Petah Tikva, Israel
Petah Tikva, Israel

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Locatelli F.,Instituto Of Ricovero E Cura A Carattere Scientifico Irccs | Locatelli F.,University of Pavia | Kabbara N.,Eurocord | Ruggeri A.,Eurocord | And 14 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.


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.


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.


PubMed | Pediatric Genetics Unit, CNR Institute of Neuroscience, Felsenstein Medical Research Center, Raphael Recanati Genetic Institute and 3 more.
Type: | Journal: Clinical genetics | Year: 2016

Mutations of several genes have been implicated in autosomal recessive osteopetrosis (OP), a disease caused by impaired function and differentiation of osteoclasts. Severe combined immune deficiencies (SCID) can likewise result from different genetic mutations. We report two siblings with SCID and an atypical phenotype of OP. A biallelic microdeletion encompassing the 5 region of TRAF6, RAG1 and RAG2 genes was identified. TRAF6, a tumor necrosis factor receptor-associated family member, plays an important role in T-cell signaling and in RANKL-dependent osteoclast differentiation and activation but its role in human OP has not been previously reported. The RAG proteins are essential for recombination of B and T cell receptors, and for the survival and differentiation of these cells. This is the first study to report a homozygous deletion of TRAF6 as a cause of human disease.


Raiola A.,IRCCS San Martino IST | Dominietto A.,IRCCS San Martino IST | Varaldo R.,IRCCS San Martino IST | Ghiso A.,IRCCS San Martino IST | And 10 more authors.
Bone Marrow Transplantation | Year: 2014

Twenty-six patients with advanced Hodgkin's disease received a related HLA haploidentical unmanipulated BMT, following a non-myeloablative conditioning with low-dose TBI, proposed by the Baltimore group; GvHD prophylaxis consisted of high-dose post-transplantation CY (PT-CY), mycophenolate and a calcineurin inhibitor. All patients had received a previous autograft, and 65% had active disease at the time of BMT. Sustained engraftment of donor cells occurred in 25 patients (96%), with a median time to neutrophil recovery (>0.5 × 109/L) and platelet recovery (>20 × 109/L) of +18 and +23 days from BMT. The incidence of grade II-IV acute GVHD and of chronic GVHD was 24% and 8%, respectively. With a median follow-up of 24 months (range 18-44) 21 patients are alive, 20 disease free. The cumulative incidence of TRM and relapse was 4% and 31%, respectively. The actuarial 3-year survival is 77%, the actuarial 3-year PFS is 63%. In conclusion, we confirm that high-dose PT-CY is effective as prophylaxis of GVHD after HLA haploidentical BMT, can prevent rejection and does not appear to eliminate the allogeneic graft versus lymphoma effect. © 2014 Macmillan Publishers Limited.


Roos-Weil D.,Hopitaux de Paris | Dietrich S.,University of Heidelberg | Dietrich S.,European Group for Blood and Marrow Transplantation Lymphoma Working Party | Boumendil A.,European Group for Blood and Marrow Transplantation Lymphoma Working Party | And 17 more authors.
Blood | Year: 2013

Patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) have a poor prognosis with conventional chemotherapy. In the present study, we retrospectively analyzed the outcome of patients with BPDCN who underwent allogeneic stem cell transplantation (allo-SCT) or autologous stem cell transplantation (auto-SCT). A total of 39 patients (allo-SCT, n = 34; auto-SCT, n = 5) were identified in the European Group for Blood and Marrow Transplantation registry. The 34 allo-SCT patients had a median age of 41 years (range, 10-70) and received transplantations from sibling (n = 11) or unrelated donors (n = 23) between 2003 and 2009. MAC was used in 74% of patients. Nineteen allo-SCT patients (56%) received transplantations in first complete remission. The 3-year cumulative incidence of relapse, disease-free survival, and overall survival was 32%, 33%, and 41%, respectively. By univariate comparison, being in first remission at allo-SCT favorably influenced survival, whereas age, donor source, and chronic GVHD had no significant impact. We conclude that high-dose therapy followed by allo-SCT from related or unrelated donors can provide durable remission even in elderly patients with BPDCN. However, it remains to be shown if graft-versus-malignancy effects can contribute significantly to BPDCN control after allo-SCT. © 2013 by The American Society of Hematology.


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.


Antonelli M.,University of Rome La Sapienza | Badiali M.,Bone Marrow Transplantation Unit | Moi L.,Bone Marrow Transplantation Unit | Buttarelli F.R.,University of Rome La Sapienza | And 5 more authors.
Pediatric Blood and Cancer | Year: 2015

The KIAA1549:BRAF fusion gene is considered a driver genetic event in pilocytic astrocytoma. We investigated a series of 69 pediatric brain neoplasms of diverse histogenesis and grade using the RT-PCR and sequencing. We detected the KIAA1549:BRAF fusion gene in five of 34 non-PA tumors (14.7%), that is, one glioblastoma, one anaplastic astrocytoma, one anaplastic pleomorphic xanthoastrocytoma, 1 ependymoma, and 1 Atypical Teratoid Rhabdoid Tumor. Our study showed that the K-B, although uncommon, it can be detected in non-PA tumors of various histogenesis and grading. Pediatr Blood Cancer 2015;62:724-727. © 2014 Wiley Periodicals, Inc.


PubMed | Bone Marrow Transplantation Unit and Ospedale Niguarda Ca Granda
Type: Journal Article | Journal: Transfusion | Year: 2016

Extracorporeal photopheresis (ECP) is a recognized second-line treatment for steroid-refractory chronic graft-versus-host disease (cGVHD). Treatment course is usually long, expensive, and demanding for patients, so predictors for response are needed. We carried out a retrospective study on cGVHD patients treated at our institution with the aim to identify a possible correlation between apheretic yields composition and probability of response.Patients treated for at least 6 months were eligible for the study. Flow cytometry data, including absolute counts of lymphocytes and their subpopulations in ECP products from cGVHD patients, were collected. For each cell population 1) the median dose per procedure harvested during the first 3 months of treatment and 2) the cumulative dose collected in the same period were compared with clinical response.A total of 726 ECP procedures were performed in 15 patients. Overall response, defined as either a complete response (CR) or a partial response according to National Institutes of Health criteria, was obtained in 10 of 15 patients (66.7%), and CR, in eight of 15 (53.3%). According to Cox regression analysis, the probability of achieving an overall response is significantly correlated with the median number of CD3+, CD3+CD4+, and CD3+CD8+ lymphocytes collected during the early treatment phase (first 3 months).Our data suggest that CD3+ cell evaluation in ECP during the early phase of treatment course could predict response and help identify patients who deserve further treatment.

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