PubMed Health⌕ Search

Biomedical subjects

Paolo Rebulla

Publications and source records attributed to Paolo Rebulla.

17 recordsLinked to original sources
PubMed2004

Identification of preleukemic precursors of hyperdiploid acute lymphoblastic leukemia in cord blood.

Previous studies involving identical twins with concordant leukemia and retrospective scrutiny of archived neonatal blood spots have shown that common chromosome translocations of pediatric leukemia frequently arise before birth. The IGH/TCR clonotypic sequences used as surrogate molecular markers suggest this is also likely to be true for hyperdiploid acute lymphoblastic leukemia (ALL). Yet evidence that hyperdiploidy itself is an early or initiating event occurring prenatally has been limited. Now, however, we can provide direct evidence of this from our identification of CD34+/CD19+ B-lineage progenitor cells with triploid chromosomes in the stored cord blood of an individual who subsequently developed hyperdiploid ALL.

Antigens, CD19↗
PubMed2004

Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice.

OBJECTIVE: Optimizing cord blood donor selection based mainly on cell dose and human leukocyte antigen (HLA) disparities may further improve results of unrelated cord blood transplants (UCBT). MATERIALS AND RESULTS: We analyzed 550 UCBTs for hematologic malignancies reported to the Eurocord Registry. Main outcomes and prognostic factors were analyzed in univariable and multivariable analyses incorporating center and period effects and using death and relapse as competitive risks for nonfatal endpoints. Nucleated cell (NC) dose before freezing and number of HLA disparities had a significant influence on outcome. Cumulative incidence (CI) of neutrophil and platelet recovery was associated with the number of HLA mismatches, number of NC before freezing, and use of granulocyte colony-stimulating factor. Coexistence of HLA class I and II disparities and high CD34 cell dose in the graft were associated with graft-vs-host disease grades III-IV. CI of disease relapse was higher in matched transplants showing a graft-vs-leukemia effect increased in HLA-mismatched transplants. Overall 3-year survival was 34.4%. Prognostic factors for survival were recipient age, gender, and disease status. CONCLUSION: Our results provide indications for a better choice of cord blood units according to cord blood cell content and HLA.

Adolescent↗
PubMed2004

Review of the quality monitoring methods used by countries using or implementing universal leukoreduction.

Several countries are implementing or have implemented universal leukoreduction (ULR). Specifications, leukocyte counting, and monitoring methods were essential elements in achieving process confidence and conformance. A review of these protocols is presented. A questionnaire was prepared, agreed, and circulated, and responses were collated. Different specifications have been adopted as well as disparate approaches to leukocyte counting and residual leukocyte monitoring. Parametric, nonparametric, and pass-rate methods of analysis were used. Despite these differences, users were satisfied that the methodologies were providing assurance of component quality.

Cell Separation↗
PubMed2004

Immune hemolytic anemia associated with teicoplanin.

BACKGROUND: Several drugs can cause immune hemolytic anemia. Here a patient who developed hemolytic anemia after treatment with teicoplanin is described. CASE REPORT: Owing to a two-vessel disease, a 68-year-old white man underwent coronary artery bypass grafting. He was readmitted for superficial sternal wound infection and sternal instability. Rewiring was required and worsening anemia characterized the course after the reoperation. Drugs used in the second admission were gentamycin, teicoplanin, paracetamol, and codeine. They were considered as a possible cause of drug-induced hemolytic anemia. RESULTS: The DAT was positive for complement and IgG. Autoanti-e was identified in the patient's undiluted serum sample. The eluate was reactive with all RBCs tested only after adding teicoplanin; when diluted 1:4, anti-e specificity was observed in the presence of teicoplanin. CONCLUSION: To our knowledge, this is the first report of immune hemolytic anemia owing to teicoplanin.

Aged↗
PubMed2004

Outcomes of an automated procedure for the selection of effective platelets for patients refractory to random donors based on cross-matching locally available platelet products.

In 1999, we implemented an automated platelet cross-matching (XM) programme to select compatible platelets from the local inventory for patients refractory to random donor platelets. In this study, we evaluated platelet count increments in 40 consecutive refractory patients (8.3% of 480 consecutive platelet recipients) given 569 cross-match-negative platelets between April 1999 and December 2001. XM was performed automatically with a commercially available immunoadherence assay. Pre-, 1- and 24-h post-transfusion platelet counts (mean +/- SD) for the 569 XM-negative platelet transfusions containing 302 +/- 71 x 109 platelets were 7.7 +/- 5.5, 32.0 +/- 21.0 and 16.8 +/- 15.5 x 109/l respectively. Increments were significantly higher (P < 0.05, t-test) than those observed in the same patients given 303 random platelet pools (dose = 318 +/- 52 x 109 platelets) during the month before refractoriness was detected, when pre-, 1- and 24-h post-transfusion counts were 7.0 +/- 8.6, 15.9 +/- 16.1 and 9.6 +/- 12.8 x 109/l respectively. The cost of the platelet XM disposable kit per transfusion to produce 1-h post-transfusion platelet count increments >10 x 109/l was euro 447. This programme enabled the rapid selection of effective platelets for refractory patients, from the local inventory.

Adolescent↗
PubMed2004

The translocation of marrow MNCs after experimental myocardial cryoinjury is proportional to the infarcted area.

BACKGROUND: The selective homing of peripherally injected marrow MNCs (MMNCs) has recently been demonstrated in a model of cryodamaged heart. However, the mechanism underlying this phenomenon is still unknown. In the hypothesis that this process is related to the necrotic area extension, the infarcted area was correlated with the number of homed MMNCs in a model of experimental cryodamaged heart. STUDY DESIGN AND METHODS: A total of 12 donor and 12 recipient inbred isogenic adult (4 weeks old) Fisher rats were used to mimic autologous transplantation. Myocardial damage was obtained in recipient rats by cryoinjury. MMNCs were purified, labeled with PKH26 (a red fluorescent cell dye), and infused 7 days after the injury through the femoral vein of recipient rats. One week after peripheral administration, the number of homed MMNCs was assessed and the infarct size was correlated with the number of cells present in the target. RESULTS: Labeled cells were found only in the injured myocardium of the treated animals (n = 6), where a mean of 12 +/- 3 PKH26+ cells per section examined were found; a significant correlation was found between the infarct size and the estimated number of cells (p = 0.008) CONCLUSION: These data indicate that the homing of MMNCs is related to the extent of the myocardial injury, suggesting that cellular therapy for regeneration of damaged myocardium should be individualized by taking into consideration the extension of the area to repair.

Animals↗
PubMed2004

Flow-cytometric approach to the prompt laboratory diagnosis of TRALI: a case report.

OBJECTIVES: Transfusion-related acute lung injury (TRALI) is a rare but serious complication which can occur after transfusion of blood components. In this report we describe our flow-cytometry approach to the laboratory diagnosis of a case of TRALI in a recipient of fresh frozen plasma containing human leukocyte antigen (HLA) class II antibodies. METHODS: The post-transfusion reaction work-up included the direct and indirect Granulocyte Immunofluorescence Test (GIFT) on the recipient's neutrophils collected before and after the reaction and on the serum from the recipient and from all implicated donors; flow-cytometry bead-based screening and identification assay for HLA class I and II antibodies in donor sera and flow cytometry cross-matching on T and B patient's lymphocytes. Finally, we investigated the reactivity of one donor serum, containing HLA class II antibodies, with the patient's neutrophils activated in vitro to induce expression of HLA class II. RESULTS: We found an increased level of IgG bound on patient's granulocytes collected after TRALI, in the absence of detectable granulocyte and HLA class I antibodies in the five implicated donors. One of them showed HLA-DR 1 and -DR 51 antibodies, which determined a positive cross-match with patient's B lymphocytes and in vitro activated granulocytes. Both HLA class II antigens were present in the recipient and absent in the donor. CONCLUSIONS: In some pathological conditions, HLA class II antibodies can react with activated granulocytes expressing HLA-DR antigens, and activate TRALI reaction. HLA class II antibodies screening and flow cytometry cross-matching techniques should be added to the current diagnostic algorithm of TRALI.

Aged↗
PubMed2004

Clinical and histological characterization of liver disease in patients with transfusion-dependent beta-thalassemia. A multicenter study of 117 cases.

BACKGROUND AND OBJECTIVES: Updated information on liver disease in transfusion-dependent beta-thalassemia is lacking. We conducted a multicenter study within the Cooleycare Group to describe the clinical and histopathological features of liver disease in currently treated thalassemics. DESIGN AND METHODS: Two-hundred and three thalassemics with laboratory signs of liver disease were eligible. Liver biopsy was performed in the 129 (63.5%) who consented (age 26+/-7 years). Biological samples were sent to the central laboratory. RESULTS: Anti-hepatitis C virus (HCV) antibodies were found in 118 patients (91%), 85 (72%) of whom were viremic. Ninety-one patients (70%) had abnormal aminotransferase concentrations. In the 117 liver biopsies that met the criteria for evaluation (88%), the median Ishak's necroinflammatory and fibrosis scores were 4 (range, 0-9) and 2 (range, 0-6), respectively. Significant fibrosis (score >or=3) was found in 53 (45%); 9 (8%) had cirrhosis. At multivariate analysis, necroinflammation was related to HCV viremia, and fibrosis to increased serum aminotransferases, higher iron stores (including serum ferritin, Deugnier's total iron score, and liver iron content) and male gender (p<0.05). In HCV-RNA negative subjects, the median total iron score was 27 (range, 0-52). Iron accumulated in both mesenchymal cells and hepatocytes, and the presence of a lobular gradient was interpreted to indicate intestinal hyperabsorption. INTERPRETATION AND CONCLUSIONS: Transfusion-dependent thalassemics have mild liver necroinflammation, mainly attributable to HCV infection. Significant fibrosis is frequent, and its progression is mostly influenced by iron overload which, with current therapy regimens, may be attributable to both erythrocyte catabolism and iron hyperabsorption.

Adult↗
PubMed2003

Methodologic issues in the use of bleeding as an outcome in transfusion medicine studies.

BACKGROUND: Prophylactic platelet transfusions are given to thrombocytopenic patients to prevent bleeding. The benefit of platelet transfusions has frequently been assessed by measuring the count increment; however, more recently, an assessment of bleeding has been used because it is a more clinically relevant outcome measure. The purpose of this study was to identify platelet transfusion trigger studies that used bleeding as an outcome measure, compare and contrast methods used to document bleeding and analyze bleeding outcomes, and identify and discuss methodologic issues to consider when bleeding is used as a study outcome. STUDY DESIGN AND METHODS: A systematic search to identify platelet transfusion trigger studies was performed. Relevant articles were reviewed to identify how bleeding data was captured and analyzed, and methodologic considerations were identified. RESULTS: Seven articles meeting the predefined entry criteria were identified. Methods used to document bleeding included chart review and clinical assessment. The frequency of assessment and the type of personnel performing the assessment were variable. Four approaches to analysis were identified: descriptive; comparison of the proportions of patients having at least one bleed; comparison of patient days with bleeding expressed as a proportion of the total days at risk of bleeding; and time-to-event (first bleed) analysis. CONCLUSION: Methodologic issues for consideration when designing a clinical study with bleeding as the outcome measure included approaches to minimize bias in the documentation and classification of bleeding and selection of an analysis approach that is appropriate to the question being asked. The need for development of a valid and reliable bleeding scale was also identified.

Data Collection↗
PubMed2003

Correlation between perioperative blood transfusion and prognosis of patients subjected to surgery for stage I lung cancer.

BACKGROUND: It has been reported, but not proven, that perioperative blood transfusions have a detrimental effect on the survival of patients undergoing surgery for lung cancer. STUDY DESIGN: and methods: A prospective study was carried out on the patients undergoing lobectomy for stage I lung cancer at our department from 1995 to 2000. The criteria for exclusion included previous cases of malignancy, autoimmune diseases, and any other relevant comorbidity. RESULTS: Two hundred eighty-one patients were observed, 24.6% of whom received transfusions. The only significant difference between the transfused and nontransfused patients was their preoperative hemoglobin (Hb) concentration (12.5 +/- 1.20 g/dL vs 13.3 +/- 1.22 g/dL, p < 0.001). The disease-free interval of the transfused patients was significantly lower than that of the nontransfused patients (53% vs 78% at 73 months, p < 0.005), as was also the case for actuarial survival (52% vs 71% at 73 months, p < 0.02). Blood transfusion was significantly predictive of tumor relapse according to the Cox model adjusted for the T state, preoperative Hb concentration, sex, age, histologic type, and grading (hazard ratio, 2.3; p = 0.017). CONCLUSIONS: Our data show that perioperative blood transfusion is significantly correlated to worse prognosis in patients undergoing surgery for stage I lung cancer.

Aged↗
PubMed2003

Homing of peripherally injected bone marrow cells in rat after experimental myocardial injury.

BACKGROUND AND OBJECTIVES: Significant progress has been achieved during the past 10 years in cell transplantation and recent research has focused on the possibility of improving ventricular function after myocardial infarction. Most studies in the field of cardiac tissue repair are performed by direct intramyocardial injection of cells of different origin. Since this approach requires a surgical intervention, in this study we investigated the feasibility of non-invasive administration of bone marrow mononuclear cells (BMMNCs) by assessing the fate of peripherally injected, purified, labeled cells in cryodamaged hearts. DESIGN AND METHODS: Ten donor and ten recipient inbred isogenic adult (4 weeks old) Fisher rats were used as models to mimic autologous transplantation. Myocardial damage was obtained in recipient rats by placing a frozen metal probe on the anterior left ventricular wall for 15 seconds (freeze-thaw injury technique). BMMNCs were purified and labeled with a red fluorescent cell dye. Seven days after the injury about 15-25x10(6) cells were infused through the femoral vein of recipient rats. Seven days after the infusion, the heart, lungs, liver, kidneys, spleen and thymus were harvested to track transplanted cells. RESULTS: Labeled cells were found only in the injured area of the heart and not in the normal tissue, and a limited number of cells were identified in the spleen of all the animals. Most of the labeled cells in the infarcted area were Thy-1(+) and some were CD34(+). INTERPRETATION AND CONCLUSIONS: Our data suggest that peripherally injected BMMNCs can traffic through the circulation to the site of damage; we hypothesize that tissue injury leads to the priming of a cytokine cascade acting as chemoattractant for the infused cells.

Animals↗
PubMed2002

Refractoriness to platelet transfusion.

This review discusses the causes of refractoriness to platelet transfusions and presents three options for its management. Platelet refractoriness is a complication of platelet transfusion that affects variable proportions of patients, mostly depending on their diagnosis, previous immunologic stimuli, and type of blood products used for transfusion. A large recent study showed that platelet refractoriness develops in 13% of patients with acute leukemia transfused with traditional blood products and in 3 to 4% of recipients of white cell-reduced blood components. Options to manage platelet refractoriness include platelets from HLA-typed donors, platelet cross-matching, and the antibody specificity prediction method. The selection of the most convenient approach depends on local skills and the available economic and organizational resources. Finally, emerging concepts are presented which could impact the management of platelet refractoriness.

Histocompatibility Testing↗
PubMed2002

Evidence- and consensus-based practice guidelines for the therapy of primary myelodysplastic syndromes. A statement from the Italian Society of Hematology.

BACKGROUND AND OBJECTIVES: Novel therapeutic agents and strategies have been introduced into the management of myelodysplastic syndromes (MDS) in the last years. This has led to more treatment options and a better chance of long-term survival for MDS patients, but also to uncertainty regarding the optimal use and possible side effects of these treatments. The Italian Society of Hematology commissioned a project to develop guidelines for the therapy of MDS using evidence-based knowledge and consensus-formation techniques. DESIGN AND METHODS: An Advisory Council (AC) shaped the project around a series of key clinical questions, performed a systematic search for evidence and graded the available evidence according to the Scottish Intercollegiate Guidelines Network (SIGN). A list of clinical questions was mailed to each of 10 senior hematologists composing the Expert Panel (EP): the panelists were asked to rank the most relevant questions, and to formulate answers to the questions according to the tables of evidence. A scenario phase followed, so as to reach a consensus on the three top ranked questions. The EP was asked to score patient profiles as appropriate or not appropriate for the therapeutic strategy under scrutiny, according to the RAND technique. Finally, from September 2001 to January 2002, four Consensus Conferences conducted according to the Nominal Group Technique were held in Milan, Italy. The overall goal of the conferences was to take a final decision upon the appropriateness of the uncertain scenarios and of the uncertain responses to the clinical questions. RESULTS: Evidence was judged sufficient for providing recommendations on the use of allogeneic stem cell transplantation, leukemia-like chemotherapy, autologous stem cell transplantation, low-dose chemotherapy, danazol, immunosuppressive therapy, hypomethylating agents and hematopoietic growth factors. Specific recommendations for supportive therapy, including iron chelation, were issued. Allogeneic stem cell transplantation was unanimously considered as the only curative treatment for MDS patients, and recommendations on its use were agreed based on patient's age, risk, clinical features and donor availability. AML-like chemotherapy was also considered a valuable therapeutic option for subsets of MDS patients. Autologous stem cell transplantation was recommended for patients who lack an HLA identical donor and have achieved complete remission with AML-like chemotherapy. Decitabine, recombinant human erythropoietin and immunosuppressive therapy were judged valuable therapeutic options for subsets of MDS patients whereas low-dose cytarabine was not. Specific therapeutic strategies for those subjects younger than 18 years or older than 75 years and the strategy of watchful waiting were decided by patient-oriented questions. INTERPRETATION AND CONCLUSIONS: Using evidence and consensus, recommendations for the treatment of MDS were issued. Statements were graded according to the strength of the supporting evidence and uncertainty was explicitly declared.

Consensus↗