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Therapy

Declining rates of treatment-related mortality in patients with newly diagnosed AML given ‘intense’ induction regimens: a report from SWOG and MD Anderson

Leukemia volume 28, pages 289–292 (2014)Cite this article

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Abstract

Less-intense remission induction regimens for adults with newly diagnosed acute myeloid leukemia (AML) aim to reduce treatment-related mortality (TRM), here defined as death within 4 weeks after starting induction therapy. This assumes that TRM rates are similar to the 15–20% observed 20 years ago. Herein we test this assumption. We examined TRM rates in 1409 patients treated on SWOG (Southwest Oncology Group) trials and 1942 patients treated at MD Anderson (MDA) from 1991 to 2009. Eighty-eight percent of SWOG patients received ‘3+7’ or regimens of similar intensity while 92% of the MDA patients received ara-C at 1.5–2.0 g/m2 daily × 3–5 days+other cytotoxic agents. We examined the relationship between time and TRM rates after accounting for other covariates. TRM rates between 1991 and 2009 decreased from 18–3% in SWOG and 16–4% at MDA. Multivariate analyses showed a significant decrease in TRM over time (P=0.001). The decrease in TRM was not limited to younger patients, those with a better performance status or a lower white blood cell count. Though our observations are limited to patients treated with intensive therapy at SWOG institutions and MDA, the decrease in TRM with time emphasizes the problem with historical controls and could be considered when selecting AML induction therapy.

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References

  1. Appelbaum F, Gundacker H, Head D, Slovak M, Willman C, Godwin J et al. Age and acute myeloid leukemia. Blood 2006; 107: 3481–3485.

    Article  CAS  Google Scholar 

  2. Walter R, Othus M, Borthakur G, Ravandi F, Cortes J, Pierce S et al. Prediction of early death after induction therapy for newly diagnosed acute myeloid leukemia with pretreatment risk scores: a novel paradigm for treatment assignment. J Clin Oncol 2011; 29: 4417–4423.

    Article  Google Scholar 

  3. Estey E, Smith TL, Keating MJ, McCredie KB, Gehan EA, Freireich EJ . Prediction of survival during induction therapy in patients with newly diagnosed acute myeloblastic leukemia. Leukemia 1989; 3: 257–263.

    CAS  Google Scholar 

  4. Burnett AK, Milligan D, Prentice AG, Goldstone AH, McMullin MF, Hills RK et al. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer 2007; 109: 1114–1124.

    Article  CAS  Google Scholar 

  5. Fenaux P, Mufti G, Hellström-Lindberg E, Santini V, Gattermann N, Germing U et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol 2010; 28: 562–569.

    Article  CAS  Google Scholar 

  6. Platzbecker U, Germing U . Combination of azacitidine and lenalidomide in myelodysplastic syndromes or acute myeloid Leukemia—a wise liaison?". Leukemia 2013; e-pub ahead of print 6 May 2013; doi: 10.1038/leu.2013.140.

    Article  CAS  Google Scholar 

  7. Pollyea D, Kohrt H, Gallegos L, Figueroa ME, Abdel-Wahab O, Zhang B et al. Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia. Leukemia 2011; 26: 893–901.

    Article  Google Scholar 

  8. Kantarjian H, Thomas X, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol 2012; 30: 2670–2677.

    Article  CAS  Google Scholar 

  9. Quintas-Cardama A, Santos F, Garcia-Manero G . Histone deacetylase inhibitors for the treatment of myelodysplastic syndrome and acute myeloid leukemia. Leukemia 2010; 25: 226–235.

    Article  Google Scholar 

  10. Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med 2010; 363: 2091–2101.

    Article  CAS  Google Scholar 

  11. Walter R, Othus M, Borthakur G, Ravandi F, Cortes J, Pierce S et al. Quantitative effect of age in predicting empirically-defined treatment-related mortality and resistance in newly diagnosed AML: case against age alone as primary determinant of treatment assignment. Blood 2010; 116: 2191 (ASH abstract # 2191).

    Article  Google Scholar 

  12. Baden L . Prevention and therapy of fungal infections in bone marrow transplantation. Leukemia 2003; 17: 1038–1041.

    Article  CAS  Google Scholar 

  13. Aperis G, Alivanis P . Posaconazole: a new antifungal weapon. Rev Recent Clin Trials 2011; 3: 204–219.

    Article  Google Scholar 

  14. Pagano L, Caira M, Candoni A, Aversa F, Castagnola C, Caramatti C et alfor the SEIFEM Group. Evaluation of the practice of antifungal prophylaxis use in patients with newly diagnosed acute myeloid leukemia: results from the SEIFEM 2010-B Registry. Clin Infect Dis 2012; 55: 1515–1521.

    Article  CAS  Google Scholar 

  15. Walsh T, Teppler H, Donowitz G, Maertens J, Baden L, Dmoszynska A et al. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med 2004; 351: 1391–1402.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Public Health Sciences Division’s Biostatistics and Biomathematics Group, Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA, USA

    M Othus, S Petersdorf, F R Appelbaum & E Estey

  2. MD Anderson Cancer Center, Houston, TX, USA

    H Kantarjian, F Ravandi, J Cortes, S Pierce & S Faderl

  3. Hematology and Oncology Division, Southern Illinois University, Springfield, IL, USA

    J Godwin

  4. Hematologic Malignancy Program, University of Alabama, Birmingham, AL, USA

    H Erba

Authors
  1. M Othus
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  2. H Kantarjian
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  3. S Petersdorf
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  4. F Ravandi
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  5. J Godwin
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  6. J Cortes
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  7. S Pierce
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  8. H Erba
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  9. S Faderl
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  10. F R Appelbaum
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  11. E Estey
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Correspondence to M Othus.

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Author contributions

MO: analyzed and interpreted data, performed statistical analysis, principal writer and corresponding author; HK, SP, FR, JG, JC, HE, SF: data collection, data interpretation and manuscript writing; SP: data collection and manuscript writing; FRA: analyzed and interpreted data, aided in writing and administrative support; EHE: designed research, analyzed and interpreted data and manuscript writing.

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Othus, M., Kantarjian, H., Petersdorf, S. et al. Declining rates of treatment-related mortality in patients with newly diagnosed AML given ‘intense’ induction regimens: a report from SWOG and MD Anderson. Leukemia 28, 289–292 (2014). https://doi.org/10.1038/leu.2013.176

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