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Petah Tikva, Israel

Da Silva Santos P.S.,University of Sao Paulo | Coracin F.L.,University of Sao Paulo | Barros J.C.D.A.,Bone Marrow Transplantation Unit | Dulley F.L.,University of Sao Paulo | And 2 more authors.
Clinical Transplantation | Year: 2011

Patients who undergo hematopoietic stem cell transplantation (HSCT) frequently experience gastrointestinal toxicity as a result of their preparative regimen. The most frequent manifestation is oral mucositis (OM) and diarrhea. We studied the effects of oral care prior to HSCT on the severity of OM. Seventy patients suffering from hematologic malignancies who had undergone HSCT were divided into two groups (35 patients - Study Group [SG] and 35 - Control Group [CG]), and the severity of OM was evaluated by two calibrated dentists, using the WHO scale. The patients from the SG received oral care prior to HSCT and those from CG did not receive any dental care. The results showed no differences (p=0.20) in the incidence or severity of OM among the groups. However, patients from the SG presented a shorter time elapsed (p<0.001) when compared with the CG (median: 10 vs. 20d). Our results show the importance of simple, inexpensive preventive intervention to control the time elapsed of OM, which reduces morbidity and, as a consequence, the cost of the treatment. © 2010 John Wiley & Sons A/S.

Ram R.,Bone Marrow Transplantation Unit | Storb R.,Fred Hutchinson Cancer Research Center
Leukemia and Lymphoma | Year: 2013

Acute graft-versus-host disease (GVHD) has compromised and continues to compromise the benefits associated with allogeneic hematopoietic cell transplant to cure malignant and non-malignant diseases. Pharmacologic interventions to prevent GVHD have emerged as a major objective of research in the immunology and transplant fields. A better understanding of the pathobiology behind the GVHD process has led the way to novel approaches and medications. Here we review the present arsenal of medications used to prevent GVHD, focusing on past experience and the current evidence, and discuss future potential targets. © 2013 Informa UK, Ltd.

Locatelli F.,Istituto di Ricovero e Cura a Carattere Scientifico | Locatelli F.,University of Pavia | Kabbara N.,Eurocord | Ruggeri A.,Eurocord | And 13 more authors.
Blood | Year: 2013

We analyzed the outcomes of 485 patients with thalassemia major (TM) or sickle cell disease (SCD) receiving HLA-identical sibling cord blood transplantation (CBT, n = 96) or bone marrow transplantation (BMT, n = 389). Compared with patients given BMT, CBT recipients were significantly younger (median age 6 vs 8 years, P = .02), and were treated more recently (median year 2001 vs 1999, P < .01). A higher proportion of patients with TM belonging to classes II-III of the Pesaro classification received BMT (44%) compared with CBT (39%, P < .01). In comparison with patients receiving BMT(n = 259, TM; n = 130, SCD), those given CBT (n = 66, TM; n = 30, SCD) had slower neutrophil recovery, less acute graft-versus-host disease (GVHD) and none had extensive chronic GVHD. With a median follow-up of 70 months, the 6-year overall survival was 95% and 97% after BMT and CBT, respectively (P = .92). The 6-year disease-free survival (DFS) was 86% and 80% in TM patients after BMT and CBT, respectively, whereas DFS in SCD patients was 92% and 90%, respectively. The cell dose infused did not influence outcome of patients given CBT. In multivariate analysis, DFS did not differ between CBT and BMT recipients. Patients with TMor SCD have excellent outcomes after both HLA-identical sibling CBT and BMT. © 2013 by The American Society of Hematology.

Valent P.,Medical University of Vienna | Bonnet D.,Cancer Research UK Research Institute | Wohrer S.,Bone Marrow Transplantation Unit | Andreeff M.,University of Texas M. D. Anderson Cancer Center | And 5 more authors.
Cancer Research | Year: 2013

Accumulating evidence suggests that human cancers develop through a step-wise, but nonlinear process of cellular diversification and evolution. Recent mutational analyses indicate that this process is more complex and diverse than anticipated before whole-genome sequencing methods were readily available. Examples are also emerging now of genetically abnormal clones of cells that have acquired mutations with known oncogenic potential but, nevertheless, may show no manifestations of malignant change for many years. To accommodate these diverse realities, we suggest the term neoplastic refer to clones of cells that have any type of somatic aberrancy associated with an increased propensity to become malignant, and the derivative term neoplastic stem cell be adopted to identify the cells responsible for the long-term maintenance of such clones. Neoplastic clones would thus include those that never evolve further, as well as those that eventually give rise to fully malignant populations, and all stages in between. The term cancer stem cells would then be more appropriately restricted to cells generating subclones that have established malignant properties. More precise molecular understanding of the different stem cell states thus distinguished should contribute to the development of more effective prognostic and therapeutic tools for cancer diagnosis and treatment. © 2012 American Association for Cancer Research.

Iskovich S.,Center for Stem Cell Research | Stein J.,Bone Marrow Transplantation Unit | Yaniv I.,Bone Marrow Transplantation Unit | Farkas D.L.,Spectral Molecular Imaging, Inc. | Askenasy N.,Center for Stem Cell Research
Stem Cells and Development | Year: 2011

The contribution of stem cells derived from adult tissues to the recovery of pancreatic islets from chemical injury is controversial. Analysis of nonhematopoietic differentiation of bone marrow-derived cells has yielded positive and negative results under different experimental conditions. Using the smallest subset of bone marrow cells lacking immuno-hematopoietic lineage markers, we have detected incorporation and conversion into insulin-producing cells. Donor cells identified by genomic markers silence green fluorescent protein (GFP) expression as a feature of differentiation, in parallel to expressing PDX-1 and proinsulin. Here we elaborate potential experimental difficulties that might result in false-negative results. The use of GFP as a reporter protein is suboptimal for differentiation experiments: (a) the bone marrow of GFP donors partially expresses the reporter protein, (b) differentiating bone marrow cells silence GFP expression, and (c) the endocrine pancreas is constitutively negative for GFP. In addition, design of the experiments, data analysis, and interpretation encounter numerous objective and subjective difficulties. Rigorous evaluation under optimized experimental conditions confirms the capacity of adult bone marrow-derived stem cells to adopt endocrine developmental traits, and demonstrates that GFP downregulation and silencing is a feature of differentiation. © Copyright 2011, Mary Ann Liebert, Inc. 2011.

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