PubMed Health⌕ Search

Biomedical subjects

L De Rosa

Publications and source records attributed to L De Rosa.

At least 19 recordsLinked to original sources

Costs of high-dose chemotherapy and peripheral blood progenitor cell autograft for breast cancer.

The aim of the study was to analyze the real cost of single or tandem high-dose chemotherapy (HDC) and peripheral blood progenitor cell autologous transplant (PBPCT) in patients with breast cancer. We analyzed the costs of 40 PBPCT performed in 20 patients. Tandem transplant was planned for each patient. Resources used and direct costs were identified for each patient. The study was carried out using the hospital perspective and monetary values were reported in 1999 Euro. The mean cost of whole procedure for single transplant was 20,816.63 Euro, while the mean cost of tandem transplant was 38,770.83 Euro. The cost distribution in the two groups was similar: the most expensive phase of procedure was the supportive phase post transplant (about 60% of total cost), with the categories of cost most represented being professional fees (about 28%) and pharmacy (about 35%). Awaiting more convincing trials of the clinical advantage of HDC in breast cancer, our analytical evaluation of transplant costs for different therapeutic options, single or tandem, permits identification of the most expensive categories in order to intervene for cost savings.

Antineoplastic Combined Chemotherapy Protocols↗

Cisplatin-paclitaxel weekly schedule in advanced solid tumors: a phase I study.

PURPOSE: The objective of our study was to determine the maximum tolerable doses (MTDs) of both paclitaxel and cisplatin when given in a weekly schedule alone or simultaneously with G-CSF in advanced solid neoplasms. PATIENTS AND METHODS: Patients with advanced cancer either chemotherapy-naive or resistant to standard treatments received paclitaxel in a three-hour infusion followed by cisplatin, with or without the addition of r-HuG-CSF (5 micrograms/kg s.c. days three to five). The starting doses of CDDP and paclitaxel were 25 mg/m2/week and 45 mg/m2/week, respectively. During the first six courses the dosages of the two drugs were alternately escalated by 20% (CDDP = 5 mg/m2/week, and paclitaxel 10 mg/m2/week) at each step until the appearance of dose-limiting toxicity (DLT) in one-third or more of the patients enrolled in that cohort. RESULTS: Fifty-five patients with cancer (16 lung, 16 breast, 11 ovarian, 7 head and neck, 1 renal, 1 esophageal, 1 cervical, 1 soft-tissue sarcoma, and 1 of unknown primary), 25 of whom were pretreated, were entered into the study. A total of 439 weekly courses were delivered. In chemotherapy-naïve patients, the MTDs of cisplatin and paclitaxel were 30 mg/m2/week and 65 mg/m2/week, respectively, in the absence of G-CSF support, which increased to 40 mg/m2/week and 85 mg/m2/week, respectively, when G-CSF was given. There were no toxic deaths in this study. Neutropenia was the main dose-limiting toxicity (100/439 courses), but was seldom severe. Neurotoxicity was quite frequent (18 of 55 patients for the total of 88 courses) but never dose-limiting. It was more frequent and clinically relevant in cisplatin-pretreated patients. Overall 18 patients (eight ovarian, five breast, three lung, and two head and neck) achieved objective responses. CONCLUSIONS: The cisplatin-paclitaxel weekly administration seems a safe, practical and effective therapeutical approach in patients with advanced solid neoplasms. Large phase II trials are warranted to accurately define the efficacy of this schedule in cisplatin-paclitaxel sensitive tumors.

Antineoplastic Combined Chemotherapy Protocols↗

Growth factor administration following autologous peripheral blood progenitor cell transplantation.

Hematopoietic growth factor (HGF) administration following autologous peripheral blood progenitor cell transplantation (APBPCT) is a current approach for shortening the duration of high-dose chemotherapy-induced transient peripheral pancytopenia. Several published clinical experiences and a retrospective study reported here show that recombinant human granulocyte colony stimulating factor (rhG-CSF) or recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) administration potentiates polymorphonuclear leukocyte (PMN) and white blood cell (WBC) recovery with some clinical benefits mainly related to the reduction of infectious complications during the shortened period of neutropenia. However, this therapeutic strategy does not produce any enhancement of platelet (PLT) recovery or potentiation of red cell production. Conversely, a recent phase I/II study carried out in our institution showed that the combined administration of rhG-CSF and recombinant human erythropoietin (rhEPO) is able to potentiate trilineage hematopoietic recovery with a reduction of PLT transfusions and to considerably simplify the clinical management of patients as compared to patients treated with APBPCT alone. The post-APBPCT administration of rhEPO with rhGM-CSF decreased the number of days with WBC < 1 x 10(9)/L but failed to produce any appreciable effect on PLT recovery. Both combined treatments significantly reduced the patients' hospital stay and allowed the abrogation of systemic antibiotic administration following APBPCT. A further group of patients were treated with the combined administration of rhEPO, rhG-CSF and rhGM-CSF; they did not show a faster hematopoietic recovery than rhG-CSF plus EPO treated patients and a consistent hyperthermia was observed in most patients as a prominent side effect. Future prospective randomized studies will clarify the efficacy of HGF administration following APBPCT. Moreover, further improvements in the hematopoietic support of transplanted patients may be obtained when stem cell factor, flt3/flk2 tyrosine kinase ligands or megakaryocyte growth and development factor will become clinically available.

Erythropoietin↗

Recombinant interleukin-2 treatment before and after autologous stem cell transplantation in hematologic malignancies: clinical and immunologic effects.

Autologous bone marrow transplantation (ABMT) for hematologic malignancies is associated with a high relapse rate. Interleukin-2 (IL-2) administration is a therapy that may prevent relapse if used when the tumor burden is minimal. In this study we administered recombinant IL-2 (rIL-2) therapy to 12 patients affected by hematologic malignancies either before or after autologous stem cell transplantation (ASCT). rIL-2 was given by a 6 day continuous intravenous infusion with escalating doses, up to 18 x 10(6)/m2/day, depending on patient tolerance. The functional immune responses of the patients were assessed as natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic activities and in vitro interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) synthesis. During rIL-2 treatment, the expected side effects occurred; only 3 patients, who showed severe cardiovascular toxicity, required suspension of the treatment. All toxicities reversed after the end of the therapy. Immunologic monitoring was carried out the day before starting rIL-2 infusion and then repeated on days 3, 7, and 14 after rIL-2 was discontinued. Following every rIL-2 course, a pronounced increase in CD3+, CD8+, CD56+ cells was found, with a peak value on day 3. The NK and LAK activities showed a significant increase on day 3 (p < 0.001) over pretherapy values; the increase lasted until day 14, although the difference at later time points was not significant. Before transplant the synthesis of both IFN-gamma and TNF-alpha decreased following rIL-2 therapy, whereas higher levels of these lymphokines were found after posttransplant rIL-2 courses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Haemopoietic reconstitution after autologous blood stem cell transplantation in patients with malignancies: a multicentre retrospective study.

A retrospective study was undertaken to evaluate the efficacy of autologous blood stem cell transplantation (ABSCT) in terms of haemopoietic reconstitution after ablative chemotherapy or chemo-radiotherapy. 55 patients with malignancies, observed in four Italian institutions from January 1987 to June 1991, were eligible for evaluation. This series included 19 non-Hodgkin's lymphoma, 11 multiple myeloma, nine ovarian cancer, seven Hodgkin's disease, seven non-lymphocytic leukaemia, one acute lymphoblastic leukaemia, one neuroblastoma. 522 PBSC collections were performed on 55 patients. Following ABSCT, the rate of engraftment was positively related to the dose of CFU-GM infused and negatively to the presence of bone marrow involvement at conditioning. 48 patients out of 55 transplanted (87%) had rapid, complete and sustained engraftment. Three patients (5%) died of transplant-related complications. Considering that 60% of the patients in this series were in partial remission or in progressive disease at the time of ABSCT, we conclude that ABSCT is a safe approach for the use of ablative conditioning therapy in patients with a wide scope of malignancies, provided that a large number of CFU-GM have been collected after mobilizing treatment.

Adolescent↗

Intraperitoneal chemotherapy with carboplatin and recombinant interferon alpha in ovarian cancer.

Twenty-five patients with Stage III ovarian cancer were entered into a trial with intraperitoneal combinations of carboplatin (400 mg/cqm) and recombinant interferon alfa (50 MU). All patients had received prior intravenous platinum-based chemotherapy and underwent 2nd look laparotomy at study entry. Our study indicates that this combination chemotherapy is safely administered by the intraperitoneal route. Myelotoxicity was frequent, but rarely of grade 3. No major local toxicity was recorded by accessing the peritoneal cavity with a temporary catheter. The response to treatment was promising in the group of patients with less then 2 cm residual disease at study entry (15 patients); in this group, all patients had no clinical evidence of disease at the completion of the therapy. In 2 cases reexploration was performed and pCR was recorded. Only one patient of this group relapsed during a mean follow-up of 21 months. Two pCRS were also recorded in the group of patients with more than 2 cm at 2nd look (9 patients), although relapse occurred after 9 and 15 months respectively. In the remaining patients of this group, persistence of disease was observed after intraperitoneal chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

[The immunological aspects of Kikuchi's disease. A clinical case report].

We report a case of histiocytic necrotizing lymphadenitis (NHL) (Kikuchi-Fujimoto disease) in a 23-year-old patient with fever, lymphadenopathy and leukopenia. There were no other significant findings in laboratory data and all bacterial and viral researches were negative. Fever resolved spontaneously after one month, but lymphadenopathy and leukopenia persisted. The immunophenotype of bone marrow and peripheral blood cells showed an increase of B lymphocytes (CD20+, CD21+, CD22+) and activated (CD30+) and NK cells (CD16+, CD56+). This finding persisted after six months. The authors suggest that the clinical feature of NHL is sustained by an immunological substrate.

Adult↗

Autologous blood stem cell collection after chemotherapy in patients with sensitive and refractory malignancies: a multicenter retrospective study.

A retrospective study was undertaken to assess the factors affecting the yield of peripheral blood stem cell (PBSC) collections after chemotherapy. Fifty-five patients with malignancies, observed in 4 Italian Institutions from January 1987 to June 1991 were eligible for evaluation. This series included 19 non-Hodgkin lymphoma, 11 multiple myeloma, 9 ovarian cancer, 7 Hodgkin disease, 7 acute non-lymphocytic leukemia, 1 acute lymphoblastic leukemia, 1 neuroblastoma. Five hundred and twenty two PBSC collections were performed on 55 patients after a median of 18 days after the start of chemotherapy. The yields of PBSC collections were related to the dose of cytoreductive chemotherapy exploited for PBSC mobilization and to the number of circulating white blood cells, colony forming unit granulocyte/macrophage (CFU-GM) and the percentage of monocytes at the time of collection. Forty-eight patients out of 55 transplanted (87%) had rapid, complete and sustained engraftment. Three patients (5%) died of transplant related complications.

Adolescent↗

Progenitor cells purging: negative selection.

Disease relapse after autologous bone marrow transplantation (ABMT) may arise from residual tumor in the recipient and/or from cancer cells that are reinfused. The aim of purging by negative selection is to remove tumor cells from the marrow without adversely affecting the engraftment potential of the normal cell. We report the results of a study on fifty-six patients (pts) with non Hodgkin's lymphoma or acute leukemia submitted to ABMT after immunomagnetobead (IMB) purging (11 pts), Maphosphamide purging (31 pts) and no purging (14 pts). The IBM procedure involved one incubation of 3 monoclonal antibodies (CD10, CD19 and CD22) and two incubations with magnetic beads (Dynabeads M-450). The median recovery of mononuclear cells and CFU-GM was 40% and 45% after IMB purging and 84% and 5% after Maphosphamide purging respectively. The rate of leukocyte, neutrophils and platelets recovery following ABMT was similar in the three groups of pts, although platelet recovery was slow in patients received graft purged with Maphosphamide. Our study confirms the clinical feasibility of the IMB procedure, but only randomized studies will be able to definitely address the question of the clinical utility of purging.

Adolescent↗

Therapy of 'high risk' myelodysplastic syndromes with an association of low-dose Ara-C, retinoic acid and 1,25-dihydroxyvitamin D3.

Forty-four patients with high risk primary myelodysplastic syndromes and an excess of marrow blasts were treated with a combination of low-dose Ara-C, retinoic acid and vitamin D3. Morphological subtypes were refractory anemia with excess of blasts (RAEB) in 16, RAEB in transformation (RAEB-T) in 20 and chronic myelomonocytic leukemia (CMML) in eight patients. The therapy was continued in responders until relapse or death. The results were compared to those of a matched control of 44 patients given a supportive therapy only. In the treated group the overall response rate was 50% (75% in RAEB, 50% in RAEB-T and 0% in CMML) and the survival was significantly better than in the control group (P < 0.025). Comparing separately each FAB subgroup gave statistical evidence that the treatment prolonged the survival in the RAEB-T subgroup only (P < 0.002). The median duration of response was 15 months and the survival in responders was statistically better than in non-responders (P < 0.0001). Myelosuppression has been the most important side effect, however, no death related to the treatment was observed. Our study suggests that patients with RAEB-T, who are not suitable candidates for aggressive chemotherapy, could benefit from our treatment schedule. The long duration of therapy seems to be of value for patients achieving a response in order to prolong the survival. The toxicity is acceptable and the therapy can be given on an outpatient basis.

Aged↗

Autologous blood stem cell transplantation in malignant lymphomas: an Italian Cooperative Study.

Twenty-three patients with malignant lymphoma, (7 Hodgkin's, and 16 non-Hodgkin's) in different phases of disease were autografted in 4 Italian Haematology institutions using only chemotherapy-mobilized blood stem cells (BSC) collected by apheresis. Clinical and laboratory data were analysed centrally and showed mean collection yields of 8.1 x 10(8) kg mononuclear cells (MNC) (SE 0.5; range 2.6-13.8) and 24.1 x 10(4) kg CFU-GM (SE 7.4; range 1.4-162.9). The mean times required to attain 0.5 x 10(9)/l neutrophils and 50 x 10(9)/l platelets after marrow-ablative high-dose chemo+radiotherapy and BSC reinfusion were 14.9 days (SE 1.5; range 7-38) and 18.6 days (SE 2.6; range 6-49) respectively. The incidence of early deaths was < 5% and the requirement for support with blood product transfusion was moderate. The progression free survival (PFS) is > 50% at 3 years with a median follow-up of 17.3 months. Results were significantly better for patients autografted in remission. These results suggest that autologous blood stem cell transplantation (ABSCT) may be proposed for the primary treatment of poor prognosis malignant lymphomas. However, ABSCT needs to be compared with autologous bone marrow transplantation (ABMT) followed by infusion of growth factors to accelerate recovery.

Adolescent↗

Origin heterogeneity of Hb Lepore-Boston gene in Italy.

Forty-three hybrid delta-beta-globin genes were characterized by DNA sequence analysis and associated RFLP haplotypes in 40 families from Abruzzo and Campania, which are on the east and west coast of Italy, respectively. All the genes had the delta-globin sequence up to the exon 2 codon 87 and had the beta-globin sequence from IVS-2-8; between these two ends, they had 58 bp in common with the delta- and beta-globin genes. Thus, they were all of the Lepore-Boston type. A chromosomal background heterogeneity was present among the mutant genes. In fact, they were all associated with (+ - - - -) 5' subhaplotype, but 23/31 from Campania were associated with (+ +) 3' subhaplotype, whereas 12/12 genes from Abruzzo and 8/31 from Campania were associated with (+ -). DNA sequencing of homozygous subjects showed that (+ +) 3' subhaplotype was associated, at IVS-2-74, with G, while (+ -) was associated with T; that is they were associated with the beta-globin gene sequence of frameworks 1 and 2, respectively. The molecular characteristics of this heterogeneity, as well as its geographical patterns in the eastern and western regions of Italy, represent strong evidence for the recurrent and multicentric origins of the mutation.

Base Sequence↗

(Alpha)alpha 5.3: a novel alpha(+)-thalassemia deletion with the breakpoints in the alpha 2-globin gene and in close proximity to an Alu family repeat between the psi alpha 2- and psi alpha 1-globin genes.

A novel 5.3-kb deletion of the alpha-globin gene cluster was observed in a family from Naples, Southern Italy. It removes the 5' end of the alpha 2-globin gene, causing an alpha (+)-thalassemia defect. Because of the presence of the residual 3' end of the alpha 2-globin gene, we indicated this new haplotype with the symbol (alpha)alpha 5.3. The 5' breakpoint, the first to be reported in the intergene region of the psi alpha 2- and psi alpha 1-globin genes, is located 822 bp upstream of the cap site of the psi alpha 1-gene and about 150 bp upstream of a 300-nt Alu family member. The 3' breakpoint is located in the IVS-1 nt 58 of the alpha 2-globin gene. The 5.3-kb deleted fragment shows particular characteristics: it contains four Alu sequences having long regions 80% complementary and the 5'-GGCC-3' short repeat at both ends. The sequences spanning across the breakpoints on the same strand and containing this repeat on their 3' and 5' ends, respectively, are 17 of 25 base complementary. These particular features led us to assume the formation of a multistem-loop due to the intrastrand interaction between the complementary regions as intermediate to the deletion. The unusual localization of the 5' breakpoint suggests that even the intergene region of the psi alpha 2- and psi alpha 1-globin genes may function as a deletion target.

Base Sequence↗

A technique for isolation of bone marrow cells using hydroxyethyl starch (HES) sedimentation agent.

Various methods have been investigated to concentrate hemopoietic stem cells before in vitro treatment and cryopreservation. Each procedure requires various degrees of cell manipulation; moreover, the extent of purification of the stem cell fraction depends on the further use of bone marrow. Fifty four bone marrows were treated with hydroxyethyl starch (HES) to isolate the mononuclear cell population. The manipulation with HES permitted to concentrate marrow stem cells in a small volume with removal of unwanted granulocytes, red blood cells and the donor isohemagglutinins in the major ABH incompatibility. We describe here a manual method which permits the transfusion of a very few number of red cells without depletion of progenitor cells and thus delay of engraftment.

Blood Group Incompatibility↗

Immunomagnetic purging procedure for autologous bone marrow transplantation in lymphoid malignancies.

In this report we describe the use of the immunomagnetic depletion of tumor cells from harvested bone marrow in two patients with acute lymphoblastic leukemia. The immunomagnetic procedure of purging involved one incubation of the marrow cells with a mixture of 4 monoclonal antibodies which bind to antigens of CD10 (ALB2), CD19 (HD37), CD20 (B1) and CD22 (HD39). Two incubations with magnetic beads (Dynabeads M-450) covered with antimouse antibodies followed by magnetic separation were performed. The bead/target B cell ratio was 50:1. After purging the recovery of mononuclear cells was 56% and 40%, while the recovery of CFU-GM was 45% and 38% respectively. Both patients engrafted rapidly without serious complications. One patient relapsed 4 months after transplant, the other remains in complete remission after 5 months. Our results confirm that the use of immunomagnetic beads is a simple, safe and reproducible technique to remove tumor cells before ABMT in patients with B malignancies using a broad mixture of MoAbs. However only a randomized trial using autologous marrow purged or not will clarify the effective clinical value of the procedure.

Adolescent↗

Alpha-2a-interferon/melphalan/prednisone versus melphalan/prednisone in previously untreated patients with multiple myeloma.

Alpha-2a-interferon (IFN) has demonstrable activity in advance and refractory multiple myeloma (MM), because of the in vitro synergism between IFNs and cytotoxic agents we report the preliminary results of a therapeutic trial of 50 patients with MM. Twenty-eight patients were randomized to receive melphalan plus prednisone (MP) and 22 were randomized to receive IFN plus MP (IFN-MP). Criteria for response, progression and relapse were those of the Southwestern Oncology Group. 95% of the patients receiving IFN-MP responded to therapy as opposed to 68% of the patients receiving MP (P less than 0.05). Response was independent of M-component immunoglobulin class but in stage III it was higher in the IFN-MP group than in the MP group (P less than 0.05). The combination IFN-MP was well tolerated without unusual or unexpected toxic effects. The response duration time was longer in the IFN-MP group than in the MP group (P less than 0.025). The median survival was 80 weeks in the MP group and in the IFN-MP group the 93% of patients were still alive after 90 weeks (P less than 0.025). Our results show that the use of the IFN as an adjuvant to MP improves the percentage of responders, the response duration time and the median survival of untreated patients with MM.

Adult↗