TY - JOUR T1 - Failure of interferon-γ pre-treated mesenchymal stem cell treatment in a patient with Crohn's disease. JF - World J Gastroenterol Y1 - 2015 A1 - Taddio, Andrea A1 - Tommasini, Alberto A1 - Valencic, Erica A1 - Biagi, Ettore A1 - Decorti, Giuliana A1 - De Iudicibus, Sara A1 - Cuzzoni, Eva A1 - Gaipa, Giuseppe A1 - Badolato, Raffaela A1 - Prandini, Alberto A1 - Biondi, Andrea A1 - Ventura, Alessandro AB -

Mesenchymal stem cells (MSC) are cells of stromal origin which exhibit unlimited self-renewal capacity and pluripotency in vitro. It has recently been observed that MSC may also exert a profound immunosuppressive and anti-inflammatory effect both in vitro and in vivo with consequent potential use in autoimmune disorders. We present the case of a patient suffering from childhood-onset, multidrug resistant and steroid-dependent Crohn's disease who underwent systemic infusions of MSC, which led to a temporary reduction in CCR4, CCR7 and CXCR4 expression by T-cells, and a temporary decrease in switched memory B-cells, In addition, following MSC infusion, lower doses of steroids were needed to inhibit proliferation of the patient's peripheral blood mononuclear cells. Despite these changes, no significant clinical benefit was observed, and the patient required rescue therapy with infliximab and subsequent autologous hematopoietic stem cell transplantation. The results of biological and in vitro observations after MSC use and the clinical effects of infusion are discussed, and a brief description is provided of previous data on MSC-based therapy in autoimmune disorders.

VL - 21 IS - 14 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25892890?dopt=Abstract ER - TY - JOUR T1 - Childhood high-risk acute lymphoblastic leukemia in first remission: results after chemotherapy or transplant from the AIEOP ALL 2000 study. JF - Blood Y1 - 2014 A1 - Conter, Valentino A1 - Valsecchi, Maria Grazia A1 - Parasole, Rosanna A1 - Putti, Maria Caterina A1 - Locatelli, Franco A1 - Barisone, Elena A1 - Lo Nigro, Luca A1 - Santoro, Nicola A1 - Aricò, Maurizio A1 - Ziino, Ottavio A1 - Pession, Andrea A1 - Testi, Anna Maria A1 - Micalizzi, Concetta A1 - Casale, Fiorina A1 - Zecca, Marco A1 - Casazza, Gabriella A1 - Tamaro, Paolo A1 - La Barba, Gaetano A1 - Notarangelo, Lucia Dora A1 - Silvestri, Daniela A1 - Colombini, Antonella A1 - Rizzari, Carmelo A1 - Biondi, Andrea A1 - Masera, Giuseppe A1 - Basso, Giuseppe KW - Adolescent KW - Antineoplastic Combined Chemotherapy Protocols KW - Child KW - Child, Preschool KW - Combined Modality Therapy KW - Female KW - Hematopoietic Stem Cell Transplantation KW - Humans KW - Infant KW - Male KW - Neoplasm, Residual KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma KW - Radiotherapy KW - Remission Induction KW - Treatment Outcome AB -

The outcome of high-risk (HR) acute lymphoblastic leukemia patients enrolled in the AIEOP-BFM ALL 2000 study in Italy is described. HR criteria were minimal residual disease (MRD) levels ≥10(-3) at day 78 (MRD-HR), no complete remission (CR) at day 33, t(4;11) translocation, and prednisone poor response (PPR). Treatment (2 years) included protocol I, 3 polychemotherapy blocks, delayed intensification (protocol IIx2 or IIIx3), cranial radiotherapy, and maintenance. A total of 312 HR patients had a 5-year event-free survival (EFS) of 58.9% (standard error [SE] = 2.8) and an overall survival of 68.9% (SE = 2.6). In hierarchical order, EFS was 45.9% (4.4) in 132 MRD-HR patients, 41.2% (11.9) in 17 patients with no CR at day 33, 36.4% (14.5) in 11 patients with t(4;11), and 74.0% (3.6) in 152 HR patients only for PPR. No statistically significant difference was found for disease-free survival in patients with very HR features [MRD-HR, no CR at day 33, t(4;11) translocation], given hematopoietic stem cell transplantation (HSCT) (n = 66) or chemotherapy only (n = 88), after adjusting for waiting time to HSCT (5.7 months). Patients at HR only for PPR have a favorable outcome. MRD-HR is associated with poor outcome despite intensive treatment and/or HSCT and may qualify for innovative therapies. The study was registered at www.clinicaltrials.gov as #NCT00613457.

VL - 123 IS - 10 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24415536?dopt=Abstract ER - TY - JOUR T1 - From bone marrow transplantation to cellular therapies: possible therapeutic strategies in managing autoimmune disorders. JF - Curr Pharm Des Y1 - 2012 A1 - Taddio, Andrea A1 - Biondi, Andrea A1 - Piscianz, Elisa A1 - Valencic, Erica A1 - Biagi, Ettore A1 - Badolato, Raffaele KW - Autoimmune Diseases KW - Bone Marrow Transplantation KW - Child KW - Chronic Disease KW - Graft vs Host Disease KW - Hematopoietic Stem Cell Transplantation KW - Humans KW - Inflammation KW - Lymphocytes KW - Mesenchymal Stem Cell Transplantation KW - T-Lymphocytes, Regulatory KW - Treatment Outcome AB -

Chronic inflammatory disorders occurring in childhood represent a serious therapeutic challenge. However, available therapies seem not to be targeted on the pathogenic mechanism of the disease and are often not actively affecting the natural history of the disease. Emerging treatments might be of some benefit to many patients who did not respond to conventional therapeutic options. Biological therapies with monoclonal antibodies and other recombinant proteins have been introduced in clinical practice. At the same time, mesenchymal stromal cells (MSC) have gained attention as a savage treatment in patients subjected to hematopoietic stem cell transplantation who develop severe graft versus host disease (GvHD); in addition, recent reports from clinical trials on larger cohorts of patients support their use as second-line treatment after failure of corticosteroid treatment. For analogy, they have been proposed for the treatment of intractable autoimmune disorders. Hematopoietic stem cell transplantation (HSCT) has been shown to be effective for treatment of rheumatic disorder cases that were resistant to traditional therapies especially if combined with cell manipulation techniques, such as selection of regulatory T cell and depletion of harmful lymphocytes. We herein present the rationale of different strategies, the preliminary data obtained in clinical trials, unsolved problems and possible next developments of novel treatment protocols of autoimmune disorders.

VL - 18 IS - 35 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22726117?dopt=Abstract ER - TY - JOUR T1 - Stem cells in severe infantile spinal muscular atrophy (SMA1). JF - Neuromuscul Disord Y1 - 2012 A1 - Carrozzi, Marco A1 - Amaddeo, Alessandro A1 - Biondi, Andrea A1 - Zanus, Caterina A1 - Monti, Fabrizio A1 - Alessandro, Ventura KW - Humans KW - Spinal Muscular Atrophies of Childhood KW - Stem Cell Transplantation KW - Stem Cells KW - Treatment Outcome VL - 22 IS - 11 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23046997?dopt=Abstract ER -