Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A prospective pilot study of a novel alemtuzumab target concentration intervention strategy


Alemtuzumab is used as part of reduced-intensity and reduced-toxicity transplant conditioning regimens for nonmalignant diseases. Prior studies identified an ideal target concentration range of 0.15–0.6 mcg/mL at day 0. However, only 24% of patients fall within this window using standard intermediate dosing. We performed a pilot study of a novel target concentration intervention strategy to target day 0 alemtuzumab concentrations to 0.15–0.6 mcg/mL. Twelve patients received model-informed alemtuzumab dosing of 0.5–0.6 mcg/kg divided over days –14 to –12. Alemtuzumab concentrations were measured, and pharmacokinetic (PK) modeling was performed on day –5 to predict day 0 concentrations. If the day 0 alemtuzumab concentration was predicted to fall below 0.15 mcg/mL, simulations were performed to identify the individual “top-up” dose needed to achieve the target day 0 concentration window. Six (50%) patients achieved day 0 alemtuzumab concentrations between 0.15 and 0.6 mcg/mL (4 received a top-up dose). Five patients had day 0 concentrations above the target window (no top-up doses). One patient had a day 0 concentration below the target range in the presence of anti-alemtuzumab antibodies. A concentration intervention strategy approach to alemtuzumab treatment can successfully target a greater proportion of patients into the ideal therapeutic window. Additional dose-reduction studies are needed to further optimize the initial dosing and achieve target attainment in all patients.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Day 0 alemtuzumab concentrations and pharmacokinetic modeling.


  1. 1.

    Chakraverty R, Orti G, Roughton M, Shen J, Fielding A, Kottaridis P. et al. Impact of in vivo alemtuzumab dose before reduced intensity conditioning and HLA-identical sibling stem cell transplantation: pharmacokinetics, GVHD, and immune reconstitution. Blood. 2010;116:3080–8.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Marsh RA, Kim MO, Liu C, Bellman D, Hart L, Grimley M. et al. An intermediate alemtuzumab schedule reduces the incidence of mixed chimerism following reduced-intensity conditioning hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis. Biol Blood Marrow Transpl. 2013;19:1625–31.

    CAS  Article  Google Scholar 

  3. 3.

    Gartner F, Hieke S, Finke J, Bertz H. Lowering the alemtuzumab dose in reduced intensity conditioning allogeneic hematopoietic cell transplantation is associated with a favorable early intense natural killer cell recovery. Cytotherapy. 2013;15:1237–44.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Lane JP, Evans PT, Nademi Z, Barge D, Jackson A, Hambleton S. et al. Low-dose serotherapy improves early immune reconstitution after cord blood transplantation for primary immunodeficiencies. Biol Blood Marrow Transpl. 2014;20:243–9.

    CAS  Article  Google Scholar 

  5. 5.

    Marsh RA, Lane A, Mehta PA, Neumeier L, Jodele S, Davies SM. et al. Alemtuzumab levels impact acute GVHD, mixed chimerism, and lymphocyte recovery following alemtuzumab, fludarabine, and melphalan RIC HCT. Blood. 2016;127:503–12.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Marsh RA, Fukuda T, Emoto C, Neumeier L, Khandelwal P, Chandra S. et al. Pretransplant Absolute Lymphocyte Counts Impact the Pharmacokinetics of Alemtuzumab. Biol Blood Marrow Transpl. 2017;23:635–41.

    CAS  Article  Google Scholar 

  7. 7.

    Morris EC, Rebello P, Thomson KJ, Peggs KS, Kyriakou C, Goldstone AH. et al. Pharmacokinetics of alemtuzumab used for in vivo and in vitro T-cell depletion in allogeneic transplantations: relevance for early adoptive immunotherapy and infectious complications. Blood. 2003;102:404–6.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Holford N, Ma G, Metz D. TDM is dead. Long live TCI! Br J Clin Pharmacol. 2020.

  9. 9.

    Dong M, Emoto C, Fukuda T, Arnold DE, Mehta PA, Marsh RA. et al. Model-informed precision dosing for alemtuzumab in pediatric and young adult patients undergoing allogeneic hematopoietic cell transplantation. Br J Clin Pharmacol. 2021.

Download references


This work was supported by a Cincinnati Children’s Research Foundation GAP award.

Author information




DA, CE, TF, MD, AV, PM, and RM analyzed data and wrote the manuscript. CE, TF, and MD performed modeling and simulation work. PM and AV contributed expertise and supervision of modeling and simulation work. RM and KM coordinated clinical aspects of the study. AL supervised statistical analyses for the manuscript. LN and RM measured or supervised alemtuzumab levels, respectively. ACL and FA measured anti-alemtuzumab antibodies. ATC coordinated pharmacy aspects of the study. SC, MBJ, ASN, KCM, SMD, PAM, and RAM contributed patients. All authors reviewed and contributed to editing of the manuscript.

Corresponding author

Correspondence to Rebecca A. Marsh.

Ethics declarations

Competing interests

SMD receives research funding from Alexion and is a consultant with Novartis Pharmaceuticals. KCM is a consultant with Novartis Pharmaceuticals. The remaining authors have no relevant conflicts of interest to disclose.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Arnold, D.E., Emoto, C., Fukuda, T. et al. A prospective pilot study of a novel alemtuzumab target concentration intervention strategy. Bone Marrow Transplant (2021).

Download citation


Quick links