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Biomedical subjects

A Cortelezzi

Publications and source records attributed to A Cortelezzi.

At least 37 records · Page 2Linked to original sources
PubMed1996

In vitro effects of IL-2 on NK-activity, clonogenic potential, blast cell proliferation and cytokine release of MDS bone marrow patients.

To evaluate the clinical usefulness of IL-2 in myelodysplastic syndromes (MDS) the in vitro effects of interleukin-2 (IL-2) on blast cell proliferation, clonogenic activity, cytokine release and cell mediated cytotoxicity were examined in 49 MDS patients. Morphological analyses of bone marrow (BM) cytospin preparations showed a significant decrease in the number of blast cells in MDS after incubation with IL-2. Incubation of bone marrow mononuclear cells (BMMNCs) with IL-2 induced a significant increase in the number of CFU-GM in comparison with untreated controls. gamma-IFN and GM-CSF, but not alpha-TNF were found to be released in significant amounts by the BMMNCs cultured with IL-2. No significant differences in the surface phenotypes of fresh lymphocytes were observed between the normal and MDS subjects. After incubation with IL-2, we observed a significant increase in the number of CD3-/CD56+ cells in both normal and MDS subjects. Peripheral blood (PB) and BM NK activity against K562 was significantly greater in MDS after stimulation with IL-2. These data suggest the clinical usefulness of IL-2 in a large subgroup of patients as it may reduce the percentage of blasts and increase clonogenic capacity and cell-mediated cytotoxicity.

Adult↗
PubMed1995

Interferon alfa-2b versus no maintenance therapy during the plateau phase in multiple myeloma: a randomized study. Cooperative Study Group.

This clinical trial was designed to investigate if maintenance therapy with alfa-interferon could prolong the plateau phase in patients with multiple myeloma. In addition, the tolerability of interferon treatment and its effect on survival were evaluated. From September 1987 to September 1989 a total of 314 patients were accrued to a multi-institutional randomized clinical trial. All patients entered into the protocol received standard melphalan-prednisone (MP) induction therapy. Response was noted in 184 (59%) and a plateau phase achieved in 155 (49%). From the latter group, 125 eligible patients were randomized to either interferon alfa-2b or no maintenance. The patients were followed for an average of 51 months (minimum 36 months) from the time of randomization. The plateau phase was significantly prolonged in the group of patients treated with interferon (median 13.9 v 5.7 months from the time of randomization; P < 0.0001). The interferon therapy was tolerated fairly well, moderate granulocytopenia and a chronic fatigue syndrome being the most frequent side-effects (22% v 18% W.H.O. grade 3 toxicity). The median survival from randomization was almost identical in both groups (36 v 35 months). The study shows that interferon maintenance therapy given to multiple myeloma patients who have achieved a response to initial treatment with MP prolongs the plateau phase duration with tolerable toxicity. The clinical value of this finding should be interpreted with caution, because survival was not prolonged. Further studies are required to clarify the role of interferon in the treatment of multiple myeloma.

Aged↗
PubMed1994

CD34 immunohistochemistry of bone marrow biopsies: prognostic significance in primary myelodysplastic syndromes.

Bone marrow (BM) biopsies from 58 patients with primary myelodysplastic syndrome (MDS) were studied using QBEND10, a monoclonal antibody that recognizes the human progenitor CD34 antigen in routine aldehyde-fixed paraffin-embedded samples. FAB subtypes were RA (5 patients), RARS (9 patients), RAEB (20 patients), RAEBt (11 patients), CMML (3 patients). In addition, 10 MDS patients whose BM biopsies revealed heavy reticulum fibrosis were included. Neither the percentage of CD34+ cells nor the number of CD34+ aggregates (defined as clusters of 3 or more cells) correlated with the presence and morphology of abnormal localizations of immature precursors (ALIP). When all patients were considered, median survival was 69 months in those with less, and 25 months in patients with more than 1% CD34+ cells (P < 0.05). Median survival was 15 months in patients with CD34+ aggregates and 41 months in those without aggregates (P = 0.0017). When RAEB patients were considered median survival was 41 months in those with less than 1%, and 29 months in those with more than 1% CD34+ cells; the 4-year survival chance was 45% in the former and 18.3% in the latter group. Therefore, CD34 positivity of more than 1% identifies a subset of RAEB patients with shorter life expectancy. In addition, leukemic transformation was observed in 11 of 35 patients (31%) with no CD34 aggregates, but in 14 of 23 patients (60%) with aggregates (P < 0.05). CD34 immunostaining, which can be easily performed on routinely prepared BM biopsies, was found to be a powerful prognostic tool for predicting survival and outcome in MDS.

Adolescent↗
PubMed1994

Quality control of red cell filtration at the patient's bedside.

BACKGROUND: Concern has been raised about the quality of white cell (WBC) reduction in blood components when it is performed by filtration at the patient's bedside. Thus, the quality of red cell (RBC) filtration performed at the bedside through two new flatbed WBC-reduction filters was evaluated. STUDY DESIGN AND METHODS: In the laboratory, 25 and 10 RBC units suspended in additive solution were stored for 1 to 2 and 14 to 21 days, respectively, and filtered through each filter. At the end of filtration, an automated complete blood count and a manual WBC count (Nageotte chamber) were determined in two samples collected from 1) a segment clamped at 5 and 25 cm below the filter along the line connecting prefiltration and postfiltration bags and 2) the postfiltration bag. In addition, 10 of the 11 nurses of the hematology outpatient clinic administered to hematologic patients 25 RBC units stored for 1 to 2 days through each type of filter. At the end of transfusion, a segment was collected from the transfusion set and a WBC count was performed as described above. No filter priming or rinsing with saline was done. RESULTS: WBC counts obtained after laboratory filtration in the segments were similar to those obtained from the postfiltration bags and from the segments collected at the bedside in all cases, with the exception of 14- to 21-day-old RBCs filtered in the laboratory through one of the filters, which produced slightly higher WBC counts in the segments than were seen in the postfiltration bags. The difference was not significant. In no case was the count in the postfiltration bag higher than that in the segment. Nurse training was easy, and bedside filtration was associated with no untoward effects. CONCLUSION: The RBC filtration at the patient's bedside can be equal in quality to that performed in the laboratory, at least in such clinical settings as hematology and oncology departments in which blood transfusion is common practice, and if simple training is provided to the nursing staff. Under the conditions of this study, it seems that quality control of RBC bedside filtration is feasible and simple.

Blood Transfusion↗
PubMed1994

Effects of recombinant human stem cell factor (rh-SCF) on colony formation and long-term bone marrow cultures (LTBMC) in patients with myelodysplastic syndromes.

Stem cell factor (SCF), the ligand of the c-kit receptor, is a potent enhancing cytokine for haematopoietic cells in the presence of IL-3, GM-CSF and erythropoietin (Epo). In the clonogenic assays of 63 MDS patients, the addition of rh-SCF + GM-CSF and/or IL-3 induced a significant increase (p < 0.001) in the number and size of CFU-GM. Never reaching the levels of controls, this increase was seen in all FAB subtypes, but particularly in RA. There was no significant increase in cluster formation, even in RAEB or RAEBt. Rh-SCF (10 ng/ml) led to mean increases of up to 26 times in the number of Epo-dependent BFU-E colonies, particularly in RA (p < 0.001) and RAEB (p < 0.05). Individual responses varied widely (especially in RA) from no response to supranormal levels. Added to the weekly refeed of 37 MDS LTBMC, SCF (10 ng/ml) induced only a 7% mean increase in both cell output and the number of clonogenic cells recovered in the supernatant. Immunohistochemical examination of the supernatant showed significant increases in differentiating myeloid cells in all examined cases, and in erythroid cells in 3 cases; blast cells increased in only 3 cases. These data suggest that rh-SCF is capable of at least partially reversing defective MDS myeloid haematopoiesis, and leads no overt risk of leukaemic transformation. Its potent effect on erythroid cells is encouraging for future clinical applications in patients, particularly if they are selected by means of in vitro tests.

Bone Marrow Cells↗
PubMed1994

Analysis of alterations of oncogenes and tumor suppressor genes in chronic lymphocytic leukemia.

B cell chronic lymphocytic leukemia (B-CLL) represents the most frequent adult leukemia in the Western world. The molecular pathogenesis of B-CLL is largely unknown. Although initial reports on small panels of cases had suggested a role for Bcl-1 and Bcl-2 oncogene activation in B-CLL, later investigations failed to confirm these data. Among tumor suppressor genes, p53 mutations have been reported in a fraction of cases. In this study, we have attempted a conclusive definition of the involvement of dominantly acting oncogenes (Bcl-1 and Bcl-2) and tumor suppressor loci (p53, 6q-) in 100 cases of B-CLL selected for their CD5 positivity and Rai's stage (0 to IV). Rearrangements of Bcl-1 and Bcl-2 and deletions of 6q and 17p were analyzed by Southern blot using multiple probes. Mutational analysis (single strand conformation polymorphism and polymerase chain reaction direct sequencing) was used to assay p53 inactivation. No alterations of Bcl-1 or Bcl-2 were detected in the 100 cases tested. Mutations of p53 were found in 10/100 cases without any significant association with clinical stage. Deletions of 6q were present in 4/100 cases. Overall, our data indicate that: 1) contrary to previous reports, Bcl-1 and Bcl-2 rearrangements are not involved in CD5+ B-CLL pathogenesis and 2) p53 mutations are present in 10% of cases at all stages of the disease.

Blotting, Southern↗
PubMed1993

Idarubicin in the therapy of acute myeloid leukemia: final analysis in 57 previously untreated patients.

Fifty-seven previously untreated adult acute myeloid leukemia patients received idarubicin (IDA) in sequential combination with cytarabine as induction therapy; post-remission treatment included two courses of IDA and cytarabine alternating with two courses of VP-16 and cytarabine. As late intensification, patients received either high-dose cytarabine or, in 10 cases, autologous bone marrow transplantation. Complete remission (CR) was achieved in 48 patients (84.2%), 41 after one induction course and seven after two courses. Median length of disease-free survival (DFS) was 26 months. Univariate analysis did not identify any of the investigated variables as having prognostic significance in predicting DFS. On the other hand, patients achieving CR after one induction course had a better DFS than those requiring two courses. Furthermore, the analysis of DFS slightly favors autologous bone marrow transplantation. In conclusion, the antileukemic activity of the present IDA protocol is testified by the high CR rate and by the possibility of minimizing the role of prognostic factors. The better outcome of patients achieving CR after one induction course further supports the opinion that the intensity of the induction treatment, offered by an agent as potent as IDA, might significantly influence DFS.

Acute Disease↗
PubMed1991

Interferon therapy during the plateau phase of multiple myeloma: an update of the Swedish study.

A multicentre clinical trial was carried out in order to evaluate the effect of interferon (IFN) in patients with multiple myeloma. Patients (n = 120) who had shown response to conventional intermittent melphalan-prednisone induction therapy, and achieved a plateau phase, were randomized at that point to receive either interferon alfa-2b in a dose of 5 million units (MU) three times per week or no therapy. This report presents the results of an interim analysis, performed when the patients had been followed for a median of 20 months. The duration of the plateau phase was significantly longer in the IFN arm (59 weeks), compared to the no therapy arm (26 weeks). A total of 34 deaths have occurred, 13 in the IFN arm and 21 in the no therapy arm. In spite of the high median age of the patients studied (70 years), most patients were able to tolerate a full or only slightly reduced IFN dose.

Aged↗
PubMed1990

Immunophenotypes in "classical" B-cell chronic lymphocytic leukemia. Correlation with normal cellular counterpart and clinical findings.

This study evaluates the expression of a series of membrane antigens, normally expressed by B-lymphocytes of the lymphocytic mantle and marginal zone, in 90 selected cases of "classical" (mouse red blood cell-receptor+, CD20+, CD5+, surface immunoglobulin +/-) B-chronic lymphocytic leukemia (B-CLL) with the aim of contributing toward identifying the normal counterpart of B-CLL and any correlations between surface antigen pattern and certain clinical characteristics. Clustered (CD23, 25, 39, 40, 27, 1c, w75) and unclustered (NuB1, 7F7, KiB3) monoclonal antibodies (MoAb) were tested. Almost all cases showed high reactivity to CD23, 27, w75, 39, 40, and NuB1: expression of CD1c was very low and that of 7F7, KiB3, and CD25 was variable. The reactivity of 7F7 and KiB3 was strictly correlated, and they correlated individually with CD25. Results show that the most frequent B-CLL phenotype (CD19+, 5+, 23+, 27+, 39+, NuB1+, KiB3 +/-, 7F7 +/-, and CD25 +/-) corresponds to one or more cellular subsets in the mantle zone. No correlation was found between MoAb expression, surface immunoglobulin (SIg) class or type, clinical stage, disease activity, or age at diagnosis. The only difference (statistically borderline) was the expression of 7F7 and KiB3 (in young versus old patients). This suggests that modulations in the expression of surface antigens do not affect the clinical behavior of the disease.

Adult↗
PubMed1990

Recombinant gamma-interferon as first line therapy for high risk myelodysplastic syndromes. Italian MDS Study Group.

Thirty patients affected by previously untreated high risk myelodysplastic syndromes (MDS) were treated with human recombinant gamma-interferon (r-IFN-gamma): 15 of them with a higher dose (HD) of 0.1 mg/sqm, three times a week and 15 with a lower dose (LD) of 0.01 mg/sqm, three times a week, both doses administered subcutaneously (s.c.). The therapy was fairly well tolerated and few major toxic events were documented. Sustained improvement of one or more clinico-hematologic parameters was observed in 43.3% of the patients (26.6% and 60.0% for the lower and higher dose, respectively). Median survival time from the start of IFN-gamma therapy was 15+ months (range: 1-26) for patients with refractory anemia with excess of blasts (RAEB) versus 5 months (range 2-12) for patients with RAEB in transformation (RAEB-t); 15+ months (range 1-26) for HD patients versus 8 months (range 2-23) for patients treated with LD regimen; 16+ months (range 9-26) for responders versus 7 months (range 1-22) for nonresponders. All these three variables (diagnosis, treatment, and response to treatment) turned out to be statistically significant (p = at least less than 0.01) at Cox's analysis.

Adult↗
PubMed1989

VMCP chemotherapy with or without interferon-alpha-2 in newly diagnosed patients with multiple myeloma.

Fifty-two previously untreated patients with multiple myeloma were randomized to either a combination of recombinant interferon (rIFN) alpha-2 and chemotherapy or chemotherapy alone. Patients were treated with vincristine, melphalan, cyclophosphamide and prednisolone every 4-6 weeks. In the combined treatment arm rIFN was administered concurrently with chemotherapy as well as during chemotherapy free intervals. The combined regimen effected 17/21 (80.9%) responses as compared to 19/27 (70.4%) responses in VMCP treated patients. Addition of rIFN to chemotherapy did not enhance hematologic toxicity. These findings suggest a somewhat higher rate of objective response in the VPMC + rIFN group, although a significant improvement in median survival by adding rIFN to conventional first line polychemotherapy in myeloma patients has not yet been achieved.

Adult↗
PubMed1989

Combined alpha-2C-interferon/VMCP polychemotherapy versus VMCP polychemotherapy as induction therapy in multiple myeloma: a prospective randomized trial.

Thirty-three previously untreated patients with multiple myeloma were randomized to either a combination of recombinant interferon-alpha-2C (rIFN-alpha-2C) plus vincristine/melphalan/cyclophosphamide and prednisone (VMCP) or VMCP chemotherapy alone. The combined regimen effected 67% responses and 26% minor responses, while 35 and 47% of VMCP-treated patients had a pathologically documented remission, respectively. Despite the somewhat earlier achievement and duration (12.0 vs. 8.0 months) of objective response, and the marginal survival benefit observed in the rIFN-alpha-2C + VMCP treatment arm, a significant improvement in therapeutic gain by adding a biologic response modifier to conventional first-line polychemotherapeutic drug treatment in myeloma patients has not yet been achieved. The combined regimen was well tolerated without unusual or unexpected toxic effects.

Adult↗
PubMed1988

Incidence of jaw lesions in 193 patients with multiple myeloma.

The incidence of alterations of the maxilla and mandible at radiographic screening was evaluated in 193 patients with multiple myeloma, both at the time of diagnosis and after the start of chemotherapy during the course of the disease. Although the study confirms that osteolytic lesions are more frequent in the mandible than in the maxilla, it showed that their incidence was lower than reported in the past. Furthermore, these lesions were mostly asymptomatic and were observed in patients who had extensive skeletal involvement, particularly at the skull level. These findings indicate that systematic radiologic monitoring of the stomatognathic system should be performed, particularly in patients with multiple myeloma at an advanced stage.

Adult↗
PubMed1987

VAD protocol for treatment of advanced refractory multiple myeloma.

Twenty-three patients with advanced refractory multiple myeloma were treated with a combination chemotherapeutic regimen consisting of four-day continuous infusion of vincristine and doxorubicin plus intermittent high-dose dexamethasone (VAD). All patients included in the study were heavily pretreated with cytostatics and radiotherapeutic measures, and generally presented in poor general condition. In 3 of the 16 evaluable patients (18%) a response, and in 7 patients (44%) an improvement as defined by a reduction in tumor mass by more than 50% was achieved. Six patients had progressive disease. Evaluation of survival for responders (15 mos) versus non-responders (2 mos) by the landmark method seems to confirm the relative therapeutic efficacy of the VAD protocol in refractory multiple myeloma. The somewhat inferior response rate as well as the occurrence of considerable toxicity in several cases (when compared to the recent M. D. Anderson trial) may be related to differences in clinical features and pretreatment status of the two studies' population.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Idarubicin in sequential combination with cytosine arabinoside in the treatment of relapsed and refractory patients with acute non-lymphoblastic leukemia.

Sixteen adult patients with refractory acute non-lymphoblastic leukemia (ANLL) underwent reinduction therapy with idarubicin (12 mg/m2) i.v. on days 1-3) followed by cytosine arabinoside (120 mg/m2 every 12 h on days 4-10). Patients achieving complete remission (CR) received consolidation and early intensification courses which included idarubicin at lower dosage. CR was reached after a single course in 70% of the patients treated at first relapse, and two of the five subjects previously resistant to daunorubicin-containing regimens responded to the idarubicin protocol. The median duration of CR was 11 months. Gastrointestinal side-effects were not important; mild and reversible ECG changes were noted whereas delayed cardiac toxicity was not observed despite previous treatment with daunorubicin. These encouraging results confirm the efficacy of idarubicin in treating acute leukemia and suggest it may have a major role in the treatment of relapsed and refractory patients with ANLL.

Acute Disease↗
PubMed1987

Therapy with interferons in blood diseases.

We report the clinical experience gained with interferon treatment of B and T cell neoplasms, as well as of myeloproliferative and myelodysplastic syndromes.

Antineoplastic Agents↗