Consolidation with autologous stem cell transplantation in first remission is safe and effective in AML patients above 65 years
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.
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.
References (17)
- et al.
Autologous bone marrow transplantation for first remission acute myeloblastic leukemia in patients older than 50 years: a retrospective analysis of the European Bone Marrow Transplant Group
Blood
(1995) - et al.
Hematopoietic stem cell transplantation for patients with AML in first complete remission
Blood
(2016) - et al.
Autologous bone marrow transplantation for acute myelocytic leukemia in first remission: a European survey of the role of marrow purging
Blood
(1990) - et al.
Nonmyeloablative stem cell transplantation for myelodysplastic syndrome or acute myeloid leukemia in patients 60 years or older
Biol. Blood. Marrow. Transplant.
(2005) - et al.
How I treat the older patient with acute myeloid leukemia
Blood
(2015) - et al.
Autologous peripheral blood stem cell transplantation for acute myeloid leukemia
Blood
(2011) - et al.
Acute myeloid leukemia
N. Engl. J. Med.
(2015) - et al.
Age has no influence on mobilization of peripheral blood stem cells in acute myeloid leukemia
Hematol. Oncol.
(2007)