Mixed chimerism and graft loss in pediatric recipients of an alemtuzumab-based reduced-intensity conditioning regimen for non-malignant disease.
BACKGROUND
Reduced-intensity conditioning (RIC) regimens can mitigate the toxicity of hematopoietic cell transplantation (HCT) in children with non-malignant diseases, but are associated with increased risk for post-transplant mixed donor/recipient chimerism (MC) and/or graft loss (GL). Intervention with donor lymphocytes or stem cell boosts (DLI/boost) may be necessary, but there is limited information about timing and results of intervention.


PROCEDURE
We retrospectively evaluated 31 consecutive pediatric recipients of an alemtuzumab-based RIC HCT at the Children's Hospital of Philadelphia from May 2007 to December 2012 to determine the incidence of MC, GL, and use of DLI/boost. All patients received alemtuzumab with either fludarabine (150 mg/m(2) )/melphalan (140 mg/m(2) ) (n = 30) or fludarabine/busulfan (n = 1), and unmanipulated marrow grafts from related (48%) or matched unrelated (52%) donors.


RESULTS
Of surviving patients, 67% and 44% displayed MC and MC with ≤80% donor contribution (MC ≤ 80%), respectively. Rates of MC, MC ≤ 80%, DLI/boost, and GL were significantly higher in recipients of proximal/intermediate (100%, 73%, 46%, and 46%, respectively) compared to distal alemtuzumab (44%, 25%, 6%, and 6%, respectively). Event-free and overall survival was significantly lower in HLH compared with non-HLH patients. Twenty percent of patients required DLI/boost, and DLI/boost did not affect the incidence of GL.


CONCLUSIONS
RIC with proximal/intermediate alemtuzumab is associated with high rates of MC, need for DLI/boost, and GL.
['Oshrine|Benjamin R|BR|', 'Olson|Timothy S|TS|', 'Bunin|Nancy|N|']
D000293:Adolescent D000074323:Alemtuzumab D061067:Antibodies, Monoclonal, Humanized D002648:Child D002675:Child, Preschool D005260:Female D006085:Graft Survival D018380:Hematopoietic Stem Cell Transplantation D006801:Humans D007223:Infant D053208:Kaplan-Meier Estimate D008297:Male D012189:Retrospective Studies D018183:Transplantation Chimera D019172:Transplantation Conditioning D016896:Treatment Outcome D055815:Young Adult
reduced-intensity conditioning non-malignant disease alemtuzumab CAMPATH bone marrow transplant