Biomedical subjects

F Ravagnani

Publications and source records attributed to F Ravagnani.

At least 19 recordsLinked to original sources

PubMed2005

Stage 4 neuroblastoma: sequential hemi-body irradiation or high-dose chemotherapy plus autologous haemopoietic stem cell transplantation to consolidate primary treatment.

The aim of the present study was to evaluate the effectiveness of two consecutive nonrandomised treatment programs applied between 1989 and 1999 at the Istituto Nazionale Tumori of Milan in an unselected cohort of 59 children over the age of one with stage 4 neuroblastoma. Both treatment programs consisted of two phases, the induction of the remission phase and the consolidation phase. The induction of the remission phase consisted of intensive chemotherapy, and remained the same throughout the study period. The consolidation phase consisted of sequential hemi-body irradiation (HBI) (10 Gy per session, 6 weeks apart) in the first period (1988-June 1994) and sequential high-dose cyclophosphamide, etoposide, mitoxantrone+L-PAM and autologous haemopoietic stem cell transplantation in the second (July 1994-1999). Intention-to-treat analysis revealed a significantly better outcome for patients treated with the second program, the 5-year event-free survival probability being 0.12 for program 1 and 0.31 for program 2 (P=0.03). This finding led us to conclude that sequential HBI is useless as consolidation treatment. The high-dose chemotherapy adopted in the second program enabled a proportion of patients to obtain long-term survival but, since the clinical results remain unsatisfactory, new treatment strategies are warranted.

Adolescent↗

PubMed2004

A new polymorphism (Ser362Thr) of the L-myc gene is not associated with lung adenocarcinoma risk and prognosis.

The non-coding variation in the second intron of the L-myc gene, generating an EcoRI polymorphism, is associated with lung cancer risk and prognosis. We carried out sequence analysis of the L-myc gene in lung adenocarcinoma (ADCA) patients to identify functional polymorphisms and identified a new single nucleotide polymorphism (SNP) in the third exon of the gene causing a Ser362Thr conservative amino acid change in the C-terminus of the encoded protein. This polymorphism showed significant linkage disequilibrium with the L-myc EcoRI polymorphism located at 1751 bp distance. Genotyping of the Ser362Thr SNP in 220 Italian ADCA patients and in 230 general population controls revealed a similar low frequency (0.10-0.11) of the Thr allele in both groups. The multivariate odds ratio was 0.68 (95% confidence interval (CI) 0.38-1.22). In the ADCA patients, no significant association between the Ser/Thr polymorphism and survival was observed. Thus, the present results do not support candidacy of the L-myc Ser362Thr polymorphism for the functional polymorphism of the L-myc genomic region.

Adenocarcinoma↗

PubMed2003

Synergistic and antagonistic interactions between haemozoin and bacterial endotoxin on human and mouse macrophages.

Haemozoin (malaria pigment) is a birefringent crystalline material made of Fe (III) Protoporphyrin IX dimers that derives from the degradation of haemoglobin by intraerythrocytic Plasmodia. At schizont rupture, it accumulates indigested inside phagocytic cells altering their immunological properties. Both pro-inflammatory and immunosuppressive activities have been associated with pigment-fed monocyte-macrophages or dendritic cells. These conflicting results were attributed to the source of macrophages or the different preparations of pigment. However, the interactions of malaria pigment with other phagocytes stimuli, such as bacterial endotoxin (LPS) or interferon-gamma have not been fully analysed, yet. The purpose of this study was to compare the immunological properties of native haemozoin (HZ), freshly extracted from Plasmodium falciparum cultures, versus beta-haematin (BH), the synthetic crystals identical to native haemozoin, and to evaluate the relationship between haemozoin and endotoxin on the immune response of different macrophages populations. The results indicate that the iron-porphyrin moiety of both native and synthetic pigment can exert either a synergistic or antagonistic effect with LPS that is related to the length and sequence of treatment, the source of macrophages and is associated with the generation of oxidative stress. These data rise the question of whether and how in vivo concomitant gram(-) bacteremia may affect the pathogenesis and/or the immune response of malaria infections and vice versa.

Animals↗

PubMed2001

Effect of lifestyle, smoking, and diet on development of intestinal metaplasia in H. pylori-positive subjects.

OBJECTIVES: This study aimed to evaluate the influence of environmental and sociodemographic factors and the effect of smoking, alcohol, and dietary habits on the risk of gastric intestinal metaplasia (IM) in Helicobacter pylori-infected subjects. METHODS: The investigation was based on 2598 consecutive volunteer blood donors tested for the presence of antibodies against H. pylori from March 1995 to March 1997. Endoscopy with multiple biopsies was offered to all H. pylori-positive, symptomatic subjects. The presence or absence of IM was diagnosed by gastric biopsies. A serologically H. pylori-positive subject with gastric IM was defined as a case, whereas serologically H. pylori-positive subjects without IM were used as controls. All patients answered a detailed questionnaire collecting sociodemographic characteristics and smoking, alcohol drinking, and dietary habits. Odds ratios (ORs) and their 95% CIs were estimated by unconditional logistic regression, including terms for age and sex, to assess the association between the data collected and IM. RESULTS: Three hundred forty-four subjects with serological H. pylori infection and upper-GI symptoms underwent GI endoscopy, during which biopsies were taken for histological diagnosis. Histology revealed metaplasia in 74 subjects (21.5%). Incomplete IM was found in 37.8% of these cases. No significant associations were found between IM and anthropometric or sociodemographic factors. There was a significant association between age and IM (chi2 for trend, 6.67; p value, 0.009). Current smokers of over 20 cigarettes per day had a 4-fold risk of IM (OR, 4.75, 95% CI, 1.33-16.99). A 2-fold increased risk was found for high butter consumers (OR, 2.17; 95% CI, 1.14-4.11). No significant specific associations were found between the variables studied and complete or incomplete IM. CONCLUSIONS: This study found that smoking and high butter consumption may increase the risk of having gastric IM in H. pylori-positive subjects.

Adult↗

PubMed2001

Inhibition of intramacrophage growth of Penicillium marneffei by 4-aminoquinolines.

The antimicrobial activities of chloroquine (CQ) and several 4-aminoquinoline drugs were tested against Penicillium marneffei, an opportunistic fungus that invades and grows inside macrophages and causes disseminated infection in AIDS patients. Human THP1 and mouse J774 macrophages were infected in vitro with P. marneffei conidia and treated with different doses of drugs for 24 to 48 h followed by cell lysis and the counting of P. marneffei CFU. CQ and amodiaquine exerted a dose-dependent inhibition of fungal growth, whereas quinine and artemisinin were fungistatic and not fungicidal. The antifungal activity of CQ was not due to an impairment of fungal iron acquisition in that it was not reversed by the addition of iron nitrilotriacetate, FeCl3, or iron ammonium citrate. Perl's staining indicated that CQ did not alter the ability of J774 cells to acquire iron from the medium. Most likely, CQ's antifungal activity is due to an increase in the intravacuolar pH and a disruption of pH-dependent metabolic processes. Indeed, we demonstrate that (i) bafilomycin A1 and ammonium chloride, two agents known to alkalinize intracellular vesicles by different mechanisms, were inhibitory as well and (ii) a newly synthesized 4-amino-7-chloroquinoline molecule (compound 9), lacking the terminal amino side chain of CQ that assists in drug accumulation, did not inhibit P. marneffei growth. These results suggest that CQ has a potential for use in prophylaxis of P. marneffei infections in human immunodeficiency virus-infected patients in countries where P. marneffei is endemic.

Aminoquinolines↗

PubMed2000

Successful in vivo purging of CD34-containing peripheral blood harvests in mantle cell and indolent lymphoma: evidence for a role of both chemotherapy and rituximab infusion.

Elimination of tumor cells ("purging") from hematopoietic stem cell products is a major goal of bone marrow-supported high-dose cancer chemotherapy. We developed an in vivo purging method capable of providing tumor-free stem cell products from most patients with mantle cell or follicular lymphoma and bone marrow involvement. In a prospective study, 15 patients with CD20(+) mantle cell or follicular lymphoma, bone marrow involvement, and polymerase chain reaction (PCR)-detectable molecular rearrangement received 2 cycles of intensive chemotherapy, each of which was followed by infusion of a growth factor and 2 doses of the anti-CD20 monoclonal antibody rituximab. The role of rituximab was established by comparison with 10 control patients prospectively treated with an identical chemotherapy regimen but no rituximab. The CD34(+) cells harvested from the patients who received both chemotherapy and rituximab were PCR-negative in 93% of cases (versus 40% of controls; P =.007). Aside from providing PCR-negative harvests, the chemoimmunotherapy treatment produced complete clinical and molecular remission in all 14 evaluable patients, including all 6 with mantle cell lymphoma (versus 70% of controls). In vivo purging of hematopoietic progenitor cells can be successfully accomplished in most patients with CD20(+) lymphoma, including mantle cell lymphoma. The results depended on the activity of both chemotherapy and rituximab infusion and provide the proof of principle that in vivo purging is feasible and possibly superior to currently available ex vivo techniques. The high short-term complete-response rate observed suggests the presence of a more-than-additive antilymphoma effect of the chemoimmunotherapy combination used.

Adult↗

PubMed2000

Differential recognition of a BCR/ABL peptide by lymphocytes from normal donors and chronic myeloid leukemia patients.

The BCR/ABL oncogenic fusion protein transforms normal bone marrow stem cells into neoplastic cells. It has been shown that peptides derived from the junctional region of this oncogenic fusion protein can be recognized by human T-lymphocytes obtained from normal donors. In this study, we investigated the immunogenicity in patients with chronic myeloid leukemia (CML) of a 17 mer b3/a2 Bcr/abl peptide (B/A1), which was shown to induce proliferative responses in lymphocytes from normal donors. A total of 56 CML patients in chronic phase were studied. Twenty-two patients were studied at diagnosis without any treatment (group I). Fourteen patients were receiving IFN (group II), 14 patients were being treated with hydroxyurea (group III), and 6 patients were on different regimens (group IV). Patients were initially assessed for general immunological competence using both in vivo and in vitro assays. Patients were also selected for the expression of HLA-DR0401, the HLA specificity known to present peptide B/A1 to CD4 lymphocytes. With the exception of the six patients in group IV, the results of all these assays (in vitro phytohemagglutinin/tetanus toxoid responses, in vivo skin reaction to ubiquitous antigens) in CML patients did not significantly differ from those obtained in normal donors, thus excluding the presence of generalized immunosuppression. Eight patients with HLA-DR0401 and a b3/a2 type of fusion were identified and further studied. In these eight patients dendritic cells were obtained from adherent peripheral blood mononuclear cells and used to stimulate CD4 lymphocytes. No patient developed a specific response to the bcr/abl peptide, although patients' lymphocytes proliferated in response to a promiscuous tetanus toxoid peptide in all but one case. In contrast, response to the bcr/abl peptide was observed in seven of eight HLA-DR0401 healthy donors tested. These data suggest that immunocompetent, HLA-DR0401+ CML patients are unable to respond to peptide B/A1, at difference from healthy donors. The implication of these results for the immunotherapy of CML is discussed.

Cell Division↗

PubMed1999

Recombinant adenoviral vector-lipofectAMINE complex for gene transduction into human T lymphocytes.

We have evaluated, as a vector for gene transfer into human T lymphocytes, a recombinant adenovirus (rAd-MFG-AP) carrying a modified, membrane-exposed, alkaline phosphatase (AP) as reporter gene. CD3+ cells were selected from the buffy coat of healthy donors by the immunomagnetic technique. The positive cell population, comprising 96+/-2% CD3+ cells, was cultured with clinical-grade cytokine(s) for 3-7 days prior to rAd-MFG-AP transduction and the transgene expression was evaluated 48 hr later by indirect immunofluorescence flow cytometry assay with an anti-alkaline phosphatase antibody. The best efficiency of transduction was achieved on incubation of CD3+ cells with IL-2 plus either IL-12 (AP+ cells, 12+/-3%) or IL-7 (AP+ cells, 11+/-3%). To increase further the efficiency of transduction, we have combined LipofectAMINE and rAd-MFG-AP with the aim to enhance the uptake of viral particles into the target cells. The percentage of CD3+ cells transduced by rAd-MFG-AP-LipofectAMINE complex was 24+/-4% (range, 20-35%) after incubation with IL-2 plus IL-7 and 22+/-4% (range, 18-32%) after incubation with II-2 plus IL-12. Forty-eight hours after the incubation with rAd-MFG-AP, the transduced T lymphocytes were subjected to fluorescence-activated cell sorting and fractionated into AP+ and AP- cell subpopulations. The AP+ cell fraction, comprising 96.8% of AP+ cells, was evaluated by FACScan analysis for T lymphocyte surface antigens. The immunophenotyping of the transduced T lymphocytes has shown that there was not a particular subtype of T lymphocytes more susceptible to rAd-MFG-AP transduction. In addition, the transgene expression did not modify T lymphocyte functions, as demonstrated by results obtained by cytotoxicity assay before and after rAd-MFG-AP-LipofectAMINE complex transduction. In conclusion, human T lymphocytes can be efficiently transduced, under clinically applicable conditions, by adenovirus-LipofectAMINE complex after 7 days of culture with IL-2 and IL-12 or IL-7.

Adenoviridae↗

PubMed1999

Novel HLA-Cw8-restricted T cell epitopes derived from tyrosinase-related protein-2 and gp100 melanoma antigens.

The identification of T cell epitopes presented by alternative HLA-B and -C alleles may provide a means to counteract the tumor escape mechanism based on the selection of tumor cells no longer susceptible to HLA-A-restricted T cell recognition. Several T cell clones and lines were obtained from T lymphocytes purified from melanoma-infiltrated or noninfiltrated lymph nodes of a patient who remained disease free 8 yr after surgery. Selected T cells recognized the autologous melanoma as evaluated by direct cytolysis and production of cytokines. These effectors were directed against the tyrosinase-related protein-2 (TRP-2) and gp100 melanoma epitopes restricted by HLA-Cw8. The nonamer and decamer peptides containing the sequence ANDPIFVVL (residues 387-395) of TRP-2 and the octamer, nonamer, and decamer peptides containing the sequence SNDGPTLI (residues 71-78) of gp100 reconstituted the epitope for TRP-2- and gp100-specific T cell lines and clones, respectively. However, only the nonameric form of TRP-2 and the nonameric and octameric forms of gp100 were able to induce peptide-specific T cells recognizing the autologous tumor in an HLA-class I-restricted fashion from PBMC of the melanoma patient studied. Together these data indicate that HLA-Cw8 can restrict the recognition of gp100 and TRP-2 epitopes by CTL, and that such peptides could stimulate a patient's PBL, suggesting that these Ags could have contributed to a systemic immunity against melanoma.

Alleles↗

PubMed1999

Improved collection of mobilized CD34+ hematopoietic progenitor cells by a novel automated leukapheresis system.

BACKGROUND: For simplification of blood cell transplantation, an automated apheresis system that exploits a dual-stage channel device for mononuclear cell (MNC) collection (AutoPBSC, designed for the COBE Spectra) was studied. STUDY DESIGN AND METHODS: The automated default software (AutoPBSC-Default) and three software modifications of the harvest frequency during leukapheresis, referred to as AutoPBSC-1.25, AutoPBSC-1.75, and AutoPBSC-2.75, were evaluated in comparison with the semiautomated Version 4.7 (V4.7) apheresis system in 119 leukapheresis procedures performed in 90 cancer patients treated with chemotherapy plus granulocyte-colony-stimulating factor. CD34+ cell and platelet collection efficiency (CE); volume and cell composition of the leukapheresis components; and patient platelet and red cell (RBC) loss during leukapheresis were measured. RESULTS: The majority of collection measures evaluated with the AutoPBSC compared favorably to those obtained with the V4.7. CD34+ cell CE increased from 55 percent with V4.7 to 68 percent with the AutoPBSC-Default (p = 0.05). The AutoPBSC provided lower platelet contamination in the collected component (1.18 x 10(11) vs. 2.26 x 10(11) with the V4.7; p<0.001). The volume of the AutoPBSC-Default component was significantly lower (67 vs. 180 mL with the V4.7; p<0.001). The MNC purity of the AutoPBSC component was greater (52 vs. 28% with the V4.7; p<0.001), and the RBC contamination lower (AutoPBSC, 0.53 x 10(11) vs. 1.04 x 10(11) with the V4.7; p<0.001). Modifications of the AutoPBSC to increase the harvest frequency by 1.25-, 1.75-, and 2.75-fold resulted in increased CD34+ cell CE (77%, 75%, and 83%, respectively; p<0.001 in all cases), but also in reduced numbers of circulating platelets, higher platelet contamination of the component, and lower MNC purity than were seen with the AutoPBSC-Default. CONCLUSION: The AutoPBSC offers the following advantages over the V4.7 system: a) better CE of CD34+ cells; b) reduced collection of platelets; c) reduced contamination of the leukapheresis component with granulocytes, platelets, and RBCs; d) reduced component volume; and e) automation.

Adolescent↗

PubMed1999

Determinants of Helicobacter pylori seroprevalence among Italian blood donors.

BACKGROUND/AIM: Helicobacter pylori is a worldwide infection. It is estimated that approximately 50% of the general population is affected, but this percentage varies considerably between countries. To investigate the prevalence of H. pylori infection, a cross-sectional epidemiological study, based on the serological determination of the IgG antibodies against H. pylori, was carried out in healthy Italian blood donors by using a commercially available kit. METHODS: From March 1995 to March 1997, a total of 2598 consecutive volunteer blood donors were tested for the presence of antibodies against H. pylori. All patients answered a detailed questionnaire which collected sociodemographic characteristics, and smoking, alcohol drinking and dietary habits. Test-positive subjects with gastrointestinal symptoms underwent endoscopy, with biopsies taken for histological diagnosis. RESULTS: The global prevalence of H. pylori infection in our study was 1161/2598 (45%). It was directly correlated with age (67% in subjects aged > or = 50 years). The prevalence of H. pylori infection was higher in men (46.4%) than women (38.4%), and more frequent in patients with a low educational level, in the lower quintile of height and in the upper quintile of body mass index (BMI). No significant association with smoking and alcohol drinking was found. Inverse associations were found with elevated consumption of milk (chi-square for trend 5.49, P < 0.05), but not other examined food groups. Multivariate analysis selected sex, age, BMI and educational level as the variables independently related to H. pylori infection. CONCLUSION: This study confirms relatively high prevalence of H. pylori seropositivity among Italian healthy adults and points to sex, age, BMI and sociocultural class as persisting determinant features of H. pylori infection.

Adult↗

PubMed1998

Adenovirus vectors for gene transduction into mobilized blood CD34+ cells.

Mobilized blood CD34+ cells from cancer patients were ex vivo infected by a recombinant adenovirus vector carrying an alkaline phosphatase gene, whose expression is evaluable by flow cytometry. A mean of 40% CD34+ cells were infected by the vector, with high levels of expression of the transgene. Among attempts to improve infection efficiency by manipulating culture conditions, only reinfection by the same vector achieved a 10% increase of transgene expression. Transduced CD34+ cells were induced to differentiate along the myeloid and the dendritic lineage, and in either case AP+ cells were detectable among the differentiated cell population. We conclude that adenovirus vectors may be useful tools for gene transduction into mobilized blood CD34+ cells, particularly for those applications in which high transgene expression for limited periods of time is required.

Adenoviridae↗

PubMed1998

Mobilized peripheral blood CD34+ cells express more amphotropic retrovirus receptor than bone marrow CD34+ cells.

BACKGROUND AND OBJECTIVE: The increased susceptibility to gene transfer by amphotropic retroviral vectors of mobilized peripheral blood (PB) CD34+ cells compared to their bone marrow (BM) counterparts may depend, among other factors, on the level of expression of the amphotropic receptor on the progenitor cell. Using a previously described flow cytometry strategy, we have studied retrovirus binding to mobilized CD+ cells, derived from cancer patients treated with high-dose chemotherapy and growth factor(s), that are efficiently transduced by N2 retrovirus vector. DESIGN AND METHODS: We measured the binding of the retrovirus to the cells using a rat monoclonal antibody reactive with the gp70 envelope glycoprotein, common to all replication-defective amphotropic retroviruses. Antibody-virus-cell complexes were indirectly labeled and analyzed by flow cytometry. We compared the binding of PA317-N2 vector to CD34+ cells derived from steady-state BM, steady-state PB and mobilized PB from cancer patients treated with high-dose chemotherapy and cytokine. RESULTS: The fluorescence intensity of mobilized CD34+ cells was approximately one log higher than that of steady-state BM or PB CD34+ cells, indicating that the expression of the amphotropic receptor was increased. Moreover, the virus binding was proportional to the gene transfer rate, as assessed by G418 resistance into mobilized PB-derived CFU-GM. The increase in fluorescence intensity appeared to be restricted to CD34+ cell subset, neither CD2+ nor CD14+ cells bound the virus in an appreciable amount. INTERPRETATION AND CONCLUSIONS: Virus binding, as assessed by indirect immunofluorescence assay, is increased in mobilized CD34+ cells. The increased binding may contribute to their high susceptibility to retrovirus vector infection.

Antigens, CD34↗

PubMed1997

High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma.

BACKGROUND: We compared a regimen of six chemotherapeutic agents administered sequentially at high doses, followed by myeloablative treatment and bone marrow transplantation, with a regimen of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) as initial or salvage treatment for adults with diffuse large-cell lymphoma. METHODS: Ninety-eight eligible patients with diffuse large-cell lymphoma of the B-cell type were randomly assigned to receive either MACOP-B (50 patients) or high-dose sequential therapy (48 patients). The study design allowed for patients in whom the assigned treatment failed to cross over to the other treatment group. RESULTS: After a median follow-up of 55 months, the patients given high-dose sequential therapy, as compared with those treated with MACOP-B, had significantly higher rates of complete response (96 percent vs. 70 percent, P=0.001), freedom from disease progression (84 percent vs. 49 percent, P<0.001), freedom from relapse (88 percent vs. 70 percent, P=0.055), and event-free survival (76 percent vs. 49 percent, P=0.004). The difference in overall survival at seven years, which also favored the group assigned to high-dose sequential therapy, was marginally significant (81 percent vs. 55 percent, P=0.09). CONCLUSIONS: High-dose sequential therapy is superior to standard-dose MACOP-B for patients with diffuse large-cell lymphoma of the B-cell type.

Adolescent↗

PubMed1997

Association of chromosome 12p genetic polymorphisms with lung adenocarcinoma risk and prognosis.

The mapping near Kras2 of pulmonary adenoma susceptibility 1 (Pas1), a major locus affecting inherited predisposition to lung cancer in mice prompted us to test the homologous human region (12p12) for association with lung adenocarcinoma, by a population-based study. We genotyped 213 lung adenocarcinoma patients and 219 healthy blood donor subjects for five polymorphic markers mapping in the putative region of interest. Three marker polymorphisms, located in a region spanning approximately 700 kb, were significantly associated with lung adenocarcinoma risk. Furthermore, polymorphisms in KRAS2 and PTHLH loci were also associated with tumor prognosis. These results suggest the existence of a human Pas1 homologous locus on chromosome 12p12.

Adenocarcinoma↗

PubMed1996

Combined negative and positive selection of mobilized CD34 blood cells.

We tested four negative and two positive selection methods for separation of CD34+ cells from mobilized blood cells, and analysed fold-enrichment, purity and recovery of CD34+ cells after selection procedures. The elimination of mature CD34- cells was achieved by adhesion to nylon-wool fibre (5.9 +/- 1.0 mean fold-enrichment and 65.2 +/- 2.3 mean recovery of CD34+ cells). Standard or modified Ficoll-Hypaque and Percoll density gradients, as well as phagocytosis with magnetic beads, were less effective in eliminating CD34- cells, both purity and fold-enrichment of CD34+ cells being lower than those obtained with separation by nylon-wool. Both positive selection methods tested. Ceprate and MiniMacs System, generated highly purified CD34+ cell populations ranging from 80% to 90%. The recovery of CD34+ cells was optimal with MiniMacs (77.9 +/- 3.6) and low with Ceprate (28.8 +/- 2.8). Based on these results, in two large-scale experiments we combined nylon-wool fibre and MiniMacs System in a two-step separation procedure obtaining a 36.9 +/- 2.6 mean fold-enrichment and a 50.5 +/- 0.3 mean recovery of CD34+ cells. In this way we achieved optimal enrichment and recovery of CD34+ cells, with a substantial saving of cost compared to either selection method alone.

Antigens, CD34↗

PubMed1996

Comparative effects of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor after high-dose cyclophosphamide cancer therapy.

PURPOSE: We compared hematologic and clinical effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) after treatment with high-dose cyclophosphamide (HD-CTX, 7 g/m2), given as the first phase of a high-dose sequential chemotherapy program that includes a myeloablative therapy with mobilized progenitor cell autografting. PATIENTS AND METHODS: Forty-nine consecutive patients with non-Hodgkin's lymphoma, Hodgkin's disease, or poor-prognosis breast cancer received GM-CSF (n = 27) or G-CSF (n = 22) after HD-CTX in two consecutive, nonrandomized studies. Cytokines were administered in continuous intravenous (i.v.) infusion for 14 to 15 days at a median dose of 5.5 and 10 micrograms/kg/d, respectively, starting 24 hours after HD-CTX. RESULTS: Neutrophil recovery was faster with G-CSF administration (11.5 v 13.2 days; P = .01), whereas platelet counts recovered more rapidly with GM-CSF (13.7 v 16.6 days; P = .01). Prophylactic platelet transfusions were administered more frequently to patients treated with G-CSF than with GM-CSF (66% v 22% of the patients; P = .02). No clinically significant difference was observed between the two groups concerning days of absolute neutropenia or neutropenic fever. Both cytokines reduced the time to eligibility for subsequent chemotherapy administration compared with historical controls not given cytokine (14 to 16 v 20 days). Both cytokines increased circulation of hematopoietic progenitors. Most side effects were World Health Organization (WHO) median grade 1 to 2, were more frequent during GM-CSF than during G-CSF treatment, and were reversible by simple supportive measures and/or by dose reduction or suspension of the cytokine. Permanent suspension of cytokine administration was never required in either group. CONCLUSION: GM-CSF or G-CSF administration after HD-CTX reduces hematologic toxicity of high-dose chemotherapy and induces circulation of large amounts of hematopoietic progenitors suitable for autografting in cancer patients.

Adult↗

PubMed1996

Benefits of blood cell transplant cryopreservation with oxypolygelatine (Gelifundol) plasma substitute.

In two groups of 11 patients with poor prognosis malignancies undergoing high-dose sequential chemotherapy, we have evaluated the cryopreservation of blood cell transplants with oxypolygelatine-containing (55% oxypolygelatine, 6% hydroxyethylstarch, 5% dimethyl sulfoxide) vs standard human serum-containing (55% human serum, 6% hydroxyethylstarch, 5% dimethyl sulfoxide) cryoprotectant mixtures. Evidence is presented demonstrating that substitution of human serum proteins with oxypolygelatine has no detrimental effect either in vitro on the post-thawing recovery of hematopoietic progenitors or in vivo on the capacity of marrow reconstituting function in patients treated with myeloablative cancer therapy and autologous blood cell transplant. Oxypolygelatine is commercially available for clinical use as a plasma expander, is 30-fold less expensive than human serum albumin, is certified free of foreign serum proteins and antibodies as well as free of pyrogen, viral, mycoplasmal and bovine spongiform encephalopathy contaminants. Because of these characteristics, oxypolygelatine permits avoidance of: (1) the use of expensive serum albumin; (2) the fastidious preparation of autologous plasma or serum, and (3) the risk of infection associated with the infusion of allogeneic serum. Because of these practical advantages, we recommend the clinical use of oxypolygelatine as a substitute for human serum proteins for the routine cryopreservation of blood cell transplants.

Adult↗