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Biomedical subjects

A M Vannucchi

Publications and source records attributed to A M Vannucchi.

At least 37 records · Page 2Linked to original sources
PubMed1998

Evaluation of breast tumour cell contamination in the bone marrow and leukapheresis collections by RT-PCR for cytokeratin-19 mRNA.

There is considerable interest in an autologous transplantation (AT) programme for patients with high-risk breast cancer; however, the issue of the incidence of occult bone marrow (BM) micrometastasis at diagnosis, and the cancer contamination of peripheral blood stem cell (PBSC) collections used for haematological rescue, is still debated. The presence of BM micrometastasis was evaluated in bilateral BM biopsies obtained at diagnosis of 33 patients with stage II/IIIA breast cancer using: (i) a 'nested' reverse transcriptase-polymerase chain reaction (RT-PCR) assay for cytokeratin 19 (K19) mRNA, (ii) histology, and (iii) immunohistochemistry (IHC) analysis with a panel of three monoclonal antibodies. The RT-PCR assay only was used to determine contamination of PBSC collections obtained after priming with recombinant human granulocyte-colony stimulating factor (rhG-CSF). K19 transcripts in one or both BM samples were detected in 48% of patients at diagnosis, with an overall 85% concordance with the results of IHC analysis. On the other hand, 56% of PCR- and IHC-positive BM samples were diagnosed as 'normal' on histological analysis. 57% of patients showed K19 mRNA in at least one PBSC collection; the possibility to have contaminated PBSC collections was significantly higher in patients with K19 positivity in BM at diagnosis. In four patients who had shown K19 positivity in BM and in PBSC collections, immunoselected CD34+ cells used for haematological rescue were K19-negative. There was a trend towards longer relapse free survival (RFS) in patients transplanted with K19-negative PBSC collections as compared to the others. In conclusion, a substantial proportion of patients with high-risk non-metastatic breast cancer present occult BM micrometastasis at diagnosis and also show cancer contamination of PBSC collections used for AT. These might represent a category of patients with poorer prognosis after AT, and possible candidates for more intensive and/or alternative therapeutic regimens, including AT with purged PBSCs.

Adult↗
PubMed1998

A randomized double-blind placebo-controlled study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes.

To evaluate the effect of recombinant human erythropoietin (rHuEpo) on the haemoglobin level and transfusion requirement in low-risk myelodysplastic syndromes (MDS), 87 patients were enrolled in a randomized double-blind placebo-controlled study, 44 patients were assigned to epoetin alpha (150 U/kg/d s.c. for 8 weeks) and 43 to placebo arms. MDS types were homogenous in both groups: refractory anaemia (RA) 47.7-48.8%. refractory anaemia with ringed sideroblasts (RAS) 20.5-25.6%, refractory anaemia with excess of blasts (RAEB) (blasts < 10%) 31.8-25.6%, 14/38 evaluable patients responded to epoetin alpha versus 4/37 to placebo (P=0.007). 50% of RA responded to epoetin alpha versus 5.9% to placebo (P=0.0072), RAS 37.5% v 18.2% (P=0.6) and RAEB 16.7% v 11.1% (P=1.00). 60% of non-pretransfused patients responded to epoetin alpha (Hb 8.35< or = 0.73 to 10.07+/-1.87 g/dl), whereas a slight decrease was observed in the placebo group (8.4+/-0.66 to 8.19+/-0.92 g/dl) (P=0.0004). Percentage of transfused patients was similar in both arms. Basal erythropoietin (Epo) serum levels > 200 mU/l predicted for a non-response. At week 4 sTfR levels were increased > 50% in responders (P=0.013), whereas an increase < 18% predicted for non-response (P=0.006). Leucocyte and platelet counts were not influenced by epoetin alpha treatment. Adverse events occurred in 31.8% of the rHuEpo-treated versus 42.99%) of the placebo-treated patients (P=0.2), and seven patients did not complete the course. In conclusion, rHuEpo was effective in the treatment of low-risk MDS. RA subtype, no transfusions prior to rHuEpo therapy, and low basal Epo levels were associated with higher probability of response. Soluble transferrin receptor level at the fourth week was an early predictor of response.

Adult↗
PubMed1997

Growth factor receptor expression during in vitro differentiation of partially purified populations containing murine stem cells.

We have investigated, by semiquantitative RT-PCR, the kinetics of activation of hematopoietic receptors and differentiation markers in partially purified murine hematopoietic stem cells (HSC) induced to differentiate in serum-free culture with combinations of growth factor (GF). The combinations of GF used sustained either multilineage [stem cell factor (SCF) + interleukin 3 (IL-3), or erythroid [SCF + IL-3 + erythropoietin (Epo)] or myeloid [SCF + IL-3 + granulocyte colony-stimulating factor (G-CSF)] differentiation. The GF receptor genes investigated were the alpha and beta subunits of the IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor, the erythropoietin receptor, the G-CSF receptor, and c-Fms, the receptor for macrophage colony-stimulating factor (M-CSF). The expression of Gata1 and alpha- and beta-globin was investigated at the same time as a marker of erythroid differentiation. HSC were purified according to standard protocols, which include partitioning of lineage-negative bone marrow cells with the mitochondrial dye Rhodamine 123 (Rho) into Rho-dull (> or = 17% of which reconstitute long-term hematopoiesis in recipient mice) and into Rho-bright (which are as capable as Rho-dull of multilineage differentiation but do not permanently reconstitute the host). The following pattern of expression was observed: the alpha subunit of the IL-3 receptor clearly was expressed in both Rho-bright and Rho-dull cells at the outset, and its expression did not change over time in culture. The beta subunits of the IL-3 and GM-CSF receptor, the alpha subunit of the GM-CSF receptor, the Epo and G-CSF receptors and Fms barely were expressed in purified Rho-bright and Rho-dull cells, but their expression increased in cells cultured both in erythroid and in myeloid GF combinations. Gata1 was expressed maximally in Rho-bright cells but was below the level of detection in Rho-dull cells. Rho-dull cells expressed Gata1 when cultured both in erythroid and in myeloid GF combinations. In contrast, alpha- and beta-globin, which also were not expressed in the purified cells, were induced only in cells stimulated with Epo. These results indicate that the genes for all the GF receptors investigated (with the exception of the alpha subunit of the IL-3 receptor) are expressed at low levels, if any, in purified Rho-bright or Rho-dull cells, but are expressed in their progeny cultured either in erythroid or myeloid GF combinations. The expression of the Epo receptor, in particular, is activated both in erythroid (alpha- and beta-globin positive and in myeloid (alpha- and beta-globin negative) cells. Therefore, activation of the expression of the Epo receptor gene and activation of the erythroid differentiation program are two independent events in normal hematopoiesis.

Animals↗
PubMed1997

An erythroid and megakaryocytic common precursor cell line (B1647) expressing both c-mpl and erythropoietin receptor (Epo-R) proliferates and modifies globin chain synthesis in response to megakaryocyte growth and development factor (MGDF) but not to erythropoietin (Epo).

A human megakaryocyte cell line (B1647) has been established from bone marrow cells obtained from a patient with acute myelogenous leukaemia (FAB M2). The cells were CD34-, CD33+, HLA-DR+, CD38+, and expressed the immunophenotypic markers of the megakaryocyte lineage (CD41 and von Willebrand factor). Moreover the cells expressed the c-mpl (thrombopoietin receptor) mRNA and protein. On the other hand, the B1647 cells also possessed erythroid lineage characteristics: the vast majority of cells were glycophorin positive, and about 10% of unstimulated cells stained with an anti-globin gamma chain MoAb. In addition, S1 protection analysis demonstrated expression of beta-globin mRNA, and Epo receptor (Epo-R) protein was detected by cytofluorimetric assay. Several growth factors, when tested alone or in combination, failed to influence the B1647 cell growth. A significant increase of cell proliferation was observed only after the addition, in serum-free culture, of recombinant human megakaryocyte growth development factor (MGDF), a recombinant c-mpl ligand encompassing the receptor-binding domain and identical to thrombopoietin (TPO), at concentrations ranging from 0.01 to 1 ng/ml. Interestingly, MGDF failed to induce megakaryocytic differentiation of the B1647 cells, but significantly increased the synthesis of the globin gamma-chain. B1647 cells could be a useful model for studying the biological effect of TPO on common megakaryocyte and erythroid progenitors.

Cell Division↗
PubMed1997

Constitutive and inducible expression of megakaryocyte-specific genes in Friend erythroleukaemia cells.

Friend murine erythroleukaemia cells (MELC) were analysed by semiquantitative RT-PCR for the constitutive and inducible expression of megakaryocyte-specific genes. Uninduced MELC expressed detectable levels of mRNAs for acethylcholinesterase (AChE), platelet factor-4 (PF4), glycoprotein IIb (GPIIb) and von Willebrand factor (VWF), whereas the erythroid alpha- and beta-globin genes were not transcribed appreciably. However, MELC exposed to 5 mM hexamethylene bisacetamide (HMBA) or 1.5% dimethyl sulphoxide (DMSO) seemed to be channelled towards a mixed erythroid/megakaryocytic phenotype characterized by unaltered levels of VWF mRNA, increased levels of AChE, GPIIb and PF4 mRNA. and simultaneous induction of the globin genes. Megakaryocyte-related genes were expressed. in the absence of globin gene transcription, by MELC treated with either phorbol-12-myristate acetate (PMA; 100 ng/ml) or colcemid (40 nM), an antimicrotubule agent capable of promoting polyploidization in this model. Moreover, PMA and colcemid induced also de novo expression of the thrombopoietin receptor c-mpl. PMA and colcemid did not affect high basal c-myb mRNA levels which, in turn, were down-regulated upon HMBA or DMSO induction. Additionally, both uninduced and induced MELC exhibited significant levels of Epo-R and IL-3R mRNAs, whereas no expression of granulocyte/macrophage-related genes was detected. Megakaryocyte gene expression of MELC was also compared to that of other haemopoietic cell populations from normal mice and mice infected with the anaemic strain of the Friend virus. According to our results, MELC should be seen as an unique erythro-megakaryocytic model of differentiation, potentially useful for studying molecular events governing lineage commitment as well as some steps of megakaryocytopoiesis.

Animals↗
PubMed1997

Randomized trial comparing netilmicin plus imipenem-cilastatin versus netilmicin plus ceftazidime as empiric therapy for febrile neutropenic bone marrow transplant recipients.

The aim of this study was to compare the clinical and microbiological efficacy of netilmicin plus imipenem-cilastatin (Net + Imi) vs netilmicin plus ceftazidime (Net + Cef) as empiric antimicrobial therapy in bone marrow transplant (BMT) febrile neutropenic patients (pts). Sixty-six pts undergoing BMT for hematological malignancies and solid tumors were randomized to receive Net + Imi or Net + Cef as first-line antibiotic therapy. A lasting return of temperature to normal and complete disappearance of either clinical or cultural signs of infection without any modification of therapy was considered as improvement; the persistence of fever after 72 hours, the addition of a third antibiotic or a protocol change was considered as failure. Sixty-nine episodes were randomized during the course of the trial; bacteriological evidence of infection was obtained in 17 (25%) febrile episodes. Overall outcome based on clinical responses was as follows: 80% of pts on Net + Imi responded compared to 73% of those on Net + Cef. For microbiologically documented infections response rates were 70% in Net + Imi group and 43% in the Net + Cef group (p = ns). Neither septic death nor toxicity were observed. Both empiric regimens were shown to be effective; Net + Imi appeared to be more effective in microbiologically documented infections but there was no statistical significance. In conclusion, both Net + Imi and Net + Cef are active and safe as empirical treatment of febrile episodes in neutropenic BMT pts.

Adolescent↗
PubMed1996

Molecular control of erythroid differentiation.

The number of circulating red cells is regulated by the daily balance between two processes: the destruction of the old red cells in the liver and the generation of new cells in the bone marrow. The process during which hematopoietic stem cells generate new red cells is called erythropoiesis. This article describes the most recent advances in molecular and cellular biology which have allowed the identification of the molecular mechanisms involved in the process of erythroid differentiation. It reviews the cellular compartments involved in the process, what is known on how these cells respond to erythroid specific growth factors and how the cells progressively activate specific transcription factors in order to express genes involved in the establishment of the erythroid phenotype.

Cell Differentiation↗
PubMed1996

Combination therapy with G-CSF and erythropoietin after autologous bone marrow transplantation for lymphoid malignancies: a randomized trial.

Previous studies have shown that, unlike in patients submitted to allogeneic BMT, administration of recombinant erythropoietin (Epo) after autologous BMT (ABMT) had no significant effect on erythroid recovery and transfusional requirements. On the other hand, it has also been shown that combining Epo with recombinant granulocyte colony-stimulating factor (G-CSF) in patients with the acquired immunodeficiency syndrome (AIDS) and with myelodysplastic syndromes resulted in additive effects on erythropoiesis. To test the effects of combined G-CSF + Epo therapy on erythroid recovery after autologous bone marrow transplantation a pilot randomized, three-arm trial was designed. Thirty patients suffering from lymphoid malignancies submitted to ABMT were randomly assigned to receive G-CSF alone (5 micrograms/kg, from day + 1 up to reaching an ANC > or = 10(9)/1), G-CSF + Epo (150 U/kg, from day +1 to +21), or neither of these (controls). Patients receiving G-CSF + Epo had significantly more reticulocytes on day +21 and reached 30 x 10(9)/1 reticulocytes earlier when compared to both G-CSF and control patients; however, the number of red blood cell (RBC) transfusions was not modified by the addition of Epo to G-CSF, although both groups had significantly fewer units transfused than controls. No effect on platelet recovery or platelet transfusional requirements was observed. Myeloid recovery was comparable in the G-CSF and G-CSF+Epo groups, and significantly accelerated as compared to controls. We conclude that the addition of Epo to G-CSF causes a slight acceleration of erythroid recovery after ABMT, but is not associated with transfusional benefits. Therefore, the present data do not support the use of Epo in association with G-CSF to hasten erythroid recovery after ABMT.

Anemia↗
PubMed1996

Megakaryocyte-like increase in ploidy of Friend's erythroleukemia cells induced to endoreplication by colcemid.

Previous work from this laboratory has shown that Friend's murine erythroleukemia cells (MELCs) express some bio-chemical traits of the megakaryocytic lineage. The supposed mixed erythroid/megakaryocytic nature of these cells has been investigated further by challenging MELCs with the antimicrotubule agent colcemid. This compound, at the concentration of 40 nM, was found to induce a striking arrest of cell growth without significant effects on viability. At the same time, the bulk of treated MELCs underwent a large increase in size to contain, after 3 days, as much as 4 times more proteins and 5 times more DNA than controls. As shown by high rates of 3H-thymidine incorporation, increase in DNA content was the result of active synthesis without completion of intervening mitosis according to a process that closely resembled endoreplication. Eventually, colcemidinduced MELCs presented multilobed nuclei and were arranged into discrete ploidy groups containing up to 16 N levels of DNA. Moreover, upon colcemid addition, MELCs initiated a polyploid response that was shown to continue, even in the absence of the inducer, to yield cells that became strongly positive for acetylcholinesterase (AChE) in the late stages of culture. These effects were compatible with a colcemid-induced commitment of MELCs to megakaryocyte differentiation, for which these cells seemed to be definitely programmed. The expression of megakaryocyte features in MELCs provided further evidence for the bipotentiality (erythroid/megakaryocytic) of this model.

Animals↗
PubMed1995

Identification and conditions for selective expression of megakaryocytic markers in Friend erythroleukemia cells.

Friend murine erythroleukemia cells (MELCs) have been reevaluated in terms of their nature and potential pathways of differentiation. MELC induced with 5 mmol/L hexamethylene bisacetamide (HMBA), in addition to expression of known markers of the erythroid phenotype, were also found to exhibit traits of the megakaryocytic lineage. Erythroid differentiation was shown by the typical synthesis and accumulation of hemoglobin (Hb); megakaryoblastoid differentiation of MELCs upon induction was shown by increased specific activity of acetylcholinesterase (AChE). Incubation of MELCs with 5 mmol/L HMBA in RPMI supplemented with 1% fetal calf serum (FCS) (instead of the usual 5%), induced cells to selectively express high levels of AChE (up to approximately 170 mU/mg protein) with little activation of Hb synthesis (less than 5% B+ cells). The increase in AChE levels was a general phenomenon affecting the whole cell population and approached its maximum within 3 days of incubation with the inducer. Subsequently, MELCs become committed to terminal division, undergoing growth arrest and expression of the megakaryocytic phenotype even after the removal of HMBA. There were no appreciable changes of basal AChE levels in MELCs that were either made resistant to HMBA or treated with 0.1 mmol/L hemin that activated differentiated erythroid function without commitment. Phorbol 12-myristate 13-acetate (PMA), known to repress induced Hb synthesis in these cells, did not prevent the full increase in AChE when incubated with MELCs 2 days before HMBA addition. HMBA-induced MELCs always underwent AChE increase that was more or less pronounced depending on the low or high serum content in culture, respectively. Conversely, Hb expression was permitted only when MELCs were transferred in the late phase or at the end of commitment from low to high serum media. Variations of FCS content in culture media proved to be a simple and reliable approach to change the MELC response to inducers and to modulate expression of either megakaryocytic or mixed erythromegakaryocytic phenotype. These findings suggested that MELC might be considered, at least, as a bipotential model of differentiation to be used for studies on regulation of either megakaryocytic or erythroid markers and on competition between the two hematopoietic lineages. In this regard, it was intriguing that AChE levels attained under selective induction (low serum) were always higher than under conditions allowing coexpression of both AChE and Hb (high serum). Moreover, MELCs were also found to bind the specific rat-antimouse platelet monoclonal antibody 4A5.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetamides↗
PubMed1995

Circulating CFU-E during hematopoietic recovery after allogeneic bone marrow transplantation: relationship to erythroid engraftment.

The more mature erythroid progenitor assayable in vitro, the colony-forming unit-erythroid (CFU-E), is normally found in the bone marrow (BM) but is virtually absent from peripheral blood (PB), unlike the more immature progenitor, the burst-forming unit-erythroid (BFU-E). We report on the detection of CFU-E in the PB of six of 18 patients during hematopoietic recovery following allogeneic bone marrow transplantation (BMT); three of six patients with PB CFU-E were under treatment with recombinant human erythropoietin (rhEpo) as well as six of 12 who did not present with PB CFU-E. PB CFU-E were found as early as day 14 following BMT, reached a peak on day 28, and were still detectable on day 60. The presence of PB CFU-E was associated with signs of stimulated erythroid engraftment--an accelerated reticulocyte recovery, an increased number of reticulocytes, higher levels of serum transferrin receptor, and a reduction in transfusional requirements were found in these patients compared to those without PB CFU-E. The numbers of PB and BM BFU-E were similar in the two groups, as well as the numbers of PB and BM CFU-granulocyte/macrophage (CFU-GM) and multipotential CFU (CFU-GEMM); on the other hand, the percentage of BM BFU-E in S phase of the cell cycle was higher in the group of patients with PB CFU-E. While there was no difference between the two groups in serum Epo levels assayed on days 14 and 28 after BMT, patients with PB CFU-E had higher Epo levels in serum samples collected before starting the BMT procedure. These data suggest that the appearance of circulating CFU-E early after BMT is characteristic of a group of patients with an accelerated erythroid engraftment, although the mechanisms leading to the circulation of CFU-E after BMT remain unclear.

Bone Marrow Transplantation↗
PubMed1994

Inhibition of erythropoietin production in vitro by human interferon gamma.

The effects of interferon-gamma (IFN-gamma), alone and in combination with IL-1, IL-6 and tumour necrosis factor-alpha (TNF-alpha), on in vitro erythropoietin (Epo) production by the human hepatoma Hep3B cell line were evaluated. The addition of IFN-gamma to either unstimulated or cobalt chloride (CoCl2)-treated Hep3B cells resulted in a dose-dependent inhibition of Epo release in the medium by as much as 70% at 1000 U/ml. Half-maximal inhibition was observed at around 50 U/ml. According to previous observations, IL-6 had a stimulatory effect on Epo production by CoCl2-treated Hep3B cells; however, the simultaneous addition of IFN-gamma and IL-6 resulted in a reversal of the stimulatory effects due to IL-6. IFN-gamma and IL-1 had an additive inhibitory effect, whereas IFN-gamma and TNF-alpha acted in a synergistic fashion in inhibiting Epo production by Hep3B cells. The inhibitory effect of IFN-gamma appeared to be due to a down-modulation of Epo mRNA levels in CoCl2-treated Hep3B cells, as shown by Northern blot analysis. These data indicate that Epo production by hepatoma cells in vitro is inhibited by IFN-gamma, and that a complex network of interacting cytokines may regulate Epo production in response to an hypoxic stimulus. Overall, these results also suggest that IFN-gamma might have a role in the defective Epo production observed in several inflammatory and immunemediated disorders characterized by relatively high IFN-gamma plasma levels.

Blotting, Northern↗
PubMed1994

Monitoring of polyomavirus BK viruria in bone marrow transplantation patients by DNA hybridization assay and by polymerase chain reaction: an approach to assess the relationship between BK viruria and hemorrhagic cystitis.

An association between long-lasting hemorrhagic cystitis (HC) in bone marrow transplantation (BMT) patients and viral infections, mostly with reactivation of the human polyomavirus BK (BKV), is suggested by several previous reports. We have carried out a prospective study in 55 (30 allogeneic, 24 autologous, 1 syngeneic) BMT recipients with the aim of evaluating the role of BKV in this frequent complication after BMT. To overcome the well known difficulties in BK virus isolation in cell cultures, a DNA hybridization assay and the polymerase chain reaction (PCR) were used for the detection and monitoring of viral urinary shedding, respectively. The presence of human polyomavirus JC and adenovirus DNA was also sought in urine specimens. BK viruria was demonstrated in 52.7% of patients (in 53.3% allogeneic and in 54.1% autologous BMT), whereas JCV and adenovirus were seldom present. Seven cases of HC (20% in allogeneic and 4% in autologous BMT) occurred and in all cases the clinical event was associated with BKV urinary shedding. This study suggests that BKV infection alone does not invariably lead to HC in BMT patients; for HC to occur the presence of other, at present unidentified, factors seems to be necessary.

Adolescent↗
PubMed1993

Effects of cyclosporin A on erythropoietin production by the human Hep3B hepatoma cell line.

There is evidence that the inadequate erythropoietin (Epo) production observed in patients undergoing allogeneic bone marrow transplantation (BMT) might be ascribed to an inhibitory effect caused by the immunosuppressive drug cyclosporin A (CsA). In this in vitro study, we have evaluated the effects of CsA on the release of Epo in the culture medium by the human Hep3B hepatoma cell line. In cultures incubated with both CsA and the nonimmunosuppressive CsA analog MeAla-6, but not with the CsA-unrelated immunosuppressive agent FK-506, the levels of Epo in the medium were significantly reduced in comparison with controls, at concentrations (0.01 to 1.6 mumol/L) not affecting total protein synthetic rate nor the constitutive secretion of alpha-fetoprotein. Hep3B cells were found to contain a CsA-binding molecule, with an M(r) of 18 Kd, as assessed by high performance liquid chromatography (HPLC) and ligand-blotting analysis. CsA did not affect the expression of the Epo gene, as judged by Northern blot analysis, but caused a significant amount of Epo to remain unsecreted within the cells; almost all (97% of total) of the intracellular Epo was associated with the plasma membrane subcellular fraction. We conclude that: (1) CsA is able to inhibit Epo release in vitro by Hep3B cells, further supporting the hypothesis that the drug might have a role in the inappropriately low Epo levels observed in BMT patients; (2) the inhibitory effect appears to be specific and not caused by a general impairment of protein synthesis and/or secretion; and (3) the reduced Epo levels found in the medium of CsA-treated Hep3B cultures are supposed to be the consequence of an inability of the cells to correctly process Epo molecules for the secretory pathway.

Amino Acid Isomerases↗
PubMed1993

Ondansetron versus chlorpromazine for preventing emesis in bone marrow transplant recipients: a double-blind randomized study.

Ondansetron, a selective 5-HT3 antagonist, is known to be effective for preventing emesis induced by cisplatin and other antineoplastic agents. We undertook a randomized double-blind study in a series of bone marrow transplantation (BMT) recipients to assess the antiemetic efficacy and the safety of ondansetron in comparison with chlorpromazine, which was being used at our institution, as the standard antiemetic agent for the conditioning regimen. Forty patients submitted to BMT (21 autologous, 19 allogeneic) were included in the study. Patients were randomly assigned to receive ondansetron (as a loading dose of 8 mg iv one hour before the beginning of the conditioning regimen followed by a continuous infusion of 1 mg per hour for the whole treatment period) or chlorpromazine 60 mg/m2/day given by continuous infusion for the same period (maximum 8 days). Twenty patients were assigned to ondansetron, while 20 were assigned to chlorpromazine. The response rate in terms of antiemetic efficacy and in nausea control was similar between the two treatment groups. On the contrary the two groups differed significantly in regard to side-effects: patients receiving ondansetron experienced significantly less sedation (p = 0.002), the absence of extrapyramidal reactions (p < 0.001) and no need for dose reduction (p < 0.001) as compared with patients treated with chlorpromazine.

Adolescent↗