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Minimal residual disease negativity in elderly patients with acute myeloid leukemia may indicate different postremission strategies than in younger patients

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Abstract

In the present analysis, we evaluated whether in elderly acute myeloid leukemia (AML) patients (>60 years), minimal residual disease (MRD) assessed by flow cytometry may have a role in guiding choice of postremission strategies. We analyzed 149 young and 61 elderly adults who achieved morphological CR after induction course of EORTC/GIMEMA protocols. Elderly patients reached a postconsolidation MRD negative status less frequently than younger ones (11 vs 28 %, p = 0.009). MRD negativity resulted in a longer 5-year disease-free survival (DFS) both in elderly (57 vs 13 %, p = 0.0197) and in younger patients (56 vs 31 %, p = 0.0017). Accordingly, 5-year cumulative incidence of relapse (CIR) of both elderly (83 vs 42 %, p = 0.045) and younger patients (59 vs 24 % p = NS) who were MRD positive doubled that of MRD negative ones. Nevertheless, CIR of MRD negative elderly patients was twofold higher than that of younger MRD negative ones (42 vs 24 %, p = NS). In conclusion, elderly patients in whom chemotherapy yields a MRD negative CR have duration of DFS and rate of CIR significantly better than those who remain MRD positive. Nonetheless, the high CIR rate observed in the elderly suggests that MRD negativity might have different therapeutic implications in this population than in the younger counterpart.

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References

  1. Thein MS, Ershler WB, Jemal A et al (2013) Outcome of older patients with acute myeloid leukemia: an analysis of SEER data over 3 decades. Cancer 11:2720–2727

    Article  Google Scholar 

  2. Burnett A, Wetzler M, Lowenberg B (2011) Therapeutic advances in acute myeloid leukemia. J Clin Oncol 29:487–494

    Article  PubMed  Google Scholar 

  3. Lowenberg B, Downing JR, Burnett A (1999) Acute myeloid leukemia. N Engl J Med 341:1051–1062

    Article  CAS  PubMed  Google Scholar 

  4. Appelbaum FR (2008) Incorporating hematopoietic cell transplantation (HCT) into the management of adults aged under 60 years with acute myeloid leukemia (AML). Best Pract Res Clin Haematol 21:85–92

    Article  PubMed  Google Scholar 

  5. Koreth J, Schlenk R, Kopecky KJ et al (2009) Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA 301:2349–2361

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Freeman SD, Jovanovic JV, Grimwade D (2008) Development of minimal residual disease-directed therapy in acute myeloid leukemia. Semin Oncol 35:388–400

    Article  CAS  PubMed  Google Scholar 

  7. Buccisano F, Maurillo L, Del Principe MI et al (2012) Prognostic and therapeutic implications of minimal residual disease detection in acute myeloid leukemia. Blood 119:332–341

    Article  CAS  PubMed  Google Scholar 

  8. Pulte D, Gondos A, Brenner H et al (2008) Improvements in survival of adults diagnosed with acute myeloblastic leukemia in the early 21st century. Haematologica 93:594–600

    Article  PubMed  Google Scholar 

  9. Buchner T, Berdel WE, Haferlach C et al (2009) Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: a study by the German Acute Myeloid Leukemia Cooperative Group. J Clin Oncol 27:61–69

    Article  PubMed  Google Scholar 

  10. Lerch E, Espeli V, Zucca E et al (2009) Prognosis of acute myeloid leukemia in the general population: data from southern Switzerland. Tumori 95:303–310

    PubMed  Google Scholar 

  11. Alibhai SM, Leach M, Minden MD et al (2009) Outcomes and quality of care in acute myeloid leukemia over 40 years. Cancer 115:2903–2911

    Article  PubMed  Google Scholar 

  12. Appelbaum F, Gundacker H, Head DR et al (2006) Age and acute myeloid leukemia. Blood 107:3481–3485

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Grimwade D, Freeman SD (2014) Defining minimal residual disease in acute myeloid leukemia: which platforms are ready for “Prime Time”? Blood 124:3345–3355

    Article  CAS  PubMed  Google Scholar 

  14. Grimwade D (2012) The changing paradigm of prognostic factors in acute myeloid leukaemia. Best Pract Res Clin Haematol 25:419–425

    Article  PubMed  Google Scholar 

  15. Venditti A, Buccisano F, Del Poeta G et al (2000) Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia. Blood 96:3948–3952

    CAS  PubMed  Google Scholar 

  16. Buccisano F, Maurillo L, Gattei V et al (2006) The kinetics of reduction of minimal residual disease impacts on duration of response and survival of patients with acute myeloid leukemia. Leukemia 20:1783–1789

    Article  CAS  PubMed  Google Scholar 

  17. Maurillo L, Buccisano F, Del Principe MI et al (2008) Toward optimization of postremission therapy for residual disease-positive patients with acute myeloid leukemia. J Clin Oncol 26:4944–4951

    Article  PubMed  Google Scholar 

  18. Buccisano F, Maurillo L, Spagnoli A et al (2010) Cytogenetic and molecular diagnostic characterization combined to post-consolidation minimal residual disease assessment by flow-cytometry improves risk stratification in adult acute myeloid leukemia. Blood 116:2295–2303

    Article  CAS  PubMed  Google Scholar 

  19. Freeman SD, Virgo P, Couzens S et al (2013) Prognostic relevance of treatment response measured by flow cytometric residual disease detection in older patients with acute myeloid leukemia. J Clin Oncol 31:4123–4131

    Article  PubMed  Google Scholar 

  20. Mandelli F, Vignetti M, Suciu S et al (2009) Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: The EORTC and GIMEMA Groups Study AML-10. J Clin Oncol 27:5397–5403

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Willemze R, Suciu S, Meloni G et al (2014) High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol 32:219–228

    Article  CAS  PubMed  Google Scholar 

  22. Amadori S, Suciu S, Jehn U et al (2005) Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study. Blood 106:27–34

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Amadori S, Suciu S, Willemze R et al (2004) Sequential administration of gemtuzumab ozogamicin and conventional chemotherapy as first line therapy in elderly patients with acute myeloid leukemia: a phase II study (AML-15) of the EORTC and GIMEMA leukemia groups. Haematologica 89:950–956

    CAS  PubMed  Google Scholar 

  24. Amadori S, Suciu S, Stasi R et al (2013) Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17). J Clin Oncol 31:4424–4430

    Article  CAS  PubMed  Google Scholar 

  25. Baer MR, Stewart CC, Dodge RK et al (2001) High frequency of immunophenotype changes in acute myeloid leukemia at relapse: implication for residual disease detection. Blood 97:3574–3580

    Article  CAS  PubMed  Google Scholar 

  26. Voskova D, Schoch C, Schnittger S et al (2004) Stability of leukemia associated aberrant immunophenotypes in patients with acute leukemia between diagnosis and relapse: comparison with cytomorphologic, cytogenetic and molecular genetic findings. Cytometry B Clin Cytom 62:25–38

    Article  PubMed  Google Scholar 

  27. Cheson BD, Bennett JM, Kopecky KJ et al (2003) Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in Acute Myeloid Leukemia. J Clin Oncol 21:4642–4649

    Article  PubMed  Google Scholar 

  28. Kaplan EL, Meier P (1958) Non parametric estimations from incomplete observations. J Am Stat Assoc 53:457–461

    Article  Google Scholar 

  29. Klein, J P and Zhang, MJ. (2005) Survival analysis, software. Encyclopedia of biostatistics 8

  30. San Miguel JF, Martinez A, Macedo A et al (1997) Immunophenotyping investigation of minimal residual disease is a useful approach for predicting relapse in acute myeloid leukemia patients. Blood 90:2465–2470

    CAS  PubMed  Google Scholar 

  31. San Miguel JF, Vidriales MB, López-Berges C et al (2001) Early immunophenotypical evaluation of minimal residual disease in acute myeloid leukemia identifies different patient risk groups and may contribute to post-induction treatment stratification. Blood 98:1746–1751

    Article  CAS  PubMed  Google Scholar 

  32. Kern W, Voskova D, Schoch C et al (2004) Prognostic impact of early response to induction therapy as assessed by multiparameter flow cytometry in acute leukemia patients. Haematologica 89:528–540

    PubMed  Google Scholar 

  33. Terwijn M, van Putten WL, Kelder A et al (2013) High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study. J Clin Oncol 31:3889–3897

    Article  PubMed  Google Scholar 

  34. Cornelissen JJ, Gratwohl A, Schlenk RF et al (2012) 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 9:579–590

    Article  CAS  PubMed  Google Scholar 

  35. Zeijlemaker W, Gratama JW, Schuurhuis GJ (2014) Tumor heterogeneity makes AML a “moving target” for detection of residual disease. Cytometry B Clin Cytom 86B:3–14

    Article  Google Scholar 

  36. Olaru D, Campos L, Flandrin P et al (2008) Multiparametric analysis of normal and postchemotherapy bone marrow: implication for the detection of leukemia-associated immunophenotypes. Cytometry B Clin Cytom 74:17–24

    Article  CAS  PubMed  Google Scholar 

  37. Terwijn M, Zeijlemaker W, Kelder A et al (2014) Leukemic stem cell frequency: a strong biomarker for clinical outcome in acute myeloid leukemia. PLoS ONE 9:e107587

    Article  PubMed Central  PubMed  Google Scholar 

  38. Bachas C, Schuurhuis GJ, Assaraf YG et al (2012) The role of minor subpopulations within the leukemic blast compartment of AML patients at initial diagnosis in the development of relapse. Leukemia 26:1313–1320

    Article  CAS  PubMed  Google Scholar 

  39. Schoch C, Kern W et al (2004) The influence of age on prognosis of de novo acute myeloid leukemia differs according to cytogenetic subgroups. Haematologica 89:1082–1090

    PubMed  Google Scholar 

  40. Prébet T, Boissel N, Reutenauer S et al (2009) Acute myeloid leukemia with translocation (8;21) or inversion (16) in elderly patients treated with conventional chemotherapy: a collaborative study of the French CBF-AML intergroup. J Clin Oncol 27:4747–4753

    Article  PubMed  Google Scholar 

  41. Ustun C, Lazarus HM, Weisdorf D (2013) To transplant or not: a dilemma for treatment of elderly AML patients in the twenty-first century. Bone Marrow Transplant 48:1497–1505

    Article  CAS  PubMed  Google Scholar 

  42. Sorror ML, Estey E (2014) Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia in older adults. Hematology 2014:21–33

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from Lazio Regional Agency for Transplantation and Related Diseases (IG grant 971/E); Ministero Istruzione Università Ricerca Projects Of National Relevance (PRIN, IG GRANT 20110AX25X7); Associazione Italiana Ricerca sul Cancro (IG grant 10555).

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The authors declare that they have no conflict of interest.

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Buccisano, F., Maurillo, L., Piciocchi, A. et al. Minimal residual disease negativity in elderly patients with acute myeloid leukemia may indicate different postremission strategies than in younger patients. Ann Hematol 94, 1319–1326 (2015). https://doi.org/10.1007/s00277-015-2364-5

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  • DOI: https://doi.org/10.1007/s00277-015-2364-5

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