title: In vivo T-cell depletion using alemtuzumab in family and unrelated donor transplantation for pediatric non-malignant disease achieves engraftment with low incidence of graft vs. host disease.
abstract: In vivo T-cell depletion, using alemtuzumab therapy prior to SCT, can reduce the incidence of GVHD. This treatment has a potential to delay immune reconstitution resulting in increased morbidity due to viral illnesses. We retrospectively analyzed data on all pediatric patients with non-malignant disorders who received alemtuzumab-based conditioning regimens in our center over the last 10 yr (n = 91). Our data show an OS of 91.2%. The incidence of acute (grade 2-4) GVHD was 18.7% and that of chronic GVHD 5.5%. Viremia due to adenovirus, EBV and CMV was seen in 19.8%, 64.8% and 39.6% patients, respectively, with only two deaths attributed to viral infection (adenovirus). Chimerism level at three month was predictive of graft outcome. Nine patients, who had graft failure after first SCT, were salvaged with a second SCT using RIC and same donor (if available). Based on these results, we conclude that the use of in vivo T-cell depletion is safe, achieves good chimerism and does not lead to increased morbidity and mortality due to viral infections. It is associated with a reduced incidence of chronic GVHD.
authors.affiliation: Department of Blood and Marrow Transplant, Royal Manchester Children's Hospital, Manchester, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Saif
authors.forename: R
authors.initials: R
authors.lastname: Borrill
authors.forename: B W
authors.initials: BW
authors.lastname: Bigger
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Logan
authors.forename: K
authors.initials: K
authors.lastname: Poulton
authors.forename: S
authors.initials: S
authors.lastname: Hughes
authors.forename: A J
authors.initials: AJ
authors.lastname: Turner
authors.forename: D K
authors.initials: DK
authors.lastname: Bonney
authors.forename: R F
authors.initials: RF
authors.lastname: Wynn
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000293:Adolescent; D000074323:Alemtuzumab; D000741:Anemia, Aplastic / Q000628:therapy; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D007223:Infant; D008297:Male; D008659:Metabolic Diseases / Q000628:therapy; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors; D014766:Viremia / Q000503:physiopathology; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab
keywords: allogeneic stem cell transplantation; chimerism; graft-vs.-host disease; viral infection