Cellular immune reconstitution after subcutaneous alemtuzumab (anti-CD52 monoclonal antibody, CAMPATH-1H) treatment as first-line therapy for B-cell chronic lymphocytic leukaemia

Abstract

Little information is available on long-term immune reconstitution after therapy with alemtuzumab in B-CLL patients. We present long-term follow-up data for blood lymphocyte subsets analysed by flow cytometry in previously untreated B-CLL patients who received alemtuzumab subcutaneously as firstline therapy. All lymphoid subsets were significantly (Po0.001) and profoundly reduced; the median end-of-treatment counts þ and CD8 þ levels in blood had reached 4100 cells/ll in 450% of the patients at 4 months after the end of treatment. One patient had a cytomegalovirus reactivation and one patient developed Pneumocystis carinii pneumonia during therapy. No opportunistic or other major infections were recorded during unmaintained, long-term follow-up. There was no correlation between the cumulative dose of alemtuzumab and the severity or length of immunosuppression. CD52À T-cell subsets occurred during the treatment and comprised 480% of all CD4 þ and CD8 þ cells in the blood at the end of therapy. These subpopulations declined gradually during unmaintained followup. The relationship between these observations and the safety/antitumour effects of alemtuzumab is discussed.

Donor CD4 T cells convert mixed to full donor T-cell chimerism and replenish the CD52-positive T-cell pool after alemtuzumab-based T-cell-depleted allo-transplantation

“…30 Transient proliferation of CD52-negative T cells after cross-linking, and subsequent downregulation of CD52 by alemtuzumab has been observed in patients treated for chronic lymphocytic leukemia. 31 Our data are the first to describe long-term persistence of substantial CD52-negative T-cell populations after alemtuzumab-mediated TCD transplantation. They also indicate that CD52 can be used as a marker to track the re-population of the T-cell repertoire with exogenously administered CD52-positive T cells of donor origin.…”

Management of infections in patients with chronic lymphocytic leukemia treated with alemtuzumab

“…The study showed that even lower cumulative doses of alemtuzumab could result in a sharp decrease in cell numbers for an extended period of time, although the cumulative dose level was not significantly associated with the extent or duration of lymphocyte depletion. There was, however, a trend toward lower levels of CD4 + and CD8 + T cells at the end of therapy in patients who received greater than median cumulative doses of alemtuzumab, although the actual bloodstream concentrations of alemtuzumab were not measured [34]. Interestingly, no late-occurring opportunistic infections or major infections were reported during unmaintained, long-term follow-up; this may partially be explained by the patients' treatment-naive status prior to alemtuzumab therapy.…”

“…An array of immune cell populations was examined by flow cytometry at baseline and through 18 months following first-line alemtuzumab treatment [34]. CD4 + and CD8 + T cells, CD3 − /56 + NK cells, CD3 + /56 + NK T cells, and CD19 + /5 − B cells were all profoundly decreased to <25% baseline through 9 months after treatment.…”

Changing therapeutic landscape – The last decade

“…The frequent and sometimes severe infusional reactions can be significantly reduced by administering the drug subcutaneously instead of intravenously [14].…”