Fabiano Pieroni - Academia.edu (original) (raw)
Papers by Fabiano Pieroni
Rev Bras Hematol Hemoter, May 1, 2009
Revista Brasileira de Hematologia e Hemoterapia
ABSTRACT
Revista Brasileira de Hematologia e Hemoterapia
Os distúrbios hereditários das hemoglobinas são as doenças genéticas mais frequentes do homem e m... more Os distúrbios hereditários das hemoglobinas são as doenças genéticas mais frequentes do homem e mais difundidas no mundo, abrangendo sobretudo continentes como África, Américas, Europa e extensas regiões da Ásia. Estima-se que haja 270 milhões de portadores de hemoglobinopatias no mundo, dos quais 80 milhões são portadores de talassemia. Aproximadamente 60 mil crianças nascem anualmente no mundo com talassemia e 250 mil com anemia falciforme, dando uma frequência de 2,4 crianças afetadas para cada 1.000 nascimentos. No Brasil, a doenca falciforme é a doença hereditária monogênica mais comum, estimando-se que haja entre 20 a 30 mil pacientes portadores desta doenca. O transplante de células-tronco hematopoéticas alogênico (TCTH alo) é atualmente a única modalidade terapêutica capaz de curar pacientes com hemoglobinopatias. Neste artigo discutiremos os dados disponíveis na literatura e sugerimos os critérios para a indicação do TCTH nas hemoglobinopatias.
Indian journal of experimental biology, 2011
The present review discusses the use of autologous hematopoietic stem cell transplantation (HSCT)... more The present review discusses the use of autologous hematopoietic stem cell transplantation (HSCT) for the treatment of diabetes mellitus type 1 (DM 1). It has been observed that high dose immunosuppression followed by HSCT shows better results among other immunotherapeutic treatments for the disease as the patients with adequate beta cell reserve achieve insulin independence. However, this response is not maintained and reoccurrence of the disease is major a major challenge to use HSCT in future to prevent or control relapse of DM 1.
Kidney international supplements, 2011
In this review, we present (1) a brief discussion of hematopoietic stem cell transplantation (HSC... more In this review, we present (1) a brief discussion of hematopoietic stem cell transplantation (HSCT) for severe and refractory autoimmune diseases (AIDs) from its beginning in 1996 through recently initiated prospective randomized clinical trials; (2) an update (up to July 2009) of clinical and laboratory outcomes of 23 patients with newly diagnosed type 1 diabetes mellitus (T1DM), who underwent autologous HSCT at the Bone Marrow Transplantation Unit of the Ribeirão Preto Medical School, University of São Paulo, Brazil; (3) a discussion of possible mechanisms of action of HSCT in AIDs, including preliminary laboratory data obtained from our patients; and (4) a discussion of future perspectives of stem cell therapy for T1DM and type 2 DM, including the use of stem cell sources other than adult bone marrow and the combination of cell therapy with regenerative compounds.
In this review, we present 1) scientific basis for the use of high dose immunosuppression followe... more In this review, we present 1) scientific basis for the use of high dose immunosuppression followed by autologous peripheral blood hematopoietic stem cell transplantation for newly diagnosed type 1 diabetes mellitus, 2) an update of clinical and laboratory outcomes in 21 patients transplanted at the University Hospital of the Ribeirão Preto Medical School, University of São Paulo, Brazil, including 6 relapses in patients without previous ketoacidosis and 3) a discussion of future prospectives of cellular therapy for type 1 diabetes mellitus. Rev. bras. hematol. hemoter. 2008; 30(Supl. 2):55-59.
Revista Brasileira de Hematologia e Hemoterapia, 2009
Nesta revisão são discutidas várias alternativas de regeneração do conjunto de células produtoras... more Nesta revisão são discutidas várias alternativas de regeneração do conjunto de células produtoras de insulina do pâncreas, usando células-tronco embrionárias do cordão umbilical e adultas, e o trabalho que está sendo realizado em nosso grupo de pesquisas utilizando imunossupressão em altas doses combinada com a infusão de células-tronco hematopoéticas autólogas em diabete do tipo 1 recém-diagnosticado. Rev. Bras.
Revista Brasileira de Hematologia e Hemoterapia, 2008
Clinical Science, 2014
Autologous hematopoietic SCT (AHSCT) has been investigated in the past as a therapeutic alternati... more Autologous hematopoietic SCT (AHSCT) has been investigated in the past as a therapeutic alternative for multiple sclerosis (MS). Despite advances in clinical management, knowledge about mechanisms involved with clinical remission post transplantation is still limited. Abnormal microRNA and gene expression patterns were described in MS and have been suggested as disease biomarkers and potential therapeutic targets. Here we assessed T-and B-cell reconstitution, microRNAs and immunoregulatory gene expression after AHSCT. Early immune reconstitution was mainly driven by peripheral homeostatic proliferation. AHSCT increased CD4 + CD25 hi FoxP3 + regulatory T-cell counts and expression of CTLA-4 and GITR (glucocorticoid-induced TNFR) on CD4 + CD25 hi T cells. We found transient increase in exhausted PD-1 + T cells and of suppressive CD8 + CD28 − CD57 + T cells. At baseline, CD4 + and CD8 + T cells from MS patients presented upregulated miR-16, miR-155 and miR-142-3p and downregulated FOXP3, FOXO1, PDCD1 and IRF2BP2. After transplantation, the expression of FOXP3, FOXO1, PDCD1 and IRF2BP2 increased, reaching control levels at 2 years. Expression of miR-16, miR-155 and miR-142-3p decreased towards normal levels at 6 months post therapy, remaining downregulated until the end of follow-up. These data strongly suggest that AHSCT normalizes microRNA and gene expression, thereby improving the immunoregulatory network. These mechanisms may be important for disease control in the early periods after AHSCT.
Revista Brasileira de Hematologia e Hemoterapia, 2010
Page 1. 46 Atualização / Update Consenso Brasileiro em Transplante de Células-Tronco Hematopoétic... more Page 1. 46 Atualização / Update Consenso Brasileiro em Transplante de Células-Tronco Hematopoéticas: Comitê de Hemoglobinopatias Brazilian Consensus Meeting on Stem Cell Transplantation: Hemoglobinopathies Committee ...
Pediatric Transplantation, 2014
Seckel syndrome is a rare autosomal recessive disease, genetically heterogeneous, characterized b... more Seckel syndrome is a rare autosomal recessive disease, genetically heterogeneous, characterized by short stature, prenatal microcephaly, intellectual disability, dysmorphic features, chromosomal instability, and hematological disorders. We report the case of a six-yr-old boy with Seckel syndrome and aplastic anemia who underwent successful allogeneic bone marrow transplantation from ten of ten HLA matched unrelated donor. Currently the patient is on D+771, in good health conditions and with no further complications. In conclusion, this case indicates that bone marrow transplantation is an acceptable therapeutic option for Seckel syndrome complicated by hematological alterations.
The Lancet, 2004
Embryonic stem cells (ESC) can be differentiated into insulin-producing cells by manipulating cul... more Embryonic stem cells (ESC) can be differentiated into insulin-producing cells by manipulating culture conditions. In-vitro differentiation of mouse ESC can generate embryoid bodies, which, after selection for nestinexpressing ESC, were stimulated to differentiate towards a -cell-like phenotype. 1 The addition of phosphoinositide kinase inhibitors promoted differentiation of larger numbers of ESC towards functional  cells. 2 Variations in ESC-culture conditions generate cells with properties of  cells. [3][4][5] With manipulation of culture conditions and use of pax4 or pdx-1, transcription factors associated with -cell lineage 6,7 yield promising results. Some doubt has been cast on whether ESC differentiation protocols truly yield cells that produce insulin, or cells that merely absorb insulin from the medium. 8 These differentiated cells must actively synthesise and secrete insulin rather than insulin being detected. Functioning molecular components of regulated secretion of insulin and insulin-containing vesicles are additional features that indicate a -cell phenotype. Transplantation of ESCderived insulin-producing cells reverses diabetes in rodents, 2,6 indicating that these cells do synthesise and release insulin. The early and uncontrolled introduction of transcription factors into ESC during in-vitro differentiation might not yield the desired results. 5 Regulated expression of introduced transcription factors that can be turned on during in-vitro differentiation of ESC might be more successful. 7 ESC, genetically selected for insulin expression and injected into diabetic rats, improve glucose control. 10 Human ESC produce insulin under different culture conditions. 11,12 Techniques that do not require murine feeder cells have been developed, allowing for singlespecies propagation of ESC and avoiding possible zoonotic infection of cells intended for clinical use. 13 Problems in control of differentiation and teratoma formation from ESC-derived insulin-producing cells remain to be overcome. 14 Existing ESC lines are not assumed to be identical or ideal for generating islets or  cells. Hence additional ESC lines continue to be generated. 15 Ethical concerns about the use of ESC need to be addressed and resolved in the face of this powerful technology.
JAMA, 2007
In Reply: Drs Ross and Philipson argue that our study of stem cell transplantation was unethical ... more In Reply: Drs Ross and Philipson argue that our study of stem cell transplantation was unethical because (1) research involving pediatric participants is unethical unless it will promote the health of children and the research cannot be performed in adults, according ...
Annals of The New York Academy of Sciences, 2008
Brazilian Dental Journal, 2009
REVISTA ROMÂNÅ DE STOMATOLOGIE -VOLUMUL LV, NR. 4
Bone Marrow Transplantation, 2010
Studies have shown that autologous hematopoietic SCT (HSCT) can be used as an intensive immunosup... more Studies have shown that autologous hematopoietic SCT (HSCT) can be used as an intensive immunosuppressive therapy to treat refractory patients and to prevent the progression of multiple sclerosis (MS). This is a prospective multicentric Brazilian MS trial comparing two conditioning regimens: BEAM/horse ATG and CY/ rabbit ATG. Most (80.4%) of the 41 subjects in the study had the secondary progressive MS subtype and the mean age was 42 years. The baseline EDSS score in 58.5% of the subjects was 6.5 and 78% had a score of 6.0 or higher, respectively. The complication rate during the intratransplantation period was 56% for all patients: 71.4% of the patients in the BEAM/hATG group and 40% in the CY/rATG group (P ¼ 0.04). Three subjects (7.5%) died of cardiac toxicity, sepsis and alveolar hemorrhage, all of them in the BEAM/ATG group. EFS was 58.54% for a ll patients: 47% in the BEAM/hATG group and 70% in the CY/rATG group (P ¼ 0.288). In conclusion, the CY/rATG regimen seems to be associated with similar outcome results, but presented less toxicity when compared with the BEAM/hATG regimen. Long-term followup would be required to fully assess the differences in therapeutic effectiveness between the two regimens.
Bone Marrow Transplantation, 2006
Bone Marrow Transplantation, 2007
We report here the first six cases of leprosy associated with HLA-identical allogeneic SCT in dif... more We report here the first six cases of leprosy associated with HLA-identical allogeneic SCT in different phases and with different findings and outcomes. Skin and peripheral nerves may be sites of leprosy associated with SCT, stressing the importance of differential diagnosis between leprosy and GVHD or drug reactions. Clinical manifestations of leprosy before or after transplantation did not influence the outcome of SCT in our cases.
Rev Bras Hematol Hemoter, May 1, 2009
Revista Brasileira de Hematologia e Hemoterapia
ABSTRACT
Revista Brasileira de Hematologia e Hemoterapia
Os distúrbios hereditários das hemoglobinas são as doenças genéticas mais frequentes do homem e m... more Os distúrbios hereditários das hemoglobinas são as doenças genéticas mais frequentes do homem e mais difundidas no mundo, abrangendo sobretudo continentes como África, Américas, Europa e extensas regiões da Ásia. Estima-se que haja 270 milhões de portadores de hemoglobinopatias no mundo, dos quais 80 milhões são portadores de talassemia. Aproximadamente 60 mil crianças nascem anualmente no mundo com talassemia e 250 mil com anemia falciforme, dando uma frequência de 2,4 crianças afetadas para cada 1.000 nascimentos. No Brasil, a doenca falciforme é a doença hereditária monogênica mais comum, estimando-se que haja entre 20 a 30 mil pacientes portadores desta doenca. O transplante de células-tronco hematopoéticas alogênico (TCTH alo) é atualmente a única modalidade terapêutica capaz de curar pacientes com hemoglobinopatias. Neste artigo discutiremos os dados disponíveis na literatura e sugerimos os critérios para a indicação do TCTH nas hemoglobinopatias.
Indian journal of experimental biology, 2011
The present review discusses the use of autologous hematopoietic stem cell transplantation (HSCT)... more The present review discusses the use of autologous hematopoietic stem cell transplantation (HSCT) for the treatment of diabetes mellitus type 1 (DM 1). It has been observed that high dose immunosuppression followed by HSCT shows better results among other immunotherapeutic treatments for the disease as the patients with adequate beta cell reserve achieve insulin independence. However, this response is not maintained and reoccurrence of the disease is major a major challenge to use HSCT in future to prevent or control relapse of DM 1.
Kidney international supplements, 2011
In this review, we present (1) a brief discussion of hematopoietic stem cell transplantation (HSC... more In this review, we present (1) a brief discussion of hematopoietic stem cell transplantation (HSCT) for severe and refractory autoimmune diseases (AIDs) from its beginning in 1996 through recently initiated prospective randomized clinical trials; (2) an update (up to July 2009) of clinical and laboratory outcomes of 23 patients with newly diagnosed type 1 diabetes mellitus (T1DM), who underwent autologous HSCT at the Bone Marrow Transplantation Unit of the Ribeirão Preto Medical School, University of São Paulo, Brazil; (3) a discussion of possible mechanisms of action of HSCT in AIDs, including preliminary laboratory data obtained from our patients; and (4) a discussion of future perspectives of stem cell therapy for T1DM and type 2 DM, including the use of stem cell sources other than adult bone marrow and the combination of cell therapy with regenerative compounds.
In this review, we present 1) scientific basis for the use of high dose immunosuppression followe... more In this review, we present 1) scientific basis for the use of high dose immunosuppression followed by autologous peripheral blood hematopoietic stem cell transplantation for newly diagnosed type 1 diabetes mellitus, 2) an update of clinical and laboratory outcomes in 21 patients transplanted at the University Hospital of the Ribeirão Preto Medical School, University of São Paulo, Brazil, including 6 relapses in patients without previous ketoacidosis and 3) a discussion of future prospectives of cellular therapy for type 1 diabetes mellitus. Rev. bras. hematol. hemoter. 2008; 30(Supl. 2):55-59.
Revista Brasileira de Hematologia e Hemoterapia, 2009
Nesta revisão são discutidas várias alternativas de regeneração do conjunto de células produtoras... more Nesta revisão são discutidas várias alternativas de regeneração do conjunto de células produtoras de insulina do pâncreas, usando células-tronco embrionárias do cordão umbilical e adultas, e o trabalho que está sendo realizado em nosso grupo de pesquisas utilizando imunossupressão em altas doses combinada com a infusão de células-tronco hematopoéticas autólogas em diabete do tipo 1 recém-diagnosticado. Rev. Bras.
Revista Brasileira de Hematologia e Hemoterapia, 2008
Clinical Science, 2014
Autologous hematopoietic SCT (AHSCT) has been investigated in the past as a therapeutic alternati... more Autologous hematopoietic SCT (AHSCT) has been investigated in the past as a therapeutic alternative for multiple sclerosis (MS). Despite advances in clinical management, knowledge about mechanisms involved with clinical remission post transplantation is still limited. Abnormal microRNA and gene expression patterns were described in MS and have been suggested as disease biomarkers and potential therapeutic targets. Here we assessed T-and B-cell reconstitution, microRNAs and immunoregulatory gene expression after AHSCT. Early immune reconstitution was mainly driven by peripheral homeostatic proliferation. AHSCT increased CD4 + CD25 hi FoxP3 + regulatory T-cell counts and expression of CTLA-4 and GITR (glucocorticoid-induced TNFR) on CD4 + CD25 hi T cells. We found transient increase in exhausted PD-1 + T cells and of suppressive CD8 + CD28 − CD57 + T cells. At baseline, CD4 + and CD8 + T cells from MS patients presented upregulated miR-16, miR-155 and miR-142-3p and downregulated FOXP3, FOXO1, PDCD1 and IRF2BP2. After transplantation, the expression of FOXP3, FOXO1, PDCD1 and IRF2BP2 increased, reaching control levels at 2 years. Expression of miR-16, miR-155 and miR-142-3p decreased towards normal levels at 6 months post therapy, remaining downregulated until the end of follow-up. These data strongly suggest that AHSCT normalizes microRNA and gene expression, thereby improving the immunoregulatory network. These mechanisms may be important for disease control in the early periods after AHSCT.
Revista Brasileira de Hematologia e Hemoterapia, 2010
Page 1. 46 Atualização / Update Consenso Brasileiro em Transplante de Células-Tronco Hematopoétic... more Page 1. 46 Atualização / Update Consenso Brasileiro em Transplante de Células-Tronco Hematopoéticas: Comitê de Hemoglobinopatias Brazilian Consensus Meeting on Stem Cell Transplantation: Hemoglobinopathies Committee ...
Pediatric Transplantation, 2014
Seckel syndrome is a rare autosomal recessive disease, genetically heterogeneous, characterized b... more Seckel syndrome is a rare autosomal recessive disease, genetically heterogeneous, characterized by short stature, prenatal microcephaly, intellectual disability, dysmorphic features, chromosomal instability, and hematological disorders. We report the case of a six-yr-old boy with Seckel syndrome and aplastic anemia who underwent successful allogeneic bone marrow transplantation from ten of ten HLA matched unrelated donor. Currently the patient is on D+771, in good health conditions and with no further complications. In conclusion, this case indicates that bone marrow transplantation is an acceptable therapeutic option for Seckel syndrome complicated by hematological alterations.
The Lancet, 2004
Embryonic stem cells (ESC) can be differentiated into insulin-producing cells by manipulating cul... more Embryonic stem cells (ESC) can be differentiated into insulin-producing cells by manipulating culture conditions. In-vitro differentiation of mouse ESC can generate embryoid bodies, which, after selection for nestinexpressing ESC, were stimulated to differentiate towards a -cell-like phenotype. 1 The addition of phosphoinositide kinase inhibitors promoted differentiation of larger numbers of ESC towards functional  cells. 2 Variations in ESC-culture conditions generate cells with properties of  cells. [3][4][5] With manipulation of culture conditions and use of pax4 or pdx-1, transcription factors associated with -cell lineage 6,7 yield promising results. Some doubt has been cast on whether ESC differentiation protocols truly yield cells that produce insulin, or cells that merely absorb insulin from the medium. 8 These differentiated cells must actively synthesise and secrete insulin rather than insulin being detected. Functioning molecular components of regulated secretion of insulin and insulin-containing vesicles are additional features that indicate a -cell phenotype. Transplantation of ESCderived insulin-producing cells reverses diabetes in rodents, 2,6 indicating that these cells do synthesise and release insulin. The early and uncontrolled introduction of transcription factors into ESC during in-vitro differentiation might not yield the desired results. 5 Regulated expression of introduced transcription factors that can be turned on during in-vitro differentiation of ESC might be more successful. 7 ESC, genetically selected for insulin expression and injected into diabetic rats, improve glucose control. 10 Human ESC produce insulin under different culture conditions. 11,12 Techniques that do not require murine feeder cells have been developed, allowing for singlespecies propagation of ESC and avoiding possible zoonotic infection of cells intended for clinical use. 13 Problems in control of differentiation and teratoma formation from ESC-derived insulin-producing cells remain to be overcome. 14 Existing ESC lines are not assumed to be identical or ideal for generating islets or  cells. Hence additional ESC lines continue to be generated. 15 Ethical concerns about the use of ESC need to be addressed and resolved in the face of this powerful technology.
JAMA, 2007
In Reply: Drs Ross and Philipson argue that our study of stem cell transplantation was unethical ... more In Reply: Drs Ross and Philipson argue that our study of stem cell transplantation was unethical because (1) research involving pediatric participants is unethical unless it will promote the health of children and the research cannot be performed in adults, according ...
Annals of The New York Academy of Sciences, 2008
Brazilian Dental Journal, 2009
REVISTA ROMÂNÅ DE STOMATOLOGIE -VOLUMUL LV, NR. 4
Bone Marrow Transplantation, 2010
Studies have shown that autologous hematopoietic SCT (HSCT) can be used as an intensive immunosup... more Studies have shown that autologous hematopoietic SCT (HSCT) can be used as an intensive immunosuppressive therapy to treat refractory patients and to prevent the progression of multiple sclerosis (MS). This is a prospective multicentric Brazilian MS trial comparing two conditioning regimens: BEAM/horse ATG and CY/ rabbit ATG. Most (80.4%) of the 41 subjects in the study had the secondary progressive MS subtype and the mean age was 42 years. The baseline EDSS score in 58.5% of the subjects was 6.5 and 78% had a score of 6.0 or higher, respectively. The complication rate during the intratransplantation period was 56% for all patients: 71.4% of the patients in the BEAM/hATG group and 40% in the CY/rATG group (P ¼ 0.04). Three subjects (7.5%) died of cardiac toxicity, sepsis and alveolar hemorrhage, all of them in the BEAM/ATG group. EFS was 58.54% for a ll patients: 47% in the BEAM/hATG group and 70% in the CY/rATG group (P ¼ 0.288). In conclusion, the CY/rATG regimen seems to be associated with similar outcome results, but presented less toxicity when compared with the BEAM/hATG regimen. Long-term followup would be required to fully assess the differences in therapeutic effectiveness between the two regimens.
Bone Marrow Transplantation, 2006
Bone Marrow Transplantation, 2007
We report here the first six cases of leprosy associated with HLA-identical allogeneic SCT in dif... more We report here the first six cases of leprosy associated with HLA-identical allogeneic SCT in different phases and with different findings and outcomes. Skin and peripheral nerves may be sites of leprosy associated with SCT, stressing the importance of differential diagnosis between leprosy and GVHD or drug reactions. Clinical manifestations of leprosy before or after transplantation did not influence the outcome of SCT in our cases.