Mixed chimerism and graft loss in pediatric recipients of an Alemtuzumab-based reduced-intensity conditioning regimen for non-malignant disease

Benjamin R. Oshrine, Timothy S. Olson, Nancy Bunin

Research output: Contribution to journalArticlepeer-review

Abstract

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 (150mg/m2)/melphalan (140mg/m2) (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.

Original languageEnglish (US)
Pages (from-to)1852-1859
Number of pages8
JournalPediatric Blood and Cancer
Volume61
Issue number10
DOIs
StatePublished - Oct 2014
Externally publishedYes

Keywords

  • Alemtuzumab
  • Bone marrow transplant
  • CAMPATH
  • Non-malignant disease
  • Reduced-intensity conditioning

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Fingerprint Dive into the research topics of 'Mixed chimerism and graft loss in pediatric recipients of an Alemtuzumab-based reduced-intensity conditioning regimen for non-malignant disease'. Together they form a unique fingerprint.

Cite this