Allogeneic stem cell transplantation using alemtuzumab-containing regimens in severe aplastic anemia

Abstract

Alemtuzumab, a humanized anti-CD52, IgG1 monoclonal antibody, is used to reduce graft-versus-host disease (GVHD) and aid engraftment after allogeneic haemopoietic stem cell transplant (HSCT). Its associated low incidence of GVHD makes it an attractive alternative to anti-thymocyte globulin (ATG) in transplant conditioning regimen for severe aplastic anaemia (SAA). We have reviewed the use of alemtuzumab-based conditioning regimen for HSCT in SAA and show that it results in sustained haematological engraftment, a very low incidence of chronic GVHD without an increase in viral infections. Intriguingly, alemtuzumab appears to induce tolerance post-HSCT with the findings of stable mixed T cell chimerism with full donor myeloid chimerism and the absence of chronic GVHD, and which persist on withdrawal of post-graft immunosuppression. Finally, its low toxicity profile may permit future application of HSCT to older patients with SAA who fail to respond to immunosuppressive therapy.

Alemtuzumab as graft-versus-host disease (GVHD) prophylaxis strategy in a developing country: lower rate of acute GVHD, increased risk of cytomegalovirus reactivation

“…The immunological mechanisms associated with the protective effect of alemtuzumab on acute GVHD remains poorly understood, but it may be associated to depletion of lymphocytes due to complement-mediated lysis and antibody-dependent cellular cytotoxicity via activation of NK cells and macrophages through fragment C antibody (11,17 –19). Our data are consistent with previous data and show that treatment with alemtuzumab is effective to prevent aGVHD development and aGVHD-related death in alloHSCT transplanted patients.…”

“…It has been increasingly used, especially in low intensity alloHSCT, in order to reduce GVHD and transplant-related mortality (TRM) (9). Alemtuzumab is useful as part of the conditioning regimen due to its capacity to deplete immunocompetent T-cells and for its characteristic long half-life in bloodstream, lasting even for weeks after administration (10,11). Mechanisms involved in alemtuzumab immunosuppression are not fully understood, but one of its well-known effects is the lysis of B and T lymphocytes, via mechanisms including complement system activation, natural killer cells (NK) and macrophages (6,10).…”

Timing of allogeneic stem cell transplantation for myelodysplastic syndromes and aplastic anemia

“…25 Others have chosen to study the use of the immunodepleting monoclonal anti-CD52 antibody alemtuzumab as a replacement for ATG preparations in allogeneic HSCT for SAA. 26 For example, Marsh et al have demonstrated good long-term survival with low rates of chronic GVHD when alemtuzumab was used with cyclophosphamide and fludarabine. 27 Although non-HSCT therapies have improved somewhat for the treatment of MDS and SAA, there have been larger advances in HSCT, predominantly due to improvement in HLA-typing, the acceptance of RIC, and the supportive care of the HSCT patient.…”

Stable Expression of Anti-CD52 Monoclonal Antibody Using a Bicistronic Vector System

“…However, allogeneic transplant is also associated with life-threatening complications such as graftversus-host disease (GvHD). Therefore, different strategies have been developed to block T-cell function including the in vitro removal of the donor T cells, the use of calcineurin inhibitors, or the in vivo administration of antibodies for lymphocyte depletion [10,11].…”