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CD34+ immunoselection of autologous grafts for the treatment of high‐risk neuroblastoma
Author(s) -
Marabelle Aurélien,
Merlin Etienne,
Halle Pascale,
Paillard Catherine,
Berger Marc,
Tchirkov Andrei,
Rousseau Raphaël,
Leverger Guy,
Piguet Christophe,
Stephan JeanLouis,
Demeocq François,
Kanold Justyna
Publication year - 2011
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.22840
Subject(s) - medicine , melphalan , transplantation , leukapheresis , surgery , neuroblastoma , cd34 , hematopoietic stem cell transplantation , chemotherapy , busulfan , gastroenterology , stem cell , biology , genetics , cell culture
Background Graft contamination has been blamed for causing relapse in children with high‐risk neuroblastoma (HRNB) after autologous hematopoietic stem cell transplantation (HSCT). Procedure We report the long‐term results of hematopoietic reconstitution, post‐transplant complications, and clinical outcome of 44 children with HRNB treated with busulfan/melphalan high‐dose chemotherapy followed by transplantation of purged CD34+ immunoselected autologous peripheral HSCT. Minimal residual disease (MRD) of grafts was evaluated by anti‐GD2 immunofluorescence or tyrosine hydroxylase reverse transcriptase‐polymerase chain reaction (RT‐PCR). Results Contaminating neuroblasts were found in 19/38 grafts (50%) before CD34+ positive selection, and none after (technique sensitivity of one cell in 10 5 ). A median of 6.5 × 10 6 CD34+ cells/kg (range 0.8–23.7) were transplanted with only 2% of TRM. Neutrophils and platelet recovery occurred within a median of 12 days (range 9–47) and 44 days (range 12–259), respectively, without any secondary graft failure. Twenty‐three percents of patients experienced a sepsis (10/44) and 14% a pyelonephritis (6/44). Recurrence of varicella zoster virus occurred in 21% of patients (9/44). Negative RT‐PCR MRD within the leukapheresis product and cis ‐retinoic acid therapy were significantly and independently associated to a better survival ( P < 0.05). Overall and event‐free survivals at 5 years post‐transplant were at 59.3% and 48.3% respectively. Conclusions Besides high rates of manageable infections due to late immune recovery, transplantation with CD34+ immunoselected grafts in HRNB children was feasible and did not affect long‐term hematopoiesis. Pediatr Blood Cancer. 2010;56:134–142. © 2010 Wiley‐Liss, Inc.