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Similar lymphocyte recovery and CMV reactivation profiles between reduced intensity conditioning with alemtuzumab and myeloablative allogeneic stem cell transplantation

Bone Marrow Transplantation volume 41, pages 749–751 (2008)Cite this article

The use of reduced intensity conditioning (RIC) with alemtuzumab is associated with a higher rate of cytomegalovirus (CMV) reactivation than RIC without alemtuzumab,1 especially when combined with fludarabine.2 Alemtuzumab, used as in vivo T-cell depletion, has a long plasma half-life, resulting in prolonged lymphopaenia. In 16 patients receiving allogeneic stem cell transplantation (allo-SCT) with in vivo alemtuzumab, the half-life was estimated at 15–21 days with a median total lymphocyte count (TLC) at 6 months of only 0.5 × 109/l.3 Morris et al.4 reported lympholytic concentrations of alemtuzumab for 56 days after RIC in patients who were treated with 100 mg in vivo alemtuzumab (n=10).4 A sustained recovery of median TLC to >1 × 109/l was reached by 4 months in the myeloablative conditioning (MAC) group but not until 9 months in the RIC group. The higher rate of infective complications (for example, CMV and adenovirus) reported in T-cell-depleted RIC has, therefore, been attributed to delayed immune reconstitution.

Although functional impairment of lymphocytes may persist after TLC recovery, with low B-cell counts and inverted CD4/8 ratios,5 delayed TLC recovery remains an important prognostic factor for infective complications and treatment outcome. Low TLC at 1 month post transplant is predictive for relapse in acute myeloblastic leukaemia (AML) and acute lymphoblastic leukaemia (ALL).6, 7, 8 Lower TLC at 6 months is predictive of treatment failure (relapse, death or graft failure) following T-cell-depleted allo-SCT,9 and lower TLC has also been identified as a risk factor for progressive adenovirus and death after RIC with alemtuzumab.10

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References

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Authors and Affiliations

  1. Haematology Department, Leeds General Infirmary, Leeds Teaching Hospitals, Leeds, UK

    Q A Hill

  2. Academic Unit of Haematology, University of Leeds, Leeds, UK

    A Hill

  3. Department of Microbiology, Leeds General Infirmary, Leeds Teaching Hospitals, Leeds, UK

    T A Collyns

  4. BSBMT, London, UK

    R M Pearce

  5. Bone Marrow Transplant Unit, St James's University Hospital, Leeds Teaching Hospitals, Leeds, UK

    G Cook

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  1. Q A Hill
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Correspondence to Q A Hill.

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This data have been presented in abstract form at the following meetings:

Hill QA, Hill A, Pearce RM and Cook G. Immune reconstitution following non-myeloablative transplantation using in vivo T cell depletion with alemtuzumab is similar to T cell replete myeloablative allogeneic stem cell transplantation. Haematologica 2005; 90(Suppl 2). Abstract no. 0450 (Poster presentation: EHA, Stockholm Sweden, 2005).

Hill QA, Hill A, Pearce RM and Cook G. Immune reconstitution following non-myeloablative transplantation using in vivo T cell depletion with alemtuzumab is similar to T cell replete myeloablative allogeneic stem cell transplantation. Br J Haematol 2005; 129(Suppl 1). Abstract no. 118 (Poster presentation: BSH, Manchester, 2005).

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Hill, Q., Hill, A., Collyns, T. et al. Similar lymphocyte recovery and CMV reactivation profiles between reduced intensity conditioning with alemtuzumab and myeloablative allogeneic stem cell transplantation. Bone Marrow Transplant 41, 749–751 (2008). https://doi.org/10.1038/sj.bmt.1705974

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