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196 Comparison of Matched-Sibling Donors Versus Unrelated Donors in Allogeneic Stem Cell Transplantation (allo-SCT) for Primary Refractory Acute Myeloid Leukemia (PRF AML): A Report of 1041 Patients from the Acute Leukemia Working Party of the EBMTClinically Relevant Abstract

Clinical Allogeneic Transplantation: Results
Program: Oral and Poster Abstracts
Type: Oral
Session: 732. Clinical Allogeneic Transplantation: Results: Matched Related, Unrelated, and Alternative Donor Allograft Outcomes for Myeloid and Lymphoid Malignancies
Sunday, December 6, 2015: 8:15 AM
W304, Level 3 (Orange County Convention Center)

Eolia Brissot, MD.PhD1*, Myriam Labopin, MD2*, Matthias Stelljes3, Gerhard Ehninger, MD4, Gernot Stuhler, MD5*, Jurgen Finke, M.D.6, Hans Jochem Kolb, member7, Arnold Ganser, M.D.8, Kerstin Schaefer-Eckart, MD9, Nicolaus Kroeger, MD10, Donald Bunjes, MD11*, Stephan Mielke, MD12, Wolfgang Bethge, MD13*, Reza Tabrizi, MD14, Kalhs Peter15*, Igor W Blau, MD, PhD16*, Bertran Glass17*, Antonin Vitek18*, Martin Gramatzki, MD19, Ernst Holler, PhD20*, Christoph Schmid21*, Jordi Esteve22, Arnon Nagler, MD, MSc23 and Mohamad Mohty, MD, PhD24

1Service d’Hématologie et Thérapie Cellulaire, Hôpital Saint-Antoine, Paris, France
2Department of Hematology and Cell Therapy, Saint Antoine Hospital, Paris, France
3Department of Medicine A/Hematology and Oncology, University of Münster, Münster, Germany
4Medical Dept. 1, University Hospital TU Dresden, Dresden, Germany
5Zentrum für Blutstammzell- und Knochenmarktransplantation, DKD Helios Klinik Wiesbaden, Wiesbaden, Germany
6Hematology, Oncology and Stem Cell Transplantation, University of Freiburg, Freiburg, Germany
7Dept for Hematopoetic Transplantations, MED3, University of Munich, Munich, Germany
8Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
9Department of Hematology and Oncology, Klinikum Nuernberg, Nuernberg, Germany
10Department of Stem Cell Transplantation, University Hospital of Hamburg, Hamburg, Germany
11Department of Internal Medicine III, University of Ulm, Ulm, Germany
12Zentrum Innere Medizin (ZIM), Abteilung Hämatologie und Onkologie, Universitätsklinikum Würzburg, Wurzburg, Germany
13Department of Hematology and Oncology, University of Tuebingen, Tuebingen, Germany
14Hematology, University Hospital of Bordeaux, Pessac, France
15Department of Internal Medicine I, Bone Marrow Transplantation Unit, Medical University of Vienna, vienna, Austria
16Department of Internal Medicine III, Charité Campus Benjamin Franklin, Berlin, Germany
172AsklepiosKlinik St. Georg, AbteilungHämatologie und Stammzelltransplantation, Hambourg, Germany
18Dept. of Hematology, Institute of Hematology and Blood Transfusion, PRAGUE, Czech Republic
19Department of Medicine, University Hospital Schleswig-Holstein Division of Stem Cell Transplantation and Immunotherapy, Kiel, Germany
20Abteilung Hamatologie/Intern.Onkologie, Klinikum der Universitat Regensburg, Regensburg, Germany
212. Medizinische Klinik, Klinikum Augsburg, Augsburg, Germany
22Hospital Clinic de Barcelona, Spanish MDS Cooperative Group, Barcelona, Spain
23Chaim Sheba Medical center and EBMT Acute Leukemia Working Party, Tel-Hashomer and Paris, Israel
24Hematology Department, Saint-Antoine Hospital, AP-HP, Universite Pierre et Marie Curie, Paris, France

Background: PRF-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 strategy. The increased availability of unrelated donors (UD) together with 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). Because of the high risk of allo-SCT in this setting, there are still questions on the patient outcome depending on the donor type.  

Aims :

The current study aimed to compare the outcomes of allo-SCT from matched sibling donors (MSD) (n=660) vs UDs (n=381), for patients with PRF AML.

Methods:

 The major endpoints were to assess overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and non relapse mortality (NRM).

Results:

660 patients received a MSD, 296 patients a matched UD (10/10) and 85 a mismatched UD (9/10), respectively. Median age was higher in the UD group (50.5 yrs (18-74) vs 47.7 yrs (18-74), p=0.006). The median time from diagnosis to allo-SCT was similar (110 days [60-180] in the MSD group vs 111days [60-178] in the UD group; p=0.33). In the MSD allo-SCT, 57 % received a MAC regimen, 29% a RIC regimen, and 14% a sequential conditioning regimen; while, in the UD transplants, 44.4 % received a MAC regimen, 24.4% a RIC regimen, and 31.2%  a sequential conditioning regimen (p<10-4). Peripheral blood stem cell (PBSC) was the main stem cell source (92% in the MSD allo-SCT vs 94.8% in the UD allo-SCT, p=0.09). Median follow-up was statistically longer in the UD group than in the MSD group (19 months [range, 1.5-143] vs 16 months [2-153], respectively, p=0.04). In univariate analysis, LFS at 2 years was 25.3% in MSD group vs 28.3% in UD group (p=0.56) (Fig.1). In multivariate analysis, 2 predictive factors were associated with lower LFS: cytogenetics (poor vs intermediary; HR=1.61, 95%CI,1.24-2.09, p=0.0004) and time from diagnosis to transplant (above the median 110 days)(HR=1.21, 95%CI,1.02-1.44, p=0.03), whereas Karnofsky status at transplant ≥90% (KS) was associated with better LFS (HR=0.67, 95%CI,0.56-0.80, p=0.0001). In univariate analysis, OS at 2 years was comparable in both groups (30.9% in MSD group vs 34.3% in UD group (p=0.57)) (Fig2). In multivariate analysis, 4 predictive factors were associated with lower OS: age>50 yrs, cytogenetics, time from diagnosis to transplant and CMV positive status whereas Karnofsky status at transplant ≥90% (KS) was associated with better OS. 71% patients with a MSD and 68.6% patents with an UD reached CR after allo-SCT (p=0.73). In univariate analysis, RI at 2 years was 53.7% in MSD group and 56.4% in UD group, respectively (p=0.038). In multivariate analysis for RI, cytogenetics and time from diagnosis to transplant were  the only risk factors associated with increased relapse [(HR=1.74, 95%CI,1.30-2.33, p=0.0002) (HR=1.29, 95%CI,1.06-1.58, p=0.01), respectively] whereas KS was a protective factor (HR=0.77, 95%CI,0.62-0.95, p=0.01). The incidence of aGVHD≥2 was higher in UD group (35.5% vs 27.9%, p=0.012). At 2 years , the cumulative incidence of chronic GVHD (cGVHD) was not statistically different between MSD and UD (28.9% and 25.8%, respectively, p=0.56) (univariate analysis).  As for, NRM at 2 years, there was not statistical difference between MSD and UD groups (21% vs 25.1%, p=0.112). In multivariate analysis, patient age (>50 yrs) and CMV positive status were factors associated with higher NRM (HR=1.77, 95%CI, 1.27-2.47, p=0.001; HR=1.68, 95%CI, 1.14-2.47, p=0.008), while RIC regimen compared to MAC regimen was the only factor associated with lower NRM (HR=0.59, 95%CI, 0.41-0.85, p=0.005).

Conclusion

Allo-SCT may rescue one third of patients with primary refractory AML. Importantly, the donor type did not have any impact on PRF patients' outcomes. In contrast, time to transplant was a major prognostic factor for LFS and OS. For patients with PRF AML, that do not have a matched sibling donor, allo-HST from UD  is  a suitable option and thus initiation of an early  search and allocating of a suitable donor is therefore  indicated.

Disclosures: Finke: Riemser: Research Funding , Speakers Bureau ; Neovii, Novartis: Consultancy , Research Funding , Speakers Bureau ; Medac: Research Funding . Esteve: Celgene: Consultancy , Honoraria ; Janssen: Consultancy , Honoraria . Mohty: Janssen: Honoraria ; Celgene: Honoraria .

*signifies non-member of ASH