A Retrospective Study of Alemtuzumab Level, T Cell Chimerism and Graft Versus Host Disease Using Intermediate Dose Alemtuzumab for Matched Related and Matched Unrelated Reduced Intensity Transplantation

• Published in: Blood 2009-11, Vol.114 (22), p.3333-3333
• Main Authors: Charlton, Andrew, Spence, Laura, Bigley, Venetia, Groves, Natasha, Hale, Geoff, Pagan, Sarah, Turner, Brie E, Jones, Gail, Jackson, Graham H, Dickinson, Anne M, Collin, Matthew
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V114.22.3333.3333

Abstract 3333 Poster Board III-221 Alemtuzumab (CAMPATH 1H) is a well established agent for effecting in vivo T cell depletion and prevention of GVHD in reduced intensity transplants. Many studies indicate that full dose alemtuzumab (100mg in 5 daily doses of 20mg) induces profound immunodeficiency, almost completely ablating GVHD in Fludarabine and Melphalan (FM) matched related donor (MRD) and matched unrelated donor (MUD) transplants. In contrast, FM conditioning alone exposes patients to a high burden of acute and chronic GVHD. Accordingly, many transplant centres have adopted policies of intermediate alemtuzumab dosing of 50mg or less. While the pharmacokinetics, rate of T cell engraftment and incidence of GVHD are well described using full dose alemtuzumab, much less is known about the in vivo action of alemtuzumab at intermediate doses. We report our experience of alemtuzumab at 30mg (day -2) for MRD and 60mg (30mg day -4 and day -2) for MUD transplants, which was adopted as standard GVHD prophylaxis for FM transplantation at our centre in 2006. We avoided giving alemtuzumab on day -1, since there is a steep drop in alemtuzumab level in the first 24 hours after infusion and the timing of stem cell infusion may vary considerably, especially with unrelated donor grafts. From May 2006 to May 2009, 24 patients received MRD and 27 patients received MUD transplants. Post transplant serum samples were available from 19 MRD transplants and 15 MUD transplants at day +1. In addition, day +3 samples were identified from 10 patients previously transplanted with 100mg alemtuzumab, 10 MUD receiving 60mg and 10 MRD transplants receiving 30mg. All patients gave consent for clinical follow up and post transplant serum sampling for research purposes, according to protocols approved by the local research ethics committee of Northumberland and North Tyneside. Alemtuzumab concentration was measured by a validated flow cytometry assay, as previously described. The mean (SEM) alemtuzumab concentration (micrograms/ml) on day +1 was 2.9 (0.3) after 30mg and 4.6 (0.6) after 60mg (t test p