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Post-transplant lymphoproliferative disorders following reduced intensity conditioning with in vivo T cell depletion

Bone Marrow Transplantation volume 31, pages 725–726 (2003)Cite this article

Ho et al1 raise the important issue of the risk of EBV-associated lymphoproliferation (PTLD) following reduced-intensity conditioning and whether patients undergoing these procedures should be routinely screened for EBV load following transplantation as a means of targeting those at greatest risk for their development. As they point out, T cell depletion is a risk factor for the development of PTLD, although the combined T and B cell depletion mediated by CAMPATH-1H (alemtuzumab) appears to be associated with a somewhat reduced risk compared to methods that selectively deplete T cells.2,3 However, T cell depleted reduced intensity regimens that also incorporate fludarabine can be associated with profound delays in reconstitution of antigen-specific immunity,4 reflected in a particularly high incidence of CMV reactivation.5 We have performed 100 reduced-intensity allografts (57 HLA-matched related, 34 HLA-matched and nine mismatched unrelated) using a conditioning protocol incorporating alemtuzumab 100 mg, fludarabine 150 mg/m2 and melphalan 140 mg/m2.6 The 100 day mortality was 13%. There were two cases of PTLD (2.3%) in the group of 87 patients who survived beyond the period historically associated with the highest risk of PTLD. The first was in a 44-year-old female transplanted for high-grade non-Hodgkin's lymphoma (NHL) from a fully HLA-matched unrelated donor. A tonsillar biopsy performed on day 147 confirmed the diagnosis (a high grade B cell infiltrate strongly positive for EBV LMP1 and with >90% Ki67 positivity). Rapid neurological deterioration occurred despite rituximab therapy and multiorgan involvement was revealed at post mortem. The second was in a 23-year-old male transplanted for transformed low-grade NHL from an HLA-identical sibling. The diagnosis was confirmed ona mesenteric lymph node biopsy performed on day 73 following the development of progressive respiratory impairment and demonstration of abdominal lymphadenopathy. Treatment with rituximab combined with unselected donor lymphocytes (1 × 106 CD3+ T cells/kg) resulted in resolution of the PTLD and the patient remains well with 206 days follow-up post-transplantation.

Two more patients developed PTLD following administration of antithymocyte globulin (ATG) for steroid-resistant graft-versus-host disease (GVHD) occurring after donor lymphocyte infusions (DLI) given for disease progression. The treatment of acute GVHD with T cell depleting antibodies is a recognised risk factor for PTLD and was reported to be associated with a 43.2-fold relative risk in a study of 18 014 patients from the IBMTR registry and Seattle.3,7 Both of our patients received DLI from HLA-identical siblings (day 250 and day 515). One was a 46-year-old male with relapsed Hodgkin's lymphoma and the other was a 53-year-old male with multiple myeloma. Both manifested as deterioration of liver function and increased diarrhoea following an initial improvement of biopsy-proven GVHD, and in both cases the diagnosis was made at post mortem. A total of eight patients have received ATG for GVHD following DLI with this reduced-intensity regimen. The incidence in this group (25%) therefore seems particularly high.

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  1. Department of Haematology, University College Hospital, 98 Chenies Mews, London, WC1E 6HX, UK

    K S Peggs, L Banerjee, K Thomson & S Mackinnon

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Peggs, K., Banerjee, L., Thomson, K. et al. Post-transplant lymphoproliferative disorders following reduced intensity conditioning with in vivo T cell depletion. Bone Marrow Transplant 31, 725–726 (2003). https://doi.org/10.1038/sj.bmt.1703893

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