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Allogeneic hematopoietic cell transplant for normal karyotype AML: indirect evidence of selection for adverse molecular profile

Bone Marrow Transplantation volume 50, pages 1004–1006 (2015)Cite this article

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Recurrent genomic abnormalities identified in AML improve prognostic stratification of patients with normal karyotype AML (NK-AML).1, 2 Retrospective studies show that mutations in FLT3, NPM1 and CEBPα are powerful tools to predict outcomes in younger and older patients with NK-AML.3, 4, 5 Limited data exist on the role of allogeneic hematopoietic cell transplant (HCT) in NK-AML patients with recurrent genomic abnormalities.6, 7, 8 In this retrospective cohort study, we evaluated the outcomes of patients with NK-AML transplanted at a single institution to determine whether the widespread implementation of molecular testing in NK-AML patients at the time of diagnosis has impacted the outcomes of patients who ultimately undergo allogeneic HCT.

The Stanford University Division of Blood and Marrow Transplantation database was interrogated to compile all adult patients (age ⩾18 years) with AML who received their first allogeneic HCT following full-dose or reduced intensity conditioning at Stanford University between 1 January 2000 and 30 September 2011 (n=349). Patients were excluded if they had acute promyelocytic leukemia, prior autologous HCT, or a graft from a syngeneic, cord blood or haploidentical donor, and if they lacked the source document diagnostic cytogenetic report. All patients were on Institutional Review Board protocols and signed written informed consent before the transplant. We identified 143 consecutive patients with NK-AML who underwent first allogeneic HCT from matched or one-antigen mismatched related or unrelated donors. Patients underwent HCT in first complete remission (CR, n=88), in second CR or beyond (n=26) or not in remission (n=29). Beginning in 2006, results were available for molecular testing of FLT3, NPM1 and CEBPα mutations from the initial diagnostic bone marrow biopsy and/or peripheral blood analysis. Using the European LeukemiaNet (ELN) classification for patients with NK-AML, mutations in NPM1 (without concurrent FLT3-ITD) or mutations in CEBPα are considered favorable, whereas FLT3-ITD or wild-type NPM1 without FLT3-ITD are identified as intermediate-1.2 Three independent investigators (MEMP, BCM and RL) reviewed the medical records of adult patients with NK-AML who underwent HCT. The majority of patients (>95%) received standard induction chemotherapy (anthracycline plus cytarabine) followed by one or two consecutive cycles of high-dose cytarabine before allogeneic HCT. Patients underwent HCT using either full-dose or reduced intensity conditioning regimens9, 10, 11, 12, 13 and received graft-versus-host-disease prophylaxis as previously described.11 Patients received unstimulated whole bone marrow or G-CSF-mobilized blood.

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References

  1. Patel JP, Gonen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 2012; 366: 1079–1089.

    Article  CAS  Google Scholar 

  2. Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010; 115: 453–474.

    Article  Google Scholar 

  3. Mrozek K, Marcucci G, Nicolet D, Maharry KS, Becker H, Whitman SP et al. Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia. J Clin Oncol 2012; 30: 4515–4523.

    Article  Google Scholar 

  4. Rollig C, Bornhauser M, Thiede C, Taube F, Kramer M, Mohr B et al. Long-term prognosis of acute myeloid leukemia according to the new genetic risk classification of the European LeukemiaNet recommendations: evaluation of the proposed reporting system. J Clin Oncol 2011; 29: 2758–2765.

    Article  Google Scholar 

  5. Medeiros BC, Tian L, Robenson S, Laport GG, Johnston LJ, Shizuru JA et al. European LeukemiaNet classification intermediate risk-1 cohort is associated with poor outcomes in adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation. Blood Cancer J 2014; 4: e216.

    Article  CAS  Google Scholar 

  6. Schlenk RF, Dohner K, Krauter J, Frohling S, Corbacioglu A, Bullinger L et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 2008; 358: 1909–1918.

    Article  CAS  Google Scholar 

  7. Brunet S, Labopin M, Esteve J, Cornelissen J, Socie G, Iori AP et al. Impact of FLT3 internal tandem duplication on the outcome of related and unrelated hematopoietic transplantation for adult acute myeloid leukemia in first remission: a retrospective analysis. J Clin Oncol 2012; 30: 735–741.

    Article  Google Scholar 

  8. Gale RE, Hills R, Kottaridis PD, Srirangan S, Wheatley K, Burnett AK et al. No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML10 and 12 trials. Blood 2005; 106: 3658–3665.

    Article  CAS  Google Scholar 

  9. Deeg HJ, Storer B, Slattery JT, Anasetti C, Doney KC, Hansen JA et al. Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome. Blood 2002; 100: 1201–1207.

    Article  CAS  Google Scholar 

  10. Naik S, Wong R, Arai S, Brown J, Laport G, Lowsky R et al. Long-term outcomes in patients with high-risk myeloid malignancies following matched related donor hematopoietic cell transplantation with myeloablative conditioning of BU, etoposide and CY. Bone Marrow Transplant 2011; 46: 192–199.

    Article  CAS  Google Scholar 

  11. Niederwieser D, Maris M, Shizuru JA, Petersdorf E, Hegenbart U, Sandmaier BM et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood 2003; 101: 1620–1629.

    Article  CAS  Google Scholar 

  12. Lowsky R, Takahashi T, Liu YP, Dejbakhsh-Jones S, Grumet FC, Shizuru JA et al. Protective conditioning for acute graft-versus-host disease. N Engl J Med 2005; 353: 1321–1331.

    Article  CAS  Google Scholar 

  13. Marks R, Potthoff K, Hahn J, Ihorst G, Bertz H, Spyridonidis A et al. Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies. Blood 2008; 112: 415–425.

    Article  CAS  Google Scholar 

  14. Appelbaum FR . Indications for allogeneic hematopoietic cell transplantation for acute myeloid leukemia in the genomic era. Am Soc Clin Oncol Educ Book 2014: e327–e333.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by a National Institute of Health grant P01 CA049605-22. This work was additionally supported by a Conquer Cancer Foundation of ASCO Young Investigator Award (M-EMP) and a KL2 Mentored Career Development Award (M-EMP) of the Stanford Clinical and Translational Science Award to Spectrum (NIH KL2 TR 001083). Any opinions, findings and conclusions expressed in this material are those of the authors and do not necessarily reflect those of the American Society of Clinical Oncology or the Conquer Cancer Foundation.

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Author notes

  1. M-E M Percival and B C Medeiros: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA

    M-E M Percival & B C Medeiros

  2. Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA

    L Tian

  3. Department of Medicine, Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, USA

    S Robeson, G G Laport, L J Johnston, J A Shizuru, D B Miklos, S Arai, W-K Weng, R S Negrin & R Lowsky

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  1. M-E M Percival
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  2. B C Medeiros
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  4. S Robeson
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  5. G G Laport
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Correspondence to B C Medeiros.

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Percival, ME., Medeiros, B., Tian, L. et al. Allogeneic hematopoietic cell transplant for normal karyotype AML: indirect evidence of selection for adverse molecular profile. Bone Marrow Transplant 50, 1004–1006 (2015). https://doi.org/10.1038/bmt.2015.62

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