Principles of alemtuzumab immunoablation in hematopoietic cell transplantation for non‐malignant diseases in children: A review

Abstract

Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell lines). A growing understanding of the PKs, dosing, and timing of administration of alemtuzumab has allowed for the study of its use as a conditioning agent for allogeneic HCT. The highly immunosuppressive properties of the drug are particularly appealing in the setting of non-malignant HCT, where GVHD provides no clinical benefit and relapse of malignancy is not applicable. In addition, the degree of immune suppression achieved with alemtuzumab has allowed for a reduction in the intensity of myeloablative cytotoxic agents included in some HCT conditioning regimens, allowing for fewer acute and late toxicities. This review paper will provide a comprehensive summary of the mechanism of action, PKs, dosing, and timing of alemtuzumab, a brief description of its use in various allogeneic HCT protocols for non-malignant conditions and a summary of the data regarding its use for GVHD therapy. The goal of this review was to provide an understanding as to how alemtuzumab might be safely incorporated into HCT conditioning regimens for children with non-malignant disease, allowing for expanded access to curative HCT therapy.

Nonmyeloablative Matched Sibling Donor Hematopoietic Cell Transplantation in Children and Adolescents with Sickle Cell Disease

“…The cumulative incidence of achieving donor CD3 + chimerism of 50% or greater (criteria to wean immune suppression) is presented in Figure 3. T-cell recovery rose over the second half of the first year post-HCT, consistent with previous alemtuzumab data [13]. Kinetics of recovery of CD4 + T cells over time is shown in Figure 4.…”

Alemtuzumab clearance, lymphocyte count, and T‐cell chimerism after hematopoietic stem cell transplant in sickle cell disease

“…Studies that infused alemtuzumab distal to transplant showed higher rates of engraftment, but also higher rates of GVHD. 26 In one such study, patients with non-malignant diseases experienced graft failure, 43% developed acute GVHD, and 25% developed chronic GVHD. However, the patients who received "proximal" alemtuzumab had a higher rate of graft rejection (33%) and a lower rate of GVHD (11%).…”

Model‐informed precision dosing for alemtuzumab in paediatric and young adult patients undergoing allogeneic haematopoietic cell transplantation

“…It is often used together with fludarabine and melphalan or other chemotherapeutic agents as part of reduced intensity conditioning (RIC) regimens for allogeneic haematopoietic cell transplantation (HCT). 1 Our group previously reported the impact of peri-transplant alemtuzumab levels on acute graft vs. host disease (GVHD), mixed chimerism, and lymphocyte recovery. 2 We found that if alemtuzumab concentrations fell within the range of 0.2-0.4 μg/mL on Day 0, the incidences of GVHD and mixed chimerism were significantly lower.…”