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Biomedical subjects

A Donfrancesco

Publications and source records attributed to A Donfrancesco.

At least 37 records · Page 2Linked to original sources
PubMed1995

Immunohistochemical detection of high-affinity nerve growth factor receptor in neuroblastoma.

High levels of mRNA (as assessed by northern blot) for the high-affinity nerve growth factor receptor (p140TRK) are predictive of favourable outcome in neuroblastoma. The feasibility of determining p140trk on frozen sections using a recently developed monoclonal antibody was evaluated, and immunohistochemical findings were compared to those obtained from northern blot analysis. Primary tumour samples from 28 untreated patients were quick frozen and an indirect immunofluorescence assay was performed on 4-microns acetone-fixed cryostat sections. 9 cases were positive with immunohistochemistry, and these were among the 15 cases also positive by northern blot. None of the cases negative by northern blot were positive with immunohistochemistry. The concordance rate was 79% (P < 0.03), with a sensitivity of 60% and a specificity of 100%. Immunohistochemistry can thus be rather reliable for assessing p140trk expression, even when only very small amounts of tissue are available, such as with needle biopsy.

Biomarkers, Tumor↗
PubMed1995

Deferoxamine followed by cyclophosphamide, etoposide, carboplatin, thiotepa, induction regimen in advanced neuroblastoma: preliminary results. Italian Neuroblastoma Cooperative Group.

Based upon phase I and II studies of deferoxamine alone and in combination with cytotoxic agents cyclophosphamide, etoposide, carboplatin, and thiotepa (D-CECaT), we initiated a single arm multicentre trial in 1992 for advanced neuroblastoma. 57 of 65 patients who entered the trial were evaluable. Following 4 courses of the D-CECaT, almost all the patients underwent surgery. Toxicity was moderate and mainly reversible myelosuppression. The post-surgically defined responses in stage 3 high risk, stage 4 moderate risk and stage 4 high risk patients included 24 complete responses, 26 partial responses, and 3 minor responses, and 4 patients had progressive disease. These patients are being followed to determine the impact of this programme on their overall survival.

Adolescent↗
PubMed1995

Localized resectable neuroblastoma: results of the second study of the Italian Cooperative Group for Neuroblastoma.

PURPOSE: To optimize treatment for children with localized resectable neuroblastoma in 21 Italian institutions using a common protocol based on previous experience. PATIENTS AND METHODS: Between January 1985 and December 1992, 152 children aged 0 to 15 years with nondisseminated neuroblastoma were entered onto this study following complete resection of tumor without tumor rupture (TR) (stage 1), or resection with minimal tumor residue, and/or tumor infiltration of regional lymph nodes (LN+), and/or TR (stage 2). Of 144 assessable children, 69 were classified as having stage 1 disease and 75 as stage 2. Of stage 2 children, 49 had low-risk (LR) characteristics (age, 0 to 11 months or 1 to 15 years but negative lymph nodes and no TR). Stage 1 and stage 2 LR children did not receive adjuvant therapy. The remaining 26 stage 2 children had high-risk (HR) characteristics (age, 1 to 15 years with LN+ and/or TR) and received adjuvant chemotherapy for 6 months. RESULTS: Of 144 children, three died of therapy-related complications and 19 relapsed, of whom six died of disease. The estimated 5-year overall survival (OS) rate was 93% and the event-free survival (EFS) rate was 83%. Of 69 stage 1 children, one died postoperatively and five relapsed (one local and four disseminated, two of whom died), for 94% OS and 90% EFS rates. Of 49 stage 2 LR children, six relapsed (four local and two disseminated); relapses occurred in five of 20 infants with LN+, in one of four infants with TR, and in none of the remaining 25 children. One child died of disease and one of toxicity, for 96% OS and 85% EFS rates. Of 26 stage 2 HR children, eight relapsed (three of 20 with LN+, three of four with TR, and two of two with LN+ and TR), of whom three died of disease and one of toxicity, for 87% OS and 61% EFS rates. CONCLUSION: Our data confirm the overall good prognosis of children with localized resectable neuroblastoma. LN+ and TR predisposed to relapse at all ages, but infants tended to have a less aggressive course after relapse. Stage 1 and 2 LR children had 94% and 96% OS rates, respectively, which justifies a policy of no adjuvant chemotherapy. Eight of 26 children with stage 2 HR relapsed despite 6 months of chemotherapy; for these children, more intensive chemotherapy may be required.

Adolescent↗
PubMed1995

[123I]MIBG scintigraphy in neuroblastoma: a comparison between planar and SPECT imaging.

The aim of the present study was to assess the utility of SPECT imaging with [123I]MIBG in patients with neuroblastoma (NB). Twenty-two children were studied (11 males and 11 females: age range: newborn to 11 years). A total of 39 studies were performed in different clinical phases. Both planar (at 24 and occasionally 48 hours) and SPECT (at 24 hours) imaging were performed in all cases. Planar studies gave a sensitivity of 87.5% (evidence of the disease in 21 of 24 studies performed in children with known NB lesions) and a specificity of 93.3% (true negative results in 14 of 15 studies performed in disease-free patients). In the same patients SPECT gave a sensitivity of 95.8% (23 of 24 positive studies and a specificity equal to that of planar scanning. In 5 of 21 studies positive at planar scanning SPECT showed 9 additional lesions. In conclusion, [123I]MIBG SPECT imaging compared to planar scanning can demonstrate a greater number of lesions. Its use seems to be indicated mainly in cases in which diagnostic assessment is difficult, such as small residual tumors or in the follow up of children no longer in therapy, in whom it can lead to an early diagnosis of relapse.

3-Iodobenzylguanidine↗
PubMed1994

Trk mRNA and low affinity nerve growth factor receptor mRNA expression and triploid DNA content in favorable neuroblastoma tumors.

Nerve growth factor (NGF) is suggested to play a role in spontaneous differentiation or regression of neuroblastoma. Expression of mRNAs for trk protooncogene and NGF low affinity receptor gene (LNGFR) were analyzed in 45 neuroblastomas with Northern Blot. Trk and LNGFR expression correlated with young age, localized tumors or IV-S disease, absence of N-myc amplification, triploid DNA content, spontaneous tumor regression and favorable prognosis. Regardless of other factors, trk and LNGFR mRNAs distinguished three prognostic subsets: one favorable (trk+, LNGFR+, n = 19, 100% survival probability), one intermediate (trk+, LNGFR-, n = 11, 62%) and one poor (trk-, n = 15, 0%). An algorithm based on the combined analysis of trk and LNGFR mRNAs and DNA ploidy divided the material in two groups with 96 and 0% survival probability respectively (p < 0.001), and predicted outcome accurately in 43 of 45 children. It is hypothesized that loss of functional NGF-receptors constitutes an early critical step in the evolution of unfavorable neuroblastomas prone to progression in spite of current therapy.

DNA, Neoplasm↗
PubMed1993

Localized but unresectable neuroblastoma: treatment and outcome of 145 cases. Italian Cooperative Group for Neuroblastoma.

PURPOSE: To define factors that influence outcome in children with localized but unresectable neuroblastoma by retrospective investigation of response to therapy and outcome in 21 Italian institutions. PATIENTS AND METHODS: Of 145 assessable children diagnosed between 1979 and 1990, 77 were treated between 1979 and 1984 with three consecutive standard-dose (SD) protocols, and 68 between 1985 and 1990 with a high-dose (HD) protocol. All protocols included chemotherapy, followed by resection of primary tumor if feasible. If at least partial resection was achieved, consolidation therapy followed, except that from 1985 onward, patients considered disease-free following surgery received no further treatment. RESULTS: Ninety-four of 145 patients (65%) achieved a complete response (CR) or partial response (PR) with chemotherapy and 75 (52%) subsequently underwent complete resection of the primary tumor. Eighty-one patients are alive (73 without disease, eight with disease), 63 have died, and one is lost to follow-up. The 5-year overall survival (OS) rate is 55% and progression-free survival (PFS) rate 50%. Both OS and PFS correlated with response to chemotherapy, removal of primary tumor, HD therapy, and serum lactate dehydrogenase (LDH) levels. Infants (< 1 year), independent of primary tumor site, and children aged 1 to 15 years with a nonabdominal primary tumor, did better compared with children aged 1 to 15 years with an abdominal primary tumor (PFS, 72% and 64% v 30%; P < .001 and < .01, respectively). Outcome of this last group improved with the HD protocol (PFS, 40% v 23%; P = .01). CONCLUSION: In children with unresectable neuroblastoma, risk categories can be defined by age and primary tumor site. HD chemotherapy should be investigated for the poor-risk category age 1 to 15 years with an abdominal primary tumor.

Adolescent↗
PubMed1993

D-CECaT: a breakthrough for patients with neuroblastoma.

In view of the high relapse rate following chemotherapy for patients with advanced neuroblastoma (NB) and primitive neuroectodermal tumors (PNET), we designed a novel chemotherapy program which incorporated the iron chelator deferoxamine. The purpose of the deferoxamine was to sensitize the cells to standard chemotherapy. The D-CECaT regimen contained (in mg/m2): deferoxamine 4500 during days 1-5; cyclophosphamide 600 mg over days 6 and 7; etoposide 300 mg over days 7 and 8; carboplatin 100 mg over days 7 and 8; and thiotepa 30 mg over days 6-8. Between October 1989 and May 1992 we entered 23 advanced NB and two PNET patients. Sepsis occurred in four courses, nausea and vomiting in 30 courses, and 50 courses required blood and platelets. Responses observed in previously untreated patients with stage III NB: six out of six CR (17+ to 41+ months), with stage IV NB, nine out of 11 CR (14+ to 28+ months), two out of 11 VGPR (22+ months), with stage IV PNET two out of two CR (1+ to 35+ months). With previously treated and failed stage IV NG, two out of six VGPR for 19+ and 20 months, and four out of six PR 1, 8, 9 and 11 months. Median survival for 19 new patients was 22+ months (6 to 41+ months; two patients in CR died at 7 months during adjuvant autologous marrow transplant). In conclusion, D-CECaT is an effective initial cytoreductive regimen for advanced stage NB/PNET patients. Additional patients and studies are required to determine its use as an alternative to autologous bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Deferoxamine, cyclophosphamide, etoposide, carboplatin, and thiotepa (D-CECaT): a new cytoreductive chelation-chemotherapy regimen in patients with advanced neuroblastoma.

Thirteen patients with Stage III (3 patients) or Stage IV (10 patients) neuroblastoma were treated with a new iron chelation-cytotoxic therapy regimen. Deferoxamine given for five consecutive days followed by 3 days of cyclophosphamide, etoposide, carboplatin, and thiotepa (D-CECaT) caused moderate to severe myelotoxicity. In 39 courses there were four episodes of sepsis; platelet and packed red blood cell transfusions were required in 72% and 82% of courses, respectively. Mild nausea and vomiting occurred in 52% of courses. Objective responses after two courses were observed in 12 of 13 patients. Three of four partial responses were achieved in previously treated relapsed patients, and seven of eight complete responses (four of which were surgically documented) were achieved in previously untreated patients. This cytoreduction regimen appears to be an improvement over other initial induction regimens and may be worth testing in larger populations.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

An improved technique for peripheral blood stem cell collection in small patients.

Peripheral Blood Stem Cell collection in adults is a consolidated method for autografting. The same procedure is less easily performed in pediatric patients due to low weight, vascular access problems and anticoagulant side effects. Great efforts have been made to overcome technical difficulties and make apheresis in children a reliable and safe procedure.

Adolescent↗
PubMed1990

Effects of a single course of deferoxamine in neuroblastoma patients.

A phase II trial of a single 5-day course of deferoxamine in 9 patients with neuroblastomas was completed. Within 2 days of completion of treatment responses were observed in 7 of 9 patients and there was no drug toxicity. These responses were a decrease in bone marrow infiltration and, in one patient, a measurable reduction in her tumor mass. We conclude that deferoxamine given as an 8-h i.v. infusion daily for 5 days at 150 mg/kg/day has antitumor activity.

Adolescent↗
PubMed1990

High-dose carboplatin in combination with etoposide (JET regimen) for childhood brain tumors.

Fourteen patients aged 1 to 15 years with medulloblastoma (six patients), low-grade astrocytoma (four patients), and high-grade astrocytoma (four patients) were treated with carboplatin and etoposide (JET regimen). Six patients had been treated previously, two of them with cisplatin at conventional doses. Carboplatin was administered at 500 mg/m2/day over 5 h on days 1 and 2, in association with pulsed etoposide at 100 mg/m2/day on days 1, 2, and 3. Courses were repeated at 3-week intervals. The disease-specific response rates were as follows: five of six with three complete responses and two partial responses for medulloblastoma; zero of four for low-grade astrocytoma; and two of four with two partial responses for high-grade astrocytoma. Myelosuppression was the main side effect: anemia (hemoglobin less than 8.0 g/dl), thrombocytopenia (less than 25,000/microliter) and leukopenia (less than 1,000 white blood cells/microliters) were noted in 19 of 54, 10 of 54, and 7 of 54 courses, respectively. Gastrointestinal toxicity was very mild, and nephro- and neurotoxicity were not observed. No audiometric abnormalities were demonstrated in seven of seven patients who had not previously received cisplatin, and preexisting audiometric abnormalities were not worsened by the administration of carboplatin in one cisplatin-pretreated patient. The combination of carboplatin and etoposide administered in this study appears to be effective and well tolerated in children with brain tumors. Further studies on a larger number of patients are needed to ascertain its real activity in childhood brain tumors.

Adolescent↗
PubMed1988

Aplastic anemia and neonatal giant-cell hepatitis.

The authors report the case of a female infant with bone marrow aplasia associated with neonatal giant-cell hepatitis. In addition to noting the exceptionality of this case, the possible interdependence of the two processes is discussed, and it is proposed that bone marrow aplasia, as in the adult, may represent a complication of viral disease (hepatitis).

Anemia, Aplastic↗
PubMed1985

Biochemical and clinical effects of vitamin E administration in homozygous beta-thalassemia.

In beta-thalassemic homozygotes, low plasma levels of tocopherols may induce a red blood cell (RBC) lipid peroxidation and consequent hemolysis. This is an indication to treat these patients with vitamin E. In this study 26 beta-thalassemic homozygotes aged 2-14 years, were given vitamin E, 10 orally and 16 parenterally, 300 mg per day for 15 days. Prior to administration and blood transfusion, as compared to normal subjects of the same age, plasma and RBC tocopherols were significantly lower, whereas RBC malonyldialdehyde (MDA) was significantly increased. In both groups, after tocopherol administration, an increase in plasma and RBC tocopherols and a decrease in RBC MDA were found. The significance of these variations was greater in the parenterally treated group than in orally treated group. The treatment with vitamin E, appears to be effective to reduce the RBC oxidative damage in homozygous beta-thalassemia, principally when administered parenterally perhaps because of its poor intestinal absorption in these subjects.

Adolescent↗