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Prognostic features in acute megakaryoblastic leukemia in children without Down syndrome: a report from the AML02 multicenter trial and the Children’s Oncology Group Study POG 9421

Leukemia volume 27, pages 731–734 (2013)Cite this article

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While increased treatment intensity has improved outcomes for children with acute megakaryoblastic leukemia (AMKL), the prognostic and therapeutic implications of megakaryoblastic differentiation remain controversial, with some groups treating such disease as high risk and recommending hematopoietic stem cell transplantation (HSCT) during first remission, while others treat as standard risk in the absence of unfavorable cytogenetics and/or a poor response to induction therapy.1, 2, 3, 4, 5 The t(1;22)(p13;q13) translocation leads to the RBM15(OTT)-MKL1(MAL) fusion protein and predominates in infants with AMKL.6, 7 Retrospective studies have reported conflicting data on long-term outcomes for the t(1;22) subgroup.8, 9 We report the outcomes of children with AMKL treated on the multicenter AML02 protocol (2002–2008) and on Pediatric Oncology Group protocol 9421 (1995–1999).5, 10 Details of patient eligibility and treatment have been previously reported; written informed consent was obtained from patients or their guardians in accordance with supervising Institutional Review Boards.

Of the 565 patients enrolled on Pediatric Oncology Group 9421, 49 (8.7%) had AMKL (Table 1). The complete response (CR) rate after two cycles of induction therapy was 79.6%, with no difference between standard and high-dose cytarabine regimens, which was similar to the non-AMKL cohort (84.5%). After induction, 44 patients with at least partial response continued on study; 6 underwent protocol-specified HSCT from a human leukocyte antigen (HLA) matched sibling donor (4 remain in first CR), while 38 received consolidation chemotherapy (13 remain in first CR). The outcomes for patients with AMKL (5-year rates: event-free survival (EFS), 34.7±7.5%; overall survival (OS), 36.3±7.5%) were similar to those of patients with other AML subtypes who lacked favorable cytogenetic features (5-year rates: EFS 33.9±2.5%; OS, 45.8±2.6%).

Table 1 AML02 and POG 9421 patient characteristics and response
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Acknowledgements

We thank Cherise Guess for expert editorial review. This work is supported in part by grant CA21765 from the National Institutes of Health and by the American Lebanese Syrian Associated Charities. A complete listing of grant support for research conducted by the Children’s Cancer Group (CCG) and the Pediatric Oncology Group (POG) before initiation of the Children’s Oncology Group (COG) grant in 2003 is available online at http://applications.childrensoncologygroup.org/admin/grantinfo.htm

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Authors and Affiliations

  1. Division of Pediatric Hematology/Oncology, Stanford University School of Medicine, Palo Alto, CA, USA

    M M O'Brien, G V Dahl & N J Lacayo

  2. Department of Biostatistics, St Jude Children’s Research Hospital and the University of Tennessee Health Science Center, Memphis, TN, USA

    X Cao & S Pounds

  3. Department of Pathology, St Jude Children’s Research Hospital and the University of Tennessee Health Science Center, Memphis, TN, USA

    S C Raimondi, D Campana & C H Pui

  4. Division of Pediatric Hematology/Oncology, Children’s Hospital of Michigan, Detroit, MI, USA

    J Taub & Y Ravindranath

  5. Department of Statistics, University of Florida, Gainesville, FL, USA

    M Chang

  6. Department of Pediatrics, Massachusetts General Hospital for Children, Boston, MA, USA

    H J Weinstein

  7. Department of Oncology, St Jude Children’s Research Hospital and the University of Tennessee Health Science Center, Memphis, TN, USA

    H Inaba, C H Pui & J E Rubnitz

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  1. M M O'Brien
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Correspondence to M M O'Brien.

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O'Brien, M., Cao, X., Pounds, S. et al. Prognostic features in acute megakaryoblastic leukemia in children without Down syndrome: a report from the AML02 multicenter trial and the Children’s Oncology Group Study POG 9421. Leukemia 27, 731–734 (2013). https://doi.org/10.1038/leu.2012.223

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