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UNRELATED DONOR (UD) ALLOGENEIC STEM CELL TRANSPLANTATION (ALLO-SCT) IN PRIMARY REFRACTORY ACUTE MYELOID LEUKEMIA (AML): REPORT OF 381 PATIENTS FROM THE ACUTE LEUKEMIA WORKING PARTY OF EBMT
Author(s): ,
Eolia Brissot
Affiliations:
Hematologie,Service d’Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, APHP, Paris, France,PARIS,France
,
Myriam Labopin
Affiliations:
Service d’Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, APHP, Paris, France,PARIS,France
,
Matthias Stelljes
Affiliations:
Department of Medicine A/ Hematology and Oncology, University of Muenster,Muenster,Germany
,
Gerhard Ehninger
Affiliations:
Universitaetsklinikum, Medizinische Klinik und Poliklinik,Dresden,Germany
,
Rainer Schwerdtfeger
Affiliations:
Deutsche Klinik für Diagnostik, KMY, Zentrum,Wiesbaden,Germany
,
Axel R. Zander
Affiliations:
University Hospital Eppendorf, Bone Marrow Transplantation Center,Hamburg,Germany
,
Stephan Mielke
Affiliations:
Department of Internal Medicine II, Würzburg University Medical Center,Würzburg,Germany
,
Arnold Ganser
Affiliations:
Hannover Medical University, Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation,Hannover,Germany
,
Jürgen Finke
Affiliations:
Department of Medicine-Hematology, Oncology, University of Freiburg,Freiburg,Germany
,
Kerstin Schufer-Eckart
Affiliations:
Klinikum Nurnberg, BMT-Unit,Nurnberg,Germany
,
Donald Bunjes
Affiliations:
Klinik fuer Innere Medzin III, Universtätklinikum,Ulm,Germany
,
Nicolaus Kröger
Affiliations:
University Hospital Hamburg-Eppendorf,Hamburg,Germany
,
Christoph Schmid
Affiliations:
Medzinische Klinik Klinikum,Augsburg,Germany
,
Wolfgang A. Bethge
Affiliations:
Medical Department, Hematology and Oncology, University of Tuebingen,Tuebingen,Germany
,
Hans-Jochem Kolb
Affiliations:
Klinikum Grosshadern, Med. Klinik III,Munich,Germany
,
Igor-Wolgang Blau
Affiliations:
Charite-Campus Benjamin Franklin Universitaetsmedizin Berlin Klinik III- Hematologie u Onkologie,Berlin,Germany
,
Antonin Vitek
Affiliations:
Department of Clinical Hematology, Institute of Hematology and Blood Transfusion,Prague,Czech Republic
,
Tilmann Bochtler
Affiliations:
Department of Internal Medicine V, University of Heidelberg,Heidelberg,Germany
,
Ralf G. Meyer
Affiliations:
University Medical Center Mainz,Mainz,Germany
,
Ernst Holler
Affiliations:
Department of Haematology/oncology, University Hospital Regensburg,Regensburg,Germany
,
Jordi Esteve
Affiliations:
Hospital Clinic Institut d'investigacions Biomèdiques August Pi i Sunyer,Barcelona,Spain
,
Arnon Nagler
Affiliations:
Chaim Sheba Medical Center,Tel Hasomer,Israel
Mohamad Mohty
Affiliations:
Service d’Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, APHP,Paris,France
EHA Library. Brissot E.
Jun 12, 2015; 103119
Disclosure(s): Service d’Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint Antoine, APHP, Paris, France
Hematologie
Eolia Brissot
Eolia Brissot
Contributions
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Abstract
Abstract: S128

Type: Oral Presentation

Presentation during EHA20: From 12.06.2015 12:00 to 12.06.2015 12:15

Location: Room Lehar 1 + 2

Background
Primary refractory AML is associated with a dismal prognosis. Approximately one third of patients younger than 60 years, and 50 % of older patients, with newly diagnosed AML fail to achieve complete remission (CR) with standard induction chemotherapy. Allo-SCT in the setting of active disease is an alternative but highly debatable strategy. The increased availability of UD and the use of reduced-intensity conditioning (RIC) regimens have opened the possibility for transplantation to a larger number of patients in comparison to standard myeloablative regimens (MAC)

Aims
The current study aimed to assess outcomes in a cohort of 381 primary refractory AML patients who received allo-SCT from an UD (10/10 or 9/10). Primary refractoriness was defined as failure to achieve CR within 60 days after starting induction.

Methods
Patients with primary refractory AML reported between 2000 and 2013 to the registry of the Acute Leukemia Working Party of the EBMT were included in this study. The major endpoints were to assess overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and non relapse mortality (NRM).

Results
Median age was 50.5 (range, 18-74) years and 56% were males. Median time from diagnosis to allo-SCT was 111 (range, 60-178) days. 51 % received a MAC regimen, and 49% a RIC regimen. Peripheral blood stem cell (PBSC) was the main stem cell source (94.8%). The median follow-up was 18 months(range, 1.2-153). 296 patients received a matched UD (10/10) and 85 a mismatched UD (9/10). Engraftment was achieved in 95.2% of cases. 70.4% patients reached CR after allo-SCT. At 2 years, the cumulative incidences of acute GVHD≥2 and chronic GVHD (cGVHD) were 35.5% and 25.8%, respectively. At 2 years, OS and LFS rates were 34.3% and 28.3%. RI was 46.4% and NRM 25.1%. In multivariate analysis, 2 predictive factors were associated with lower OS: cytogenetics (poor vs intermediary; HR=2.00, 95%CI,1.25-3.18, p=0.004) and positive CMV status of the recipient (HR=1.52, 95%CI,1.09-2.11, P=0.01), whereas Karnofsky status at transplant ≥80% (KS) was associated with better OS (HR=0.65, 95%CI,0.43-0.98, p=0.04) (Fig1). The same factors were predictive for LFS: cytogenetics (HR=1.86, 95%CI,1.19-2.92, p=0.01) and positive CMV status of the recipient (HR=1.46, 95%CI, 1.07-1.99, p=0.02) were negative predictive factors, whereas KS was a positive one (HR=0.61, 95%CI,0.41-0.91, p=0.02). In multivariate analysis for RI, cytogenetics was the only risk factor associated with increased relapse (HR=1.92, 95%CI,1.15-3.19, p=0.001). As for NRM, patient gender (female vs male) and KS were factors associated with lower NRM (HR=0.49, 95%CI,0.29-0.84, p=0.01; HR=0.41, 95%CI,0.22-0.76, p=0.004), while CMV positive status was the only factor associated with higher NRM (HR=1.96, 95%CI=1.11-3.43, p=0.02). 

Summary
Unrelated donor transplantation (10/10 or 9/10) may rescue about one third of the patients with primary refractory AML. Moreover, this study identifies cytogenetics, KS, and CMV status as major prognostic factors. Finally, these data pave the way not only for improving  patients’ selection, but also for investigating more intensive additional approaches relying on sequential conditioning regimens (debulking phase followed by RIC) and/or post-transplant treatments such as 5-azacytidine, prophylactic donor lymphocytes infusions, or targeted therapy which further improve results in this devastating group of patients.

Keyword(s): Acute myeloid leukemia, Allo-SCT, Clinical outcome, Prognostic factor



Session topic: Stem cell transplantation: Clinical 1
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