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Marta Donini,
Stefania Fontana,
Gianfranco Savoldi,
William Vermi,
Laura Tassone,
Francesca Gentili,
Elena Zenaro,
Daniela Ferrari,
Lucia D Notarangelo, Fulvio Porta,
Fabio Facchetti,
Luigi D Notarangelo,
Stefano Dusi,
Raffaele Badolato
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Marta Donini,
Stefania Fontana,
Gianfranco Savoldi,
William Vermi,
Laura Tassone,
Francesca Gentili,
Elena Zenaro,
Daniela Ferrari,
Lucia D Notarangelo, Fulvio Porta,
Fabio Facchetti,
Luigi D Notarangelo,
Stefano Dusi,
Raffaele Badolato
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Amel Hassan,
Claire Booth,
Alex Brightwell,
Zoe Allwood,
Paul Veys,
Kanchan Rao,
Manfred Hönig,
Wilhelm Friedrich,
Andrew Gennery,
Mary Slatter, [......],
Nizar Mahlaoui,
Kim E Nichols,
Eyal Grunebaum,
Daifulah Al Zahrani,
Chaim M Roifman,
Jaap Boelens,
E Graham Davies,
Marina Cavazzana-Calvo,
Luigi Notarangelo,
H Bobby Gaspar
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ABSTRACT: Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed outcome of HCT in 106 patients with ADA-SCID who received a total of 119 transplants. HCT from matched sibling and family donors (MSDs, MFDs) had significantly better overall survival (86% and 81%) in comparison with HCT from matched unrelated (66%; P < .05) and haploidentical donors (43%; P < .001). Superior overall survival was also seen in patients who received unconditioned transplants in comparison with myeloablative procedures (81% vs 54%; P < .003), although in unconditioned haploidentical donor HCT, nonengraftment was a major problem. Long-term immune recovery showed that regardless of transplant type, overall T-cell numbers were similar, although a faster rate of T-cell recovery was observed after MSD/MFD HCT. Humoral immunity and donor B-cell engraftment was achieved in nearly all evaluable surviving patients and was seen even after unconditioned HCT. These data detail for the first time the outcomes of HCT for ADA-SCID and show that, if patients survive HCT, long-term cellular and humoral immune recovery is achieved.
Blood 07/2012; 120(17):3615-3624. · 9.90 Impact Factor
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ABSTRACT: Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare immunodeficiency disorder. We report three patients with WHIM syndrome who are affected by Tetralogy of Fallot (TOF). This observation suggests a possible increased risk of TOF in WHIM syndrome and that birth presentation of TOF and neutropenia should lead to suspect WHIM syndrome.
The Journal of pediatrics 06/2012; 161(4):763-5. · 4.02 Impact Factor
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Juliana F Fernandes,
Vanderson Rocha,
Myriam Labopin,
Benedicte Neven,
Despina Moshous,
Andrew R Gennery,
Wilhelm Friedrich, Fulvio Porta,
Cristina Diaz de Heredia,
Donna Wall, [......],
Wolfram Ebell,
Carmem Bonfim,
Krzysztof Kalwak,
Pierre Taupin,
Stéphane Blanche,
H Bobby Gaspar,
Paul Landais,
Alain Fischer,
Eliane Gluckman,
Marina Cavazzana-Calvo
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ABSTRACT: Pediatric patients with SCID constitute medical emergencies. In the absence of an HLA-identical hematopoietic stem cell (HSC) donor, mismatched related-donor transplantation (MMRDT) or unrelated-donor umbilical cord blood transplantation (UCBT) are valuable treatment options. To help transplantation centers choose the best treatment option, we retrospectively compared outcomes after 175 MMRDTs and 74 UCBTs in patients with SCID or Omenn syndrome. Median follow-up time was 83 months and 58 months for UCBT and MMRDT, respectively. Most UCB recipients received a myeloablative conditioning regimen; most MMRDT recipients did not. UCB recipients presented a higher frequency of complete donor chimerism (P = .04) and faster total lymphocyte count recovery (P = .04) without any statistically significance with the preparative regimen they received. The MMRDT and UCBT groups did not differ in terms of T-cell engraftment, CD4(+) and CD3(+) cell recoveries, while Ig replacement therapy was discontinued sooner after UCBT (adjusted P = .02). There was a trend toward a greater incidence of grades II-IV acute GVHD (P = .06) and more chronic GVHD (P = .03) after UCBT. The estimated 5-year overall survival rates were 62% ± 4% after MMRDT and 57% ± 6% after UCBT. For children with SCID and no HLA-identical sibling donor, both UCBT and MMRDT represent available HSC sources for transplantation with quite similar outcomes.
Blood 02/2012; 119(12):2949-55. · 9.90 Impact Factor
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Gaetana Lanzi,
Daniele Moratto,
Donatella Vairo,
Stefania Masneri,
Ottavia Delmonte,
Tiziana Paganini,
Silvia Parolini,
Giovanna Tabellini,
Cinzia Mazza,
Gianfranco Savoldi, [......],
Silvana Martino,
Pierangelo Tovo,
Itai M Pessach,
Michel J Massaad,
Narayanaswamy Ramesh, Fulvio Porta,
Alessandro Plebani,
Luigi D Notarangelo,
Raif S Geha,
Silvia Giliani
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ABSTRACT: A female offspring of consanguineous parents, showed features of Wiskott-Aldrich syndrome (WAS), including recurrent infections, eczema, thrombocytopenia, defective T cell proliferation and chemotaxis, and impaired natural killer cell function. Cells from this patient had undetectable WAS protein (WASP), but normal WAS sequence and messenger RNA levels. WASP interacting protein (WIP), which stabilizes WASP, was also undetectable. A homozygous c.1301C>G stop codon mutation was found in the WIPF1 gene, which encodes WIP. Introduction of WIP into the patient's T cells restored WASP expression. These findings indicate that WIP deficiency should be suspected in patients with features of WAS in whom WAS sequence and mRNA levels are normal.
Journal of Experimental Medicine 01/2012; 209(1):29-34. · 13.85 Impact Factor
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Susanna Livadiotti,
Giuseppe Maria Milano,
Annalisa Serra,
Laura Folgori,
Alessandro Jenkner,
Elio Castagnola,
Simone Cesaro,
Mario R Rossi,
Angelica Barone,
Giulio Zanazzo,
Francesca Nesi,
Maria Licciardello,
Raffaella De Santis,
Ottavio Ziino,
Monica Cellini, Fulvio Porta,
Desiree Caselli,
Giuseppe Pontrelli
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ABSTRACT: A nationwide questionnaire-based survey was designed to evaluate the management and prophylaxis of febrile neutropenia in pediatric patients admitted to hematology-oncology and hematopoietic stem cell transplant units. Of the 34 participating centers, 40 and 63%, respectively, continue to prescribe antibacterial and antimycotic prophylaxis in low-risk subjects and 78 and 94% in transplant patients. Approximately half of the centers prescribe a combination antibiotic regimen as first-line therapy in low-risk patients and up to 81% in high-risk patients. When initial empirical therapy fails after seven days, 63% of the centers add empirical antimycotic therapy in low-and 81% in high-risk patients. Overall management varies significantly across centers. Preventive nursing procedures are in accordance with international guidelines. This survey is the first to focus on prescribing practices in children with cancer and could help to implement practice guidelines.
Haematologica 01/2012; 97(1):147-50. · 6.42 Impact Factor
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Giorgio Dini,
Marco Zecca,
Adriana Balduzzi,
Chiara Messina,
Riccardo Masetti,
Franca Fagioli,
Claudio Favre,
Marco Rabusin, Fulvio Porta,
Erika Biral,
Mimmo Ripaldi,
Anna Paola Iori,
Carla Rognoni,
Arcangelo Prete,
Franco Locatelli
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ABSTRACT: Acute lymphoblastic leukemia (ALL) in second complete remission is one of the most common indications for allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients. We compared the outcome after HCST of adolescents, aged 14 to 18 years, with that of children (ie, patients < 14 years of age). Enrolled in the study were 395 patients given the allograft between January 1990 and December 2007; both children (334) and adolescents (61) were transplanted in the same pediatric institutions. All patients received a myeloablative regimen that included total body irradiation in the majority of them. The donor was an HLA-identical sibling for 199 patients and an unrelated volunteer in the remaining 196 patients. Children and adolescents had a comparable cumulative incidence of transplantation-related mortality, disease recurrence, and of both acute and chronic graft-versus-host disease. The 10-year probability of overall survival and event-free survival for the whole cohort of patients were 57% (95% confidence interval, 52%-62%) and 54% (95% confidence interval, 49%-59%), respectively, with no difference between children and adolescents. This study documents that adolescents with ALL in second complete remission given HSCT in pediatric centers have an outcome that does not differ from that of patients younger than 14 years of age.
Blood 12/2011; 118(25):6683-90. · 9.90 Impact Factor
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Roberto Rondelli,
Giorgio Dini,
Marisa De Rosa,
Paola Quarello,
Gianni Bisogno,
Maurizio Aricò,
Carivaldo Vasconcelos,
Paolo Tamaro,
Gabriella Casazza,
Marco Zecca,
Clementina De Laurentis, Fulvio Porta,
Andrea Pession
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ABSTRACT: There has been a noticeable annual increase in the number of children coming to Italy for medical treatment, just like it has happened in the rest of the European Union. In Italy, the assistance to children suffering from cancer is assured by the current network of 54 centres members of the Italian Association of Paediatric Haematology and Oncology (AIEOP), which has kept records of all demographic and clinical data in the database of Mod.1.01 Registry since 1989.
We used the information stored in the already mentioned database to assess the impact of immigration of foreign children with cancer on centres' activity, with the scope of drawing a map of the assistance to these cases.
Out of 14,738 cases recorded by all centres in the period from 1999 to 2008, 92.2% were born and resident in Italy, 4.1% (608) were born abroad and living abroad and 3.7% (538) were born abroad and living in Italy. Foreign children cases have increased over the years from 2.5% in 1999 to. 8.1% in 2008.Most immigrant children came from Europe (65.7%), whereas patients who came from America, Asia and Oceania amounted to 13.2%, 10.1%, 0.2%, respectively. The immigrant survival rate was lower compared to that of children who were born in Italy. This is especially true for acute lymphoblastic leukaemia patients entered an AIEOP protocol, who showed a 10-years survival rate of 71.0% vs. 80.7% (p < 0.001) for immigrants and patients born in Italy, respectively.
Children and adolescents are an increasingly important part of the immigration phenomenon, which occurs in many parts of the world. In Italy the vast majority of children affected by malignancies are treated in AIEOP centres. Since immigrant children are predominantly treated in northern Italy, these centres have developed a special expertise in treating immigrant patients, which is certainly very useful for the entire AIEOP network.
Italian Journal of Pediatrics 09/2011; 37:44.
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Donatella Vairo,
Laura Tassone,
Giovanna Tabellini,
Nicola Tamassia,
Sara Gasperini,
Flavia Bazzoni,
Alessandro Plebani, Fulvio Porta,
Luigi D Notarangelo,
Silvia Parolini,
Silvia Giliani,
Raffaele Badolato
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ABSTRACT: Subjects affected by Signal Transducer and Activator of Transcription 1 (STAT1) deficiency have lethal bacterial and viral infections. Complete STAT1 deficiency is inherited as an autosomal recessive disease; partial STAT1 deficiency is inherited as an autosomal recessive or autosomal dominant trait. Here, we report a patient who developed disseminated mycobacteriosis early in life and had several viral infections, including herpetic skin infection and interstitial pneumonia by cytomegalovirus with severe respiratory distress. Molecular analysis of STAT1 showed a novel homozygous mutation affecting a splice site, leading to exon 3 skipping and to synthesis of a lower molecular weight STAT1 protein. This mutation leads to marked reduction of STAT1 phosphorylation; the electromobility shift assay showed a complete defect of DNA-binding activity, which accounts for the complete impairment of peripheral blood mononuclear cell functional response to both IFN-γ and IFN-α. Moreover, analysis of natural killer cells showed a defective STAT1 phosphorylation in response to IFN-α and impaired basal cytolytic activity, suggesting that the STAT1-dependent pathway might be important for natural killer cell function. These results suggested that exon 3 skipping of STAT1 leads to abnormal signaling in response to IFN-γ and IFN-α, which is associated with susceptibility to intracellular pathogens and viruses.
Blood 08/2011; 118(7):1806-17. · 9.90 Impact Factor
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ABSTRACT: Tumor lysis syndrome (TLS) is a life-threatening complication in patients with hematological disease and/or solid tumors that results from rapid, large-scale tumor necrosis occurring spontaneously, or more commonly, as a result of chemotherapy. TLS is characterized by metabolic and electrolyte imbalances that include hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. Identification of risk groups as well as early detection of TLS is crucial for the establishment of appropriate strategies of prophylaxis and treatment.
A review of the peer-reviewed literature on TLS between 1990 and 2011 was conducted via a systematic search of the PubMed database using the keywords "TLS" [AND] "management," "risk evaluation," "prophylaxis," and "treatment." An expert opinion-based approach was used to review the national and international recommendations and guidelines on the topic.
The PubMed search produced 90 results, all of which were evaluated. These studies, together with a recent international consensus panel provided recommendations for evaluating the risk of TLS and providing prophylaxis. Five algorithms are presented that consider all of the factors when assessing the risk for neoplastic disease in general, and specifically for leukemia and lymphoma.
The present report provides clinicians with an easily consultable tool to guide the evidence-based management of this oncohematological emergency.
Advances in Therapy 08/2011; 28(8):684-97. · 2.11 Impact Factor
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ABSTRACT: A limited proportion of adolescents with cancer currently receives treatment at pediatric oncology centers and this factor is considered one of the possible explanations for the lack of improvement in survival trends observed over the years in this age group. The adoption of inflexible upper age limits for admitting patients to pediatric units may help to explain this situation. This paper reports the results of a national survey on adolescents' access to, and age limits adopted by, Italian pediatric oncology centers, briefly discussing possible actions to bridge the gap in adolescents' access to care. The analysis showed a great variability in the upper age limits adopted at Italian pediatric oncology centers; in many cases age limits are set at 16, 15, or even 14 years. As major finding, a correlation was documented between age limits and number of adolescents treated in the pediatric centers. In principle, this finding should suggest that increasing the upper age limit may result in an increase of the access of adolescents in pediatric oncology centers.
Pediatric Hematology and Oncology 06/2011; 29(1):55-61. · 0.89 Impact Factor
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Daniele Moratto,
Silvia Giliani,
Carmem Bonfim,
Evelina Mazzolari,
Alain Fischer,
Hans D Ochs,
Andrew J Cant,
Adrian J Thrasher,
Morton J Cowan,
Michael H Albert, [......],
Adriana Koliski,
Jose Zanis Neto, Fulvio Porta,
Waseem Qasim,
Paul Veys,
Kristina Kavanau,
Manfred Hönig,
Ansgar Schulz,
Wilhelm Friedrich,
Luigi D Notarangelo
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ABSTRACT: In this retrospective collaborative study, we have analyzed long-term outcome and donor cell engraftment in 194 patients with Wiskott-Aldrich syndrome (WAS) who have been treated by hematopoietic cell transplantation (HCT) in the period 1980- 2009. Overall survival was 84.0% and was even higher (89.1% 5-year survival) for those who received HCT since the year 2000, reflecting recent improvement of outcome after transplantation from mismatched family donors and for patients who received HCT from an unrelated donor at older than 5 years. Patients who went to transplantation in better clinical conditions had a lower rate of post-HCT complications. Retrospective analysis of lineage-specific donor cell engraftment showed that stable full donor chimerism was attained by 72.3% of the patients who survived for at least 1 year after HCT. Mixed chimerism was associated with an increased risk of incomplete reconstitution of lymphocyte count and post-HCT autoimmunity, and myeloid donor cell chimerism < 50% was associated with persistent thrombocytopenia. These observations indicate continuous improvement of outcome after HCT for WAS and may have important implications for the development of novel protocols aiming to obtain full correction of the disease and reduce post-HCT complications.
Blood 06/2011; 118(6):1675-84. · 9.90 Impact Factor
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Filippo Spreafico,
Lucia Dora Notarangelo,
Richard Fabian Schumacher,
Gianfranco Savoldi,
Beatrice Gamba,
Monica Terenziani,
Paola Collini,
Silvia Fasoli,
Lucio Giordano,
Bercich Luisa, Fulvio Porta,
Maura Massimino,
Paolo Radice,
Daniela Perotti
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ABSTRACT: We report on a girl affected with tuberous sclerosis, carrying a germline de novo TSC2 mutation, c.4934-4935delTT, leading to a p.F1645CfsX7, who developed a unilateral Wilms tumor (WT). Molecular investigation of the tumor biopsy at diagnosis revealed the loss of the constitutional wild-type TSC2 allele, and loss of heterozygosity for the WT1 gene. Deletion of the WTX gene was also present, but it involved the functionally inactive X chromosome. No mutation affecting the remaining WT1 and WTX alleles, as well as the CTNNB1 gene was found. Pathological examination of the surgical specimen documented the presence of diffuse anaplasia and p53 immunoreactivity. To the best of our knowledge, this is the second report of a patient with tuberous sclerosis who developed a WT, and it represents the first case in which a detailed clinical and molecular description is provided.
American Journal of Medical Genetics Part A 06/2011; 155A(6):1419-24. · 2.39 Impact Factor
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ABSTRACT: Warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome is a genetic disease that is caused by heterozygous mutations of the CXCR4 gene. These mutations confer an increased leukocyte response to the CXCR4-ligand CXCL12, resulting in abnormal homeostasis of many leukocyte types, including neutrophils and lymphocytes. Analysis of the myeloid and plasmacytoid dendritic cell blood counts in WHIM patients revealed a striking defect in the number of plasmacytoid dendritic cells as well as a partial reduction of the number of myeloid dendritic cells, compared with healthy subjects. Moreover, the production of interferon-α by mononuclear cells in response to herpes simplex infection, or after stimulation with the Toll-like receptor 9 ligand CpG, was undetectable in WHIM patients. Because plasmacytoid dendritic cells play a key role in the defense against viruses and their generation and motility are in part dependent on CXCR4, we hypothesized that the susceptibility of WHIM patients to warts is related to the abnormal homeostasis of plasmacytoid dendritic cells.
Blood 12/2010; 116(23):4870-3. · 9.90 Impact Factor
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Andrew R Gennery,
Mary A Slatter,
Laure Grandin,
Pierre Taupin,
Andrew J Cant,
Paul Veys,
Persis J Amrolia,
H Bobby Gaspar,
E Graham Davies,
Wilhelm Friedrich, [......],
Nico M Wulffraat,
Reinhard Seger,
Tayfun Güngör,
Anders Fasth,
Petr Sedlacek,
Benedicte Neven,
Stephane Blanche,
Alain Fischer,
Marina Cavazzana-Calvo,
Paul Landais
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ABSTRACT: Hematopoietic stem cell transplantation remains the only treatment for most patients with severe combined immunodeficiencies (SCIDs) or other primary immunodeficiencies (non-SCID PIDs).
To analyze the long-term outcome of patients with SCID and non-SCID PID from European centers treated between 1968 and 2005.
The product-limit method estimated cumulative survival; the log-rank test compared survival between groups. A Cox proportional-hazard model evaluated the impact of independent predictors on patient survival.
In patients with SCID, survival with genoidentical donors (n = 25) from 2000 to 2005 was 90%. Survival using a mismatched relative (n = 96) has improved (66%), similar to that using an unrelated donor (n = 46; 69%; P = .005). Transplantation after year 1995, a younger age, B(+) phenotype, genoidentical and phenoidentical donors, absence of respiratory impairment, or viral infection before transplantation were associated with better prognosis on multivariate analysis. For non-SCID PID, in contrast with patients with SCID, we confirm that, in the 2000 to 2005 period, using an unrelated donor (n = 124) gave a 3-year survival rate similar to a genoidentical donor (n = 73), 79% for both. Survival was 76% in phenoidentical transplants (n = 23) and worse in mismatched related donor transplants (n = 47; 46%; P = .016).
This is the largest cohort study of such patients with the longest follow-up. Specific issues arise for different patient groups. Patients with B-SCID have worse survival than other patients with SCID, despite improvements in each group. For non-SCID PID, survival is worse than SCID, although more conditions are now treated. Individual disease categories now need to be analyzed so that disease-specific prognosis may be better understood and the best treatments planned.
The Journal of allergy and clinical immunology 09/2010; 126(3):602-10.e1-11. · 9.17 Impact Factor
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ABSTRACT: A major problem in the field of stem cell transplantation is the difficulty to monitor the efficacy of immune reconstitution. By modifying the widely used method of measuring T-cell receptor excision circles (TRECs) and the recently proposed kappa-deleting recombination excision circles (KRECs) assay, we set up a duplex Real-Time PCR that allowed the simultaneous quantification of newly produced T and B cells in children with primary immunodeficiency undergone to transplantation. We found that lymphocyte recovery involves the mobilization of both new T and B cells from production and maturation sites, and that the increase of TRECs and KRECs can be or strictly associated or independent one from the other. Some patients showed a "lymphocyte rebound" which is followed by a progressive decrease of newly produced T and B lymphocytes starting about 2years after transplantation. In other patients, TRECs and KRECs number remained very low for the entire period of study.
Clinical Immunology 05/2010; 136(2):217-27. · 4.05 Impact Factor
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Barbara Cassani,
Pietro Luigi Poliani,
Daniele Moratto,
Cristina Sobacchi,
Veronica Marrella,
Laura Imperatori,
Donatella Vairo,
Alessandro Plebani,
Silvia Giliani,
Paolo Vezzoni,
Fabio Facchetti, Fulvio Porta,
Luigi D Notarangelo,
Anna Villa,
Raffaele Badolato
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ABSTRACT: Omenn syndrome (OS) is an autosomal-recessive disorder characterized by severe immunodeficiency and T-cell-mediated autoimmunity. The disease is caused by hypomorphic mutations in recombination-activating genes that hamper the process of Variable (V) Diversity (D) Joining (J) recombination, leading to the generation of autoreactive T cells. We have previously shown that in OS the expression of autoimmune regulator, a key factor governing central tolerance, is markedly reduced.
Here, we have addressed the role of peripheral tolerance in the disease pathogenesis.
We have analyzed forkhead box protein P3 (FOXP3) expression in peripheral blood T cells of 4 patients with OS and in lymphoid organs of 8 patients with OS and have tested the suppressive activity of sorted CD4(+) CD25(high) peripheral blood T cells in 2 of these patients.
We have observed that CD4(+)CD25(high)T cells isolated ex vivo from patients with OS failed to suppress proliferation of autologous or allogenic CD4(+) responder T cells. Moreover, despite individual variability in the fraction of circulating FOXP3(+) CD4 cells in patients with OS, the immunohistochemical analysis of FOXP3 expression in lymph nodes and thymus of patients with OS demonstrated a severe reduction of this cell subset compared with control tissues.
Overall, these results suggest a defect of regulatory T cells in OS leading to a breakdown of peripheral tolerance, which may actively concur to the development of autoimmune manifestations in the disease.
The Journal of allergy and clinical immunology 01/2010; 125(1):209-16. · 9.17 Impact Factor
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ABSTRACT: The aim of the most recent studies on regenerative medicine was to focus on capability of stem cells deriving not only from haematopoietic system, but also from other organ and tissues, to regenerate damaged tissues. Stem cells derived from foetal annexes such as cord blood, placenta and amniotic fluid can be currently used in the effort to treat prenatally diagnosed genetic diseases. Cells derived from cord blood have been used since 1988 as an alternative source to realize stem cell transplantation. Compared with bone marrow, cord blood has shown the advantages of quick availability, less risk of GHVD, together with higher compatibility rates, and less risk of infections. Mesenchymal stem cells (MSCs) are multi-potent stem cells able to differentiate into different lineages, including osteocytes, chondrocytes, and adipocytes. Because of their trafficking capacity to injured tissues, clinical trials have been started evaluating the use of MSCs in the treatment of metabolic diseases like Hurler syndrome and metachromatic leukodystrophy, or Osteogenesis Imperfecta. MSCs were initially identified in adult bone marrow (BM-MSC), but cells resembling BM-MSCs have also been found in other tissues, both adult (peripheral blood, synovial membrane) and foetal (peripheral blood, liver, spleen, placenta, umbilical cord, and amniotic membrane). BM-MSCs have been widely used in clinical applications, as for cell-based therapy of Osteogenesis Imperfecta and metabolic diseases. In addition, human multi-potent MSCs present in second-trimester amniotic fluids may be a good target for prenatal gene therapy because of their expandability, their ability to differentiate into multiple lineages and their high transduction efficiency.
Early human development 10/2009; 85(10 Suppl):S15-8. · 2.12 Impact Factor
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ABSTRACT: Adenosine deaminase deficiency is a disorder of purine metabolism leading to severe combined immunodeficiency (ADA-SCID). Without treatment, the condition is fatal and requires early intervention. Haematopoietic stem cell transplantation is the major treatment for ADA-SCID, although survival following different donor sources varies considerably. Unlike other SCID forms, 2 other options are available for ADA-SCID: enzyme replacement therapy (ERT) with pegylated bovine ADA, and autologous haematopoietic stem cell gene therapy (GT). Due to the rarity of the condition, the lack of large scale outcome studies, and availability of different treatments, guidance on treatment strategies is limited. We have reviewed the currently available evidence and together with our experience of managing this condition propose a consensus management strategy. Matched sibling donor transplants represent a successful treatment option with high survival rates and excellent immune recovery. Mismatched parental donor transplants have a poor survival outcome and should be avoided unless other treatments are unavailable. ERT and GT both show excellent survival, and therefore the choice between ERT, MUD transplant, or GT is difficult and dependent on several factors, including accessibility to the different modalities, response of patients to long-term ERT, and the attitudes of physicians and parents to the short- and potential long-term risks associated with different treatments.
Blood 08/2009; 114(17):3524-32. · 9.90 Impact Factor
