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Transplantation of CD34+ enriched allografts in children with nonmalignant diseases: does graft manipulation necessarily result in high incidence of graft failure?

Bone Marrow Transplantation volume 33, pages 125–126 (2004)Cite this article

In a recent paper in BMT, McDonough et al1 reported their results with transplantation of CD34+ augmented elutriated allografts in children. An important finding was that patients with nonmalignant diseases had a remarkably high risk for graft failure. Our own experience was different in such patients,2 and we believe that an analysis of the differences between both therapeutical approaches may be of interest. The study of McDonough et al comprised 40 children with leukemias and 14 children with nonmalignant diseases (thalassemia, severe combined immunodeficiency (SCID), adrenoleukodystrophy (ALD), Fanconi anemia, congenital pancytopenia and autoimmune disease). The patients had received T-cell depleted bone marrow from matched related (n=18), mismatched related (n=10), matched unrelated (n=20) and one antigen mismatched unrelated donors (n=6). Counter flow centrifugal elutriation followed by CD34+ selection (Ceprate system) of the elutriated small lymphocyte fraction was used for graft manipulation. A mean number of 4.7 × 106 CD34+ cells/kg of body weight and 6.3 × 105 residual T cells/kg of bodyweight were transplanted. In patients with nonmalignant diseases, the authors stated a clearly higher incidence of graft failure (8/14 patients, 57%). Four out of eight patients could be rescued by DLIs or a second BMT. The authors conclude that, for children with nonmalignant diseases, it will be necessary to increase the immune ablation of the preparative regimen and/or to improve post transplant immune suppression in order to prevent graft failure.

In our patients, a lower incidence of graft failure was observed. A similar patient group with various nonmalignant diseases (severe aplastic anemia, thalassemia, sickle cell disease, Diamond–Blackfan anemia, SCID, Wiskott–Aldrich syndrome, ALD, osteopetrosis, porphyria, polycythemia vera rubra and lymphohistiocytosis) has been transplanted with purified CD34+ stem cells in our institution.2 Four patients had matched related donors and 21 patients had unrelated or mismatched related donors. In contrast to McDonough et al, stem cell selection was carried out in our study with anti-CD34 mAb-coated magnetic microbeads (Miltenyi Biotec). Moreover, G-CSF-stimulated apheresis products were used instead of bone marrow. With this approach, a median number of 12.9 (3.4–40) × 106 CD34+/kg bodyweight could be obtained for transplantation, which was markedly higher than the amount of stem cells given by McDonough et al. T cells were depleted to a higher extent and the median number of residual T cells was approximately one-hundredth (6.1 (0.3–26) × 103/kg bodyweight) of the T-cell dose given by McDonough et al. Another difference was that our conditioning regimen routinely comprised ATG or OKT3, and that no further post transplant immunosuppression was administered (Table 1). Moreover, chimerism was assessed weekly in peripheral blood samples and low doses of donor T cells (starting at 2.5 × 104/kg) were given to patients who showed decreasing donor chimerism, in order to maintain stable engraftment without causing GvHD.

Table 1 Comparison of therapeutic approaches
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References

  1. McDonough CH, Jacobsohn DA, Vogelsang GB et al. High incidence of graft failure in children receiving CD34+ augmented elutriated allografts for nonmalignant diseases. Bone Marrow Transplant 2003; 31: 1073–1080.

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  2. Lang P, Klingebiel T, Bader P et al. Transplantation of highly purified peripheral blood CD34+ progenitor cells from related and unrelated donors in children with nonmalignant diseases. Bone Marrow Transplant 2003; 32: 1630–1636, (1704303, should be in issue 12 or 12).

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  3. Handgretinger R, Klingebiel T, Lang P et al. Megadose transplantation of purified peripheral blood CD34(+) progenitor cells from HLA-mismatched parental donors in children. Bone Marrow Transplant 2001; 27: 777–783.

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  4. Lang P, Handgretinger R, Niethammer D et al. Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia. Blood 2003; 101: 1630–1636.

    Article  CAS  Google Scholar 

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  1. Department of Pediatric Oncology, University Children's Hospital, Eberhard Karl's Universität, Hoppe Seyler Strasse 1, Tübingen, D 72076, Germany

    P Lang, R Handgretinger, J Greil, P Bader, M Schumm, T Klingebiel & D Niethammer

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  1. P Lang
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Lang, P., Handgretinger, R., Greil, J. et al. Transplantation of CD34+ enriched allografts in children with nonmalignant diseases: does graft manipulation necessarily result in high incidence of graft failure?. Bone Marrow Transplant 33, 125–126 (2004). https://doi.org/10.1038/sj.bmt.1704348

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