PubMed Health⌕ Search

Biomedical subjects

L Resegotti

Publications and source records attributed to L Resegotti.

At least 37 records · Page 2Linked to original sources

Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups.

BACKGROUND: Allogeneic or autologous bone marrow transplantation and intensive consolidation chemotherapy are used to treat acute myelogenous leukemia in a first complete remission. METHODS: After induction treatment with daunorubicin and cytarabine, patients who had a complete remission received a first course of intensive consolidation chemotherapy, combining intermediate-dose cytarabine and amsacrine. Patients with an HLA-identical sibling were assigned to undergo allogeneic bone marrow transplantation; the others were randomly assigned to undergo autologous bone marrow transplantation (with unpurged bone marrow) or a second course of intensive chemotherapy, combining high-dose cytarabine and daunorubicin. Comparisons were made on the basis of the intention to treat. RESULTS: A total of 623 patients had a complete remission; 168 were assigned to undergo allogeneic bone marrow transplantation, and 254 were randomly assigned to one of the other two groups. Of these patients, 343 completed the treatment assignment: 144 in the allogeneic-transplantation group, 95 in the autologous-transplantation group, and 104 in the intensive-chemotherapy group. The relapse rate was highest in the intensive-chemotherapy group and lowest in the allogeneic-transplantation group, whereas the mortality rate was highest after allogeneic transplantation and lowest after intensive chemotherapy. The projected rate of disease-free survival at four years was 55 percent for allogeneic transplantation, 48 percent for autologous transplantation, and 30 percent for intensive chemotherapy. However, the overall survival after complete remission was similar in the three groups, since more patients who relapsed after a second course of intensive chemotherapy had a response to subsequent autologous bone marrow transplantation. Other differences were also observed, especially with regard to hematopoietic recovery (it occurred later after autologous transplantation) and the duration of hospitalization (it was longer with bone marrow transplantation). CONCLUSIONS: Autologous as well as allogeneic bone marrow transplantation results in better disease-free survival than intensive consolidation chemotherapy with high-dose cytarabine and daunorubicin. Transplantation soon after a relapse or during a second complete remission might also be appropriate.

Adolescent↗

Long-term results of a multicentre randomised, comparative phase III trial of CHOP versus CNOP regimens in patients with intermediate- and high-grade non-Hodgkin's lymphomas. Novantrone International Study Group.

59 previously untreated patients with intermediate- or high-grade, stage II-IV non-Hodgkin's lymphoma (NHL) were entered into an open-label, randomised, multicentre study to compare the efficacy and safety of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) with that of CNOP (cyclophosphamide, mitoxantrone, vincristine and prednisolone). 10 patients refused treatment following randomisation. The remaining 349 patients received either the CHOP or CNOP regimen every 3 weeks for a maximum of six to eight cycles. The randomisation procedure was violated for 34 patients treated at two study centres. Data from these 34 patients were analysed separately for efficacy and survival. Data from the remaining 325 patients, 164 assigned to CHOP and 161 to CNOP, were used in the major efficacy and survival analyses. Of these 325 patients, 263 (81%) met the eligibility criteria of the protocol. Supplementary analyses of data from these 263 patients, 132 assigned to CHOP and 131 to CNOP, were conducted for efficacy and survival. Data from all 349 treated patients were analysed for safety. In the 325 randomised patients, the overall objective response rate was not significantly different between the two groups (chi 2 test, P = 0.35). The CHOP regimen had a 51% (83/164) complete remission (CR) rate compared with 40% (64/161) for the CNOP regimen (P = 0.05). Among those with CR, the median time to response was 104 days with the CHOP regimen and 77 days with the CNOP regimen, and the median duration of CR was 667 and 1833 days, respectively. The median time to progression was 449 days for CHOP patients and 564 days for CNOP patients. The median survival time was 932 days for CHOP patients and 1801 days for CNOP patients, with a risk of death on CNOP relative to CHOP of 0.93% (95% confidence interval 0.68-1.27). After 5 years, 50% of patients in the CNOP arm and 40% of patients in the CHOP arm were still alive; these differences between treatment groups were not statistically significant. The median time to treatment failure (TTF) was 285 days for patients on the CHOP arm and 282 days for patients on the CNOP arm. Separate analyses of 263 eligible randomised patients, and 34 patients in whom the randomisation procedure was not followed, yielded similar results for remission rate, TTF, duration of CR and estimated overall survival. The incidence of non-haematological events, such as severe nausea and vomiting (P < 0.01), mucositis (P < 0.05) and alopecia (P < 0.001), were significantly lower in were significantly lower in patients treated with CNOP as compared with those who received the CHOP regimen. The incidence of cardiovascular toxicity of any severity was similar in the two groups. While severe and potentially life-threatening neutropenia occurred more frequently in patients treated with CNOP compared with CHOP (0.05 > P > 0.10), the incidence of infection of any severity was similar in both arms. We conclude that CHOP and CNOP regimens were both efficacious in patients with previously untreated aggressive NHL.

Adult↗

Polyclonal haemopoieses associated with long-term persistence of the AML1-ETO transcript in patients with FAB M2 acute myeloid leukaemia in continous clinical remission.

The t(8;21) (q22;q22) translocation is a recurring chromosomal abnormality observed in about 20-40% of AML patients with subtype FAB M2 (AML-M2). The molecular facet of this translocation is represented by the formation of a new hybrid gene, the AML1-ETO, which is regularly transcribed in a chimaeric mRNA and translated into a new fusion protein believed to have a key role in the pathogenesis of this type of leukaemia. We looked for the presence of AML1-ETO transcripts, by RT-PCR, in 49 unselected patients affected by AML-M2 diagnosed at various Italian Institutions. A hybrid transcript was detected in 11 cases (23%). Minimal residual disease status was investigated in three patients in continuous complete remission (CCR) after a median follow-up of 44 months; at least one sample from each subject was found positive for the AML1-ETO transcript suggesting a long-term persistence of t(8;21) leukaemic cells. In two female patients in CCR a 'clonality' analysis was performed on peripheral blood DNA by exploiting the X chromosome inactivation pattern of the human androgen-receptor gene (HUMARA); in both cases the results were consistent with the presence of a polyclonal haemopoiesis. Our data confirm that the persistence of residual cells expressing the AML1-ETO transcripts is a frequent occurrence even in patients with long-term remission; on the other hand, clonality assays indicate that in t(8;21) leukaemias long-term remission haemopoiesis is sustained by a polyclonal bone marrow reconstitution.

Adult↗

B-cell chronic lymphocytic leukaemia stage 0. An immunophenotypic study of 66 cases and comparison with B small cell lymphomas.

The cells of 66 B-CLL stage 0 patients were analyzed using a large panel of monoclonal antibodies in order to better define the immunophenotype of B-CLL. The data were compared with the immunophenotypes of lymph node cells from 51 patients with diffuse B small cell lymphoma or leukaemia with lymph node enlargement. The most frequent immunophenotype of B-CLL stage 0 was SIgM(D)+ EmR+ CD5+ CD9+ CD21+ CD23+ CD35- CD38-. Among the lymphomas, EmR-positive and EmR-negative cases were identified. The vast majority of the EmR-positive cases usually showed the leukaemic pattern, immunophenotype and lymph node histology of B-CLL. The EmR-negative cases usually had immunophenotypes quite different from those of B-CLL and the histology of indented cell lymphoma (centrocytic or intermediate) or features of lymphoplasmacytoid/cytic lymphoma. More than 20% of EmR-positive cells proved to be the most important marker to distinguish B-CLL from other lymphocytic lymphomas. Indeed this was a sign of better prognosis. Lymphoplasmacytoid/cytic lymphomas were EmR-positive with the immunophenotype of B-CLL or EmR-negative with a definitely different immunological profile. This suggests two morphologically similar but biologically different subgroups of these diseases.

Antigens, CD↗

Long term results of interferon treatment in hairy cell leukemia. Italian Cooperative Group of Hairy Cell Leukemia (ICGHCL).

Eighty nine of 104 patients with hairy cell leukemia (HCL), enrolled between 1985 and 1987 in a multicenter prospective study on human lymphoblastoid IFN alpha-n1, were evaluable for long-term follow-up. The induction treatment, 3 MU/mq daily for a median of 5.7 months, produced a response of 93%, complete+partial response (CR+PR) = 80%, minor (MR) = 13%. Neither prior splenectomy nor pre-treatment variables were associated with the rate of response to IFN. However maintenance treatment of 3 MU/mq weekly given randomly had a slightly significant effect on failure free survival (FFS). Of the 43 patients who relapsed, 31/36 (86%) obtained a new response with IFN. No differences in FFS were recorded between first and second response. At the third induction 7/11 patients were treated again with IFN, 4/7 obtaining some response, but the FFS was significantly worse. The overall survival is still 85%. We conclude that (1) IFN should be used as chronic uninterrupted treatment for HCL, (2) reduced dosage is sufficient to prolong the disease free status and (3) continuous lymphoblastoid IFN administration seems not to be associated with the development of resistance to retreatment.

Aged↗

Hairy cell leukemia: a clinical review based on 725 cases of the Italian Cooperative Group (ICGHCL). Italian Cooperative Group for Hairy Cell Leukemia.

The Italian Registry for hairy cell leukemia (HCL) has recorded 725 patients with HCL diagnosed over 25 years. We analysed this large series of patients with the aim of providing an evaluation of changes in clinical presentation, impact of initial therapy and modifications in prognostic factors over the period of two decades. Over time, a progressive down-staging of the disease at the onset, along with a reduction of patients with severe anemia and marked splenomegaly, has been observed. A second malignancy was found in 3.7% of patients, mostly detected several years after the onset of HCL. A striking improvement of survival rates has been observed, from 58.9% survival at five years for patients diagnosed before 1985 to 87.5% at five years for patients diagnosed after 1985 (p < 0.0001). Before 1985 hemoglobin alone provided prognostic information, whereas after 1985, clinical stage and the number of leukocytes correlated better with patient outcome. Survivals at 5 and 10 years were 34.4% and 29.6% respectively for untreated patients, 58.8% and 44.1% for patients receiving chemotherapy, steroids or other drugs, 64.1% and 56.1% for splenectomized patients and 88.9% (at 5 years) for alpha interferon (IFN)-treated patients (p < 0.0001). Our findings suggest that IFN has improved the prognosis of HCL, and that it must be considered a good initial treatment for patients with HCL.

Adult↗

Quantitative expression of HLA class I molecules in acute non-lymphoblastic leukaemia cells.

The present study concerns a panel of 33 acute non lymphoblastic leukaemia (ANLL) patients, previously typed for HLA-A,B serological specificities and including samples with a normal HLA-A,B phenotype (3,4 detected specificities) as well as samples with missing and extra specificities. Samples were analysed at the protein and/or RNA level in order to verify whether the observed typing anomalies were due to a modified quantitative expression of class I molecules. The number of HLA-A,B assigned specificities correlated significantly with the cell surface class I expression detected by indirect immunofluorescence using the monomorphic anti-class I MoAb W6/32 (Spearman rank correlation test, P < 0.01) and with the amount of class I Heavy Chain (HC, P < 0.05) and beta-2-microglobulin (beta 2m, P < 0.05) evaluated by Western blot in whole cell extracts. The RNA analysis suggested a HC-beta 2m coordinated down regulation at the mRNA level in a patient with no assigned HLA-A,B specificities. Another patient with no detectable HLA-A,B specificities showed a low expression selectively of the beta 2m protein. The results reported here demonstrate a heterogenous quantitative HLA class I expression in ANLL blasts, analogous to results reported for solid tumours.

Antigens, Neoplasm↗

Idarubicin in combination with intermediate-dose cytarabine and VP-16 in the treatment of refractory or rapidly relapsed patients with acute myeloid leukemia. The GIMEMA Cooperative Group.

Ninety-seven patients with refractory or relapsed acute myelogenous leukemia (AML), median age 37 years, received as salvage therapy a single course of idarubicin 6 mg/m2 as an intravenous (i.v.) bolus daily for 5 days, cytarabine (Ara-C) 600 mg/m2 i.v. for a period of 2 hours daily for 5 days and etoposide (VP-16) 150 mg/m2 for a period of 2 hours daily for 3 days (ICE protocol). Thirty-six patients were primarily resistant to standard inductive therapy with daunorubicin and Ara-C; 50 patients were in first relapse, three patients in second or third relapse, and eight patients in relapse after transplants. Forty-two (43%) out of 97 patients achieved complete remission, 11 patients died of infection or hemorrhage during induction, and 44 patients (45%) had resistant disease. Of the various variables examined, only disease status (i.e. refractory versus relapsed AML) was predictive for a significantly lower response rate. The median remission duration was 16 weeks; the overall median survival was 10 weeks. Nausea, vomiting, and oral mucositis were common but were rarely severe. No patient experienced treatment-related cardiac toxicity. In conclusion, the ICE protocol is a tolerable regimen providing effective antileukemic activity in patients with advanced AML. The evolution of this protocol in previously untreated patients with AML appears indicated.

Adolescent↗

Argyrophilic nucleolar organizer region counts and prognosis in multiple myeloma.

The prognostic significance of argyrophilic nucleolar organizer regions (AgNORs) has been evaluated in bone marrow trephine biopsies from 64 patients with multiple myeloma (MM) prior to therapy. The univariate Kaplan-Meyer survival analysis showed a significant correlation between survivals and AgNOR counts (median of survival 51.3 months for cases with < or = 4.62 AgNORs per plasma cell (PC) versus 16 months for cases with > 4.62 AgNORs per PC; P = 0.0000) or AgNOR distribution in PC nucleus (AgNOR configuration) (median of survival 71.67 months for cases with tightly grouped AgNORs, 16.26 for partially grouped and 11.74 for dispersed AgNORs; P = 0.001). Significant prognostic correlations were also found for monoclonal immunoglobulin type (P = 0.008), platelet counts (P = 0.0078), serum creatinine level (P = 0.0001), Durie's clinical stage (P = 0.02), percentage of plasma cells in bone marrow biopsies (BMPC%) (P = 0.005), pattern of medullary involvement (P = 0.003) and PC atypia (P = 0.009). Borderline result was detected for the percentage of PCs in aspirates (P = 0.06). No significant correlation was found between prognosis and patients age, sex, haemoglobin level, serum albumin or calcium level, marrow cellularity and excess of haemosiderin. Multivariate survival analysis showed that only two variables were significantly correlated with prognosis: AgNOR counts (P = 0.003) and AgNOR configuration (P < 0.001). In addition, the analysis of variance showed significant association between AgNOR number and platelet counts, haemoglobin level, calcaemia, creatininaemia, clinical stage, percentage of PCs in aspirates, BMPC%, pattern of medullary involvement, PC atypia, marrow cellularity and configuration of AgNORs. Our results indicate that AgNOR counts and configuration have prognostic and diagnostic value and therefore they are useful independent parameters to assess the pretherapeutic aggressiveness of multiple myeloma.

Adult↗

Evaluation of bone marrow cellularity by magnetic resonance imaging in patients with myelodysplastic syndrome.

Magnetic resonance imaging (MRI) is a safe modality for examining the bone marrow and it is quite effective in revealing marrow involvement in hematological malignancies. MRI has been compared with needle marrow biopsy in 22 patients with myelodysplastic disorders. A fairly good concordance has been demonstrated in 79% of cases. However, in 5 patients MRI revealed that bone marrow hyperplasia was not generalized. Therefore in elderly patients with MDS, MRI of the spine allows the quantification of bone marrow hyperplasia with a greater accuracy than bone marrow biopsy and this may be useful for monitoring the effect of cytostatic treatment.

Adult↗

Early intensification followed by allo-BMT or auto-BMT or a second intensification in adult ALL: a randomized multicenter study.

In January 1987 we started a multicenter study in order to evaluate in adult ALL patients the results of an intensive chemotherapy effected early after CR, and to compare the efficacy of allogeneic BMT vs autologous BMT vs prolonged intensive chemotherapy in the attempt to eradicate minimal residual leukemia. To September 1990 ninety-six patients entered this study; of the 87 evaluable for induction 25 were at low risk and 62 at high risk; 67 (77%) achieved CR by an induction chemotherapy including vincristine, adriamycin, cyclophosphamide, dexamethasone. Fifty-six out of 67 remitters were enrolled for the early intensification, which consisted of HDAra-C+amsacrine (or IDAra-C+mitoxantrone) followed by vincristine+adriamycin+cyclophosphamide and etoposide+Ara-C. During the early intensification an unexpectedly high number of relapses (10/56) was observed, showing that very intensive treatment with myelosuppressive agents is not useful at this point of the post-remission therapy. One patient suffered toxic death. Out of 45 patients who completed the early intensification 16 had a related well-matched donor and were selected for allogeneic BMT (performed in 11); of the remaining 29 patients, 14 were randomized for autologous BMT (performed in 9) and 15 for a second intensification. The overall DFS at 3 years is 35%. The high number of early relapses makes it difficult to draw conclusions from the comparison of the three eradication modalities. The best results, although without statistical significance, were obtained after allogeneic BMT; in high-risk patients this procedure should be effected as soon as possible after attainment of CR. Autologous BMT and prolonged intensive chemotherapy gave results similar to each other; both were sometimes followed by delayed relapses.

Adolescent↗

Treatment of acute non lymphoid leukemia (ANLL) in elderly patients. The GIMEMA experience.

The results of four consecutive trials designed by the GIMEMA group for the treatment of ANLL in elderly patients are reviewed. Complete remission (CR) has been achieved in 20.8% of patients older than 60 years treated with 5-day courses of ARA-C plus thioguanine, in 22.7% of patients treated with high dose ARA-C (HDARAC) plus Asparaginase, in 39.5% of patients aged 55 to 80 receiving either Idarubicin or Daunorubicin in combination with Cytarabine in a standard 3+7 protocol and in 51% of patients older than 60 years treated with intermediate dose ARA-A (IDARAC) plus Mitoxantrone. From 1988, patients ineligible for aggressive chemotherapy entered a study of palliative treatment with Thioguanine and ARA-C. This 18 year GIMEMA experience showed that: CR can be obtained only with regimens producing marrow aplasia, the inclusion of anthracyclines or Mitoxantrone improves the CR rate, without prohibitive toxicity, haematological toxicity is very high in elderly patients and account for the most frequent cause of treatment failure namely death in aplasia, palliative treatment does not improve the quality of life and prolongs median survival only slightly. When comparing the results of these trials, it appears that in the GIMEMA group the capability of offering effective treatment to elderly patients with ANLL has continuously improved and that IDARAC plus Mitoxantrone is so far the most active and best tolerated regimen. Death in aplasia remains a major problem and future trials will be aimed at exploiting the possibility of reducing the haematological toxicity by using recombinant colony stimulating factors.

Age Factors↗

[Magnetic resonance in the study of residual mediastinal masses after therapy of lymphoma].

Forty-five patients with mediastinal spread of malignant, Hodgkin's and non-Hodgkin's lymphomas were examined with MR Imaging at 0.5 T. Ninety-two examinations were performed at diagnosis and/or during and after treatment to investigate MR capabilities in distinguishing fibrous tissue from active disease in the masses residuing after therapy--which cannot be done by means of CT. MR results indicated T2-weighted sequences to be the most useful. MR results were compared with the data collected from follow-up, clinics, and biology. MR Imaging had high accuracy (92.1%). The number of false negatives was very low, thanks to the low intensity of fibrous tissue, while a relatively high number of false positives was observed, probably due to the difficulties in discriminating inflammatory from neoplastic tissue.

Follow-Up Studies↗