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A comparative study of reduced dose alemtuzumab in matched unrelated donor and related donor reduced intensity transplants.
Br J Haematol. 2015 Mar; 168(6):874-81.BJ

Abstract

In vivo T cell depletion with 100 mg alemtuzumab prevents graft-versus-host disease (GVHD) in reduced intensity conditioned transplants but is associated with delayed immune reconstitution, a higher risk of infection and relapse. De-escalation studies have shown that a reduced dose of 30 mg is as effective as 100 mg in preventing GVHD in matched related donor (MRD) transplants. Dose reduction in matched unrelated donor (MUD) transplants is feasible but the comparative efficacy of alemtuzumab in this setting is not known and opinions vary widely concerning the optimal level of GVHD prophylaxis that should be achieved. Through retrospective analysis we made an objective comparison of MUD transplants receiving an empirically reduced dose of 60 mg, with MRD transplants receiving a 30 mg dose. We observed proportionate levels of alemtuzumab according to dose but an inverse relationship with body surface area particularly in MRD transplants. MUD transplants experienced more acute and chronic GVHD, higher T cell chimerism, more sustained use of ciclosporin and less need for donor lymphocyte infusion than MRD transplants. Thus, doubling the dose of alemtuzumab to 60 mg did not provide equivalent prevention of GVHD after MUD transplant although there was no difference in non-relapse mortality or survival compared with MRD transplants.

Authors+Show Affiliations

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK; Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25640315

Citation

Jardine, Laura, et al. "A Comparative Study of Reduced Dose Alemtuzumab in Matched Unrelated Donor and Related Donor Reduced Intensity Transplants." British Journal of Haematology, vol. 168, no. 6, 2015, pp. 874-81.
Jardine L, Publicover A, Bigley V, et al. A comparative study of reduced dose alemtuzumab in matched unrelated donor and related donor reduced intensity transplants. Br J Haematol. 2015;168(6):874-81.
Jardine, L., Publicover, A., Bigley, V., Hale, G., Pearce, K., Dickinson, A., Jackson, G., & Collin, M. (2015). A comparative study of reduced dose alemtuzumab in matched unrelated donor and related donor reduced intensity transplants. British Journal of Haematology, 168(6), 874-81. https://doi.org/10.1111/bjh.13239
Jardine L, et al. A Comparative Study of Reduced Dose Alemtuzumab in Matched Unrelated Donor and Related Donor Reduced Intensity Transplants. Br J Haematol. 2015;168(6):874-81. PubMed PMID: 25640315.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A comparative study of reduced dose alemtuzumab in matched unrelated donor and related donor reduced intensity transplants. AU - Jardine,Laura, AU - Publicover,Amy, AU - Bigley,Venetia, AU - Hale,Geoff, AU - Pearce,Kim, AU - Dickinson,Anne, AU - Jackson,Graham, AU - Collin,Matthew, Y1 - 2015/01/29/ PY - 2014/07/23/received PY - 2014/10/15/accepted PY - 2015/2/3/entrez PY - 2015/2/3/pubmed PY - 2015/5/15/medline KW - T cell depletion KW - bone marrow transplantation KW - graft-versus-host disease SP - 874 EP - 81 JF - British journal of haematology JO - Br J Haematol VL - 168 IS - 6 N2 - In vivo T cell depletion with 100 mg alemtuzumab prevents graft-versus-host disease (GVHD) in reduced intensity conditioned transplants but is associated with delayed immune reconstitution, a higher risk of infection and relapse. De-escalation studies have shown that a reduced dose of 30 mg is as effective as 100 mg in preventing GVHD in matched related donor (MRD) transplants. Dose reduction in matched unrelated donor (MUD) transplants is feasible but the comparative efficacy of alemtuzumab in this setting is not known and opinions vary widely concerning the optimal level of GVHD prophylaxis that should be achieved. Through retrospective analysis we made an objective comparison of MUD transplants receiving an empirically reduced dose of 60 mg, with MRD transplants receiving a 30 mg dose. We observed proportionate levels of alemtuzumab according to dose but an inverse relationship with body surface area particularly in MRD transplants. MUD transplants experienced more acute and chronic GVHD, higher T cell chimerism, more sustained use of ciclosporin and less need for donor lymphocyte infusion than MRD transplants. Thus, doubling the dose of alemtuzumab to 60 mg did not provide equivalent prevention of GVHD after MUD transplant although there was no difference in non-relapse mortality or survival compared with MRD transplants. SN - 1365-2141 UR - https://www.unboundmedicine.com/medline/citation/25640315/A_comparative_study_of_reduced_dose_alemtuzumab_in_matched_unrelated_donor_and_related_donor_reduced_intensity_transplants_ L2 - https://doi.org/10.1111/bjh.13239 DB - PRIME DP - Unbound Medicine ER -