidate the clinical and biological features of childhood acute myeloid leukemia (AML) with the t(8;21), we reviewed the records of patients with AML treated at St Jude Children's Research Hospital over a 17-year period (1980 to 1996). Of 298 patients with AML, 40 (13%) had blast cells that contained the t(8;21). This translocation was associated with a high frequency of French–American–British M2 morphology (82%) and the presence of granulocytic sarcoma (23%). Molecular analysis detected the AML1-ETO fusion transcript in all 25 cases with the t(8;21) tested, but failed to identify additional cases with AML1-ETO among the 127 cases with other cytogenetic findings. Compared to patients with other genetic abnormalities, those with the t(8;21) were less likely to have internal tandem duplications of the FLT3 gene (none of 10 vs 16 of 68). The 6-year overall survival estimate was 55% ± 9% and the event-free survival estimate, 33% ± 7%. Of the clinical and biological features examined, only gender was prognostically significant: the 6-year overall survival estimate for males was 68% ± 10%, compared to 33% ± 11 for female patients (P = 0.03). Treatment outcome was not influenced by the chemotherapy regimen used or by the use of autologous hematopoietic stem cell transplantation. These results suggest that t(8;21)-positive AML represents a heterogeneous disease with variable outcome. The reported favorable outcome for t(8;21)-positive AML in other studies may be due to the use of high-dose cytarabine.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Hurwitz CA, Raimondi SC, Head D, Krance R, Mirro J Jr, Kalwinsky DK, Ayers GD, Behm FG . Distinctive immunophenotypic features of t(8;21)(q22;q22) acute myeloblastic leukemia in children Blood 1992 80: 3182–3188

    CAS  PubMed  Google Scholar 

  2. Tallman MS, Hakimian D, Shaw JM, Lissner GS, Russell EJ, Variakojis D . Granulocytic sarcoma is associated with the 8;21 translocation in acute myeloid leukemia J Clin Oncol 1993 11: 690–697

    Article  CAS  PubMed  Google Scholar 

  3. Trujillo JM, Cork A, Ahearn MJ, Youness EL, McCredie KB . Hematologic and cytologic characterization of 8/21 translocation acute granulocytic leukemia Blood 1979 53: 695–706

    CAS  PubMed  Google Scholar 

  4. Swirsky DM, Li YS, Matthews JG, Flemans RJ, Rees JK, Hayhoe FG . 8;21 translocation in acute granulocytic leukaemia: cytological, cytochemical and clinical features Br J Haematol 1984 56: 199–213

    Article  CAS  PubMed  Google Scholar 

  5. Byrd JC, Edenfield WJ, Shields DJ, Dawson NA . Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review J Clin Oncol 1995 13: 1800–1816

    Article  CAS  PubMed  Google Scholar 

  6. Bloomfield CD, Lawrence D, Byrd JC, Carroll A, Pettenati MJ, Tantravahi r, Patil SR, Davey FR, Berg DT, Schiffer CA, Arthur DC, Mayer RJ . Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype Cancer Res 1998 58: 4173–4179

    CAS  PubMed  Google Scholar 

  7. Byrd JC, Dodge RK, Carroll A, Baer MR, Edwards C, Stamberg J, Qumsiyeh M, Moore JO, Mayer RJ, Davey F, Schiffer CA, Bloomfield CD . Patients with t(8;21)(q22;q22) and acute myeloid leukemia have superior failure-free and overall survival when repetitive cycles of high-dose cytarabine are administered J Clin Oncol 1999 17: 3767–3775

    Article  CAS  PubMed  Google Scholar 

  8. Raimondi SC, Chang MN, Ravindranath Y, Behm FG, Gresik MV, Steuber CP, Weinstein HJ, Carroll AJ . Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a cooperative Pediatric Oncology Group study-POG 8821 Blood 1999 94: 3707–3716

    CAS  PubMed  Google Scholar 

  9. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, Rees J, Hann I, Stevens R, Burnett A, Goldstone A . The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties Blood 1998 92: 2322–2333

    CAS  PubMed  Google Scholar 

  10. Byrd JC, Weiss RB, Arthur DC, Lawrence D, Baer MR, Davey F, Trikha ES, Carroll AJ, Tantravahi r, Qumsiyeh M, Patil SR, Moore JO, Mayer RJ, Schiffer CA, Bloomfield CD . Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): results from Cancer and Leukemia Group B 8461 J Clin Oncol 1997 15: 466–475

    Article  CAS  PubMed  Google Scholar 

  11. Felice MS, Zubizarreta PA, Alfaro EM, Gallego MS, Cygler AM, Rosso DA, Rossi JG, Sackmann-Muriel F . Good outcome of children with acute myeloid leukemia and t(8;21)(q22;q22), even when associated with granulocytic sarcoma: a report from a single institution in Argentina Cancer 2000 88: 1939–1944

    Article  CAS  PubMed  Google Scholar 

  12. Schwyzer R, Sherman GG, Cohn RJ, Poole JE, Willem P . Granulocytic sarcoma in children with acute myeloblastic leukemia and t(8;21) Med Pediatr Oncol 1998 31: 144–149

    Article  CAS  PubMed  Google Scholar 

  13. Jenkin RD, Al Shabanah M, Al Nasser A, El Solh H, Aur R, Al Sudairy R, Mustafa MM, Al FI, Gray A, da Cunha M, Ayas M, Al Mahr M, Kofide A, Mahgoub AN, Rifai S, Belgaumi A, Al Jefri A, Al Musa A, Sabbah R . Extramedullary myeloid tumors in children: the limited value of local treatment J Pediatr Hematol Oncol 2000 22: 34–40

    Article  CAS  PubMed  Google Scholar 

  14. Bisschop MM, Revesz T, Bierings M, van Weerden JF, Van Wering ER, Hahlen K, Does-van den Berg A . Extramedullary infiltrates at diagnosis have no prognostic significance in children with acute myeloid leukaemia Leukemia 2001 15: 46–49

    Article  CAS  PubMed  Google Scholar 

  15. Lowenberg B, Downing J, Brunett A . Acute myeloid leukemia N Engl J Med 1999 341: 1051–1062

    Article  CAS  PubMed  Google Scholar 

  16. Downing JR . The AML1-ETO chimaeric transcription factor in acute myeloid leukaemia: biology and clinical significance Br J Haematol 1999 106: 296–308

    Article  CAS  PubMed  Google Scholar 

  17. Downing JR . AML1/CBFbeta transcription complex: its role in normal hematopoiesis and leukemia Leukemia 2001 15: 664–665

    Article  CAS  PubMed  Google Scholar 

  18. Downing JR, Head DR, Curcio-Brint AM, Hulshof MG, Motroni TA, Raimondi SC, Carroll AJ, Drabkin HA, Willman C, Theil KS et al. An AML1/ETO fusion transcript is consistently detected by RNA- based polymerase chain reaction in acute myelogenous leukemia containing the (8;21)(q22;q22) translocation Blood 1993 81: 2860–2865

    CAS  PubMed  Google Scholar 

  19. Langabeer SE, Walker H, Rogers JR, Burnett AK, Wheatley K, Swirsky D, Goldstone AH, Linch DC . Incidence of AML1/ETO fusion transcripts in patients entered into the MRC AML trials. MRC Adult Leukaemia Working Party Br J Haematol 1997 99: 925–928

    Article  CAS  PubMed  Google Scholar 

  20. Krauter J, Peter W, Pascheberg U, Heinze B, Bergmann L, Hoelzer D, Lubbert M, Schlimok G, Arnold R, Kirchner H, Port M, Ganser A, Heil G . Detection of karyotypic aberrations in acute myeloblastic leukaemia: a prospective comparison between PCR/FISH and standard cytogenetics in 140 patients with de novo AML Br J Haematol 1998 103: 72–78

    Article  CAS  PubMed  Google Scholar 

  21. Mitterbauer M, Kusec R, Schwarzinger I, Haas OA, Lechner K, Jaeger U . Comparison of karyotype analysis and RT-PCR for AML1/ETO in 204 unselected patients with AML Ann Hematol 1998 76: 139–143

    Article  CAS  PubMed  Google Scholar 

  22. Sarriera JE, Albitar M, Estrov Z, Gidel C, Aboul-Nasr R, Manshouri T, Kornblau S, Chang KS, Kantarjian H, Estey E . Comparison of outcome in acute myelogenous leukemia patients with translocation (8;21) found by standard cytogenetic analysis and patients with AML1/ETO fusion transcript found only by PCR testing Leukemia 2001 15: 57–61

    Article  CAS  PubMed  Google Scholar 

  23. Andrieu V, Radford-Weiss I, Troussard X, Chane C, Valensi F, Guesnu M, Haddad E, Viguier F, Dreyfus F, Varet B, Flandrin G, Macintyre E . Molecular detection of t(8;21)/AML1-ETO in AML M1/M2: correlation with cytogenetics, morphology and immunophenotype Br J Haematol 1996 92: 855–865

    Article  CAS  PubMed  Google Scholar 

  24. Mrozek K, Prior TW, Edwards C, Marcucci G, Carroll AJ, Snyder PJ, Koduru PR, Theil KS, Pettenati MJ, Archer KJ, Caligiuri MA, Vardiman JW, Kolitz JE, Larson RA, Bloomfield CD . Comparison of cytogenetic and molecular genetic detection of t(8;21) and inv(16) in a prospective series of adults with de novo acute myeloid leukemia: a Cancer and Leukemia Group B Study J Clin Oncol 2001 19: 2482–2492

    Article  CAS  PubMed  Google Scholar 

  25. Rowe D, Cotterill SJ, Ross FM, Bunyan DJ, Vickers SJ, Bryon J, McMullan DJ, Griffiths MJ, Reilly JT, Vandenberghe EA, Wilson G, Watmore AE, Bown NP . Cytogenetically cryptic AML1-ETO and CBF beta-MYH11 gene rearrangements: incidence in 412 cases of acute myeloid leukaemia Br J Haematol 2000 111: 1051–1056

    Article  CAS  PubMed  Google Scholar 

  26. Dahl GV, Kalwinsky DK, Mirro J Jr, Look AT, Pui CH, Murphy SB, Mason C, Ruggiero M, Schell M, Johnson FL . Allogeneic bone marrow transplantation in a program of intensive sequential chemotherapy for children and young adults with acute nonlymphocytic leukemia in first remission J Clin Oncol 1990 8: 295–303

    Article  CAS  PubMed  Google Scholar 

  27. Kalwinsky D, Mirro J Jr, Schell M, Behm F, Mason C, Dahl GV . Early intensification of chemotherapy for childhood acute nonlymphoblastic leukemia: improved remission induction with a five- drug regimen including etoposide J Clin Oncol 1988 6: 1134–1143

    Article  CAS  PubMed  Google Scholar 

  28. Arnaout MK, Radomski KM, Srivastava DK, Tong X, Belt JR, Raimondi SC, Behm FG, Santana VM, Crom WR, Mirro J Jr, Ribeiro RC . Treatment of childhood acute myelogenous leukemia with an intensive regimen (AML-87) that individualizes etoposide and cytarabine dosages: short- and long-term effects Leukemia 2000 14: 1736–1742

    Article  CAS  PubMed  Google Scholar 

  29. Krance RA, Hurwitz CA, Head DR, Raimondi SC, Behm FG, Crews KR, Srivastava DK, Mahmoud H, Roberts WM, Tong X, Blakley RL, Ribeiro RC . Experience with 2-chlorodeoxyadenosine in previously untreated children with newly diagnosed acute myeloid leukemia and myelodysplastic diseases J Clin Oncol 2001 19: 2804–2811

    Article  CAS  PubMed  Google Scholar 

  30. Williams DL, Harris S, Williams KJ, Brosius MJ, Lemonds W . A direct bone marrow chromosome technique for acute lymphoblastic leukemia Cancer Genet Cytogenet 1984 13: 239–257

    Article  CAS  PubMed  Google Scholar 

  31. Kaplan EL, Meier P . Non-parametric estimation for incomplete observations Am Stat Assoc 1958 53: 457–481

    Article  Google Scholar 

  32. Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Peto J, Smith PG . Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples Br J Cancer 1977 35: 1–39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kiyoi H, Naoe T, Nakano Y, Yokota S, Minami S, Miyawaki S, Asou N, Kuriyama K, Jinnai I, Shimazaki C, Akiyama H, Saito K, Oh H, Motoji T, Omoto E, Saito H, Ohno R, Ueda R . Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia Blood 1999 93: 3074–3080

    CAS  PubMed  Google Scholar 

  34. Iwai T, Yokota S, Nakao M, Okamoto T, Taniwaki M, Onodera N, Watanabe A, Kikuta A, Tanaka A, Asami K, Sekine I, Mugishima H, Nishimura Y, Koizumi S, Horikoshi Y, Mimaya J, Ohta S, Nishikawa K, Iwai A, Shimokawa T, Nakayama M, Kawakami K, Gushiken T, Hyakuna N, Fujimoto T . Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. The Children's Cancer and Leukemia Study Group, Japan Leukemia 1999 13: 38–43

    Article  CAS  PubMed  Google Scholar 

  35. Abu-Duhier FM, Goodeve AC, Wilson GA, Gari MA, Peake IR, Rees DC, Vandenberghe EA, Winship PR, Reilly JT . FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group Br J Haematol 2000 111: 190–195

    Article  CAS  PubMed  Google Scholar 

  36. Kottaridis PD, Gale RE, Frew ME, Harrison G, Langabeer SE, Belton AA, Walker H, Wheatley K, Bowen DT, Burnett AK, Goldstone AH, Linch DC . The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials Blood 2001 98: 1752–1759

    Article  CAS  PubMed  Google Scholar 

  37. Meshinchi S, Woods WG, Stirewalt DL, Sweetser DA, Buckley JD, Tjoa TK, Bernstein ID, Radich JP . Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia Blood 2001 97: 89–94

    Article  CAS  PubMed  Google Scholar 

  38. Whitman SP, Archer KJ, Feng L, Baldus C, Becknell B, Carlson BD, Carroll AJ, Mrozek K, Vardiman JW, George SL, Kolitz JE, Larson RA, Bloomfield CD, Caligiuri MA . Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study Cancer Res 2001 61: 7233–7239

    CAS  PubMed  Google Scholar 

  39. Mrozek K, Heinonen K, Bloomfield CD . Clinical importance of cytogenetics in acute myeloid leukaemia Best Pract Res Clin Haematol 2001 14: 19–47

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Flo Witte for expert editorial review and Annette Stone for assistance in data collection. This work was supported by grants CA-20180 and CA-21765 from the National Institutes of Health, by a Center of Excellence Grant from the State of Tennessee, and by the American Lebanese Syrian Associated Charities (ALSAC).

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rubnitz, J., Raimondi, S., Halbert, A. et al. Characteristics and outcome of t(8;21)-positive childhood acute myeloid leukemia: a single institution's experience. Leukemia 16, 2072–2077 (2002). https://doi.org/10.1038/sj.leu.2402633

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2402633

Keywords

This article is cited by

Search

Quick links