Davide Zanon - Academia.edu (original) (raw)
Papers by Davide Zanon
Journal of Pediatric Hematology/Oncology, 2015
Background: Sickle cell disease (SCD) is a well-known multisystem illness characterized by vascul... more Background: Sickle cell disease (SCD) is a well-known multisystem illness characterized by vascular injury due to vasoocclusion and hemolysis, as well as infectious complications and iron overload, all of which contribute to high morbidity and mortality rates among children. In these patients, some authors have previously described iron cortical deposition in the kidney. We here report the first case in the literature of a girl affected by SCD showing an anomalous metal and rare element retention in the renal cortex. Case Presentation: A 10-year-old white girl affected by SCD underwent a routine magnetic resonance imaging investigation that evidenced a reduced signal intensity in the renal cortex, compatible with hemosiderin precipitation. Histologic and elemental analyses of the hepatic and the renal biotic samples, performed with inductively coupled plasma mass spectrometry, revealed that concomitant with the high iron deposition, toxic and potentially carcinogenic elements such as nickel, magnesium, rubidium, and gadolinuim were anomalously retained particularly in the kidney. Conclusions: The finding of rare and toxic elements in the kidney of SCD patients might be linked to the development of specific neoplastic transformations already described in this patient cohort. To be confirmed, our speculations need to be demonstrated in large sampling of patients.
Introduction: Brain infections are still a life threatening event in immunocompromised patients. ... more Introduction: Brain infections are still a life threatening event in immunocompromised patients. Due to delays in etiological diagnosis, severe complications and related mortality rate are still too high. Brain Supporters is a multidisciplinary team working to develop a software tool which would be helpful for physicians trying to minimize this event in an innovative way. Material and methods: All biological and clinical data we have selected, related to immunosuppressed patients with suspected or proven brain infectious diseases, and radiologic images (MR or CT) of their brain, will be collected in an international database freely accessible to transplant centres world-wide through a secure web site: www.brainsupporters.eu. Every case will be subject to a blind evaluation by two teams of specialists in radiologic and microbiology, in accordance with guidelines we have defined starting from an international criterion for proven diagnosis and then classified by aetiological agent. Ai...
ABSTRACT Purpose-objective. Brain infections in patients undergoing haemopoietic stem cell transp... more ABSTRACT Purpose-objective. Brain infections in patients undergoing haemopoietic stem cell transplants or solid organ transplants are very complex to deal with and lead to higher mortality rates. The Brain Supporters Project aims at creating an international database of radiologic images of brain lesions together with clinical, laboratory and microbiological data. Starting from this database we’ll develop an ‘intelligent’ software that through the use of multidimensional analysis techniques, variational methods and classification procedures, can detect, highlight and differentiate the minimal and yet peculiar differences in the ‘radiologic footprint’ connected with the local alterations of brain tissue produced by each individual pathogen, thus becoming an objective diagnostic aid. Material and methods. An internet site has been created, www.brainsupporters.eu, freely accessible to transplant centres world-wide. The radiologic images with confirmed diagnosis collected in the database(hosted on CNR-ISMAR, Venice) will then be subject to a blind evaluation by a team of specialists. Results. The images will then be classified by aetiologic agent and subsequently by age group and by clinical characteristics of the patients. It will thus be possible to evaluate if and how the ‘radiologic footprint’ of lesions due to the same pathogen is modified depending on the different characteristics of the host. Discussion and conclusions. The database is now online. We are sending invitations to every relevant centre, inserting our data in the database and we started working on data analysis tools with the following objective: obtain the probability of presence of the most spread pathological agents.
European Journal of Pharmaceutical Sciences
Journal of Clinical Medicine
Acute graft-versus-host disease (GvHD) remains the second leading cause of death, after disease r... more Acute graft-versus-host disease (GvHD) remains the second leading cause of death, after disease relapse, in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). The medical records of 112 pediatric patients who underwent allo-HSCT from matched unrelated and haploidentical donors were analyzed. Patients were divided into two groups, according to the GvHD prophylactic regimen used. In the control group, GvHD prophylaxis consisted of cyclosporine A (CsA) and methotrexate (MTX) or CsA and mycophenolate mofetil (MMF) at a standard daily dose of 30 mg/kg. All subjects in the study group received tacrolimus (FK506) and MMF. In this group, MMF was subjected to therapeutic drug monitoring (TDM) through mycophenolic acid (MPA) area under the curve AUC0–12. We found a statistically significant difference in both overall acute GvHD (p < 0.0001) and overall chronic GvHD (p < 0.05) incidence between the study and the control group. The initial daily MMF dose a...
Clinical & Translational Immunology
Cancers
Acute myeloid leukemia with myelodysplastic changes and monosomy 7 is a rare form of pediatric le... more Acute myeloid leukemia with myelodysplastic changes and monosomy 7 is a rare form of pediatric leukemia associated with very poor disease-free survival. The refractoriness of the disease is due to the protection offered by the bone marrow niche, making leukemic stem cells impervious to whatever chemotherapy or myeloablative regimen is chosen. Using a mobilizing agent for haematopoietic stem cells, Plerixafor, could sensitise leukemic cells to the myeloablative therapy. This approach was not previously used in a pediatric population, and in adult populations, was used in combination with busulphan with no difference in overall survival. We describe the case of a 4-year-old boy affected by refractory acute myeloid leukemia with myelodysplastic changes and monosomy 7. The child had never achieved a remission. We proposed a combined time-scheduled scheme of therapy with plerixafor and melphalan. Combining pharmacokinetics of plerixafor with pharmacokinetics and rapid and elevated myeloa...
Cancers, Aug 27, 2018
Acute myeloid leukemia with myelodysplastic changes and monosomy 7 is a rare form of pediatric le... more Acute myeloid leukemia with myelodysplastic changes and monosomy 7 is a rare form of pediatric leukemia associated with very poor disease-free survival. The refractoriness of the disease is due to the protection offered by the bone marrow niche, making leukemic stem cells impervious to whatever chemotherapy or myeloablative regimen is chosen. Using a mobilizing agent for haematopoietic stem cells, Plerixafor, could sensitise leukemic cells to the myeloablative therapy. This approach was not previously used in a pediatric population, and in adult populations, was used in combination with busulphan with no difference in overall survival. We describe the case of a 4-year-old boy affected by refractory acute myeloid leukemia with myelodysplastic changes and monosomy 7. The child had never achieved a remission. We proposed a combined time-scheduled scheme of therapy with plerixafor and melphalan. Combining pharmacokinetics of plerixafor with pharmacokinetics and rapid and elevated myeloablative potential of melphalan in high dosage (200 mg/m 2), we succeeded in mobilizing more than 85% of stem blasts immediately before infusion of Melphalan. The count of residual blasts after 8 h from melphalan infusion was only 1.3 cells/µL. The child achieved an engraftment at day +32 with full donor chimerism. Sixteen months after haematopoietic stem cell transplantation (HSCT), he is well and in complete remission. Our case suggests that the use of plerixafor before a conditioning therapy with melphalan could induce remission in acute myeloid leukemia refractory to the usual conditioning therapy in pediatric patients. This work adds strength to the body of knowledge regarding the "personalized" conditioning regimen for high-risk leukemic patients.
National Poster Prize Winners
Journal for ImmunoTherapy of Cancer
BackgroundImmune checkpoint inhibitors such as nivolumab and targeted BRAF inhibitors have dramat... more BackgroundImmune checkpoint inhibitors such as nivolumab and targeted BRAF inhibitors have dramatically altered the treatment outcomes of metastatic melanoma over the past few years. Skin toxicity is the most common adverse event (AE) related to the commonly used BRAF inhibitor vemurafenib, affecting more than 90% of patients. Vemurafenib-related severe AEs with early onset are reported in patients who were previously treated with anti-programmed cell death-1 (anti PD-1) antibodies. A prolonged administration of systemic steroids is the first-line treatment of severe or life-threatening AEs. We report the case of a woman suffering from vemurafenib-related severe, rapidly worsening Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome, resolved in a few hours after single-dose administration of a combination of TNF-α antagonist infliximab with interleukin (IL)-6 receptor antagonist tocilizumab.Case presentationA 41-year-old woman treated with single-agent nivolumab prese...
Oncotarget
Whereas many studies have addressed the risk of organ dysfunction following hematopoietic stem ce... more Whereas many studies have addressed the risk of organ dysfunction following hematopoietic stem cell transplantation (HSCT), little is known about pancreatic susceptibility in this setting. We aimed to investigate the effect of iron overload (IO) and total body irradiation (TBI) on pancreatic function of children undergoing HSCT. We retrospectively evaluated children admitted between 2012-2016 fulfilling the following criteria: normal pancreatic iron concentration (PIC), regular pancreatic function before HSCT, availability of abdominal magnetic resonance imaging with gradient-recalled-echo sequences and a full set of biochemical markers of IO and pancreatic function performed before HSCT and at discharge. We divided the patients according to the use of TBI or myeloablative chemotherapy (MCHT) in the conditioning regimen. All patients with severe IO or moderate IO with a high risk of engraftment delay or transplantation-related complications underwent chelation therapy with deferoxamine (DFO) from the first day of conditioning to discharge. 63 patients had a HSCT in the study period, 13 did not fulfill the inclusion criteria; 50 (25 in each group) are included in the analysis, and did not show differences at baseline evaluation. At follow up testing the TBI group showed a significantly higher PIC (107,8±100,3 μmol/g vs 28,4±37,9 in MCHT group, p<0,0001). In the TBI group the patients who had DFO treatment had higher PIC (223,2±48,8 μmol/g vs 55,7±10,5 without DFO treatment, p<0,0001), and all patients having PIC >100 μmol/g at follow up had DFO-based chelation therapy, versus 26% of those with lower PIC (p<0,0001). The number of patients presenting exocrine pancreatic dysfunctions one month after transplantation was significantly higher in the TBI group (48% vs 4%; p<0.0001). The mean pancreatic volume reduction was significantly greater in the TBI group (39,1% vs 0,9% in the MCHT group; p<0,05), and was significantly worse on those who received DFO therapy.
European Journal of Medicinal Chemistry
Cancer Medicine
This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Acta paediatrica (Oslo, Norway : 1992), Jan 24, 2018
Acute abdominal pain is a frequent complaint in children attending emergency departments. The aim... more Acute abdominal pain is a frequent complaint in children attending emergency departments. The aim of this study was to investigate the pain score reductions when children with acute abdominal pain received medication sublingually. We carried out a multicentre randomised controlled trial in three children's hospitals in Italy between March 2015 and June 2017. Children from four to 18 years of age with acute abdominal pain were recruited if their self-reported pain was at least six on a scale from 0-10. The children were randomised to receive ketorolac 0.5mg/kg (n=70) or tramadol 2mg/kg (n=70) sublingually or a melt in the mouth powder of 20mg/kg paracetamol (n=70). The main study outcome was the pain scores for the three drugs after two hours. The 210 children (58.6% girls) had a median age of 12 years with an interquartile range of 9-14.3. The median pain scores at two hours were not significantly different between ketorolac 2.0 (IQR 0.0-4.3) and tramadol 3.0 (IQR 1.0-5.0) versu...
Oncotarget, Jan 3, 2017
The medical records of 44 pediatric patients who underwent allogeneic transplantation from 2011 t... more The medical records of 44 pediatric patients who underwent allogeneic transplantation from 2011 to 2015 were retrospectively reviewed. Magnetic resonance imaging was used to measure iron concentrations in the liver, spleen, pancreas and bone. These patients were divided into two groups, 18 with non-elevated (< 100 μmol/g; Group 1) liver iron concentration before transplantation and 26 with elevated (> 100 μmol/g; Group 2) concentration . We compared transplant-related outcomes in the two groups. Iron overload was a negative prognostic risk factor for sinusoidal obstruction syndrome (OR = 17), osteoporosis (OR = 6.8), pancreatic insufficiency (OR = 17) and metabolic syndrome (OR = 15.1). No statistically significant differences in overall survival, disease-free survival, relapse incidence and incidence of acute or chronic graft-versus host disease were observed between the two groups. Mean times to engraftment of platelets (43.0 ± 35.3 days vs. 22.1 ± 9.5 days, p < 0.05) and...
Journal of Pediatric Hematology/Oncology, 2015
Background: Sickle cell disease (SCD) is a well-known multisystem illness characterized by vascul... more Background: Sickle cell disease (SCD) is a well-known multisystem illness characterized by vascular injury due to vasoocclusion and hemolysis, as well as infectious complications and iron overload, all of which contribute to high morbidity and mortality rates among children. In these patients, some authors have previously described iron cortical deposition in the kidney. We here report the first case in the literature of a girl affected by SCD showing an anomalous metal and rare element retention in the renal cortex. Case Presentation: A 10-year-old white girl affected by SCD underwent a routine magnetic resonance imaging investigation that evidenced a reduced signal intensity in the renal cortex, compatible with hemosiderin precipitation. Histologic and elemental analyses of the hepatic and the renal biotic samples, performed with inductively coupled plasma mass spectrometry, revealed that concomitant with the high iron deposition, toxic and potentially carcinogenic elements such as nickel, magnesium, rubidium, and gadolinuim were anomalously retained particularly in the kidney. Conclusions: The finding of rare and toxic elements in the kidney of SCD patients might be linked to the development of specific neoplastic transformations already described in this patient cohort. To be confirmed, our speculations need to be demonstrated in large sampling of patients.
Introduction: Brain infections are still a life threatening event in immunocompromised patients. ... more Introduction: Brain infections are still a life threatening event in immunocompromised patients. Due to delays in etiological diagnosis, severe complications and related mortality rate are still too high. Brain Supporters is a multidisciplinary team working to develop a software tool which would be helpful for physicians trying to minimize this event in an innovative way. Material and methods: All biological and clinical data we have selected, related to immunosuppressed patients with suspected or proven brain infectious diseases, and radiologic images (MR or CT) of their brain, will be collected in an international database freely accessible to transplant centres world-wide through a secure web site: www.brainsupporters.eu. Every case will be subject to a blind evaluation by two teams of specialists in radiologic and microbiology, in accordance with guidelines we have defined starting from an international criterion for proven diagnosis and then classified by aetiological agent. Ai...
ABSTRACT Purpose-objective. Brain infections in patients undergoing haemopoietic stem cell transp... more ABSTRACT Purpose-objective. Brain infections in patients undergoing haemopoietic stem cell transplants or solid organ transplants are very complex to deal with and lead to higher mortality rates. The Brain Supporters Project aims at creating an international database of radiologic images of brain lesions together with clinical, laboratory and microbiological data. Starting from this database we’ll develop an ‘intelligent’ software that through the use of multidimensional analysis techniques, variational methods and classification procedures, can detect, highlight and differentiate the minimal and yet peculiar differences in the ‘radiologic footprint’ connected with the local alterations of brain tissue produced by each individual pathogen, thus becoming an objective diagnostic aid. Material and methods. An internet site has been created, www.brainsupporters.eu, freely accessible to transplant centres world-wide. The radiologic images with confirmed diagnosis collected in the database(hosted on CNR-ISMAR, Venice) will then be subject to a blind evaluation by a team of specialists. Results. The images will then be classified by aetiologic agent and subsequently by age group and by clinical characteristics of the patients. It will thus be possible to evaluate if and how the ‘radiologic footprint’ of lesions due to the same pathogen is modified depending on the different characteristics of the host. Discussion and conclusions. The database is now online. We are sending invitations to every relevant centre, inserting our data in the database and we started working on data analysis tools with the following objective: obtain the probability of presence of the most spread pathological agents.
European Journal of Pharmaceutical Sciences
Journal of Clinical Medicine
Acute graft-versus-host disease (GvHD) remains the second leading cause of death, after disease r... more Acute graft-versus-host disease (GvHD) remains the second leading cause of death, after disease relapse, in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). The medical records of 112 pediatric patients who underwent allo-HSCT from matched unrelated and haploidentical donors were analyzed. Patients were divided into two groups, according to the GvHD prophylactic regimen used. In the control group, GvHD prophylaxis consisted of cyclosporine A (CsA) and methotrexate (MTX) or CsA and mycophenolate mofetil (MMF) at a standard daily dose of 30 mg/kg. All subjects in the study group received tacrolimus (FK506) and MMF. In this group, MMF was subjected to therapeutic drug monitoring (TDM) through mycophenolic acid (MPA) area under the curve AUC0–12. We found a statistically significant difference in both overall acute GvHD (p < 0.0001) and overall chronic GvHD (p < 0.05) incidence between the study and the control group. The initial daily MMF dose a...
Clinical & Translational Immunology
Cancers
Acute myeloid leukemia with myelodysplastic changes and monosomy 7 is a rare form of pediatric le... more Acute myeloid leukemia with myelodysplastic changes and monosomy 7 is a rare form of pediatric leukemia associated with very poor disease-free survival. The refractoriness of the disease is due to the protection offered by the bone marrow niche, making leukemic stem cells impervious to whatever chemotherapy or myeloablative regimen is chosen. Using a mobilizing agent for haematopoietic stem cells, Plerixafor, could sensitise leukemic cells to the myeloablative therapy. This approach was not previously used in a pediatric population, and in adult populations, was used in combination with busulphan with no difference in overall survival. We describe the case of a 4-year-old boy affected by refractory acute myeloid leukemia with myelodysplastic changes and monosomy 7. The child had never achieved a remission. We proposed a combined time-scheduled scheme of therapy with plerixafor and melphalan. Combining pharmacokinetics of plerixafor with pharmacokinetics and rapid and elevated myeloa...
Cancers, Aug 27, 2018
Acute myeloid leukemia with myelodysplastic changes and monosomy 7 is a rare form of pediatric le... more Acute myeloid leukemia with myelodysplastic changes and monosomy 7 is a rare form of pediatric leukemia associated with very poor disease-free survival. The refractoriness of the disease is due to the protection offered by the bone marrow niche, making leukemic stem cells impervious to whatever chemotherapy or myeloablative regimen is chosen. Using a mobilizing agent for haematopoietic stem cells, Plerixafor, could sensitise leukemic cells to the myeloablative therapy. This approach was not previously used in a pediatric population, and in adult populations, was used in combination with busulphan with no difference in overall survival. We describe the case of a 4-year-old boy affected by refractory acute myeloid leukemia with myelodysplastic changes and monosomy 7. The child had never achieved a remission. We proposed a combined time-scheduled scheme of therapy with plerixafor and melphalan. Combining pharmacokinetics of plerixafor with pharmacokinetics and rapid and elevated myeloablative potential of melphalan in high dosage (200 mg/m 2), we succeeded in mobilizing more than 85% of stem blasts immediately before infusion of Melphalan. The count of residual blasts after 8 h from melphalan infusion was only 1.3 cells/µL. The child achieved an engraftment at day +32 with full donor chimerism. Sixteen months after haematopoietic stem cell transplantation (HSCT), he is well and in complete remission. Our case suggests that the use of plerixafor before a conditioning therapy with melphalan could induce remission in acute myeloid leukemia refractory to the usual conditioning therapy in pediatric patients. This work adds strength to the body of knowledge regarding the "personalized" conditioning regimen for high-risk leukemic patients.
National Poster Prize Winners
Journal for ImmunoTherapy of Cancer
BackgroundImmune checkpoint inhibitors such as nivolumab and targeted BRAF inhibitors have dramat... more BackgroundImmune checkpoint inhibitors such as nivolumab and targeted BRAF inhibitors have dramatically altered the treatment outcomes of metastatic melanoma over the past few years. Skin toxicity is the most common adverse event (AE) related to the commonly used BRAF inhibitor vemurafenib, affecting more than 90% of patients. Vemurafenib-related severe AEs with early onset are reported in patients who were previously treated with anti-programmed cell death-1 (anti PD-1) antibodies. A prolonged administration of systemic steroids is the first-line treatment of severe or life-threatening AEs. We report the case of a woman suffering from vemurafenib-related severe, rapidly worsening Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome, resolved in a few hours after single-dose administration of a combination of TNF-α antagonist infliximab with interleukin (IL)-6 receptor antagonist tocilizumab.Case presentationA 41-year-old woman treated with single-agent nivolumab prese...
Oncotarget
Whereas many studies have addressed the risk of organ dysfunction following hematopoietic stem ce... more Whereas many studies have addressed the risk of organ dysfunction following hematopoietic stem cell transplantation (HSCT), little is known about pancreatic susceptibility in this setting. We aimed to investigate the effect of iron overload (IO) and total body irradiation (TBI) on pancreatic function of children undergoing HSCT. We retrospectively evaluated children admitted between 2012-2016 fulfilling the following criteria: normal pancreatic iron concentration (PIC), regular pancreatic function before HSCT, availability of abdominal magnetic resonance imaging with gradient-recalled-echo sequences and a full set of biochemical markers of IO and pancreatic function performed before HSCT and at discharge. We divided the patients according to the use of TBI or myeloablative chemotherapy (MCHT) in the conditioning regimen. All patients with severe IO or moderate IO with a high risk of engraftment delay or transplantation-related complications underwent chelation therapy with deferoxamine (DFO) from the first day of conditioning to discharge. 63 patients had a HSCT in the study period, 13 did not fulfill the inclusion criteria; 50 (25 in each group) are included in the analysis, and did not show differences at baseline evaluation. At follow up testing the TBI group showed a significantly higher PIC (107,8±100,3 μmol/g vs 28,4±37,9 in MCHT group, p<0,0001). In the TBI group the patients who had DFO treatment had higher PIC (223,2±48,8 μmol/g vs 55,7±10,5 without DFO treatment, p<0,0001), and all patients having PIC >100 μmol/g at follow up had DFO-based chelation therapy, versus 26% of those with lower PIC (p<0,0001). The number of patients presenting exocrine pancreatic dysfunctions one month after transplantation was significantly higher in the TBI group (48% vs 4%; p<0.0001). The mean pancreatic volume reduction was significantly greater in the TBI group (39,1% vs 0,9% in the MCHT group; p<0,05), and was significantly worse on those who received DFO therapy.
European Journal of Medicinal Chemistry
Cancer Medicine
This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Acta paediatrica (Oslo, Norway : 1992), Jan 24, 2018
Acute abdominal pain is a frequent complaint in children attending emergency departments. The aim... more Acute abdominal pain is a frequent complaint in children attending emergency departments. The aim of this study was to investigate the pain score reductions when children with acute abdominal pain received medication sublingually. We carried out a multicentre randomised controlled trial in three children's hospitals in Italy between March 2015 and June 2017. Children from four to 18 years of age with acute abdominal pain were recruited if their self-reported pain was at least six on a scale from 0-10. The children were randomised to receive ketorolac 0.5mg/kg (n=70) or tramadol 2mg/kg (n=70) sublingually or a melt in the mouth powder of 20mg/kg paracetamol (n=70). The main study outcome was the pain scores for the three drugs after two hours. The 210 children (58.6% girls) had a median age of 12 years with an interquartile range of 9-14.3. The median pain scores at two hours were not significantly different between ketorolac 2.0 (IQR 0.0-4.3) and tramadol 3.0 (IQR 1.0-5.0) versu...
Oncotarget, Jan 3, 2017
The medical records of 44 pediatric patients who underwent allogeneic transplantation from 2011 t... more The medical records of 44 pediatric patients who underwent allogeneic transplantation from 2011 to 2015 were retrospectively reviewed. Magnetic resonance imaging was used to measure iron concentrations in the liver, spleen, pancreas and bone. These patients were divided into two groups, 18 with non-elevated (< 100 μmol/g; Group 1) liver iron concentration before transplantation and 26 with elevated (> 100 μmol/g; Group 2) concentration . We compared transplant-related outcomes in the two groups. Iron overload was a negative prognostic risk factor for sinusoidal obstruction syndrome (OR = 17), osteoporosis (OR = 6.8), pancreatic insufficiency (OR = 17) and metabolic syndrome (OR = 15.1). No statistically significant differences in overall survival, disease-free survival, relapse incidence and incidence of acute or chronic graft-versus host disease were observed between the two groups. Mean times to engraftment of platelets (43.0 ± 35.3 days vs. 22.1 ± 9.5 days, p < 0.05) and...