Tito Roccia

Publications (2)8.09 Total impact

• Article: Unpredictability of intravenous busulfan pharmacokinetics in children undergoing hematopoietic stem cell transplantation for advanced beta thalassemia: limited toxicity with a dose-adjustment policy.

  Robert Chiesa, Barbara Cappelli, Roberto Crocchiolo, Ilaria Frugnoli, Erika Biral, Anna Noè, Costanza Evangelio, Marco Fossati, Tito Roccia, Alessandra Biffi, Valentina Finizio, Alessandro Aiuti, Monica Broglia, Antonella Bartoli, Fabio Ciceri, Maria Grazia Roncarolo, Sarah Marktel
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  ABSTRACT: beta-thalassemia is a major health problem worldwide, and stem cell transplantation (SCT) is the only curative option. Oral Busulfan (Bu) based conditioning is widely used in this setting. Due to the variability of Bu systemic exposure, intravenous (i.v.) Bu has been proposed as a standard of care, with no need for drug monitoring and dose adjustment. Patients with beta-thalassemia from countries with limited resources might be at higher risk of erratic Bu metabolism because of liver dysfunction, severe iron overload, and specific ethnic/genetic features. We studied Bu pharmacokinetics in 53 children with advanced beta-thalassemia from Middle Eastern countries who underwent a total of 57 matched related donor SCTs. Forty-two percent of the children required dose adjustment because they did not achieve the therapeutic window after the first dose. With a Bu dose-adjustment policy, regimen-related toxicity was limited. At a median follow-up of 564 days, the probabilities of 2-year survival, current thalassemia-free survival, rejection, and treatment-related mortality were 96%, 88%, 21%, and 4%, respectively. Conditioning with i.v. Bu and dose adjustment is feasible and well tolerated, although recurrence of thalassemia remains an unsolved problem in children with advanced disease.
  Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2009; 16(5):622-8. · 3.15 Impact Factor
• Article: Absence of VOD in paediatric thalassaemic HSCT recipients using defibrotide prophylaxis and intravenous Busulphan.

  Barbara Cappelli, Robert Chiesa, Costanza Evangelio, Alessandra Biffi, Tito Roccia, Ilaria Frugnoli, Erika Biral, Anna Noè, Marco Fossati, Valentina Finizio, Roberto Miniero, Sara Napolitano, Francesca Ferrua, Clara Soliman, Fabio Ciceri, Maria G Roncarolo, Sarah Marktel
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  ABSTRACT: Hepatic veno-occlusive disease (VOD) is a common complication of haematopoietic stem cell transplantation (HSCT), with reported incidences of 5-40% in children. Recently, defibrotide (DF) has been successfully used as prophylaxis and treatment of VOD. This study reports data on 63 human leucocyte antigen-matched HSCT performed in 57 children affected by beta thalassemia at very high risk for developing VOD (liver fibrosis, iron overload, hepatitis C virus infections, busulphan-based conditioning, methotraexate + ciclosporine). All patients received a busulphan-based conditioning regimen, either orally (four HSCT) or intravenously (59 HSCT). All patients received oral DF (40 mg/kg per day, final dose) as VOD prophylaxis from median day -9 to median day +29. In order to overcome the lack of oral paediatric formulations, a galenic formulation was administered. DF was well tolerated. Only one patient fulfilled Seattle Criteria for VOD diagnosis. This patient had discontinued DF 6 d prior to VOD onset, due to high risk of haemorrhage. We concluded that oral defibrotide prophylaxis and i.v. busulphan safely abated VOD incidence in high-risk patients who had undergone HSCT. A galenic preparation of oral DF also permits this treatment in low-weight patients. Costs of DF prophylaxis are acceptable considering the reduced incidence of VOD.
  British Journal of Haematology 08/2009; 147(4):554-60. · 4.94 Impact Factor