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Research Papers:

High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia — an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Tomasz Czerw _, Myriam Labopin, Christoph Schmid, Jan J. Cornelissen, Patrice Chevallier, Didier Blaise, Jürgen Kuball, Stephane Vigouroux, Frédéric Garban, Bruno Lioure, Nathalie Fegueux, Laurence Clement, Anna Sandstedt, Johan Maertens, Gaëlle Guillerm, Dominique Bordessoule, Mohamad Mohty and Arnon Nagler

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Oncotarget. 2016; 7:27255-27266. https://doi.org/10.18632/oncotarget.8463

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Abstract

Tomasz Czerw1, Myriam Labopin2,3,4, Christoph Schmid5, Jan J. Cornelissen6, Patrice Chevallier7, Didier Blaise8, Jürgen Kuball9, Stephane Vigouroux10, Frédéric Garban11, Bruno Lioure12, Nathalie Fegueux13, Laurence Clement14, Anna Sandstedt15, Johan Maertens16, Gaëlle Guillerm17, Dominique Bordessoule18, Mohamad Mohty2,3,4,* and Arnon Nagler19,2,*

1 Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Gliwice, Poland

2 Clinical Hematology and Cellular Therapy Department, The Acute Leukemia Working Party of the EBMT office, Hopital Saint-Antoine APHP Paris, France

3 INSERM UMRs 938, Paris, France

4 Université Pierre et Marie Curie (UPMC, Paris VI), Paris, France

5 Klinikum Augsburg, University of Munich, Munich, Germany

6 Department of Hematology, Erasmus University medical center Cancer Institute, Rotterdam, The Netherlands

7 CHU Nantes, Dept. D`Hematologie, Nantes, France

8 Unité de transplantation et de thérapie cellulaire, Institut Paoli Calmettes, Marseille, France

9 University Medical Centre, Dept. of Haematology, Utrecht, The Netherlands

10 CHU Bordeaux, Hôpital Haut-leveque, Pessac, France

11 Hopital A. Michallon, Hématologie Clinique, Pole Cancérologie, Grenoble, France

12 Nouvel Hopital Civil, Strasbourg, France

13 CHU Lapeyronie, Département d`Hématologie Clinique, Montpellier, France

14 Hôpital de Brabois, Centre Hospitalier Universitaire (CHU) de Nancy, Vandoeuvres les Nancy, France

15 University Hospital, Dept. of Hematology, Linköping, Sweden

16 University Hospital Gasthuisberg, Dept. of Hematology, Leuven, Belgium

17 CHU Morvan, Brest, France

18 CHRU Limoges, Service d`Hématologie Clinique, Limoges, France

19 Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel

* These authors have contributed equally to this work

Correspondence to:

Tomasz Czerw, email:

Keywords: allogenic transplantation, stem cell transplantation, acute myeloid leukemia (AML), reduced-intensity conditioning, cell dose

Received: March 17, 2016 Accepted: March 23, 2016 Published: March 29, 2016

Abstract

Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, >347 x 10^6/kg and >8.25 x 10^6 /kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes.


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