Positive selection for CD34+ reduces the incidence and severity of veno-occlusive disease of the liver after HLA-identical sibling allogeneic peripheral blood stem cell transplantation

OBJECTIVE: T-cell depletion (TCD), primarily developed to prevent graft-vs-host disease (GVHD), might reduce early liver dysfunction after allogeneic hematopoietic stem cell transplantation. However, no comparative studies have been performed to investigate this. We analyzed the influence of selection for CD34(+) cells on the incidence and severity of hepatic veno-occlusive disease (VOD). PATIENTS AND METHODS: Five hundred and one patients who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from HLA-identical siblings were included in the present study. Two hundred and ninety patients (59%) were grafted with CD34+ positively selected grafts and 211 (41%) with nonmanipulated grafts. Their mean age was 38 years (range 17-63). All patients had hematological malignancies and 96% were conditioned with combinations either of cyclophosphamide plus total-body irradiation or of cyclophosphamide plus busulphan. Most of the patients received GVHD prophylaxis with methotrexate (MTX) or cyclosporin A. RESULTS: Fifty-two patients (10.4%) developed VOD. VOD was more frequent in patients receiving nonmanipulated grafts (16.1% vs 6.2%; p<0.0009), in those with a Karnofsky score less than 90 (17.5% vs 7.8%; p=0.001), and with the use of MTX for GVHD prophylaxis (14.8% vs 7%; p=0.005). In multivariate analyses, only CD34+ positive selection (p=0.0007) and Karnofsky score (p=0.004) emerged as independent risk factors for VOD. The same effect was observed in the subset of patients with severe VOD. CONCLUSION: These findings show that CD34+ selection not only decreases the incidence of GVHD but also prevents VOD after HLA-identical sibling PBSCT.