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155 Reduced-Intensity Versus Myeloablative Conditioning for Unrelated Cord Blood Transplantation in Adults with Acute Leukemia: A Report from Eurocord, the Acute Leukemia Working Party and the Cord Blood Committee of the Cellular Therapy & Immunobiology Working Party of the European Group for Blood and Marrow Transplantation

Clinical Allogeneic Transplantation: Results
Program: Oral and Poster Abstracts
Type: Oral
Session: 732. Clinical Allogeneic Transplantation: Results II
Saturday, December 5, 2015: 5:00 PM
W304, Level 3 (Orange County Convention Center)

Frederic Baron, MD, PhD1, Ruggeri Annalisa, MD2*, Eric Beohou3*, Myriam Labopin, MD4*, Guillermo Sanz, MD, PhD5, Noel Milpied6, Mauricette Michallet, MD, PhD7, Andrea Bacigalupo, MD8, Gerard Socie9, Didier Blaise10, Jorge Sierra11, Jan Cornelissen, MD, PhD12, Mohamad Mohty, MD, PhD13, Christoph Schmid, MD14, Sebastian Giebel, MD, PhD15*, Norbert Claude Gorin, Pr, MD, PhD16, Jordi Esteve, MD, PhD17, Fabio Ciceri, MD18*, Bipin N. Savani, MD19, Eliane Gluckman, MD20 and Arnon Nagler, MD, MSc4,21

1Hematology and GIGA Research, CHU Sart Tilman, Liege, Belgium
2Eurocord, Hospital Saint Louis, AP-HP, and IUH University Paris VII, Paris, France
3EBMT Paris Office, Hospital Saint Antoine, Paris, France
4EBMT, Acute Leukemia Working Party, Paris, France
5Hospital Universitario La Fe, Spanish MDS Cooperative Group, Valencia, Spain
6Service d’Hematologie Clinique et Therapie Cellulaire, CHU Haut-Lévêque, Bordeaux, France
7Department of Hematology, Centre Hospitalier Lyon-Sud, Lyon, France
8Ospedale S. Martino, Genova, Italy
9St-Louis Hospital, Paris, France
10Department of Hematology, Institut Paoli Calmettes, Marseille, France
11Department of Hematology, Hospital de la Santa Creu i Sant Pau. Universitat Autònoma de Barcelona, Barcelona, Spain
12Department of Hematology, Erasmus MC-Daniel den Hoed Cancer Centre, Rotterdam, Netherlands
13Hematology Department, Saint-Antoine Hospital, AP-HP, Universite Pierre et Marie Curie, Paris, France
14Ludwig-Maximilians-University of Munich, Germany, Department of Hematology and Oncology, Klinikum Augsburg, Augsburg, Germany
15Dept. of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland
16Hematology-cell therapy and EBMT, Hopital Saint-Antoine and Universite Pierre et Marie Curie UPMC, Paris, France
17Hematology, Hospital Clínic, IDIBAPS, Barcelona, Spain
18Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
19Department of Medicine, Division of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN
20Eurocord International Registry, Paris, France
21Hematology Division, Chaim Sheba Medical Center and Tel Aviv University, Tel-Hashomer, Ramat-Gan, Israel

BACKRGOUND. Non-relapse mortality (NRM) is the first cause of treatment failure after unrelated cord blood transplantation (UCBT) following myeloablative conditioning (MAC). In the last decade, reduced-intensity conditionings (RIC) for UCBT have been developed with the aim of reducing NRM and allowing older patients and those with medical comorbidities to benefit from UCBT. The aim of our retrospective registry study was to compare outcomes of acute leukemia (AL) adult patients given UCBT after either RIC or MAC regimens. Regimens were classified as MAC or RIC based on EBMT criteria.

PATIENTS AND METHODS. Data from 1352 adult (> 18 yrs) patients with AL (acute myeloid leukemia [AML; n=894] or acute lymphoblastic leukemia [ALL; n=458]) given a first single or double UCBT from 2004 to 2013 at EBMT-affiliated centers were included in this retrospective study.  

RESULTS. 518 patients were given UCB after RIC, while 834 patients were administered MAC. The most frequently used conditioning regimens combined either TBI, cyclophosphamide and Flu (TCF regimen, given in 22% of MAC vs 75% of RIC recipients, P<0.001), or thiotepa, Bu and Flu (TBF, given in 32% of MAC vs 6% of RIC recipients, P<0.001). In comparison to MAC recipients, RIC recipients were almost 2 decades older (median age 52.5 vs 33.7 yrs, P<0.001), were more often transplanted for AML (80% vs 57%, P=0.001), received more frequently 2 cord blood units (61 vs 32%, P<0.001), received more frequently units with > or = 2 HLA-mismatches (69% vs 58%, P<0.001), received more TNC (median 3.5x10E7 vs 2.9x10E7, P<0.001), and received less frequently ATG in the conditioning (23% versus 57%).  Disease status at UCBT was comparable in both groups (51% of patients in CR1 and 17% >CR). Median follow-up for survivors was 25 months. In univariate analyses, in comparison to patients given MAC, RIC recipients had a similar rate of neutrophil engraftment (89.5 vs 89%, P=0.7), and a similar incidence of grade II-IV acute (34% vs 29%, P=0.1) and chronic (22% vs 26%, P= 0.22) GVHD. In contrast, at 2-yr, RIC recipients had a higher incidence of disease relapse (41 vs 24%, P<0.001) but a lower NRM (19 vs 37%, P<0.001), translating to similar leukemia-free survival (LFS, 40% vs 38%, P=0.6) but better overall survival (OS, 47 vs 42%, P=0.01) than MAC recipients (Figure 1). Further, among ALL patients, the use of TCF regimen (n=159) was associated lower NRM (21 vs 40% at 2-yr, P<0.001), lower relapse incidence (24 vs 34%, P=0.07), and better OS (63 vs 34%, P<0.001) and LFS (55 vs 27%, P<0.001). We performed separate multivariate analyses (MVA) for patients with AML and ALL. In MVA for AML patients, the use of RIC regimen was associated with a higher incidence of relapse (HR=1.6, P=0.005) but a suggestion for lower NRM (HR=0.7, P=0.1) translating to similar OS (HR=1.0, P=0.9) and LFS (HR=1.1, P=0.3). Similarly, in MVA for ALL patients, the use of RIC regimen was associated with a higher incidence of relapse (HR=2.0, P=0.002) but a lower NRM (HR=0.6, P=0.04) translating to similar OS (HR=0.8, P=0.2) and LFS (HR=1.1, P=0.5). Further, interestingly, conditioning with TCF-based regimen was associated with a lower incidence of relapse (HR=0.5, P=0.004) translating into better OS (HR=0.6, P=0.013) and LFS (HR 0.6, P=0.002) in ALL patients in MVA adjusted for conditioning intensity (RIC vs MAC).

CONCLUSIONS. These data suggest that LFS and OS might be as good with RIC than with MAC in adults AL patients offered UCBT. These observations could serve as basis for future prospective randomized studies.

Figure 1. Unadjusted UCBT outcomes in patients transplanted following RIC versus MAC.

Disclosures: Milpied: Celgene: Honoraria , Research Funding . Sierra: Amgen: Research Funding ; Novartis: Research Funding ; Celgene: Research Funding . Mohty: Janssen: Honoraria ; Celgene: Honoraria . Schmid: Neovii: Consultancy ; Janssen Cilag: Other: Travel grand .

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