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Non-myeloablative transplantation with CD8-depleted or unmanipulated peripheral blood stem cells: a phase II randomized trial

Leukemia volume 23, pages 608–610 (2009)Cite this article

Allogeneic hematopoietic cell transplantation (HCT) following non-myeloablative conditioning has been an effective treatment for many patients with malignancies. This approach relies on graft-versus-tumor effects for tumor eradication.1 Following non-myeloablative conditioning, acute graft-versus-host disease (GVHD) has not been associated with significant graft-versus-tumor effects, but has rather been associated with a high risk of non-relapse mortality,1 indicating that efforts aimed at decreasing the incidence of acute GVHD are needed. On the basis of previous studies suggesting that CD8 depletion of the graft could reduce the incidence of acute GVHD without apparently impairing graft-versus-tumor effects,2 and that CD8-depleted donor lymphocyte infusion (DLI) induced strong graft-versus-tumor effects with a low incidence of acute GVHD (<10%),3 we designed a phase II prospective randomized trial evaluating the impact of CD8 depletion of peripheral blood stem cells (PBSCs) on HCT outcomes after non-myeloablative conditioning. The protocol was approved by the local Ethics Committee, and written informed consent was obtained from each patient. The trial started in March 2002, and the study was retrospectively registered in ClinicalTrials.gov (protocol no. NCT00693927) in June 2008. Immune recovery in these patients has been previously reported.4

After being stratified for donor type, patients were randomized 1:1 between the ‘unmanipulated’ (n=28) and ‘CD8-depleted’ (n=25) arms. Conditioning regimen consisted of 2 Gy total body irradiation with or without fludarabine (90 mg/m2). Postgrafting immunosuppression included cyclosporine plus mycophenolate mofetil. Clinical management and chimerism analyses were performed as reported earlier.4 In total, 23 patients received DLI for disease persistence or progression (1 in the unmanipulated group and 2 in the CD8-depleted group), or poor T-cell chimerism with or without persistent disease (12 in the unmanipulated group and 8 in the CD8-depleted group), including 5 patients in the unmanipulated group and 4 patients in the CD8-depleted group who received DLI preceded by 2 Gy total body irradiation as part of a prospective study evaluating this strategy to prevent graft rejection in patients with low donor T-cell chimerism levels. Results were analyzed as of 29 May 2008. Survival and progression-free survival were estimated using the Kaplan–Meier method. The incidences of acute and chronic GVHD, relapse and non-relapse mortality were calculated using cumulative incidence estimates as reported earlier.1 Patients who received DLI were censured for acute GVHD at the time of DLI, patients with graft rejection were censured at the time of graft rejection for GVHD analyses. Multivariate logistic regression models were fitted with the SAS LOGISTIC procedure (SAS Institute, Cary, NC, USA) for graft rejection and GVHD. Multivariate Cox models were fitted for analyzing progression-free and overall survivals, non-relapse mortality and relapse risk.

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References

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Acknowledgements

FB is a research associate and YB is the research director of the National Fund for Scientific Research (FNRS) Belgium. EW is the recipient of grant from FNRS-télévie. This study was supported by funds from: the FNRS, the fund Leon Fredericq and Anti-cancer Center at the University of Liège, and the Belgian Federation against Cancer.

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Author notes

  1. E Willems and F Baron: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology, Department of Medicine, University of Liège, Liège, Belgium

    E Willems, F Baron, E Baudoux, P Frère, C Bonnet, K Hafraoui, G Fillet & Y Beguin

  2. Department of Hematology, Giga-Research, University of Liège, Liège, Belgium

    E Willems, F Baron, A Gothot, G Fillet & Y Beguin

  3. CHU of Liège (CHU-Liège), Liège, Belgium

    E Willems, F Baron, E Baudoux, N Wanten, J-F Vanbellinghen, C Herens, A Gothot, P Frère, C Bonnet, K Hafraoui, G Fillet & Y Beguin

  4. Laboratory of Cell and Genetic Therapy, University of Liège, Liège, Belgium

    E Baudoux & N Wanten

  5. Department of Statistics, University of Liège, Liège, Belgium

    L Seidel

  6. Department of Genetics, CHU of Liège, Liège, Belgium

    J-F Vanbellinghen & C Herens

  7. Department of Laboratory Hematology, CHU of Liège, Liège, Belgium

    A Gothot

  8. Department of Hematology, Regional Hospital Pelzer la Tourelle, Verviers, Belgium

    G Vanstraelen

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  1. E Willems
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Correspondence to F Baron.

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Willems, E., Baron, F., Baudoux, E. et al. Non-myeloablative transplantation with CD8-depleted or unmanipulated peripheral blood stem cells: a phase II randomized trial. Leukemia 23, 608–610 (2009). https://doi.org/10.1038/leu.2008.248

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