title: Higher CD3(+) and CD34(+) cell doses in the graft increase the incidence of acute GVHD in children receiving BMT for thalassemia.
abstract: We evaluated the incidence of GVHD, risk factors and the impact of graft composition on acute GVHD (aGVHD) in 92 children who underwent BMT for thalassemia following busulfan/cyclophosphamide (BUCY)-based conditioning regimens and GVHD prophylaxis with CSA/short-MTX and methylprednisolone. The incidence of grade 2-4 and 3-4 aGVHD was 35% (95% confidence interval (CI) 25-44) and 9% (95% CI 4-16), respectively. We found that CD3(+) and CD34(+) cell doses above the median were associated with high incidence of grade 2-4 aGVHD (49 vs 20%, P=0.005 and 46 vs 23%, P=0.021, respectively). In multivariate analysis, high CD3(+) (hazard ratio (HR) 4.6; 95% CI 1.4-14.7; P=0.010) and CD34(+) (HR 4.3; 95% CI 1.4-12.7; P=0.011) cell doses were associated with grade 2-4 aGVHD. We further examined the effect of CD3(+) and CD34(+) cell doses on aGVHD using quartile cutoff points and found a minimum threshold for CD3(+) (38 × 10(6)/kg) and CD34(+) (4 × 10(6)/kg) cells above which the incidence of grade 2-4 aGVHD is significantly increased. This study shows for the first time a positive correlation between the number of CD3(+) and CD34(+) cells and aGVHD in children receiving sibling BMT, and indicates that using tailored and more intensive post transplant immunosuppression may permit to better control aGVHD.
authors.affiliation: International Center for Transplantation in Thalassemia and Sickle Cell Anemia, Mediterranean Institute of Hematology, Policlinico Tor Vergata, Rome, Italy. j.gaziev@fondazioneime.org
authors.forename: J
authors.initials: J
authors.lastname: Gaziev
authors.forename: A
authors.initials: A
authors.lastname: Isgrò
authors.forename: M
authors.initials: M
authors.lastname: Marziali
authors.forename: N
authors.initials: N
authors.lastname: Daniele
authors.forename: C
authors.initials: C
authors.lastname: Gallucci
authors.forename: P
authors.initials: P
authors.lastname: Sodani
authors.forename: M D
authors.initials: MD
authors.lastname: Simone
authors.forename: G
authors.initials: G
authors.lastname: Adorno
authors.forename: K
authors.initials: K
authors.lastname: Paciaroni
authors.forename: M
authors.initials: M
authors.lastname: Andreani
authors.forename: A
authors.initials: A
authors.lastname: Lanti
authors.forename: G
authors.initials: G
authors.lastname: Del Proposto
authors.forename: M
authors.initials: M
authors.lastname: Testi
authors.forename: G
authors.initials: G
authors.lastname: De Angelis
authors.forename: A
authors.initials: A
authors.lastname: Roveda
authors.forename: C
authors.initials: C
authors.lastname: Alfieri
authors.forename: F
authors.initials: F
authors.lastname: Saltarelli
authors.forename: G
authors.initials: G
authors.lastname: Lucarelli
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D018952:Antigens, CD34; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000008:administration & dosage; D017252:CD3 Complex; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D015994:Incidence; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008775:Methylprednisolone / Q000008:administration & dosage; D019653:Myeloablative Agonists / Q000008:administration & dosage; D035781:Siblings; D013789:Thalassemia / Q000628:therapy*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D000893:Anti-Inflammatory Agents; D018952:Antigens, CD34; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D002066:Busulfan; D008775:Methylprednisolone; D008727:Methotrexate