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Biomedical subjects

B Gamberi

Publications and source records attributed to B Gamberi.

36 records · Page 2Linked to original sources
PubMed1994

Pre-treatment with all-trans retinoic acid accelerates polymorphonuclear recovery after chemotherapy in patients with acute promyelocytic leukemia.

All-trans retinoic acid (ATRA) is currently being used as remission induction treatment for acute promyelocytic leukemia (APL). Conventional chemotherapy is added both during and after ATRA treatment, in order to avoid the occurrence of hyperleukocytosis, and to improve the duration of complete remission. In this study we analysed the hematopoietic recovery of 18 consecutive APL patients after standard Idarubicin or Daunorubicin +/- Cytosine-Arabinoside regimens. 9 of the patients were at the onset of the disease, (CHT group) while 9 had been pre-treated with ATRA 45 mg/sqm/day for at least 3 months (ATRA group). 500 PMN/mmc were reached after 20.8 day from the end of treatment in CHT group and after 12.0 days in ATRA group (p = 0.007). Platelets recovery was faster, even though not significantly in ATRA group. Interestingly, PMN recovery in ATRA group was even shorter (p = 0.004) than that obtained in CHT group, after the first course of chemotherapy (treatment in CR vs treatment in CR). If these results are confirmed in a larger study, a protective effect of ATRA on normal residual hemopoiesis should be postulated.

Adult↗
PubMed1994

FLAG (fludarabine + high-dose cytarabine + G-CSF): an effective and tolerable protocol for the treatment of 'poor risk' acute myeloid leukemias.

Twenty-eight patients with poor prognosis acute myeloid leukemia (AML) received therapy with two courses of fludarabine 30 mg/m2/day + ara-C 2 g/m2/day (days 1-5) and G-CSF 5 mg/kg/day (FLAG) (from day 0 to polymorphonuclear recovery). Eighteen patients were considered 'refractory' (eight primarily resistant, five relapsing within 6 months of initial remission, or at a second relapse; five relapsing after an autologous bone marrow transplantation procedure. Ten cases were defined 'secondary' AML (diagnosis of AML made after a preexisting diagnosis of: myelodysplastic syndrome: five cases; myelodysplastic syndrome after therapy for breast cancer: one case; previously untreated, and concomitant, non-Hodgkin's lymphoma: two cases; Hodgkin's disease treated with chemoradiotherapy: one case). Overall, 15 patients (58%) achieved a complete remission (CR). Two patients died of infection during induction, and 11 had resistant disease. Analyzing the data in relation to selected host and disease characteristics, the response varied widely. The highest CR rates (89%) were obtained in secondary AML; in particular, two cases of 'second-primary' (concomitant with low-grade non-Hodgkin's lymphoma) AML obtained CR for both diseases. Refractory AML differed widely for response: high CR rate (75%), although with short mean CR duration for primary resistance AML, and very poor response (11% CR) for relapsed (early, second, after ABMT) cases. Interestingly, a slow kinetic of leukemic growth in vivo before FLAG administration was significantly related to the response and outcome (p = 0.0002). Hematological and nonhematological toxicities were acceptable. In conclusion, the FLAG regimen has significant antileukemic activity and acceptable toxicity especially in secondary AML, both with and without coexisting lymphoid malignancy.

Acute Disease↗
PubMed1994

Acute myeloid leukemia from diagnosis to bone marrow transplantation: experience from a single centre.

We analysed the use of allogeneic bone marrow transplantation (BMT) in the treatment of acute myelogenous leukemia (AML). We evaluated 271 adult patients with newly diagnosed AML treated here between 1983 and 1992; 113 patients (42%) were eligible for BMT because of their age (< 45 years until 1986 and < 50 years later). Of these, HLA typing was performed on 81 patients (72%); 32 patients were not typed (19 had no sibling, 8 had a primary refractory leukemia, 3 died during induction, 1 had important previous toxicity and for one patient there was no recorded reason). Of the 81 typed, 36 patients (44.4%) were found to have an HLA-matched sibling donor and 21 (25%) underwent BMT (8% of the total population); 15 patients did not undergo BMT (6 relapsed before transplantation and did not obtain a second remission, 3 declined the procedure, 1 died during induction, 1 had positive MLR, 1 had positive MLR and HCV hepatitis, 1 was a drug addict with HCV hepatitis, 1 had previous organ toxicity, 1 was psychotic). These data show that only a small fraction of unselected patients with AML can undergo BMT. Such findings make the comparison of BMT with other types of post-remission therapy more complex.

Adolescent↗
PubMed1993

Relief of intractable pruritus in polycythemia vera with recombinant interferon alfa.

Following reports that recombinant interferon alfa (rIFN alpha), besides inducing clinical and hematologic remission in polycythemia vera (PV), can also resolve intractable pruritus, we used rIFN alpha to treat 13 PV patients complaining of severe pruritus refractory to conventional treatment (venesection and/or cytostatics). rIFN alpha was administered intramuscularly three times a week at a dosage of 3.0 x 10(6) U. Eight patients (61.5%) reported a > or = 50% reduction of pruritus, which occurred within 2-8 weeks from the start of rIFN alpha treatment, leading to a substantial improvement in their quality of life. Three patients had to stop rIFN alpha within the first month of therapy because of unacceptable side effects. Thus rIFN alpha seems to be capable of providing considerable relief of otherwise intractable pruritus in a good proportion of PV patients.

Aged↗
PubMed1993

Comparative effects of racemic verapamil vs R-verapamil on normal and leukemic progenitors.

R-Verapamil (R-VPM), an enantiomer of racemic verapamil (VPM), has been recently reported to possess an activity equivalent to VPM in reverting drug resistance in vitro, without showing remarkable cardiovascular toxicity in animal models, even in doses three times higher than VPM. In this study, we assessed the effects of R-VPM in vitro, on clonogenic leukemia cells (CFU-L) from 15 patients with acute nonlymphoid leukemia (ANLL) at diagnosis, and on bone marrow erythroid (BFU-E) and myeloid (CFU-GM) progenitors from 15 healthy volunteers. On CFU-L, continuous exposure to VPM or R-VPM alone showed a slight inhibitory activity; in combination with daunorubicin (DNR), R-VPM proved more effective (mean IC50 of DNR: alone = 24.53 ng/ml +/- 6.2 SE, + VPM = 18.8 ng/ml +/- 4.6 SE, +R-VPM = 17.9 ng/ml +/- 4.8 SE). On CFU-GM, both VPM and R-VPM were minimally toxic at the lowest concentration used, but 30 microM VPM were significantly more toxic than R-VPM at the same dose (residual growth = 39.2% +/- 6.5% vs. 71.8% +/- 9.3% with R-VPM, p = 0.005). On BFU-E, both VPM and R-VPM caused more consistent growth inhibition; at high doses, VPM was again more toxic than R-VPM (33.4% +/- 12.8% vs 53.4% +/- 10.4% residual growth at 30 microM, p = 0.03). DNR toxicity on bone marrow was more greatly enhanced by VPM than R-VPM, and this difference was statistically significant on erythroid progenitor colony growth (p = 0.04). In conclusion, in comparison to VPM, R-VPM appeared to be at least equally effective on leukemic clonogenic cells and less toxic on normal bone marrow precursors, thus suggesting a possible safe use in vivo, even in concentrations that cannot be achieved with VPM, owing to its toxic effects.

Bone Marrow Cells↗
PubMed1993

Impairment of GM-CSF production in myelodysplastic syndromes.

In this study we evaluated the production of granulocyte/macrophage-colony stimulating factor (GM-CSF), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) by enriched bone marrow (BM) macrophages in 15 patients affected by myelodysplasia and 20 normal BM donors. The presence of GM-CSF, IL-6 and TNF-alpha in the culture supernatants of BM macrophages was detectable only after stimulation with lipopolysaccharide (LPS), whereas no differences were present in the amount of IL-6 and TNF-alpha between myelodysplastic patients and normal controls, GM-CSF production appeared eight-fold reduced in BM macrophage culture supernatants from myelodysplastic patients with respect to normal controls. After further experiments, we concluded that the impaired release of GM-CSF by BM macrophages could not be due to a different production kinetic in myelodysplastic patients. Moreover, the number of multipotent (CFU-GEMM), granulocyte/macrophage (CFU-GM) and erythroid (BFU-E) progenitors was significantly impaired in myelodysplastic patients. In conclusion, we demonstrated that the production of GM-CSF by purified adherent cells from MDS patients is markedly impaired in spite of the peripheral blood cytopenia. This selective defect in GM-CSF production, along with an intrinsic defect of haematopoietic progenitor cells, might contribute to the impairment of haematopoiesis always observed in myelodysplastic patients.

Adult↗
PubMed1993

Synergistic cytotoxicity of AZT plus alpha and gamma interferon in chronic myeloid leukemia cell line K562.

We have previously reported that the antineoplastic activity of 3'-azido 3' deoxythymidine (AZT) can be increased by drugs that inhibit "de novo" thymidylate synthesis, such as 5-fluorouracil, methotrexate and hydroxyurea. In the present study we tested the combinations AZT+alpha interferon (IFN) and AZT+gamma IFN on in vitro growth of the human acute-phase chronic myeloid leukemia (CML) cell line K562. After 72 hours incubation, not only AZT+alpha-IFN but also AZT+gamma-IFN were synergistic in inhibiting K562 growth, as demonstrated by isobologram analysis of the data. This enhanced cytotoxicity was confirmed by the evaluation of [3H]AZT incorporation into cellular DNA, that was increased by 50% and 222% in the presence of alpha- and gamma-IFN, respectively. The addition of 50 mumol/l thymidine to the culture medium was able to reduce the cytotoxicity of the drug combinations to the degree observed with each compound alone; furthermore, the increased incorporation of AZT into DNA was completely reversed. These data indicate the existence of a biochemical interaction between AZT and IFNs that results in an increased cytotoxic effect. While the combination AZT+alpha-IFN is currently being tested in HIV-related malignancies, AZT+gamma-IFN is new and deserves further study in human CML acute and chronic phase models, in view of possible clinical applications.

Cell Division↗
PubMed1991

Granulocyte-macrophage colony-stimulating factor in acute non-lymphocytic leukemia before and after chemotherapy.

The introduction of hematopoietic growth factors into the management of leukemia can influence the outcome of treatment in several ways, depending on the sensitivity and the response of normal and leukemic cells. In this paper we report on the effects of the administration of Escherichia coli-produced, human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) in 15 adult patients with acute nonlymphocytic leukemia (ANLL) resistant to first-line treatment or in relapse. GM-CSF was given at a dose of 5-10 micrograms/kg/day as a 6-h i.v. infusion, prior to chemotherapy (CHT) (for 7 days) and after CHT (until evidence of failure or of remission). In the pre-CHT period there was a clear trend towards an increase of circulating neutrophils (PMN) and/or blast cell count (median 0.3 vs. 1.0 x 10(9)/l for PMN, and 0.5 vs. 2.3 for blast cells). After chemotherapy, in the patients who achieved complete remission (CR), the median time to a PMN count greater than 0.5 x 10(9)/l and greater than 1 x 10(9)/l was 16 days (range 13-27) and 19 days (range 13-42) respectively. The outcome of treatment was CR for 8/15 (53%), death during induction for 3/15 (20%), and failure for 4/15 (27%). All failures occurred in patients with an increase of blast cell count during pre-CHT GM-CSF administration. Toxicity and side effects were minor, apart from an acute respiratory syndrome that developed twice in the same patient, at doses of 10 and 3 micrograms/kg/day. These data suggest that investigation of GM-CSF in the treatment of ANLL is worth pursuing, with special attention to GM-CSF effects prior to chemotherapy.

Adult↗
PubMed1990

Sensitivity of chronic myeloid leukemia hemopoietic progenitors to PTT-119 in combination with human recombinant interferon alpha and gamma.

PTT-119, a new synthetic alkylating compound, has shown a marked "in vitro" inhibitory effect on chronic myeloid leukemia (CML) granulo-monocytic precursors (CFU-GM) at doses greater than 5 micrograms/ml. Based on previous experiences of synergistic associations between alkylating drugs and biological modifiers, we tested the effects of low doses of PTT-119 (from 0.1 to 1 microgram/ml) in concert with alpha, gamma, or alpha + gamma interferons and compared to IFNs alone, in order to investigate an alternative choice for treatment of CML patients in chronic phase. Our results showed a significantly higher CFU-GM cloning inhibition after addition of 100 or 1,000 U/ml of alpha IFN to 0.1 microgram/ml PTT-119 (from 39.6% +/- 26.6 SD to 80.7% +/- 10 SD and 91.5% +/- 8 SD, respectively), while gamma IFN resulted in only a slight increase in colony growth inhibition when compared to the drug used alone. The association of alpha plus gamma IFN coupled with PTT-119 treatment did not significantly improve the results observed after exposure of leukemic progenitors to PTT-119 and alpha IFN alone. We conclude that a combined treatment with PTT-119 and IFN is probably worth testing both for purging methods before autologous bone marrow transplantation and for in vivo administration in chronic myeloid leukemia.

Antineoplastic Agents↗
PubMedDate not supplied

Effect of in vivo treatment with rh GM-CSF on in vitro growth of haematopoietic progenitors in patients with myelodysplastic syndromes.

BACKGROUND: Recombinant (r) human (h) granulocyte/macrophage colony stimulating factor (rh GM-CSF) has been shown to increase the number of peripheral blood (PB) neutrophils, eosinophils and monocytes in myelodysplastic syndromes (MDS). The aims of this study were: 1) to evaluate the effect of rh GM-CSF therapy on the in vitro growth of granulocyte-erythroid-macrophage-megakaryocyte colonies (CFU-GEMM), erythroid colonies (BFU-E), and granulocyte-macrophage colonies (CFU-GM) in patients with MDS; 2) to assess in these patients, while they are being treated in vivo with rh GM-CSF, the possible additive effect of rh IL-3 and rh G-CSF on the in vitro growth of haematopoietic progenitors. METHODS: The in vitro growth of CFU-GEMM, BFU-E and CFU-GM was studies in 10 myelodysplastic (MDS) patients, before and after in vivo administration of rh GM-CSF. RESULTS: After rh GM-CSF administration, the number of CFU-GM increased in all standard risk MDS patients. In 2 out of 5 cases, this effect was more pronounced and persisted up to 30 days after the end of rh GM-CSF treatment. On the other hand, the number of CFU-GEMM and BFU-E was substantially unchanged. When rh GM-CSF, rh G-CSF and rh IL-3 were added in vitro alone or in combination as the source of colony stimulating activity, no significant increase of the CFU-GM colony number was noticed. CONCLUSIONS: Rh GM-CSF therapy appears useful for increasing the number of peripheral blood granulocytes and of marrow CFU-GM in standard-risk MDS patients. High-risk MDS patients are far less responsive to rh GM-CSF treatment, probably reflecting a more aggressive and/or advanced disease.

Colony-Forming Units Assay↗
PubMedDate not supplied

In vitro effects of bisantrene on fresh clonogenic leukemia cells: a preliminary study on 15 cases.

In vitro clonogenic assays may be useful for determining the sensitivity of leukemic cells to chemotherapeutic agents. We evaluated the antileukemic effect of Bisantrene (an anthracene derivative now undergoing phase II clinical trials in relapsed/resistant acute non lymphoid leukemias-ANLL) using the ANLL cell clonogenic assay. Fifteen cases were studied (9 newly diagnosed, 5 relapsed and 1 refractory ANLL). Normal CFU-GM sensitivity was tested in a subset of 10 normal controls. A wide range of concentrations (from 0.01 to 10 micrograms/ml) at 3 durations of exposure (30 min, 120 min, continuous) was employed. Bisantrene proved effective in 12 out of 15 ANLL cases, inhibiting blast colony growth (50% at 1 micrograms/ml; nearly 100% at 10 micrograms/ml) in a dose-dependent, time-independent way. Three cases were unresponsive both in vitro and in vivo. Normal CFU-GM were inhibited at lower doses (50% at 0.5 micrograms/ml; 100% at 5 micrograms/ml). We conclude that: 1) Bisantrene is active in vitro on leukemic clonogenic cells at doses corresponding to plasmatic levels achievable in patients, with a parallel activity in vivo in 3 relapsed cases. It should be tested in vitro before therapeutic use in order to avoid, if possible, improper use in resistant patients. 2) Normal CFU-GM are more sensitive than clonogenic leukemic cells. This must be taken into account, in view of possible prolonged neutropenias after therapy. 3) The time-independent effect of the drug should be evaluated in the design of new therapeutic schedules.

Anthracenes↗
PubMedDate not supplied

Accelerated hemopoietic recovery after chemotherapy and autologous bone marrow transplantation in hematological malignancies using recombinant GM-CSF: preliminary results obtained in 14 cases.

Human recombinant granulocyte-macrophage colony-stimulating-factor has been employed, on a compassionate basis, in 14 hematological patients in order to reduce the duration of the neutropenic period after high-dose chemotherapy for the treatment of hematological malignancies (7 traditional CHT courses, 7 autologous bone marrow transplantations). The compound was administered intravenously by 6-hour infusion at a dose of 5 microgram/kg/day until the patient reached at least 1000 PMN in the peripheral blood. Eleven out of the 13 evaluable patients showed a significative improvement in hemopoietic recovery, even though in CHT patients hematological reconstitution was higher in terms of PMN counts. The ABMT patients, however, showed a faster myeloid recovery than that obtained both in a group of 14 NHL and in a series of 8 MM previously submitted to ABMT in our Institution. Moreover the increase in peripheral neutrophils appeared to be stable, since it was maintained throughout one month after the end of rhGM-CSF therapy. We did not observe effects on platelet or erythrocyte recovery. We conclude that rhGM-CSF is active in accelerating the recovery of myelopoiesis, without significant toxic or collateral effects.

Adolescent↗
PubMedDate not supplied

Sweet's syndrome and chronic lymphocytic leukemia associated with scirrhous breast cancer. A case report.

A 55-year-old woman developed Sweet's syndrome (acute febrile neutrophilic dermatosis, AFND) 5 years after a diagnosis of chronic lymphocytic leukemia (CLL). Two months later she developed a scirrhous carcinoma of the breast. The patient died 7 months later from sepsis. To our knowledge, this is the first case of an association among a cancer of the breast, CLL and Sweet's syndrome.

Adenocarcinoma, Scirrhous↗