Journal Article

Higher CD3+ and CD34+ cell doses in the graft increase the incidence of acute GVHD in children receiving BMT for thalassemia

Lanti, A, Simone, M D, Saltarelli, F, Lucarelli, G, Isgrò, A, Gallucci, C, Testi, M, Gaziev, J, Daniele, N, Sodani, P, Roveda, A, Paciaroni, K, Marziali, M, De Angelis, G, Del Proposto, G, Alfieri, C, Andreani, M, Adorno, G

2012

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Acute Disease / Adolescent / Anemias. Hemoglobinopathies / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Anti-Inflammatory Agents - administration & dosage / Antigens, CD34 / Biological and medical sciences / Bone marrow / Bone Marrow Transplantation / Bone marrow, stem cells transplantation. Graft versus host reaction / Busulfan - administration & dosage / CD3 Complex / Cell Biology / Child / Child, Preschool / Cyclophosphamide - administration & dosage / Diseases of red blood cells / Female / Graft vs Host Disease - epidemiology / Graft vs Host Disease - prevention & control / Hematologic and hematopoietic diseases / Hematology / Humans / Immunosuppression - methods / Immunosuppressive Agents - administration & dosage / Incidence / Infant / Internal Medicine / Male / Medical sciences / Medicine / Medicine & Public Health / Methotrexate - administration & dosage / Methylprednisolone - administration & dosage / Myeloablative Agonists - administration & dosage / original-article / Public Health / Siblings / Stem cell transplantation / Stem Cells / Thalassemia - therapy / Transfusions. Complications. Transfusion reactions. Cell and gene therapy / Transplantation Conditioning / Transplantation, Homologous