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Biomedical subjects

M Baccarani

Publications and source records attributed to M Baccarani.

At least 109 records · Page 6Linked to original sources
PubMed1997

Treatment intensification of malignant lymphomas with autologous bone marrow transplantation and granulocyte colony stimulating factor.

Treatment intensification with autologous bone marrow transplantation (ABMT) was administered to 37 cases of Hodgkin's and non-Hodgkin's lymphoma (HL and NHL) who were in complete or partial remission (CR or PR) after chemotherapy (MOPP/ABVD or F-MACHOP respectively) and to 12 cases of HL and NHL who were in relapse. ABMT treatment was BAVC for NHL and BEAM for HL. Marrow cells were harvested from the marrow and cryopreserved. The number of mononuclear marrow cells that was reinfused ranged between 0.19 and 0.80 x 108/Kg b.w. (median 0.39). All the patients were treated with granulocyte colony stimulating factor (G-CSF, Filgrastim) at a dose of 5 mg/Kg b.w. from day +4 until the absolute neutrophil count exceeded 1 x109/L for 3 consecutive days. Engraftment was observed in all cases, and no transplant-related deaths occurred. The patients with NHL and HL received a median of 12 (range 2-19) and 14.5 (range 9-27) doses of G-CSF respectively. Median time to 20 x 109/L platelet count was 14 to 17 days. Median time to an absolute neutrophil count 0.5x109/L was 13 days. A febrile episode during the period of post-transplant aplasia was documented in 35 patients (71%). Fever was associated with Gram+ bacteraemia in 31% of the cases and with Gram- bacteraemia in 11% of cases. Herpes Simplex infection was documented in two cases. No fungal infections were recorded. Median hospitalisation time from reinfusion ranged between 19.5 days (NHL) and 23 days (HL). Thirty-four of 37 cases (92%) who were transplanted in CR or in PR are currently alive and in continuous CR with a median follow-up time of 37 months after ABMT. Three of 12 cases (25%) who were transplanted in relapse are alive and in CR. Our data point out that ABMT followed by G-CSF is a safe and a very effective procedure for high risk malignant lymphomas, when ABMT is planned and is performed not as a rescue procedure but when it is integrated in the treatment strategy from the very beginning.

Journal Article↗
PubMed1997

Myasthenia gravis after allogeneic bone marrow transplantation. A case report and a review of the literature.

A 26-year-old man, affected by acute non-lymphocytic leukemia, received a bone marrow transplantation from his HLA identical sister. A mild (grade 1) acute graft-versus-host disease (GVHD) developed during the first month after BMT. A moderate (grade 2) muco-cutaneous GVHD was present from the 4th month on, in association with recurrent oral herpes simplex infection. A typical clinical and electromyographic picture of myasthenia gravis (MG) developed 46 months after BMT, requiring continuous medication with pyridostigmine. A high titer of antibiotics against the acetylcholine receptor was found in the serum of the patient but not in the serum of the donor. Since the donor had no evidence of MG or other autoimmune disorders, this is likely to be an autoimmune complication of chronic GVHD. Other cases described in the literature are reviewed: a recurrent expression or coexpression of some HLA antigens was recorded, indicating that some genetic factors could predispose to this acquired disorder.

Adult↗
PubMed1996

Interferon-alpha and hydroxyurea in early chronic myeloid leukemia: a comparative analysis of the Italian and German chronic myeloid leukemia trials with interferon-alpha.

In 1994, the Italian and the German Chronic myeloid leukemia (CML) trials comparing interferon-alpha (IFN-alpha) with conventional chemotherapy were published. The survival advantage in favor of IFN-alpha compared with hydroxyurea (HU; 72 v 52 months) was significant in the Italian (P < .002), but not in the German trial (66 v 56 months, P < .44). We set up a collaborative study to identify the reasons for the different outcomes. There are major differences in the trial protocols concerning admission criteria, treatment strategy, and definitions. The German patients were older and more seriously sick. Fifty-two of the 327 patients in the German IFN and HU arms did not fulfil Italian admission criteria, and 41 of the 322 Italian patients did not fulfil German admission criteria. Using mutually uniform admission criteria, the median survival times of the IFN patients are 76 (Italian) and 72 (German) months (P = .56). The Italian group administered IFN combined with HU as needed, whereas the German group strictly used IFN as monotherapy with rerandomization to busulfan (BU) or HU after IFN resistance or intolerability. The differences seen between the Italian and the German trial results can be accounted for by objective differences in study design, especially the admission criteria, treatment strategy, and bias due to intention to treat analysis. The detailed analysis of the data suggests that the combination of IFN with HU as needed is more effective than either agent alone.

Adult↗
PubMed1996

Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders.

It has been recently hypothesized that the hepatitis C virus (HCV) might be involved in the pathogenesis of malignant B-cell non-Hodgkin's lymphomas (NHL). On the basis of this observation we sought to determine the prevalence of HCV infection in the patients affected by B-cell NHL and extended our analysis to all the patients affected by lymphoproliferation disorders seen at our institution in the last 30 months. Five hundred and thirty-seven unselected, consecutive patients were studied. HCV infection was investigated through detection of anti-HCV antibodies and HCV-RNA. HCV genotyping was performed on HCV-RNA positive specimens. The risk of being infected by HCV was compared with that of the general population of our area. Among all lymphoproliferative disorders, the prevalence and the relative risk (RR) of being infected by HCV were increased only among B-cell NHL (9%; RR 3.24; p < .0001). Among these, a strong prevalence of HCV was found only in the subgroup of immunocytomas (30%; RR 10.27; P < .0001), while other histotypes were associated with it only occasionally. Because HCV-positive lymphomas clinically behave as essential mixed cryoglobulinemia (EMC), the close association between HCV infection and EMC is confirmed, and evidence is provided that the pathological substrate of EMC corresponds to the immunocytoma. HCV genomic sequences were found in 84% of patients analyzed. Viral genotypes were those more frequent in our area.

Adult↗
PubMed1996

Neutralizing anti-interferon-alpha antibodies and response to treatment in patients with Ph+ chronic myeloid leukaemia sequentially treated with recombinant (alpha 2a) and lymphoblastoid interferon-alpha.

Neutralizing anti-IFN alpha antibodies (nIFN alpha Abs) occur in a significant proportion of patients with hairy cell leukaemia, hepatitis or solid tumours treated with recombinant IFN alpha (IFN alpha 2a or IFN alpha 2b), but information on their incidence in chronic myeloid leukaemia (CML) is scanty and their clinical relevance is not yet completely defined. By using an IFN alpha antiviral neutralization bioassay, the frequency of nIFN alpha 2a Abs was evaluated in 67Ph+ CML patients during IFN alpha 2a therapy at doses ranging from 6 to 9 MU/d. 15 patients (22%) developed nIFN alpha 2a Abs (titre ranging from 1:40 to 1:20480) and 11/15 (73%) were haematologically and/or karyotypically unresponsive to treatment. 52 patients did not develop antibodies and 11 of them (21%) were unresponsive. The negative relationship between the positivity for nIFN alpha 2a Abs and the response to treatment was highly significant (P = 0.0001). In nine nIFN alpha 2a Abs positive patients, treatment was changed from recombinant IFN alpha 2a to lymphoblastoid IFN alpha (IFN alpha-ly), at the same dose and schedule. After 9 months of IFN alpha-ly treatment a haematological response was achieved in 4/7 cases who were non-responsive to prior IFN alpha 2a therapy and was maintained in the other two patients previously responsive to IFN alpha 2a. However, no karyotypic response was observed. This data shows that a significant proportion of Ph+ CML patients receiving treatment with IFN alpha 2a can develop neutralizing antibodies and that these antibodies are associated with a loss of IFN alpha 2a efficacy. Changing the patients to treatment with lymphoblastoid IFN alpha may restore haematological response but it is not likely to induce a karyotypic response.

Adult↗
PubMed1996

Screening for multidrug resistance in leukemia: cell reactivity to MRK-16 correlates with anthracycline retention and sensitivity of leukemic cells.

The biologic and clinical importance of the multidrug resistance (MDR) that is related with the overexpression of the P170 glycoprotein (Pgp) is widely recognized. However, a major issue that has not yet been solved is the definition of the degree of Pgp expression which is associated with a significant decrease of the sensitivity of the cells to chemotherapy. For this reason we studied the leukemic cells from 83 cases of acute leukemia. Leukemic cells were fixed in PLP and treated with saponine. Pgp expression was assayed by flow cytometry, using the anti Pgp monoclonal antibody MRK-16. Results were expressed both as the number of positive cells and by the intensity of the reaction as defined by the mean fluorescence index (MFI), i.e. the ratio between the mean fluorescence intensity of the MRK-16 incubated cells and of the IgG2a incubated cells. Thus, Pgp expression was compared with the results of two in vitro tests of cell sensitivity to anthracyclines, daunorubicin (DNR) cell retention and DNR cytotoxicity. We found that it was not the number of MRK-16 positive cells, but the degree of the reaction with MRK-16 (MFI) that significantly related to the anthracycline toxicity tests. Therefore, we propose that for clinical purposes a quick and cheap determination of Pgp-related MDR in leukemic cells may be obtained by measuring the MFI with MRK-16 in a standard flow cytometry assay and that the assay may indeed be sufficient to estimate Pgp expression as well as the influence of Pgp on cell sensitivity to anthracyclines.

Anthracyclines↗
PubMed1996

Immunophenotypic and molecular genetic characterization of a case of CD8+ B cell chronic lymphocytic leukemia.

We report the case of a patient with chronic B lymphocytic leukemia, with stable clinical and hematological conditions in the absence of any treatment. The flow cytometry analysis of the patient's cells revealed a CD19+, CD5+, IgM+, IgD+, lambda chain-phenotype, along with an unusual expression of CD8 alpha/alpha homodimer. B cells did not stain with the anti CD8 beta monoclonal antibody T8/2T8 5H7. Molecular biology analyses confirmed the monoclonal rearrangements of immunoglobulin heavy and lambda light chain genes in the presence of a germline configuration of T cell receptor genes. Moreover, an abnormal configuration of the CD8A gene was found in the CD8+B lymphocytic clone. We suggest that the aberrant expression of the CD8 gene could be related to its abnormal configuration.

Base Sequence↗
PubMed1996

Interferon-alpha in the treatment of chronic myeloid leukemia. A summary and an update of the Italian studies.

Six-hundred patients were recruited between 1986 and 1991 for studies of the treatment of Ph positive chronic myeloid leukemia (CML) with interferon-alpha (IFN-alpha). The median survival of the patients who were assigned to treatment with IFN-alpha was 6 years or longer than 6 years, and was more than the survival of the patients who were assigned to conventional chemotherapy. Survival prolongation was significantly related with the achievement of a cytogenetic response. IFN-alpha treatment was not harmful for subsequent allogeneic or autologous bone marrow transplantation.

Adult↗
PubMed1995

Incidence and diagnosis of EDTA-dependent pseudothrombocytopenia in a consecutive outpatient population referred for isolated thrombocytopenia.

Among 111 patients referred to our outpatient clinic for isolated thrombocytopenia during a 24-month period, 17 (15.3%) cases of EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) were identified. EDTA-PTCP represented the second most frequent cause of thrombocytopenia in this population. The diagnosis was confirmed by the following findings: (a) normal platelet numbers immediately after blood withdrawal; (b) progressive fall of platelet counts and evident platelet clumping over time, only in EDTA-anticoagulated blood. A simple, inexpensive and quick diagnostic method was devised, that consists in evaluating the platelet number in a blood sample anticoagulated with EDTA immediately after blood withdrawal and 4 h later.

Adult↗
PubMed1995

Granulocyte colony-stimulating factor (G-CSF) allows the delivery of effective doses of CHOP and CVP regimens in non-Hodgkin lymphomas.

The aim of this study was to evaluate the role and potential benefit of G-CSF administered following standard regimen chemotherapy (CHT) in non-Hodgkin lymphomas. Twenty patients with NHL were given CHOP or CHOP/CVP CHT every 21 days. None was given G-CSF after the first cycle. After each cycle, G-CSF was administered only for: 1) ANC < 1 x 10(9)/L between cycles; or 2) delay in cycle schedule due to ANC < 1 x 10(9)/L on the planned day of treatment; or 3) development of a febrile syndrome or a documented infection, regardless the ANC. Once administered, G-CSF was maintained in the following cycles. Nineteen patients required administration of G-CSF (5 micrograms/Kg B.W.), but for different reasons only 16 were treated (a mean of 10 +/- 3 doses/cycle). Comparing 48 cycles where G-CSF was not administered, with 50 where it was, in this last group we observed: 1) a ANC significantly higher at day 7 (p < 0.0001), day 14 (p < 0.0001) and day 21 (p = 0.0030); 2) a significantly lower (p = 0.0001) incidence of neutropenias (6 vs 29); 3) a trend (p = 0.1040) in favour of lower incidence of febrile neutropenias of infections (1 vs 6); 4) a significantly lower (p < 0.0001) incidence of cycle delays (1 vs 22) with a median of 8 days (1 to 20); and 5) a significantly higher (p < 0.0001) dose intensity (99.5% vs 87.8%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

P170 glycoprotein expression and impaired anthracycline retention in chronic myeloid leukaemia.

Chronic myeloid leukaemia (CML) is a well known model of a disease refractory to chemotherapy, including anthracyclines and other drugs that are believed to be pumped out of the cells by a 170 Kd transmembrane glycoprotein (P170). In 35 cases of Ph+ CML we investigated the reactivity of leukaemic cells to a P170-directed monoclonal antibody (MRK-16), by means of flow cytometry. P170 overexpression was found in 4/14 (29%) chronic phase CML cases and in 16/23 (70%) accelerated and blastic phase CML cases (P = 0.01). The same cells were assayed for their ability to retain Daunorubicin and Idarubicin after 2-hours in vitro incubation with 1000 ng/ml of either drug. It was found that anthracycline cell concentration was negatively related with the degree of the reactivity to MRK-16. In accelerated and blastic phase, CML cells simultaneously expressed P170 and the stem cell related marker, CD34. These data confirm that Ph+ leukaemic cells overexpress P170, show that P170 overexpression is functionally relevant, and suggest that P170-related multidrug resistance may be an important factor for chemotherapy failure in Ph+ CML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗