Repopulation of blood lymphocyte sub‐populations in rheumatoid arthritis patients treated with the depleting humanized monoclonal antibody, CAMPATH‐1H

Abstract

SUMMARYPatients with severe rheumatoid arthritis who had failed treatment with conventional therapies were treated with a course of five or 10 daily intravenous infusions of CAMPATH-1H, a humanized antibody against the CD52 antigen, resulting in profound depletion of peripheral blood mononuclear cells. During the subsequent 18 months, lymphocytes were analysed for sub-populations by fluorescenceactivated cell sorter (FACS) and for proliferation in response to polyclonal T-cell stimulation with anti-CD3 or staphylococcal enterotoxin B (SEB). Treatment resulted in almost complete depletion of lymphocytes from the blood followed by gradual repopulation. CD16 natural killer (NK) cells and CD14 monocytes returned to pretreatment levels within 1-2 months. CD19 B cells returned to within 50% of pre-treatment levels by day 66 and to within normal range by day 150, whereas CD8T cells recovered to 50% of pretreatment levels by day 66, but did not show any further increase during the rest of the study period. The most profound effects were on the CD4T lymphocyte sub-population, as the mean CD4 count did not increase above 20% of pre-treatment level at any time during the study period (550 days), at all the doses tested. The T cells which initially repopulated the blood 1-2 months after treatment, nearly all expressed the activation markers human leucocyte antigen (HLA)-DR and CD45RO, although the percentage of T cells expressing these molecules gradually declined to normal levels over time. Proliferative responses to polyclonal T-cell stimulation (anti-CD3 and SEB) were also significantly reduced in the first few months after treatment, but recovered to pre-treatment levels by day 250. The relationship between these observations and the clinical response is discussed.

Imbalance of effector and regulatory CD4 T cells is associated with graft-versus-host disease after hematopoietic stem cell transplantation using a reduced intensity conditioning regimen and alemtuzumab

“…The T-cell population that recovered seems to have originated from residual mature cells because very few naïve T cells were present and there was little evidence of thymopoiesis prior to day 180. Studies of lymphocyte repopulation after lymphocyte depletion with alemtuzumab in the clinical setting of autoimmune disease, 47,48 and solid organ transplantation 49,50 all report a predominance of memory CD4 T cells in the residual population. In vitro studies suggest that alemtuzumab is less efficient at depleting memory CD4 T cells.…”

Cytomegalovirus (CMV) infections and CMV-specific cellular immune reconstitution following reduced intensity conditioning allogeneic stem cell transplantation with Alemtuzumab

“…[18][19][20] There has been a variable incidence of opportunistic infections. [18][19][20][21][22] The incidence of CMV infection following nonmyeloablative SCT containing fludarabine-based conditioning regimes but without anti-lymphocyte antibody has been reported to be from 21 to 53%. 23,24 The much higher incidence of CMV infections after RIC with Alemtuzumab has been reported previously.…”

Pharmacokinetics of alemtuzumab used for in vivo and in vitro T-cell depletion in allogeneic transplantations: relevance for early adoptive immunotherapy and infectious complications

“…Cyclosporin A (CsA) was also administered from day Ϫ 1 at 3 mg/kg/d. On day 0, patients received granulocyte colony-stimulating factor (G-CSF)-mobilized unmanipulated allogeneic peripheral blood stem cells (PBSCs) 6 or bone marrow. 3 CsA was tailed from 2 to 3 months after transplantation.…”