title: Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis.
abstract: There is currently a major concern regarding the optimal immunosuppression therapy to be administered after hematopoietic stem cell transplantation (HSCT) to reduce both the toxicity of GvHD and the rate of relapse. We report the outcome of high-risk leukemia children transplanted with a new way of managing cyclosporine (CsA)-based GvHD prophylaxis. A total of 110 HSCT in 109 ALL or AML children who received CsA without mycophenolate or methotrexate in matched related as well as in matched or mismatched unrelated stem cell transplantation were included. CsA dosage regimens were individualized to obtain specific trough blood concentrations values. The incidences of grade I-II and III-IV acute GvHD were 69.1% and 1.8%, respectively, and 8.4% for chronic GvHD. GvHD was neither more frequent nor severe in unrelated than in related HSCT. GvHD occurred in 87% of patients with a mean CsA trough concentration ⩽120 ng/mL versus 43% with concentration >120 ng/mL (P<0.0001). Five-year disease-free survival (DFS) and overall survival were 78% and 83.6%, respectively. DFS was 76.9% for ALL and 80.4% for AML patients. There was no difference in DFS between matched siblings and matched unrelated or mismatched unrelated HSCT. DFS in patients with minimal residual disease (MRD) ⩾10(-3) and in those with MRD <10(-3) before SCT was comparable. Our results indicate that a GvHD prophylaxis regimen based on CsA without mycophenolate or methotrexate is safe and effective whatever the donor compatibility is. These results suggest that GvL effect may be enhanced by this strategy of GvHD prophylaxis.
authors.affiliation: Institute of Pediatric Hematology and Oncology, Hospices Civils de Lyon and Claude Bernard Lyon 1 University, Lyon, France.|EMR 3738, Team 2 - PK/PD Modeling in Oncology, Lyon-Sud Faculty of Medicine, Oullins, France.
authors.forename: N
authors.initials: N
authors.lastname: Bleyzac
authors.affiliation: Institute of Pediatric Hematology and Oncology, Hospices Civils de Lyon and Claude Bernard Lyon 1 University, Lyon, France.
authors.forename: D
authors.initials: D
authors.lastname: Cuzzubbo
authors.affiliation: Institute of Pediatric Hematology and Oncology, Hospices Civils de Lyon and Claude Bernard Lyon 1 University, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Rénard
authors.affiliation: Institute of Pediatric Hematology and Oncology, Hospices Civils de Lyon and Claude Bernard Lyon 1 University, Lyon, France.
authors.forename: N
authors.initials: N
authors.lastname: Garnier
authors.affiliation: Laboratory of Histocompatibility, French Agency of Blood (EFS), Lyon, France.
authors.forename: V
authors.initials: V
authors.lastname: Dubois
authors.affiliation: Institute of Pediatric Hematology and Oncology, Hospices Civils de Lyon and Claude Bernard Lyon 1 University, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Domenech
authors.affiliation: Institute of Pediatric Hematology and Oncology, Hospices Civils de Lyon and Claude Bernard Lyon 1 University, Lyon, France.
authors.forename: M-P
authors.initials: MP
authors.lastname: Goutagny
authors.affiliation: Laboratory of Immunology, Lyon Sud University Hospital, Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Plesa
authors.affiliation: Laboratory of Molecular Biology, University Hospital, Lille, France.
authors.forename: N
authors.initials: N
authors.lastname: Grardel
authors.affiliation: Institute of Pharmaceutical and Biological Sciences, Lyon 1 University, Lyon, France.
authors.forename: S
authors.initials: S
authors.lastname: Goutelle
authors.affiliation: Institute of Pharmaceutical and Biological Sciences, Lyon 1 University, Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Janoly-Duménil
authors.affiliation: Institute of Pediatric Hematology and Oncology, Hospices Civils de Lyon and Claude Bernard Lyon 1 University, Lyon, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Bertrand
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage* / Q000627:therapeutic use; D018572:Disease-Free Survival; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D015994:Incidence; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy*; D011292:Premedication / Q000379:methods*; D012306:Risk; D015996:Survival Rate; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D016572:Cyclosporine