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Biomedical subjects

G Dini

Publications and source records attributed to G Dini.

At least 55 records · Page 3Linked to original sources
PubMed1999

Processing of human cord blood by three different procedures for red blood cell depletion and mononuclear cell recovery.

BACKGROUND AND OBJECTIVES: Human cord blood (CB) is an important source of stem cells which may be used for hematopoietic reconstitution as an alternative to bone marrow transplantation. Banking of CB would be accomplished by removing red blood cells (RBC) and plasma from CB collections. Our aim was to compare three different procedures for CB processing. MATERIALS AND METHODS: Poligeline, hydroxyethyl starch gel (HES) and gelatin were used as separation media in processing 79 CB units for RBC depletion and mononuclear cell (MNC) recovery. RESULTS: The best MNC recoveries were obtained performing the HES- and the gelatin-based procedures (80.9 and 84.7%, respectively), but the gelatin procedure allowed us to obtain the highest RBC depletion (96.4%); CD34+ cell recovery was higher using HES or gelatin as separation media (85.6 and 85.9%, respectively). CONCLUSION: The best results, as far as RBC removal and MNC recovery are concerned, were obtained by using gelatin as RBC sedimentation medium. Gelatin is a low-cost, animal-derived reagent, which has been successfully used for CB transplantation; the procedure is simple to perform and appears to be suitable for large-scale banking in view of CB transplantation.

Blood Component Removal↗
PubMed1999

Strategies for cost-containment: once-daily ceftriaxone plus amikacin as empiric therapy for febrile granulocytopenic children with cancer.

Administration of broad-spectrum antibiotics as empiric therapy to febrile granulocytopenic patients has become a widely accepted practice. In order to evaluate the cost-effectiveness of ceftriaxone plus amikacin in single daily doses as empiric treatment for febrile granulocytopenic children with cancer, a retrospective review (January-December 1996) of all febrile episodes at our institution was carried out. Overall, 101 febrile episodes in 89 granulocytopenic children with cancer were empirically treated with a once-daily ceftriaxone plus amikacin combination. 59/101 (59%) patients had absolute granulocyte count lower than 100/mm3 at entry; 46 (45%) were affected by solid tumors, 16 (15%) by Hodgkin's disease or lymphoma, and 30 (30%) patients underwent bone marrow transplantation. The ceftriaxone plus amikacin combination was effective in 72/101 (72%) patients with a median time to defervescence of 3 days (range, 1-4). We also evaluated the economic advantages of the ceftriaxone plus amikacin once-daily regimen when compared with another treatment regimen such as ceftazidime plus amikacin requiring three daily doses. Compared with the multiple daily dose regimen of ceftazidime plus amikacin, there is a cost saving of US $11 (17,500 Italian liras) and US $66 (105,000 Italian liras) for both 1-day and 6-day treatments, respectively, by using the single daily dose regimen of ceftriaxone plus amikacin. The potential of ceftriaxone to lower costs in hospitalized patients depends upon its comparable efficacy with other extended-spectrum beta-lactams, in which case it can reduce overall treatment costs because of its once-daily administration schedule.

Adolescent↗
PubMed1999

[Transplantation of bone marrow from unrelated donors in Italy: activity and results].

Unrelated donor (UD) bone marrow transplantation (BMT) represents an attractive option for patients with haematological, oncological or genetic diseases lacking a compatible familiar donor. Between September 1988 and December 1997 the search of a donor has been activated for 1724 patients in Italy. Until May 1998, 413 BMT from UD have been performed in 28 different authorized italian centres. Forty out of these patients were affected by genetic diseases apart from SCID (severe combined immunodeficiency). Sixty-month disease free survival (DFS) of this group was 62%. Seventy-four out of 215 children with acute lymphoblastic leukemia (ALL) for whom a donor search was started underwent a BMT. Six year DFS was 25%. Fifty-nine out of 379 patients with chronic myeloid leukemia (CML) for whom a donor search was activated underwent BMT. Forty-eight month DFS was 41.5%. Inborn errors curable with BMT, relapsed ALL and CML represent an absolute indication for UD BMT. In these cases donor search should be activated yearly.

Bone Marrow Transplantation↗
PubMed1998

Early treatment of acute graft-versus-host disease with high- or low-dose 6-methylprednisolone: a multicenter randomized trial from the Italian Group for Bone Marrow Transplantation.

Ninety-five patients undergoing an allogeneic bone marrow transplant (BMT) and developing acute graft-versus-host disease (aGvHD) were randomized to receive low-dose intravenous 6-methylprednisolone (6MPred; 2 mg/kg /d; n = 47) or high-dose 6MPred (10 mg/kg/d; n = 48) for 5 days, with subsequent tapering doses. On day 5 patients not responding or progressing on low-dose 6MPred could be switched to high-dose 6MPred. All patients, aged 1 to 55 years, were recipients of unmanipulated BMT from HLA identical sibling donors. Patients were stratified at randomization for age (</>/= 20 years), disease (acute leukemia, chronic myeloid leukemia [CML], nonneoplastic disease), disease status (early/advanced), and GvHD prophylaxis (cyclosporin/cyclosporin + methotrexate). Primary endpoints were response to treatment and evolution of aGvHD to grade III-IV. Secondary endpoints were cytomegalovirus (CMV) infections, transplant-related mortality (TRM), and relapse. The median interval between BMT and treatment was 12 days (6 to 43). Results in the two groups (2 v 10 mg/kg) were as follows: response of aGvHD 68% versus 71% (P = .9), evolution to aGvHD grade III-IV 17% versus 20% (P = . 6), CMV infections 55% versus 60% (P = .7), 3-year actuarial TRM 28% versus 32% (P = .7), relapse 17% versus 7% (P = .1). The actuarial survival at 3 years was 63% versus 62% (P = .9) with a median follow up of 580 and 778 days. On day 5 of therapy, 26 patients assigned to low-dose (2 mg/kg) 6MPred were switched to a higher dose of 6MPred because of no response or progression. Their actuarial TRM was 46%, which is significantly higher than TRM of patients who responded on 2 mg/kg and continued with tapering doses (TRM = 16%, P = .007). In conclusion, early treatment of acute GvHD with 6MPred 10 mg/kg/d does not improve the response rate as compared with 2 mg/kg/d, nor does it prevent evolution to aGvHD grade III-IV. CMV infections, TRM, and survival were also comparable. A group of patients at high risk of TRM can be identified after 5 days of treatment with 6MPred 2 mg/kg and could be eligible for alternative forms of therapy.

Actuarial Analysis↗
PubMed1998

Synoviocytes from osteoarthritis and rheumatoid arthritis produce plasminogen activators and plasminogen activator inhibitor-1 and display u-PA receptors on their surface.

The production of plasminogen activators and their inhibitors was studied in vitro in osteoarthritic (OA) and rheumatoid arthritic (RA) synovial fibroblasts (SF), obtained from RA and OA patients undergoing joint surgery. Subcultured SF were cultivated for 2, 4, 6, 8, 10 and 13 days and the medium assayed for the presence of both plasminogen activators (PAs) and plasminogen activator inhibitor-1 (PAI-1). The presence of urokinase-Plasminogen Activator (u-PA) receptors (u-PAR) on the surface of synovial cells was investigated by radio-ligand binding assay and cross-linking and by transmission electron microscopy (TEM) of a gold-u-PA complex. Our results showed a low production of tissue-type-Plasminogen Activator (t-PA) in both OA and RA SF, but relatively high levels of u-PA, until confluence, both in OA and in RA. SF were also able to produce plasminogen activator inhibitor in large amounts, in particular in RA since the very beginning of the culture. Receptors for u-PA were evident on both RA and OA SF. Our data show that SF in vitro produce mainly u-PA, the most important plasminogen activator involved in tissue modifications. The demonstration of u-PA receptors on the surface of OA and RA SF represents a step forward in the understanding of the possible role of fibrinolytic and tissue destructive proteinase cascade in joint inflammation.

Arthritis, Rheumatoid↗
PubMed1998

Autologous bone marrow transplantation for treatment of isolated central nervous system relapse of childhood acute lymphoblastic leukemia. AIEOP/FONOP-TMO group. Associzione Italiana Emato-Oncologia Pediatrica.

The purpose of this study was to assess the role of ABMT in children with ALL who are in 2nd CR after an early isolated CNS relapse. All children experiencing an isolated CNS relapse at 10 AIEOP centers (Associazione Italiana Emato-Oncologia Pediatrica) from 1986 to 1992 were eligible for this study. The series included 69 patients who relapsed within 3 years from diagnosis: 19 underwent ABMT, nine patients underwent ALLO-BMT from an HLA-identical sibling, and 41 received conventional chemotherapy (CHEMO). Statistical analysis was performed using a Cox's regression model, adjusting for the waiting time before transplantation and prognostic factors. The 5 years DFS was 56.3% (s.e. 12.3) for patients in the ABMT group. This compared favorably with the poor result (12.6% (s.e. 5.9)) seen in the CHEMO group. The risk of failures was reduced by one-third in the ABMT group as compared to the CHEMO group in the multivariate analysis (P < 0.01). In the ALLO group four out of nine patients were in CCR 4-5 years post-transplant. This study suggests that ABMT may also represent a valuable therapeutic choice for patients lacking a matched familiar donor in 2nd CR after an early isolated CNS relapse.

Adolescent↗
PubMed1998

Survival after cytomegalovirus pneumonia in two children receiving autologous peripheral blood progenitor cell transplantation (PBPCT).

Cytomegalovirus (CMV) pneumonia is a very rare but often fatal complication of autologous bone marrow or peripheral blood progenitor cell transplantation. Diagnosis is usually made by means of CMV antigenemia which is strongly predictive of CMV disease. We describe two cases of PBPC transplantation who survived after CMV pneumonia which was diagnosed only by bronchoalveolar lavage in the absence of CMV-antigenemia.

Bronchoalveolar Lavage Fluid↗
PubMed1998

Autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in Italy. AIEOP/FONOP-TMO Group. Italian Association of Paediatric Haemato-Oncology.

From January 1984 to December 1994, ABMT was performed on 154 children (101 males, 53 females; median age 10, range 3-21 years) with ALL and registered for BMT by the AIEOP (Italian Association of Paediatric Haemato-Oncology). All patients were in CR: 98 were in 2nd CR and 56 were in >2nd CR. Fifteen children (9.7%) died of transplant-related mortality. Ninety-five patients (61.6%) relapsed at a median of 5 (range 1-42) months after ABMT. The 8-year EFS according to pre-BMT status was 34.6% (s.e. 4.9) for 2nd CR patients and 10.6% (s.e. 5.6) for patients in >2nd CR. By univariate analysis, site of relapse (isolated extramedullary (IE) vs BM: EFS = 68.5% vs 18.2%; P < 0.0001) and TBI containing regimen (TBI vs no TBI: EFS = 48.1 vs 15.4%; P = 0.0023) were significant factors for 2nd CR patients. When the 2nd CR subset with BM involvement was analysed, TBI became insignificant (EFS = 25.4 vs 11.8%). No factors influenced EFS in patients in >2nd CR. By multivariate analysis, site of relapse was the only significant factor in 2nd CR patients (P < 0.0001). In conclusion, ABMT is an effective treatment after one early IE relapse. Few patients can be rescued after BM relapse.

Adolescent↗
PubMed1998

Transplantation activities and treatment strategies in paediatric stem cell transplantation centres: a report from the EBMT Working Party on Paediatric Diseases. European Group for Blood and Marrow Transplantation.

To determine the current approach to stem cell transplantation (SCT) in centres which treat predominantly paediatric patients, a questionnaire was sent to 67 centres known by the EBMT registry to perform SCT mainly in children. Fifty-five centres from 19 countries responded. Forty centres (75%) started their transplantation activities between 1980 and 1992. Median number of transplants/centre was 95 (range 8-400). Median number of transplants/centre/year was 18 (range 5-85). On average, there was one physician responsible for seven SCT/year while one nurse was involved for a median of 1.7 SCT/year. Median four rooms/centre (range 1-17) were available for paediatric SCT. The most common isolation facilities were rooms with high efficiency particulate air filtration (HEPA). Eighty-two percent (45/55) of the centres performed allogeneic as well as autologous SCT, while 5% (three centres) offered exclusively allogeneic SCT and 13% (seven centres) used only autologous stem cell rescue. Stem cell source for allogeneic SCT was bone marrow in 87%, peripheral blood (PB) in 10% and umbilical cord blood in 3%. Donors were HLA matched related in 57%, mismatched related in 13%, and matched unrelated in 30% of allogeneic SCT. PB was the most commonly used stem cell source for autologous SCT (48%), followed by BM (41%) and the two together (11%). Data analysis revealed substantial differences in protective care, stem cell processing and transplantation procedures within the centres, irrespective of the country, centre size and transplant type.

Adolescent↗
PubMed1998

Unrelated donor marrow transplantation for chronic myelogenous leukaemia.

Between January 1989 and July 1995 the search for an unrelated donor (UD) was started for 379 consecutive Italian patients with Philadelphia positive (Ph+) chronic myelogenous leukaemia (CML). 89 (23%) were transplanted. The overall probability of transplant before and after December 1991 was 16% and 49%, respectively (P=0.0001), and average interval between search activation and graft was 23 months and 13 months, respectively (P=0.0001). Disease-free survival (DFS) following 60 consecutive transplants performed before February 1996 was 41.5% at 48 months and was 64% for patients grafted after January 1993. In univariate analysis, five variables had a favourable effect on DFS: year of bone marrow transplantation (BMT) after 1993 (P=0.0002), HLA-DRB1 donor/recipient (D/R) match (P=0.0006), total body irradiation (TBI) containing regimen (P=0.0006), graft-versus-host disease (GvHD) prophylaxis including 'early' cyclosporin before the transplant, and a marrow cell dose > 3 x 10(8)/kg of recipient body weight (P=0.04). Multivariate analysis confirmed that HLA identity (P=0.006), TBI-containing regimen (P=0.0001) and 'early cyclosporin' (P=0.04) were associated with higher DFS. Transplant-related mortality (TRM) was 67% in patients grafted before January 1993 and 30% in patients grafted subsequently (P=0.002). Multivariate analysis confirmed DRB1 identity (P=0.03) and TBI-containing regimen (P=0.0005) to be independent factors predictive of low TRM. This suggests that the outcome of patients transplanted from an HLA DRB1 matched donor, after a TBI-containing preparative regimen, is similar to results recently reported in patients transplanted from geno-identical siblings. These results indicate that the search should be initiated at diagnosis for patients < 45 years of age and UD BMT should be considered early in the disease course for those with an available DRB1-matched unrelated donor.

Adolescent↗
PubMed1998

The mechanism of inhibition of benzylamine oxidase by 3,5-diethoxy-4-aminomethylpyridine (B24).

B24, 3,5-diethoxy-4-aminomethylpyridine, is a specific inhibitor of the semicarbazide-sensitive amine oxidase with high affinity for benzylamine (BnNH2.SSAO). It is a site-directed inhibitor of pig plasma benzylamine oxidase (BAO) with an affinity for the enzyme much higher than that for benzylamine. B24 inhibition is dependent on the molar ratio B24/BAO because the inhibitor reacts mole to mole with the enzyme and benzylamine appears to be ineffective in removing the inhibitor from the adduct [EI]. B24 is a weak substrate of BAO and for this reason the degree of inhibition (when the molar ratio B24/BAO is lower than 1) decreases with the incubation time as well as with the preincubation time. This decrease is dependent on the gradual release of free enzyme which reacts with the substrate, giving [ES] without any interfering free B24. When the B24/BAO molar ratio is higher than 1, the free enzyme released by the oxidative deamination of B24 reacts with the substrate, but the free B24 present competitively inhibits the formation of [ES] and the affinity of benzylamine is therefore reduced. This is the reason why B24, in the kinetic experiments in which the inhibitor is not pre-incubated with the enzyme, may appear to be a competitive inhibitor or a mixed inhibitor, mainly competitive. When B24 is preincubated with the enzyme and the initial rate of benzylamine oxidation is measured, it appears as a non-competitive inhibitor becoming a mixed one only when the B24/BAO molar ratio is high and the incubation time is long.

Aldehydes↗
PubMed1998

Unrelated donor marrow transplantation for inborn errors.

From December 1989 to December 1997 40 children aged 1 year to 19 years with inborn errors other than severe combined immunodeficiencies underwent unrelated donor (UD) bone marrow transplantation (BMT) in one of 10 institutions of the Italian Bone Marrow Transplant Group participating in this program. The diseases leading to BMT included Fanconi Anemia (10), Thalassemia (8), Wiskott Aldrich syndrome (5), haemophagocytic lymphohystiocytosis (6), osteopetrosis (3), storage diseases (6), Chediak Higashi syndrome (1), Schwachman syndrome (1). Thirty-three pairs were A, B, DRB1 matched. Three pairs were one antigen mismatched and one pair was two antigens mismatched. The remaining three pairs lacked information on molecular biology. Twelve children underwent a preparative regimen including radiotherapy. The remaining 28 children were conditioned with a chemotherapy regimen which included Busulfan. GvHD disease prophylaxis included CSA and MTX alone (9) or associated with ALG (17) or in vivo Campath 1G (12). The remaining two children received CSA alone. Thirty-five children showed donor engraftment; three children with thalassemia and one with osteopetrosis failed to engraft. Five children developed secondary graft failure. Actuarial 5 year disease-free survival was 62%; grade III-IV acute GvHD developed in seven of 38 evaluable children (18%); chronic GvHD developed in seven of 27 evaluable children (26%). We confirm that Wiskott Aldrich syndrome, HLH, and osteopetrosis represent an absolute indication for UD-BMT. Prognosis of UD-BMT for FA could improve in children grafted in an early phase, but a better preparative regimen has to be identified. UD-BMT in thalassemia is acceptable only in a restricted subset of patients selected for poor compliance to therapy.

Adolescent↗
PubMed1998

Peripheral blood stem cell collection from G-CSF-stimulated unrelated donors for second transplant.

Peripheral blood stem cells (PBSCs) collected following stimulation with cytokines are commonly used for autologous haematopoietic transplants. Currently, PBSCs are being used for syngeneic or allogeneic transplants from matched or haploidentical donors. However, many issues are still unanswered regarding the early or late side-effects cytokines have on recipients and on healthy donors. The aims of this paper were to evaluate the experience acquired worldwide in this field, to define the acceptability of stem cell donation by G-CSF-stimulated apheresis from unrelated donors after the failure of a first donation, and to assess side-effects of G-CSF on unrelated donors. The use of PBSCs has increased tremendously over the last few years and in the near future PBSCs will probably become the most relevant source of stem cells. Studies conducted so far have definitely concluded that G-CSF is safe and well tolerated. Results observed in transplants utilizing marrow stem cells compared with results obtained in transplants utilizing PBSCs have shown that patients undergoing this latter procedure recover earlier, require a lower number of transfusions and spend fewer days in hospital with a consequent decrease in costs. We concluded that a second transplant by G-CSF-stimulated apheresis from an unrelated donor is definitely acceptable and we designed a prospective study to better define all controversial aspects. Donors will be given 10 microg/kg/day of G-CSF subcutaneously for 5 days. One or two PBSC collection procedures will be performed: the first on day 5 and the second, if necessary, on day 6. Donors will be surveyed and blood counts monitored in a standardized manner during the process.

Blood Donors↗
PubMed1997

Photopheresis in paediatric patients with drug-resistant chronic graft-versus-host disease.

Photopheresis (ECP) is a new type of photochemotherapy, used for the treatment of oncological and autoimmune diseases. Lymphocytes are drawn from the patients by leukapheresis, treated with 8-methoxypsoralen (8-MOP) and ultraviolet light A (UVA) in an extracorporeal system and then reinfused. Skin exposure to 8-MOP and UVA (PUVA) has been shown to relieve cutaneous symptoms of graft-versus-host disease (GVHD) in bone marrow transplant (BMT) recipients. ECP, which is similar in some ways to PUVA, has been used in this study to treat four paediatric patients who developed chronic GVHD following BMT and in whom GVHD had failed to respond to conventional immunosuppressive therapy. Following ECP, skin lesions cleared almost completely and pulmonary function tests improved in two of three patients with cutaneous and lung involvement. Serum bilirubin and transaminases gradually normalized, and gammaGT decreased considerably in the remaining patient who had a severe cholestatic hepatopathy. The Karnofsky performance score increased to 90% in the three patients with positive responses to ECP and remained unchanged (40%) in the patient who did not respond. Immunosuppressive therapy was reduced in three patients and eventually discontinued in two. No significant side-effects were observed during the treatment. Our results suggest that ECP is a non-aggressive treatment that may benefit patients with chronic GVHD who do not respond to standard immunosuppressive therapy.

Adolescent↗
PubMed1997

Allogeneic bone marrow transplantation versus chemotherapy in high-risk childhood acute lymphoblastic leukaemia in first remission. Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) and the Gruppo Italiano Trapianto di Midollo Osseo (GITMO).

We compared the outcome of children with high-risk acute lymphoblastic leukaemia (HR-ALL) in first complete remission (first CR) treated with chemotherapy (CHEMO) or with allogeneic bone marrow transplantation (BMT) in a multicentre study. All children treated by the Italian Paediatric Haematology Oncology Association for HR-ALL in first CR between 1986 and 1994 were eligible for the study. 30 children were given BMT at a median of 4 months from first CR, with preparative regimens including total-body irradiation (n = 25/30). 130 matched controls for BMT patients were identified among 397 HR-ALL CHEMO patients. Matching on main prognostic factors and duration of first CR was adopted to control the selection and time-to-transplant biases. The comparative analysis was based on the results of a stratified Cox model. The estimated hazard ratios of BMT versus CHEMO at 6 months, 1 year and 2 years after CR were 1.38 (CI 0.59-3.24), 0.69 (CI 0.27-1.77) and 0.35 (CI 0.06-1.91), with an overall non-significant difference between the two groups (P = 0.34). With a median follow-up of 4 years, the disease-free survival was 58.5% (SE 9.3) in the BMT group and 47.7% (SE 4.8) in the CHEMO group, at 4 years from CR. Non-leukaemic death occurred in 4% of CHEMO and 10% of BMT patients. In the BMT group the estimated cumulative incidence of relapse at 1.5 years from CR was 31.5% (SE 8.8) and did not change thereafter, whereas in the CHEMO group the corresponding figure was 29.2% (SE 4.1) and the incidence continued to increase thereafter (48.2% (SE 4.8) at 4 years from CR). The results of this study suggest that, with respect to the CHEMO group, the higher risk of early failure in the BMT group is outweighed by the lower risk of relapse after 1 year. Results prompt the need for a prospective study, in order to demonstrate the likely advantage of BMT in HR childhood ALL in first CR.

Antineoplastic Agents↗
PubMed1997

Isolated intracranial metastasis of neuroblastoma 2 years after completion of therapy.

Metastatic neuroblastoma in the brain without evidence of intracranial or extracranial disease elsewhere, is a very rare event. The pattern of spread is believed to be via the hematogenous route or cerebrospinal fluid. A child with a cystic neuroblastoma mass in the right temporal lobe 23 months following completion of therapy for the initial disease is described here. Chemotherapy with the protocol 'eight drugs in 1 day' was initially effective for this patient.

Adrenal Gland Neoplasms↗
PubMed1997

Bronchiolitis obliterans organizing pneumonia in three children with acute leukaemias treated with cytosine arabinoside and anthracyclines.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinicopathological entity with well-defined diagnostic criteria, which can be idiopathic or produced by a variety of biological processes. We describe the occurrence of BOOP in three children, one with acute lymphoblastic leukaemia and two with acute promyelocytic leukaemia. In the three patients, BOOP developed 10-20 days after a course of therapy with cytosine arabinoside and anthracyclines. The possible relationships between the small conducting airway lesions, lung toxic reaction to the drugs and/or nonidentified infectious agents are discussed.

Anthracyclines↗