Elena Bergami - Academia.edu (original) (raw)

Papers by Elena Bergami

Blood, Dec 6, 2014

Background. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective t... more Background. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective treatment option for patients with malignant and non-malignant hematologic disorders lacking an HLA-compatible donor. Strategies for T-cell depletion (TCD) of the graft, such as positive selection of CD34+ cells, offer the potential to prevent acute and chronic graft-versus-host disease (GVHD). The risk of graft rejection associated with the extensive depletion of both T lymphocytes and accessory cells can be overcome by infusing a very high number (megadose) of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) (exceeding 10x106/kg recipient body weight) to overcome the HLA barrier (Aversa F. et al. Blood 1994). Moreover, the infusion of a megadose of CD34+ cells (higher than 20x106/kg and 12.4x106/kg, respectively) has been shown to result in faster immunological recovery and improved leukemia-free survival probability in children (Handgretinger R. et al. Bone Marrow Transplant 2001; Klingebiel T. et al. Blood 2010). Nevertheless, in the case of donors considered “poor mobilizers” (10-30% of cases), the threshold dose of CD34+ cells needed to ensure the inoculum of a megadose of stem cells might not be achieved. In the setting of cord blood (CB) transplantation, one of the strategies aimed at overcoming the problem of low cellularity is represented by the intrabone injection of CB stem cells, with good engraftment rates even in adult patients. We explored the same strategy in the context of T-cell depleted haplo-HSCT and low graft cellularity due to poor donor mobilization, ensuing in inadequate dose of CD34+cells available after positive selection TCD. Patients and methods. From September 2009 to April 2013, 11 pediatric patients affected by malignant or non-malignant hematological disorders (5 acute lymphoblastic leukemias, 1 acute myeloid leukemia, 1 myelodysplastic syndrome, 2 dyskeratosis congenita, 1 Fanconi anemia) received a T-cell depleted CD34+positively selected PBSC allograft from an HLA-haploidentical related donor. Due to the failure to achieve a target cell dose higher than 12x106 purified CD34+ cells/kg, part of the stem cell inoculum was infused as intrabone injection. The procedure was carried out at the patient bedside by multiple intrabone injections in the superior-posterior iliac crests under sedoanalgesia, as previously described (Frassoni F. et al. Lancet Oncol 2008). The median dose of CD34+ cells infused was 9x106/kg (range, 5-12) while the median number of CD3+ lymphocytes was 0.7x104/kg recipient body weight (range, 0.3-11). About one third of the stem cell inoculum, corresponding to a total volume of 20-40 ml, was given intrabone, while the remaining stem cell portion was infused intravenously. Results.No complication occurred during, or immediately after, the intrabone injection. Nine out of the 11 patients achieved a complete donor engraftment, while graft rejection occurred in 2 patients. The median time for neutrophil engraftment was 13.5 days (range, 12-20), while the median time for platelet recovery was 14 days (range, 13-24). One patient developed grade II acute GVHD and only 1 case of limited chronic GVHD was observed. No transplant-related deaths were observed. Conclusions. Our data suggest that, in the haplo-HSCT setting, the intrabone injection of positively selected CD34+ cells, can be safely used in cases of low graft cellularity due to poor donor mobilization, with the aim of minimizing the risk of graft rejection or poor engraftment. Our preliminary data need to be confirmed in larger series of patients and compared with those obtained with conventional intravenous administration of comparable dose of CD34+ cells. Disclosures No relevant conflicts of interest to declare.

Tumori Journal, Jun 19, 2022

In recent years, the influence of nutrition on the health and growth of children has become incre... more In recent years, the influence of nutrition on the health and growth of children has become increasingly important. The relevance of nutrition is even greater for children who are facing cancer. Malnutrition, within the context of undernutrition and overnutrition, may impact not only the effectiveness of treatments and outcomes, but also the quality of life for patients and their families. In this article, we review nutritional assessment methods for children with cancer, focusing on the specific characteristics of this population and analyze the efficacy of nutritional interventions, which include enteral, parenteral, and nutritional education. From our analysis, two important conclusions emerged: i) there is a need to focus our attention on the nutritional status and the body composition of oncologic children, since these factors have a relevant impact on clinical outcomes during treatment as well as after their conclusion; ii) the support of skilled clinical nutrition personnel would be extremely helpful for the global management of these patients.

Hematology Meeting Reports (formerly Haematologica Reports), Jun 9, 2009

Blood, Nov 29, 2018

Introduction. Hematopoietic stem cell transplantation (HSCT) exposes the recipient to a high risk... more Introduction. Hematopoietic stem cell transplantation (HSCT) exposes the recipient to a high risk of developing viral reactivations especially during the first weeks after HSCT. Neutropenia and lymphopenia, together with the breakdown of physical barriers expose patients not only to bacterial and fungal infections but also to viral infection/reactivations. HHV-6 is usually acquired during infancy, and seroprevalence in the adult population may reach 90%. Like other herpesviruses, HHV-6 persists latently within permissive cells and it can reactivate during immunosuppression. A high incidence of HHV-6 reactivation is frequently detected after HSCT, but its clinical relevance is still debated. The objectives of this retrospective study were to estimate the incidence of HHV6 reactivation after pediatric HSCT, analyze the possible risk factors and evaluate the impact on outcome. Patients and methods. We analyzed 234 pediatric subjects given HSCT from a matched family donor (MFD, 17.5%), a matched unrelated donor (MUD, 43.6%) or a partially matched family donor (PMFD, 38.9%) for malignant (55.2%) or non-malignant hematologic diseases (25.6%) between 2010 and 2017. Data have been analyzed according to patient, donor and transplant characteristics. Risk factors analysis was computed throughout the comparison of the cumulative incidence (CI) of HHV-6 reactivation according to descriptive variables. Kaplan Mayer curves were used to illustrate survival results (OS and EFS), and Log-rank test was used to compare groups. The analysis of outcome was completed by analyzing the CI of neutrophils and platelets engraftment, rejection, acute and chronic GvHD, NRM according to presence or absence of HHV-6 reactivation. Gray-test was used to compare different CI curves. The quantification of HHV-6 exposure was calculated using the area under the curve (AUC) of viremia level over time. AUC expresses the kinetics of the DNA viral load in a time-concentration chart. The stratification of patients according to HHV-6 AUC quartiles (AUCq = each of 4 equal groups into which the HHV6 positive population was divided according to distribution of the value of AUC) allowed to describe the viral burden and the intensity of viral exposure. Risk factors analysis and survival analysis were then performed using the parameter AUC and AUC quartiles. Results. The cumulative incidence of HHV-6 reactivation was 58%, with onset usually within the first month after transplantation (median 19 days). The peak viral load was detected at an average time of 55 days after onset (median 25 days) with a median of 5850 cp/mL (range 50 - 219^106 cp/mL). In univariate analysis, a diagnosis of malignant disease (p=0.021), transplant from PMFD (p=0.010), the use of a busulfan/TBI-based vs Treo-based conditioning regimen (p=0.020), the use of ex vivo T cell-depletion (p&amp;amp;lt;0.001) and the use of ATG (p&amp;amp;lt;0.001) were risk factors for HHV6 reactivation. In multivariate analysis, only the use of ATG remained statistically significant (p=0.025). The occurrence of HHV-6 infection, considered as a categorical variable, did not affect transplant outcome, in particular neutrophils and platelets engraftment, acute and chronic GvHD, rejection, OS, EFS and NRM. All analysis for risk factors and outcomes were then repeated using the AUC and AUCq parameters. HHV-6 exposure measured as AUC or AUCq again failed to demonstrate any impact on outcome. However, in the PMFD group, OS and EFS were worse, although not statistically significant, for the 3rd-4th AUCq compared to negative or 1st-2nd AUCq. Conclusions. Based on the results obtained, HHV-6 infection/reactivation, measured as categorical variable or as viral exposure, does not seem to have an impact on HSCT outcomes. Therefore, routine viral monitoring may not give added benefit in the pediatric HSCT setting. However, in selected populations, early restricted monitoring may identify HSCT recipients at risk of HHV6-related disease. Disclosures Zecca: Chimerix: Honoraria.

Pediatric Reports

Cancer in adolescence is considered a family disease that can have numerous negative psychologica... more Cancer in adolescence is considered a family disease that can have numerous negative psychological consequences for adolescents and the entire household. The aim of this study was to investigate the impact of oncological disease in adolescence, with particular reference to the psychological and post-traumatic consequences for the adolescents themselves and the family system. An explorative case–control study was conducted with 31 adolescents (mean age 18.03 ± 2.799) hospitalised for cancer at IRCCS San Matteo Hospital in Pavia and 47 healthy adolescents (mean age 16.17 ± 2.099). The two samples completed a survey that included sociodemographic information and questionnaires assessing psychological well-being, traumatic effects of the disease, and adequacy of the relationship with parents. 56.7% of oncology adolescents scored below average in psychological well-being, and a small proportion of them fell within the range of clinical concern for anger (9.7%), PTS (12.9%), and dissociat...

International Journal of Molecular Sciences

Shwachman–Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by bone mar... more Shwachman–Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by bone marrow failure, exocrine pancreatic insufficiency, and skeletal abnormalities, caused by loss-of-function mutations in the SBDS gene, a factor involved in ribosome biogenesis. By analyzing osteoblasts from SDS patients (SDS-OBs), we show that SDS-OBs displayed reduced SBDS gene expression and reduced/undetectable SBDS protein compared to osteoblasts from healthy subjects (H-OBs). SDS-OBs cultured in an osteogenic medium displayed a lower mineralization capacity compared to H-OBs. Whole transcriptome analysis showed significant differences in the gene expression of SDS-OBs vs. H-OBs, particularly in the ossification pathway. SDS-OBs expressed lower levels of the main genes responsible for osteoblastogenesis. Of all downregulated genes, Western blot analyses confirmed lower levels of alkaline phosphatase and collagen type I in SDS-OBs than in H-OBs. Interestingly, SDS-OBs showed higher protei...

Frontiers in Genetics

Background: Shwachman–Diamond syndrome (SDS) is a rare autosomal recessive ribosomopathy mainly c... more Background: Shwachman–Diamond syndrome (SDS) is a rare autosomal recessive ribosomopathy mainly characterized by exocrine pancreatic insufficiency, skeletal alterations, neutropenia, and a relevant risk of hematological transformation. At least 90% of SDS patients have pathogenic variants in SBDS, the first gene associated with the disease with very low allelic heterogeneity; three variants, derived from events of genetic conversion between SBDS and its pseudogene, SBDSP1, provided the alleles observed in about 62% of SDS patients.Methods: We performed a reanalysis of the available WES files of a group of SDS patients with biallelic SBDS pathogenic variants, studying the results by next bioinformatic and protein structural analysis. Parallelly, careful clinical attention was given to the patient focused in this study.Results: We found and confirmed in one SDS patient a germline heterozygous missense variant (c.100T>C; p.Phe34Leu) in the EIF6 gene. This variant, inherited from his...

Tumori Journal

Additional file 1: Figures S1, S2, S3, S4, S5 and S6. PCA and cluster analysis, with heatmaps and... more Additional file 1: Figures S1, S2, S3, S4, S5 and S6. PCA and cluster analysis, with heatmaps and dendrograms, of the three gene sets chosen as relevant in haemopoiesis and leukaemogenesis and defined in the Results section.

Additional file 2: Table S1. Blood count and bone marrow cellularity of all the SDS patients here... more Additional file 2: Table S1. Blood count and bone marrow cellularity of all the SDS patients here reported at the date of sampling for RNA expression study.

During the nearly 40 years elapsed since the first successful bone marrow transplantation, signif... more During the nearly 40 years elapsed since the first successful bone marrow transplantation, significant improvements have been registered in the field of allograft, also in connection with the use of cord blood as a source of hematopoietic stem cells. The number of cord blood transplants is increasing worldwide with the establishment of related and unrelated cord blood banks. The incidence of both acute and chronic graft-versus-host disease, the most important and life-threatening immune complications after transplantation, is significantly reduced with cord blood grafts and, in view of this fact, cord blood transplantation offers the opportunity of using HLA-disparate donors. This latter finding, together with the immediate availability of cryopreserved cells, is the main advantage for children who lack an HLA-identical sibling and who need transplantation from an unrelated donor. Moreover, in patients with hematological malignancies, the rate of relapse appears to be similar to tha...

Lo studio si propone di analizzare la fattibilita di un trattamento con probiotici per la prevenz... more Lo studio si propone di analizzare la fattibilita di un trattamento con probiotici per la prevenzione delle complicanze gastrointestinali e delle infezioni in riceventi pediatrici di trapianto di cellule staminali emopoietiche, alla luce del dibattito tuttora in corso sulla sicurezza di impiego dei probiotici nell’ospite immunocompromesso, valutandone l’impatto sulla composizione della flora fecale, sul profilo della ricostituzione immunologica e sull’outcome clinico.

Frontiers in Immunology, 2020

Molecular Cytogenetics, 2020

Background Clonal chromosome changes are often found in the bone marrow (BM) of patients with Shw... more Background Clonal chromosome changes are often found in the bone marrow (BM) of patients with Shwachman-Diamond syndrome (SDS). The most frequent ones include an isochromosome of the long arm of chromosome 7, i (7)(q10), and an interstitial deletion of the long arm of chromosome 20, del (20)(q). These two imbalances are mechanisms of somatic genetic rescue. The literature offers few expression studies on SDS. Results We report the expression analysis of bone marrow (BM) cells of patients with SDS in relation to normal karyotype or to the presence of clonal chromosome anomalies: del (20)(q) (five cases), i (7)(q10) (one case), and other anomalies (two cases). The study was performed using the microarray technique considering the whole transcriptome (WT) and three gene subsets selected as relevant in BM functions. The expression patterns of nine healthy controls and SDS patients with or without chromosome anomalies in the bone marrow showed clear differences. Conclusions There is a si...

Blood, 2018

Blood, 2014

Journal of Diabetes, 2019

The new microbiologica, 2016

We describe a case of isolated acute appendicitis due to Aspergillus carneus in a neutropenic chi... more We describe a case of isolated acute appendicitis due to Aspergillus carneus in a neutropenic child with acute myeloid leukemia (AML) treated according to the AIEOP AML 2002/01 protocol. Despite prophylaxis with acyclovir, ciprofloxacin and fluconazole administered during the neutropenic phase, 16 days after the end of chemotherapy the child developed fever without identified infective foci, which prompted a therapy shift to meropenem and liposomial amphotericin B. After five days of persisting fever he developed ingravescent abdominal lower right quadrant pain. Abdominal ultrasound was consistent with acute appendicitis and he underwent appendectomy with prompt defervescence. PAS+ fungal elements were found at histopathology examination of the resected vermiform appendix, and galactomannan was low positive. A. carneus, a rare species of Aspergillus formerly placed in section Flavipedes and recently considered a member of section Terrei, was identified in the specimen. Treatment wit...