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Biomedical subjects

G Visani

Publications and source records attributed to G Visani.

198 records · Page 11Linked to original sources
PubMedDate not supplied

Phase II study of bisantrene in relapsed/refractory acute non lymphoid leukemias (ANLL).

The antileukemic activity of Bisantrene, a new anthracene derivative, has been evaluated in a phase II clinical study in 10 patients affected by refractory or primary relapsed ANLL. The patients received an induction course consisting of 250 mg/m2/day for 7 days followed, in case of CR, by 250 mg/m2/day for 3 days (consolidation treatment). In case of partial response a reinduction course (250 mg/m2/day for 3 days) was administered. Four out of the 10 patients obtained CR (3 of them after a single induction course). No significant toxic effect was noticed, apart from fever (due to myelosuppression) and hypotension in one patient who soon recovered without residual effects. These preliminary results could suggest further evaluation of Bisantrene in association with other drugs in both relapsed patients and those at onset of the disease.

Adult↗
PubMedDate not supplied

Persistence of non clonal hematopoietic progenitor cells in blastic phase chronic myelogenous leukemia (CML). Working Party on Severe Aplastic Anemia (WPSAA) of the European Group of Bone Marrow Transplantation (EBMT).

Normal and clonal hematopoietic progenitor cells have been demonstrated to coexist in chronic-phase chronic myelogenous leukemia (CML), but few data are available on the presence of non neoplastic hematopoiesis during the blastic transformation phase. We used reverse transcription-polymerase chain reaction (RT-PCR) to investigate expression of the BCR/ABL transcript of individual hematopoietic progenitors from a CML patient in blastic phase. We demonstrate that non clonal hematopoiesis is induced to re-emerge by conventional chemotherapy containing fludarabine. In addition, we confirm that some pluripotent CD34+/CD33-/DR- cells circulating in the peripheral blood are not clonal. Our data provide an encouraging basis for further studies of in vitro purification of normal hematopoietic stem cells in advanced stage CML and of their use in the context of autologous bone marrow transplantation.

Adult↗
PubMedDate not supplied

Ifosfamide, epirubicin and etoposide (IEV) therapy in relapsed and refractory high-grade non-Hodgkin's lymphoma and Hodgkin's disease.

BACKGROUND: A fundamental principle in the therapeutic strategy for recurrent lymphomas is the employment of agents that are not part of the usual front line combination regimens. Ideally, the cytotoxic agents should lack complete cross resistance with those utilized up front. PATIENTS AND METHODS: A three-drug combination of ifosfamide, epirubicin and etoposide (IEV) was used to treat 20 patients with relapsing or refractory high-grade non-Hodgkin's lymphoma (HG-NHL) or Hodgkin's disease (HD). RESULTS: Of 14 patients with HG-NHL, 5 (36%) achieved a complete response (CR) and 4 partial remission (PR), giving an overall response rate of 64%. To date, all the complete responders are still in CR at +5, +5, +6, +7, and +9 months, respectively. Of 6 patients with HD, 4 (66%) obtained CR and 2 PR, giving an overall response rate of 100%. The 4 CRs are still in remission after +4, +5, +9, and +13 months, respectively. Clinical and hematologic toxic effects were moderate: neutropenia was responsible for delaying treatment for a week in 6 patients. CONCLUSIONS: These results confirm the efficacy of the IEV regimen in inducing a good remission rate with moderate side effects in relapsing/refractory HG-NHL and HD patients and they show that further investigations with this combination are warranted.

Adult↗
PubMedDate not supplied

AZT+methotrexate in high-grade HIV-related non-Hodgkin lymphomas: interim report on feasibility and tolerance.

BACKGROUND: 3' azido-3' deoxythymidine (AZT) is a thymidine analogue useful in the treatment of AIDS. We have previously demonstrated that AZT can possess significant antineoplastic activity when combined with de novo thymidylate synthesis inhibitors, such as 5-fluorouracil or methotrexate (MTX). We report here on the feasibility and tolerance of the combination AZT+MTX in the treatment of HIV-related non-Hodgkin lymphomas (NHL). PATIENTS AND METHODS: IV-positive patients with high-grade NHL were treated, at weekly intervals, with three consecutive courses of MTX 1 g/m2 plus increasing doses of oral AZT (2, 4 and 6 g/m2) and folinic acid rescue. RESULTS: From July 1992 to June 1994, 16 patients were enrolled in the trial after giving informed consent. Grade III-IV neutropenia was observed after 22% of the courses, but was prevented by G-CSF administration in 34/59 courses. Grade III-IV anemia was observed after 15% of the courses. No non hematological toxicity was observed. CONCLUSIONS: The combination AZT+MTX was extremely well tolerated in this series of HIV-related NHL patients. If these results are confirmed in terms of antineoplastic efficacy, the protocol will deserve wider application.

Adult↗
PubMedDate not supplied

Hematological recovery after autologous bone marrow transplantation for high-grade non Hodgkin's lymphomas: a single center experience.

BACKGROUND: Both rhGM-CSF and rhG-CSF can accelerate hematological recovery after high-dose therapy and autologous bone marrow transplantation in patients with high grade non Hodgkin's lymphoma and reduce transplant-related morbidity after ABMT. METHODS: The clinical course of 23 non randomized patients was analyzed and compared with a historical control group of 10 patients. Ten patients received GM-CSF at a dose of 10 micrograms/kg in a 6-h IV infusion, and 13 received G-CSF at a dose of 5 micrograms/kg subcutaneously. Control patients received no GFs. RESULTS: Mean granulocytic recovery to 0.5 x 10(9)/L was obtained 13.1 +/- 3.2 days after marrow reinfusion in the G-CSF arm vs 16 +/- 2.7 in GM-CSF pts (p = 0.03) and vs 19.6 +/- 7.6 in controls (p < 0.01); this reduction led to a statistically significant shorter duration of fever and parenteral antibiotic therapy. Platelet recovery to 20 x 10(9)/L was not significantly influenced by GFs. CONCLUSIONS: These results indicate that only G-CSF accelerates hematological recovery after high-dose chemotherapy and autologous bone marrow transplantation and induces a significant decrease in terms of infection morbidity and duration of hospital stay.

Adolescent↗
PubMedDate not supplied

Apoptosis induction with fludarabine on freshly isolated chronic myeloid leukemia cells.

BACKGROUND: Fludarabine (FLU) is a fluorinated purine analogue with antineoplastic activity in lymphoproliferative malignancies. Recently, some in vitro reports have showed the effective role of FLU on the activation of apoptosis. MATERIALS AND METHODS: The induction of programmed cell death (apoptosis) by fludarabine (FLU), an adenine nucleoside analogue, alpha-interferon (alpha-IFN), and FLU plus alpha-IFN was evaluated in vitro against freshly isolated, chronic-phase Ph1+ chronic myeloid leukemia (CML). Apoptosis was detected by electrophoresis gel of DNA oligonucleosomal fragments in 8 CML samples. RESULTS: Only FLU and FLU plus alpha-IFN significantly activated apoptosis in all the samples, suggesting selective activity on CML cells. On the other hand, alpha-IFN alone did not activate programmed cell death. CONCLUSIONS: Our data show apoptotic activity for FLU on CML cells. Programmed cell death may be suppressed in cells carrying the bcr-abl transcript, and FLU might remove this resistance in the neoplastic cell cycle. This preliminary report justifies using FLU in pilot clinical trials for chronic phase Ph1+ CML patients.

Antineoplastic Agents↗
PubMedDate not supplied

Epidemiology of acute promyelocytic leukemia.

BACKGROUND: The estimated incidence of acute promyelocytic leukemia (APL) is approximately 6 cases per 10 million people per year with no apparent differences between sexes. The age of APL cases is younger than that of other acute myeloid leukemias (AML). Spatial and temporal clusters of APL have been reported. These observations suggest a possible selective role for environmental and/or occupational factors in APL development. METHODS: A multicenter case-control study was carried out on risk factors for acute leukemias and preleukemias. In this report data related to APL are selectively analyzed from the larger study to identify specific risk factors. RESULTS: The case-control study on 38 cases of APL showed a strong association with shoemaking (odds ration 6.3, 95% confidence interval 1.3-31.1). A moderate leukemogenic effect from living in houses built with tuff, a polous building material containing gamma-emitting radionuclides and having a high radon concentration, and from using hair dyes was also suggested. CONCLUSIONS: These data, together with the reported spatial and temporal clustering of APL, support the hypothesis of specific environmental and/or occupational risk factors for APL among other AML subtypes and indicate the need for additional ad hoc multicenter studies.

Adolescent↗
PubMedDate not supplied

All-trans-retinoic acid and pseudotumor cerebri in a young adult with acute promyelocytic leukemia: a possible disease association.

Pseudotumor cerebri or idiopathic intracranial hypertension is a neurological syndrome characterized by signs and symptoms of intracranial hypertension without clinical or radiological evidence of infective or space occupying lesions. Iatrogenic factors are frequent; in particular, cases of pseudotumor cerebri associated with all-trans-retinoic acid treatment in acute promyelocytic leukemia (APL) have been frequently described in pediatric patients. We report on a case observed in an older patient (young adult age) and give diagnostic and therapeutic guidelines.

Adolescent↗
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All-trans retinoic acid in hematological malignancies, an update. GER (Gruppo Ematologico Retinoidi).

BACKGROUND AND OBJECTIVE: During the past ten years, the study of retinoids has undergone a total transformation. The Italian Society of Experimental Hematology decided to discuss these advances at a meeting in Florence on April 18, 1996. INFORMATION SOURCES: The material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. In addition, all the authors of the present article have been actively working in the field of retinoids and have contributed several papers. Summaries of their oral presentations at the Florence meeting are reported in the Appendix to this review article. STATE OF ART AND PERSPECTIVES: One of the most important advances has been the elucidation of new molecular mechanisms of control of gene expression by retinoids. A number of new retinoids have been synthesized by chemists, some of which are being screened for potential clinical use, and a few have already had a tremendous impact on clinical practice. The most important achievements have been obtained in acute promyelocytic leukemia. In 1988 a Chinese group working in Shanghai showed that using all-trans retinoic acid (ATRA) alone 94% of acute promyelocytic leukemic patients obtained complete remission through differentiation of the leukemic clone. This result transformed a dream into reality and allowed researchers to move from laboratory experience to clinical applications of this differentiating therapy. Expanding the spectrum of hematological malignancies that may respond to ATRA remains a challenge; however, several results show some activity of retinoids alone or in combination with other drugs in juvenile chronic myeloid leukemia (CML), myelodysplastic syndrome, cutaneous T-cell lymphoma and CML. Particularly interesting are the studies that explored the potential clinical synergism of ATRA-based combination therapies with growth factors, other differentiating agents such as vitamin D3, immunomodulators like interferons, or chemotherapeutic agents, in particular Ara-C, all of which show promising in vitro effects when used in combination with retinoids.

Adult↗
PubMedDate not supplied

The expression of proliferation and quiescence associated antigens in acute myeloid leukemia correlates with survival duration: analysis of 15 refractory cases.

In this study, blast cells from 15 patients with acute myeloid leukemia resistant to induction therapy were examined with two monoclonal antibodies that identify, respectively, the nuclear protein specifically expressed in non proliferating cells (statin) and the proliferating cell nuclear antigen (PCNA). We found that statin values varied widely, ranging from 0.6% to 14.7% (mean value 6.4%). When the patients were subdivided according to the mean value, those presenting with higher statin values survived for a shorter period of time than the ones characterized by lower levels (p = 0.003). We observed a wide variation in the range of PCNA values; however, if an agreement between survival duration and at least one of the proposed markers was considered, all but one case displayed concordance between survival duration and PCNA and/or statin values (in addition, 4/15 cases showed agreement for both markers). These preliminary data could indicate a possible discriminating prognostic factor between categories of patients characterized by different aspects of resistance, perhaps susceptible to different salvage therapy approaches.

Acute Disease↗
PubMedDate not supplied

Adenoviral mediated gene transfer can be accomplished in human myeloid cell lines and is inhibited by all-trans retinoic acid-induced differentiation.

BACKGROUND AND OBJECTIVE: Gene transfection could potentially represent a useful therapeutic tool for genetic and neoplastic hematological diseases. After having long been considered poorly able to transfect myeloid cells, adenoviral vectors have recently been demonstrated to be capable of introducing foreign DNA into purified CD34+ cells from human bone marrow or cord blood. In the present study we evaluated the feasibility of adenoviral-mediated gene transfer in two human leukemic cell lines, both at baseline and after differentiation induction by all-trans retinoic acid (ATRA). METHODS: We used a recombinant adenovirus expressing beta-galactosidase (Ad-RSV-beta-gal) to transfect K562 and HL-60 cell lines. The effects of 10(-6)M ATRA were evaluated after 8 days of exposure. The efficacy of transfection was verified by X-gal staining. RESULTS: Ad-RSV-beta-gal was able to transfect both the HL-60 and, to a minor extent, the K562 cell lines. The addition of ATRA had no effect on transfection of K562 cells, while a lower percentage of beta-gal-positive cells was detected in HL-60, which underwent differentiation upon ATRA treatment. INTERPRETATION AND CONCLUSIONS: These data suggest that adenoviral-mediated gene transfer could be feasible in myeloid leukemia cell lines and that it is inhibited by ATRA in differentiation-sensitive cells. The latter effect merits further investigation in order to verify whether this represents an ATRA-related or a differentiation-related phenomenon.

Adenoviridae↗