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.
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.
Authors: Rebecca A Marsh; Marepalli B Rao; Aharon Gefen; Denise Bellman; Parinda A Mehta; Pooja Khandelwal; Sharat Chandra; Sonata Jodele; Kasiani C Myers; Michael Grimley; Christopher Dandoy; Javier El-Bietar; Ashish R Kumar; Tom Leemhuis; Kejian Zhang; Jack J Bleesing; Michael B Jordan; Alexandra H Filipovich; Stella M Davies Journal: Biol Blood Marrow Transplant Date: 2015-04-10 Impact factor: 5.742
Authors: Mark T Vander Lugt; Xiaohua Chen; Maria L Escolar; Beth A Carella; Jessie L Barnum; Randy M Windreich; Memphis J Hill; Michelle Poe; Rebecca A Marsh; Heather Stanczak; Elizabeth O Stenger; Paul Szabolcs Journal: Blood Adv Date: 2020-07-14
Authors: Young Bae Choi; Ji Won Lee; Ki Woong Sung; Hong Hoe Koo; Hee-Jin Kim; Keon Hee Yoo Journal: J Korean Med Sci Date: 2019-01-29 Impact factor: 2.153