Elsevier

Leukemia Research

Volume 53, February 2017, Pages 28-34
Leukemia Research

Consolidation with autologous stem cell transplantation in first remission is safe and effective in AML patients above 65 years

https://doi.org/10.1016/j.leukres.2016.12.001Get rights and content

Highlights

  • The outcome of AML patients ≥65 years remains disappointing.

  • Consolidation with autologous transplantation is feasible in elderly AML patients.

  • ASCT consolidation in first remission provides longer PFS and OS in elderly AML.

  • ASCT provides similar survival benefits in young and elderly AML patients.

Abstract

The outcome of AML patients ≥65 years remains disappointing. Current post-induction strategies for elderly AML patients fit for intensive treatment involve additional cycles of chemotherapy or allogeneic transplantation. Consolidation with autologous transplantation (ASCT) is poorly studied in these patients. In this single-center retrospective analysis, we determined survival rates of AML patients ≥65 years undergoing busulfan/cyclophosphamide conditioning before ASCT in first remission between 2007 and 2015. We found elderly AML patients with ASCT to have longer progression-free survival (PFS; 16.3 vs. 5.1 months, P = 0.0166) and overall survival (OS; n.r. vs. 8.2 months; P = 0.0255) than elderly AML patients without ASCT consolidation. In addition, elderly AML patients undergoing ASCT had comparable PFS (P = 0.9462) and OS (P = 0.7867) as AML patients below 65 years receiving ASCT consolidation in CR1. Our data suggest that ASCT is an option in elderly fit AML patients who appear to benefit from autologous consolidation similarly to younger AML patients.

Graphical abstract

Elderly AML patients above 65 years derive similar benefits in overall survival from ASCT consolidation in CR1 as AML patients below 65 years.

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Introduction

Acute myeloid leukemia (AML) is predominantly diagnosed in elderly people with a median age at diagnosis of 67 years [3], [14]. The outcome of elderly AML patients remains disappointing due to the overrepresentation of adverse prognostic factors [13]. Even if complete remission rates are achieved in up to 60% after standard intensive induction treatment in elderly AML patients, relapses are common leading to 2-year survival rates of only 10–20% [11]. Since relapses emerge from residual leukemic cells escaping chemotherapy, intensification of AML treatment appears as a rational strategy. Accepted modalities to prevent relapse in first complete remission in younger AML patients comprise further conventional chemotherapy, allogeneic or autologous stem cell transplantation, whereas in elderly AML patients chemotherapy consolidation and (less commonly) allogeneic transplantation are applied [13].

Autologous stem cell transplantation (ASCT) has become a therapeutic option for first-line consolidation in younger adults with AML with good and intermediate risk features [15]. In such patients, it offers distinct anti-leukemic effectiveness and prolongs survival similar to allogeneic transplantation while avoiding morbidity and mortality of graft versus host disease associated with allogeneic transplantation [2], [17]. However, prospective studies in elderly AML patients comparing chemotherapy consolidation with autologous stem cell transplantation (ASCT) or allogeneic transplantation are lacking.

Various retrospective reports have investigated the use of ASCT in elderly AML patients with promising results, albeit mostly in highly selected patients [1], [5], [7], [12]. Acceptable toxicity and a low rate of transplant-related mortality were reported without compromising the rate of relapse, which, irrespective of age, still remains the major cause of treatment failure after ASCT in AML. However, the definition of an elderly AML patient has widely varied among the available studies. Whereas earlier reports separated such patients as being older than 50 years [1], more recent studies defined such patients as older than 60 years [12]. However, an analysis investigating the benefit and tolerance of ASCT consolidation specifically in AML patients ≥65 years in first remission is currently missing.

Section snippets

Pretreatment assessments

In this single-center, retrospective analysis, we investigated busulfan/cyclophosphamide conditioning before ASCT in AML patients ≥65 years in first remission treated at the University Hospital Bern, Switzerland between 2007 and 2015. We compared this cohort to two control groups: (I) AML patients ≥65 years in first CR (CR1) after one or two induction cycles without subsequent consolidation treatment, and (II) AML patients <65 years undergoing ASCT in CR1 after two cycles of induction treatment

Treatment

40 AML patients ≥65 years in CR1 after one or two cycles of intensive induction chemotherapy were identified. Patients in this period were treated in subsequent HOVON/SAKK protocols (HOVON-81, −93, and −103), and 24 of these patients received no consolidation treatment as per protocol. 16 Patients ≥65 years diagnosed with AML in interval periods without an active protocol and considered to be fit for consolidation treatment underwent ASCT for consolidation of first remission. Induction

Discussion

Our data suggest that fit AML patients ≥65 years may tolerate ASCT consolidation in CR1 and equally benefit from such treatment as young AML patients in CR1. Obvious limitations of this study are its retrospective, single center and non-randomized design inevitably leading to a relevant selection bias. Accordingly, physicians may have tended to offer ASCT more likely to patients with favorable risk features, good tolerance of induction treatment, and achievement of early remission (already

Funding source

This work was supported by a grant from the Bernische Krebsstiftung, the Berne Cancer League, and the EMPIRIS Stiftung Zurich.

Author’s contributions

A.H. performed research, analyzed data and wrote the paper; M.D.B. and K.S. analyzed data, reviewed the manuscript and were involved in the final writing of the paper; G.M.B., B.M.T., K.L., Y.B., and U.N. contributed relevant data, reviewed the manuscript and were involved in the final writing of the paper; T.P. designed research, analyzed data and wrote the paper.

Acknowledgements

The authors wish to thank the stem cell coordinating team, the stem cell data-management team, the members of the stem cell collection unit and of the stem cell processing unit associated with the stem cell program at the University Hospital Berne for providing some of the data used in this analysis. Also, the authors wish to thank all staff members involved in the patient care of the patients reported in this study.

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