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 Article
  • Published:

Minimal Residual Disease

Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation

Leukemia volume 29, pages 137–144 (2015)Cite this article

Subjects

Abstract

Minimal residual disease (MRD) is associated with adverse outcome in acute myeloid leukemia (AML) after myeloablative (MA) hematopoietic cell transplantation (HCT). We compared this association with that seen after nonmyeloablative (NMA) conditioning in 241 adults receiving NMA (n=86) or MA (n=155) HCT for AML in first remission with pre-HCT bone marrow aspirates assessed by flow cytometry. NMA patients were older and had more comorbidities and secondary leukemias. Three-year relapse estimates were 28% and 57% for MRDneg and MRDpos NMA patients, and 22% and 63% for MA patients. Three-year overall survival (OS) estimates were 48% and 41% for MRDneg and MRDpos NMA patients and 76% and 25% for MA patients. This similar OS after NMA conditioning was largely accounted for by higher non-relapse mortality (NRM) in MRDneg (30%) compared with MRDpos (10%) patients, whereas the reverse was found for MRDneg (7%) and MRDpos (23%) MA patients. A statistically significant difference between MA and NMA patients in the association of MRD with OS (P<0.001) and NRM (P=0.002) but not relapse (P=0.17) was confirmed. After adjustment, the risk of relapse was 4.51 times (P<0.001) higher for MRDpos patients. These data indicate that the negative impact of MRD on relapse risk is similar after NMA and MA conditioning.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Hamilton BK, Copelan EA . Concise review: the role of hematopoietic stem cell transplantation in the treatment of acute myeloid leukemia. Stem Cells 2012; 30: 1581–1586.

    Article  CAS  PubMed  Google Scholar 

  2. Cornelissen JJ, Gratwohl A, Schlenk RF, Sierra J, Bornhäuser M, Juliusson G et al. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol 2012; 9: 579–590.

    Article  CAS  PubMed  Google Scholar 

  3. Buckley SA, Appelbaum FR, Walter RB . Prognostic and therapeutic implications of minimal residual disease at the time of transplantation in acute leukemia. Bone Marrow Transplant 2013; 48: 630–641.

    Article  CAS  PubMed  Google Scholar 

  4. Laane E, Derolf AR, Björklund E, Mazur J, Everaus H, Söderhäll S et al. The effect of allogeneic stem cell transplantation on outcome in younger acute myeloid leukemia patients with minimal residual disease detected by flow cytometry at the end of post-remission chemotherapy. Haematologica 2006; 91: 833–836.

    PubMed  Google Scholar 

  5. Maurillo L, Buccisano F, Del Principe MI, Del Poeta G, Spagnoli A, Panetta P et al. Toward optimization of postremission therapy for residual disease-positive patients with acute myeloid leukemia. J Clin Oncol 2008; 26: 4944–4951.

    Article  PubMed  Google Scholar 

  6. Leung W, Campana D, Yang J, Pei D, Coustan-Smith E, Gan K et al. High success rate of hematopoietic cell transplantation regardless of donor source in children with very high-risk leukemia. Blood 2011; 118: 223–230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Leung W, Pui CH, Coustan-Smith E, Yang J, Pei D, Gan K et al. Detectable minimal residual disease before hematopoietic cell transplantation is prognostic but does not preclude cure for children with very-high-risk leukemia. Blood 2012; 120: 468–472.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Walter RB, Gooley TA, Wood BL, Milano F, Fang M, Sorror ML et al. Impact of pretransplantation minimal residual disease, as detected by multiparametric flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute myeloid leukemia. J Clin Oncol 2011; 29: 1190–1197.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Walter RB, Buckley SA, Pagel JM, Wood BL, Storer BE, Sandmaier BM et al. Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission. Blood 2013; 122: 1813–1821.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA et al. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol 2010; 28: 2859–2867.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ustun C, Wiseman AC, Defor TE, Yohe S, Linden MA, Oran B et al. Achieving stringent CR is essential before reduced-intensity conditioning allogeneic hematopoietic cell transplantation in AML. Bone Marrow Transplant 2013; 48: 1415–1420.

    Article  CAS  PubMed  Google Scholar 

  12. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009; 114: 937–951.

    Article  CAS  PubMed  Google Scholar 

  13. Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 2010; 116: 354–365.

    Article  CAS  PubMed  Google Scholar 

  14. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 2005; 106: 2912–2919.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sorror ML . How I assess comorbidities before hematopoietic cell transplantation. Blood 2013; 121: 2854–2863.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner 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  PubMed  Google Scholar 

  17. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  18. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956.

    Article  PubMed  Google Scholar 

  19. Fang M, Storer B, Wood B, Gyurkocza B, Sandmaier BM, Appelbaum FR . Prognostic impact of discordant results from cytogenetics and flow cytometry in patients with acute myeloid leukemia undergoing hematopoietic cell transplantation. Cancer 2012; 118: 2411–2419.

    Article  PubMed  Google Scholar 

  20. DiNardo CD, Luger SM . Beyond morphology: minimal residual disease detection in acute myeloid leukemia. Curr Opin Hematol 2012; 19: 82–88.

    PubMed  Google Scholar 

  21. Ravandi F, Jorgensen JL . Monitoring minimal residual disease in acute myeloid leukemia: ready for prime time? J Natl Compr Canc Netw 2012; 10: 1029–1036.

    Article  PubMed  Google Scholar 

  22. Paietta E . Minimal residual disease in acute myeloid leukemia: coming of age. Hematology Am Soc Hematol Educ Program 2012; 2012: 35–42.

    PubMed  Google Scholar 

  23. Kebriaei P, Kline J, Stock W, Kasza K, Le Beau MM, Larson RA et al. Impact of disease burden at time of allogeneic stem cell transplantation in adults with acute myeloid leukemia and myelodysplastic syndromes. Bone Marrow Transplant 2005; 35: 965–970.

    Article  CAS  PubMed  Google Scholar 

  24. Jacobsohn DA, Tse WT, Chaleff S, Rademaker A, Duerst R, Olszewski M et al. High WT1 gene expression before haematopoietic stem cell transplant in children with acute myeloid leukaemia predicts poor event-free survival. Br J Haematol 2009; 146: 669–674.

    Article  CAS  PubMed  Google Scholar 

  25. Nelson RP Jr, Yu M, Schwartz JE, Robertson MJ, Hromas R, Fausel CA et al. Long-term disease-free survival after nonmyeloablative cyclophosphamide/fludarabine conditioning and related/unrelated allotransplantation for acute myeloid leukemia/myelodysplasia. Bone Marrow Transplant 2010; 45: 1300–1308.

    Article  CAS  PubMed  Google Scholar 

  26. Baron F, Labopin M, Niederwieser D, Vigouroux S, Cornelissen JJ, Malm C et al. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation. Leukemia 2012; 26: 2462–2468.

    Article  CAS  PubMed  Google Scholar 

  27. Martino R, de Wreede L, Fiocco M, van Biezen A, von dem Borne PA, Hamladji RM et al. Comparison of conditioning regimens of various intensities for allogeneic hematopoietic SCT using HLA-identical sibling donors in AML and MDS with &lt;10% BM blasts: a report from EBMT. Bone Marrow Transplant 2013; 48: 761–770.

    Article  CAS  PubMed  Google Scholar 

  28. Davies JK, Taussig D, Oakervee H, Smith M, Agrawal S, Cavenagh JD et al. Long-term survival with low toxicity after allogeneic transplantation for acute myeloid leukaemia and myelodysplasia using non-myeloablative conditioning without T cell depletion. Br J Haematol 2013; 162: 525–529.

    Article  CAS  PubMed  Google Scholar 

  29. Peffault de Latour R, Brunstein CG, Porcher R, Chevallier P, Robin M, Warlick E et al. Similar overall survival using sibling, unrelated donor, and cord blood grafts after reduced-intensity conditioning for older patients with acute myelogenous leukemia. Biol Blood Marrow Transplant 2013; 19: 1355–1360.

    Article  PubMed  Google Scholar 

  30. Sengelov H, Gerds TA, Braendstrup P, Kornblit B, Mortensen BK, Petersen SL et al. Long-term survival after allogeneic haematopoietic cell transplantation for AML in remission: single-centre results after TBI-based myeloablative and non-myeloablative conditioning. Bone Marrow Transplant 2013; 48: 1185–1191.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Research reported in this publication was supported by grants P01-CA078902, P01-CA018029 and R00-HL088021 from the National Cancer Institute/National Institutes of Health, Bethesda, MD, USA. RBW is a Leukemia and Lymphoma Society Scholar in Clinical Research. SAB is the recipient of a Trainee Research Award and a ‘Hematology Opportunity for the Next-Generation of Research Scientists’ (HONORS) Award from the American Society of Hematology.

Author information

Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    R B Walter, B Gyurkocza, B E Storer, J M Pagel, M L Sorror, R Storb, F R Appelbaum & B M Sandmaier

  2. Division of Hematology, Department of Medicine, University of Washington, Seattle, WA, USA

    R B Walter

  3. Department of Epidemiology, University of Washington, Seattle, WA, USA

    R B Walter

  4. Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA

    B Gyurkocza, J M Pagel, M L Sorror, R Storb, F R Appelbaum & B M Sandmaier

  5. Department of Medicine, Residency Program, University of Washington, Seattle, WA, USA

    C D Godwin & S A Buckley

  6. Division of Hematopathology, Department of Laboratory Medicine, University of Washington, Seattle, WA, USA

    B L Wood

Authors
  1. R B Walter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B Gyurkocza
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B E Storer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C D Godwin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J M Pagel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S A Buckley
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M L Sorror
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. B L Wood
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. R Storb
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. F R Appelbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. B M Sandmaier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R B Walter.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Presented in part at the 55th Annual Meeting of the American Society of Hematology; 7–10 December 2013; New Orleans, LA, USA, Version: 1 May 2014.

Supplementary Information accompanies this paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Walter, R., Gyurkocza, B., Storer, B. et al. Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation. Leukemia 29, 137–144 (2015). https://doi.org/10.1038/leu.2014.173

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2014.173

This article is cited by

Search

Advanced search

Quick links