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Excellent outcome with a high proportion of mixed chimerism in patients with severe aplastic anemia treated with partially T-cell-depleted peripheral hematopoietic stem cell transplants

Bone Marrow Transplantation volume 51, pages 860–862 (2016)Cite this article

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The outcome of hematopoietic stem cell transplantation (HSCT) in patients with severe aplastic anemia (SAA) has improved considerably over the last few decades,1 but graft rejection rates at 10–15%, acute GvHD grade II–IV rates at 11–26% and, particularly, chronic GvHD rates at 30% remain important challenges.2, 3 Optimal transplantation strategies for patients undergoing HSCT from an HLA-matched sibling donor (MSD) are considered to be conditioning with cyclophosphamide (CY) and ATG, cyclosporin-A (CsA) and short-term methotrexate as GvHD prophylaxis and bone marrow (BM), as a stem cell source given lower GvHD risks.4 However, the advantage of BM over PBSC may be less evident when modulated in vitro T-cell depletion is used. Here we report a series of 12 patients transplanted for SAA at the Bone Marrow Transplant Unit of the Geneva University Hospital with T-cell depleted PBSC followed by a T-cell add-back the next day. We report the incidence of post-transplant infections and an analysis of the hematopoietic chimerism associated with a low incidence of both acute and chronic GvHD, sustained engraftment and excellent long-term survival.

We retrospectively evaluated 12 consecutive patients with acquired SAA receiving first transplants from an MSD or HLA-matched unrelated donors after a conditioning regimen consisting of CY and ATG with partially T-cell-depleted PBSC from 1997 to 2015. All patients provided written informed consent. The stem cell source was G-CSF-mobilized peripheral blood of which a part was T-cell depleted with 20 mg of alemtuzumab (CAMPATH-1H (Genzyme Corporation, Cambridge, MA, USA)) in vitro for infusion at day 0, whereas the rest, containing 100 × 106 CD3+ cells/kg, was given as a T-cell add-back at day 1.5 GvHD prophylaxis consisted of CsA, titrated to trough levels between 150 and 200 μg/L and continued for at least 12 months post HSCT in combination with a short course of methotrexate.

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Authors and Affiliations

  1. Division of Hematology, Stem Cell and Bone Marrow Transplant Centre, Geneva’s University Hospitals and University of Geneva Faculty of Medicine, Geneva, Switzerland

    S Masouridi-Levrat, F Simonetta, Y Beauverd, O Tsopra, Y Tirefort, C Stephan, M Ansari, E Roosnek & Y Chalandon

  2. Department of Hemato-oncology, Hôpital Fribourgeois, Fribourg, Switzerland

    E Levrat

  3. Sanofi-Aventis, Vernier, Switzerland

    F Verholen

  4. Division of Hematology, Basel University Hospital, Basel, Switzerland

    J R Passweg

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  1. S Masouridi-Levrat
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Correspondence to Y Chalandon.

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Masouridi-Levrat, S., Simonetta, F., Beauverd, Y. et al. Excellent outcome with a high proportion of mixed chimerism in patients with severe aplastic anemia treated with partially T-cell-depleted peripheral hematopoietic stem cell transplants. Bone Marrow Transplant 51, 860–862 (2016). https://doi.org/10.1038/bmt.2015.356

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