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Early intervention with allogeneic hematopoietic cell transplantation during chemotherapy-induced aplasia in patients with high-risk acute myeloid leukemia

Leukemia volume 27, pages 2068–2072 (2013)Cite this article

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Allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment option for most adult patients with high-risk or relapsed acute myeloid leukemia (AML), with conventional conditioning being the standard-of-care consolidation therapy for patients with cytogenetically defined high-risk AML.1 Unfortunately, only 40–50% of patients in this category achieve a first complete remission (CR). The remaining patients experience refractory disease or early death that also applies for patients with relapsed AML. Novel strategies that allow earlier allogeneic HCT could lead to a higher number of patients being sufficiently transplanted before refractory disease develops and, most importantly, before cumulative toxicities occur during induction and salvage therapy and render patients ineligible for allogeneic HCT. In addition, reduced-intensity conditioning (RIC) regimens can be administered in older patients with AML or those who present with a reduced performance status and in whom intensive conditioning procedures may be harmful and may facilitate the initiation of conditioning therapy as early as 5–10 days after the end of cytarabine-containing induction or salvage chemotherapy.1, 2, 3, 4 Different forms of RIC regimens have been administered showing feasibility, durable remission and acceptable transplant-related mortality.3, 5, 6, 7, 8, 9 Our intent-to-treat approach included allogeneic HCT during chemotherapy-induced aplasia after a maximal reduction of ‘leukemia burden’. We analyzed all sequential patients undergoing allogeneic HCT during chemotherapy-induced aplasia for primary refractory AML, high-risk or relapsed AML at our institution since the introduction of this novel concept.

We performed a retrospective, single-center cohort analysis in a study population comprising 95 patients with a median age of 52 years (range, 17–71 years). Inclusion criteria was AML diagnosis according to the current WHO criteria and first allogeneic HCT during chemotherapy-induced aplasia between December 1998 and March 2009. Patients with cord-blood, haploidentical and second allogeneic HCT were excluded from the analysis. The study was approved by the ethics committee of the Technical University Dresden and the institutional review board. Allogeneic HCT during chemotherapy-induced aplasia was performed in 65 patients with high-risk AML and in 30 patients with relapsed AML. High-risk AML was defined on the basis of cytogenetics, FLT3-ITD mutation status and blast clearance in the bone marrow on day 15 after initiation of induction chemotherapy as described recently.10 Therefore, of the 65 high-risk patients, 47 were primary refractory to induction chemotherapy and 18 patients were transplanted during chemotherapy-induced aplasia due to high-risk genetic features. Previously untreated patients were not included in this analysis. A total of 44 patients in this analysis were treated in the prospective, randomized, multicenter AML2003 trial of the Study Alliance Leukemia (SAL). Allogeneic HCT was part of the intensified therapy arm of the AML2003 trial as described recently.11 Of the 44 patients treated within the AML2003 trial, 21 patients were transplanted during chemotherapy-induced aplasia because of primary refractory disease, 12 patients were transplanted because of relapsed AML, whereas the remaining 11 patients were a priori included because of the underlying high-risk genetic features. The protocol was in accordance with the Helsinki Declaration and registered with the NCT numbers 00180102. Written informed consent was obtained from all patients.

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Acknowledgements

We wish to thank Catrin Theuser, Christian Klesse, Nils Dagenbach, and all nurses, data managers, and physicians within the ‘Study Alliance Leukemia’ who contributed to this analysis. The fast donor search was logistically supported by the ‘German Bone Marrow Donor Center’ (DKMS). Supported in part by a grant from the Deutsche Krebshilfe e.V. (German Cancer Aid), Bonn, Germany, Grant No. 70-2210-Eh5.

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Authors and Affiliations

  1. Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Dresden, Germany

    F Stölzel, U Platzbecker, B Mohr, C Röllig, J M Middeke, C Thiede, M Schaich, G Ehninger, J Schetelig & M Bornhäuser

  2. DKMS Life Science Lab Dresden, Dresden, Germany

    M Füssel

  3. Klinik für Innere Medizin III, Klinikum Chemnitz, Chemnitz, Germany

    M Hänel

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  1. F Stölzel
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  10. G Ehninger
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Correspondence to F Stölzel.

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Competing interests

MF holds employment at the DKMS Life Science Lab. The other authors declare no conflict of interest.

Additional information

This study was presented in part at the 35th Annual Meeting of the European Group for Blood and Marrow Transplantation, 29 March–1 April 2009, Gothenburg, Sweden.

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Stölzel, F., Platzbecker, U., Mohr, B. et al. Early intervention with allogeneic hematopoietic cell transplantation during chemotherapy-induced aplasia in patients with high-risk acute myeloid leukemia. Leukemia 27, 2068–2072 (2013). https://doi.org/10.1038/leu.2013.142

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