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Acute myeloid leukemia

Second cycle remission achievement with 7+3 and survival in adults with newly diagnosed acute myeloid leukemia: analysis of recent SWOG trials

Leukemia volume 33, pages 554–558 (2019)Cite this article

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Intensive chemotherapy will induce a complete morphologic remission (CR) in many persons with acute myeloid leukemia (AML). Even with continued treatment, however, relapse is common [1, 2]. Many pretreatment factors, most notably cytogenetic and molecular profiles, are associated with disease recurrence and shorter survival and allow outcome prediction, albeit with limited accuracy, at the individual patient level [3,4,5]. It is increasingly recognized that post-treatment information provides valuable insight into which remissions are of higher quality. One important characteristic of more durable remissions is the lack of measurable residual disease (MRD) [6]. On the other hand, whether it matters that a remission is obtained early, i.e., with the first cycle of chemotherapy, has remained controversial. Data from historic and contemporary trials with double induction chemotherapies showed patients who achieved a CR with the first induction cycle were less likely to relapse than those requiring two courses of therapy to enter CR [7, 8]. Contrasting these findings, an analysis of six ECOG (now ECOG-ACRIN) trials conducted between 1983 and 1993 indicated patients who achieved a CR after one or two cycles of induction chemotherapy had similar prognoses [9]. The relationship between timing of remission achievement and outcome has not been examined in contemporary cohorts of adults treated with 7+3. Here, we used data from participants of five SWOG trials between 1983 and 2015 and studied the association between prognosis and need for 7+3 reinduction therapy and how it has changed over time.

We analyzed 1247 patients randomized to 7+3 in treatment arms of five National Cancer Institute (NCI)/National Clinical Trials Network (NCTN) trials conducted by SWOG. We analyzed patients aged 65 and younger: S8600 [10] (n = 530), S9031 [11] (n = 98), S9333 [12] (n = 57), S0106 [13] (n = 301), and S1203 [14] (n = 261). S8600 enrolled patients between November 1986 and December 1991, S9031 between November 1991 and January 1995, S9333 between January 1995 and December 1998, S0106 between May 2004 and August 2009, and S1203 between December 2012 and November 2015. While all studies were limited to patients with newly diagnosed AML, the exact eligibility criteria differed between these trials. For example, trials S9031 and S9333 were restricted to patients aged 55 and older; the other studies included patients aged 18 and older. Patients with secondary AML were not eligible for S0106, which tested the addition of the CD33 antibody–drug conjugate gemtuzumab ozogamicin to induction chemotherapy. There were also differences in the chemotherapy regimens administered since, in all five trials, 7+3 was given as per standard at that time. Specifically, in S8600, S9031, and S9333, the cytarabine and daunorubicin doses were 200 mg/m2 and 45 mg/m2, respectively, In S0106, doses used were 100 mg/m2 and 60 mg/m2, respectively. Finally, in S1203, doses of 100 mg/m2 for cytarabine and 90 mg/m2 for daunorubicin were used. Institutional review boards of participating institutions approved all protocols, and patients were treated according to the Declaration of Helsinki.

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Acknowledgements

The authors gratefully acknowledge the important contributions of the late Dr. Stephen H. Petersdorf to SWOG and to study S0106. Research reported in this publication was supported by a grant from the National Cancer Institute/National Institutes of Health grants CA180888 and CA180819. RBW is a Leukemia & Lymphoma Society Scholar in clinical research.

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Author notes

  1. Harry P. Erba

    Present address: Duke University, Durham, NC, USA

Authors and Affiliations

  1. Public Health Division and SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Megan Othus

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

    Elihu H. Estey, Derek L. Stirewalt, Frederick R. Appelbaum & Roland B. Walter

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

    Elihu H. Estey & Roland B. Walter

  4. Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA

    Guillermo Garcia-Manero

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

    Brent L. Wood

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

    Derek L. Stirewalt & Frederick R. Appelbaum

  7. Providence Cancer Center Oncology and Hematology Care Clinic, Portland, OR, USA

    John E. Godwin

  8. VA Medical Center, North Palm Beach, FL, USA

    James K. Weick

  9. Katmai Oncology Group, Anchorage, AK, USA

    Jeanne E. Anderson

  10. University of Alabama at Birmingham, Birmingham, AL, USA

    Harry P. Erba

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

    Roland B. Walter

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Correspondence to Megan Othus.

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Othus, M., Estey, E.H., Garcia-Manero, G. et al. Second cycle remission achievement with 7+3 and survival in adults with newly diagnosed acute myeloid leukemia: analysis of recent SWOG trials. Leukemia 33, 554–558 (2019). https://doi.org/10.1038/s41375-018-0274-y

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