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In vivo Campath for the prevention of GvHD following allogeneic HSCT: effects of dose, schedule and antibody type

Bone Marrow Transplantation volume 34, pages 1101–1102 (2004)Cite this article

In their recent paper, Khouri et al1 reported on the efficacy of low-dose Alemtuzumab for the prevention of acute GvHD following allogeneic transplantation from predominantly sibling donors. The authors used a dose of 10 mg/day for 5 days given on days −7 to −3 prior to transplant. This paper raises the question of what is the optimal dose and scheduling of in vivo Alemtuzumab in this setting. We have previously reported on the use of an identical dose (50 mg) of pre-transplant Campath, using initially Campath IG and latterly the humanized antibody Campath 1H (Alemtuzumab) for the prevention of rejection and GvHD following allogeneic transplantation using BEAM or TBI/cyclophosphamide conditioning from both matched sibling and unrelated donors.2, 3 In both studies, Campath was given on days −5 to −1 at a dose of 10 mg/day (total dose 50 mg) followed by post-transplant cyclosporine and a short course of methotrexate (10 mg/m2 × 3). In both studies, the majority of patients did not develop acute GvHD and none developed >grade II disease. We recently extended these observations to a series of 65 patients receiving BEAM–Campath conditioning where the overall incidence of grade I/II GvHD was 17.2% with no patients developing >grade II disease.4 In 46 patients receiving unrelated donor transplants with TBI and cyclophosphamide conditioning combined with pre-transplant Campath 1G or 1H, a recent update has shown an overall incidence of grade I/II GvHD of 26%, with 24% of patients developing predominately limited chronic GvHD.5 Certainly this dose and schedule of pre-transplant Campath is highly effective in the prevention of both acute and chronic GvHD following sibling and unrelated donor transplantation, using conventional and reduced-intensity conditioning. Other groups have used higher doses of Alemtuzumab (total dose 100 mg) given on days −8 to −4 (20 mg/day) with reduced-intensity conditioning.6 This regimen also proved highly effective in the prevention of acute and chronic GvHD with low transplant-related mortality in both the sibling and unrelated donor transplant setting.6, 7 However, with this dose of Alemtuzumab both delayed immune reconstitution and a high risk of post-transplant CMV infection have been reported.8 Furthermore, in patients receiving BEAM–Campath conditioning, we found that those patients receiving a total dose of 50 mg of Campath did not have a greater risk of developing GvHD than those receiving a total dose of 100 mg, suggesting that higher doses are not required at least with this schedule of administration (days −1 to −5).

The mechanism of action of pre-transplant Campath in preventing GvHD has generally been ascribed to the in vivo depletion of donor T cells by Campath circulating at the time of infusion and in the post-transplant period.6 Certainly some studies have detected significant levels of both Campath IG and IH2, 9 present at the time of stem cell infusion, which were capable of inducing a substantial degree of ADCC of infused donor T cells in the majority of patients. The negative effects of in vivo T-cell depletion including delayed immune reconstitution and a greater risk of disease relapse may be particularly apparent using Alemtuzumab, which has a significantly longer half-life than Campath IG (8 days vs 13 h).2, 9

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References

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  1. Department of Haematology, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK

    N H Russell & J L Byrne

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Russell, N., Byrne, J. In vivo Campath for the prevention of GvHD following allogeneic HSCT: effects of dose, schedule and antibody type. Bone Marrow Transplant 34, 1101–1102 (2004). https://doi.org/10.1038/sj.bmt.1704695

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