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L Resegotti

Publications and source records attributed to L Resegotti.

At least 55 records · Page 3Linked to original sources
PubMed1991

Should alpha interferon be used as primary treatment for hairy cell leukemia? Italian Cooperative Group for Hairy Cell Leukemia.

To answer the question of whether interferon (IFN) should replace splenectomy, we reviewed the Italian HCL Registry: the records of 450 patients with hairy cell leukemia (HCL), seen from 1975 to 1988 were analysed. Of these, 321 were considered for the study: 231 had been splenectomized, 46 of them receiving subsequently IFN and 90 patients had IFN as initial therapy. Patients treated with splenectomy showed different survival according to Jansen and Hermans' staging system, which identified two risk groups: stage 1 and stages 2 and 3, p = 0.0329. On the contrary, patients treated with IFN did not show significantly different survival according to stage. By the comparison of stage 1 patients, either treated with splenectomy or with IFN, no statistical difference in survival was registered. Different survivals emerged for patients stage 2 + 3, which improved when treated with IFN, p = 0.0324. The median failure free survival (FFS) after splenectomy resulted in 89 months versus 33 months after IFN. In conclusion, splenectomy still remains the primary therapy for HCL patients stage 1. For high risk patients, stages 2 and 3, IFN should be adopted as first line therapy, improving substantially the survival. The short duration of response to IFN suggests a sequential combination of the two treatments for this group of patients, IFN reducing tumor mass quite safely and splenectomy assuring long lasting stable disease.

Humans↗
PubMed1991

Lack of correlation between objective response and death rate in multiple myeloma patients treated with oral melphalan and prednisone.

An analysis of survival by response category was performed on 76 patients with stage II and III multiple myeloma, who were treated with oral melphalan and prednisone. The analysis demonstrated a survival advantage for responders over non-responders only in stage III patients (32.3 months for responders vs. 15.6 months for non-responders, p = 0.03). However, two possible sources of error must be considered: a) the poor prognosis of early responders that may adversely affect the survival of all responders, and b) the bias introduced by the 'guarantee time' of responders (i.e., the time on-study required to detect the response). Exclusion from the analysis of the unfavourable subgroup of 'early' responders (median survival 14.7 mos.) provided an improvement of the difference in survival between the remaining 'slow' responders and non-responders in stage III (p = 0.005) as well as in the series as a whole (p = 0.025). Because of the consistent 'guarantee time' of slow responders, the Mantel-Byar test (which credits survival to responders only after the response has been obtained) was then applied. The survival advantage of slow responders over non-responders, previously observed in all patients, particularly those with stage III, was not confirmed by the Mantel-Byar test (chi-square 0.831 and 1.457, respectively), thus supporting the hypothesis of an equal death rate over time in each response category. It therefore appears that the usual response criteria (which require at least a 50% reduction of the myeloma protein) should perhaps be reassessed, as they seem to be an inadequate parameter for evaluation of treatment effectiveness in multiple myeloma.

Administration, Oral↗
PubMed1991

MACOP-B for advanced stage large cell lymphoma (DLCL). More is better? Italian Multiregional Cooperative Study Group (IMCSGL).

A study of the predictive value for CR, DFS and OS of the presenting features was carried out on 180 patients with advanced stage DLCL treated with MACOP-B between June 1986 and March 1989. A multivariate regression analysis identified LDH level, bone marrow involvement and tumor burden as independent risk factors with a 4 year survival rate of 79%, 58% and 28% respectively. Therefore MACOP-B proved to be an adequate treatment for the first two groups of patients but not for the third which requires a more aggressive treatment. A sequential single drug high dose chemotherapy with collection of peripheral blood stem cell program followed by bone marrow harvesting, super-intensive radio-chemotherapy and bone marrow transplant has been activated. Seven patients have been so far enrolled: preliminary results demonstrated the feasibility of the program. A larger number of cases and a longer follow-up is required for assessing the efficacy of this approach.

Adolescent↗
PubMed1990

Idarubicin and high-dose cytarabine in the treatment of refractory and relapsed acute lymphoblastic leukemia.

Between August 1985 and April 1989, 88 patients (31 children and 57 adults) with refractory of relapsed acute lymphoblastic leukemia (ALL) were treated in a cooperative Italian trial by an induction schedule of high-dose Cytarabine (HDAra-C) plus Idarubicin (IDA). Complete remission (CR) was achieved in 52 of the 88 patients (59%); 23 patients (26%) did not respond to treatment and 13 (15%) died during induction. The CR rate was significantly affected by the WBC count at the beginning of treatment and by the duration of first CR of the patients treated at first relapse. All of the patients experienced profound myelosuppression; the median time to recovery to neutrophils greater than 0.5 x 10(9)/l was 15 days (range 4-40), and 14 days (range 3-50) to platelets greater than 50 x 10(9)/l. The most common non-hematologic side effects observed were nausea and vomiting (51%), mucositis (40%) and diarrhea (23%). Twenty-one of the 52 patients who achieved CR underwent bone marrow transplantation (BMT), 16 autologous and 5 allogeneic. Eleven patients relapsed at a median of 4 months (range 1-31) after the transplantation, and three patients died while in CR. Seven patients have been in continuous CR (CCR) for a median of 36 months (range 26-42 months). Thirty-one patients were not entered in the BMT program: for two adults it was too early, three adults died in CR and 25 patients relapsed at a median of four months (range 1-25). Only one adult is still in CCR at 33 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Different sensitivity of normal and leukaemic progenitor cells to Ara-C and IL-3 combined treatment.

In the present study the effects of a combined treatment with cytosine-arabinoside (Ara-C) and interleukin-3 (IL-3) on acute myeloblastic leukaemia clonogenic cells and on normal haemopoietic progenitors was investigated, with the aim of improving the tumoricidal effect of cycle specific drugs. Blast cells from 24 acute myeloblastic leukaemia (AML) patients were screened with a short-term proliferative assay based on 3H-thymidine (3H-TdR) uptake for their response to IL-3. To evaluate the synergism between the growth factor and Ara-C, the cells were pretreated for 3 d in liquid culture in the presence or absence of IL-3 (10 U/ml) and for the last 24 h with Ara-C (3 micrograms/ml). The cells were then washed and seeded in semisolid media to assess their clonogenic ability. The results showed that, in those cases which were good responders to IL-3 in the 3H-TdR uptake assay (19 out of 24), Ara-C exposure eliminated a greater proportion of clonogenic cells if pretreated with IL-3 than if untreated (P less than 0.001), while in cases unresponsive to IL-3 this effect was not significant. Moreover, when the same protocol was applied to bone marrow cells from normal donors, it was found that IL-3 pretreatment did not significantly enhance the toxic effect of Ara-C on day 14 granulocyte-macrophage colony forming units (CFU-GM) and erythroid burst forming units (BFU-E). Finally IL-3 pretreatment was also able to increase the cytotoxic effect of Ara-C on leukaemic cells co-cultured, to simulate clinical AML remission, with normal bone marrow cells. The results indicate that IL-3 may improve the therapeutic index of cycle-specific drugs in AML therapy.

Cell Division↗
PubMed1990

Altered expression of HLA-A,B specificities on acute lymphoid and myeloid leukaemia blasts.

HLA-A,B specificities were analysed on the neoplastic blasts of a panel of 69 lymphoblastic (ALL) and 50 non lymphoblastic (ANLL) acute leukaemias at onset using the standard lymphocytotoxicity technique. Analysis of the number of detected specificities per locus and, when possible, comparison of the results with those obtained on lymphocytes of the same patients during remission revealed many alterations in the expression of A,B specificities including extra specificities both at the HLA-A and -B loci mainly on lymphoblasts and missed specificities mainly at the HLA-B locus on myeloblasts. Lack of A,B antigens was complete in 6.2% of all tested samples (9% of ANLL) and selective for all the products of one locus in 16.8% of all tested samples (27.7% of ANLL). A decrease of class I molecules on the cell surface was evidenced with MoAb W6/32 on blasts missing detectable serological specificities.

HLA-A Antigens↗
PubMed1989

Gamma-IFN induces a differential expression of HLA-DR, DQ and DP antigens on peripheral blood myeloid leukemic blasts at various stages of differentiation.

Using specific monoclonal antibodies and the indirect immunofluorescence technique, peripheral blood myeloid leukemic blasts from 49 patients were studied for DR expression, 42 for DQ and nine for DP after four days of culture without and with gamma-IFN. The expression of class II molecules on untreated cells depended upon the stage of differentiation and was maximal for DR antigens and lower for DP, while DQ was present only in a small percentage of M2, M4 or M5 blasts. M3 blasts lacked both DR and DQ. Maximal increase of surface expression induced by gamma-IFN was observed for DR molecules independently from the differentiation stage. No significant modification was seen for DQ. Preliminary data concerning DP indicate an increased expression in some of the tested samples. Thus the results obtained on peripheral blood blasts parallel previous observations on leukemic cell lines.

Antibodies, Monoclonal↗
PubMed1989

Human lymphoblastoid interferon as initial therapy in hairy cell leukaemia: a multicentre study in non-splenectomized patients. Italian Cooperative Group for Hairy Cell Leukemia.

The Italian Cooperative Group for Hairy Cell Leukaemia (ICGHCL), between April 1985 and June 1987, conducted a multicentre study using human lymphoblastoid alpha-interferon as primary therapy as an alternative to splenectomy. Forty-eight evaluable patients with HCL entered the study, 38 of them had splenomegaly, in five patients the spleen was not palpable and five were unfit for surgery because of age and general condition. Daily dose of 3 MU s.c. alpha-IFN was given for 12 weeks, or until a satisfactory and stable response was obtained. Among these 48 patients the response rate after 3 months of therapy was 63%, with seven patients (15%) achieving complete remission and 23 (48%) partial remission; 13 (27%) patients had a minor response. In five patients no response was observed and they died within 2 months of treatment. Five other patients, after an initial response, presented a re-expansion of the disease. Actuarial survival at 30 months was 88.8% for the entire group of 48 patients and 92% for the 38 patients who would normally be treated by splenectomy. Thus, alpha-IFN as primary treatment in HCL offered a reasonable therapy for splenomegalic patients. The timing and validity of splenectomy still remains an open question.

Adult↗
PubMed1989

Trisomy 11 in myelodysplastic syndrome-derived acute myeloblastic leukaemias.

Here we report 3 cases of trisomy 11 observed in 1 patient with secondary acute myeloblastic leukaemia and in 2 patients with spontaneous acute myeloblastic leukaemia. In all 3 patients, the picture of overt acute leukaemia arose following a clinically established myelodysplastic syndrome. These findings, together with the previously reported occurrence of trisomy 11 in myelodysplastic syndrome and in acute myeloblastic leukaemia, suggest that this abnormality can be considered specifically associated with myelodysplastic syndrome and with the subsequent and related acute myeloblastic leukaemia.

Aged↗
PubMed1988

Effect of interferon-gamma on HLA class II antigen expression and sensitivity to prostaglandin E1 by normal and leukemic myeloid progenitors.

Chronic myelogenous leukemia (CML) granulo-monocyte committed progenitors (CFU-GM) are markedly less sensitive than normal progenitors to the inhibitory action of prostaglandin E (PGE). This phenomenon has been ascribed to their abnormal expression of HLA class II (mainly DR) determinants. Since interferon gamma (IFN-gamma) is a potent inducer of the expression of HLA class II (DR and to a lesser extent DQ) antigens, we have sought to determine the extent to which this agent can modulate both the antigenic pattern of normal and leukemic progenitors and their sensitivity to PGE 1. 72-h preincubation of normal and CML bone marrow cells with or without IFN-gamma does not significantly change DR and DQ expression by CFU-GM. Pre-incubation for 72 h with and without IFN-gamma produces the following changes in PGE 1 sensitivity: (1) normal CFU-GM lose some sensitivity to PGE 1. This is only marginally counteracted by the presence of IFN-gamma. (2) CML CFU-GM, preincubated with IFN-gamma regain a significant sensitivity to high concentrations of PGE 1. Our data confirm the expression of DR molecules on normal and leukemic progenitors. They also show that, although incubation with IFN-gamma for 72 h in a liquid culture system does not significantly affect the expression of HLA class II molecules by progenitor cells, it may increase their sensitivity to PGE, particularly in the case of CML CFU-GM. Thus expression of HLA class II antigens and sensitivity to PGE may be dissociated.

Alprostadil↗
PubMed1988

Induction of proliferation of acute myeloblastic leukemia (AML) cells with hemopoietic growth factors.

Like their normal counterparts, leukemic blasts have recently been shown to respond to hemopoietic growth factors in both suspension culture and in semisolid media. In the present study, we have evaluated the proliferative response of 35 AML cases to colony-stimulating factors (CSFs) containing conditioned media derived from the human cell lines GCT, 5637, MO and MG U87, and to human recombinant IL-1 (rh-IL1), IL-3 (rhIL-3), GM-CSF (rhGM-CSF) and G-CSF (rhG-CSF). In the great majority of cases, an increase of 3H-thymidine (3H-TdR) uptake was obtained in response to at least one conditioned medium. The labeling index (LI) and the growth fraction (GF), evaluated in a restricted group of cases, were also increased by the growth factors, suggesting that they act by recruiting leukemic cells in cycle from the resting compartment. The ability of blast populations to form colonies was also studied. Conditioned media were found to induce or significantly increase the clonogenic capacity in 20 cases out of 22. The response of leukemic cells to human recombinant CSFs and rhIL-1, used alone or in combination, was also assayed. The results, in agreement with those obtained with conditioned media, show that each leukemic case displays a different pattern of response to CSFs, and that optimal growth conditions must be individually assessed. The possibility of increasing the fraction of cycling cells in AML populations may represent a way to render them more sensitive to cytostatic agents, with a view to new therapeutic strategies.

Adolescent↗