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Biomedical subjects

A Guerci

Publications and source records attributed to A Guerci.

At least 55 records · Page 3Linked to original sources

Effect of granulocyte colony-stimulating factor administration in elderly patients with aggressive non-Hodgkin's lymphoma treated with a pirarubicin-combination chemotherapy regimen. Groupe d'Etudes des Lymphomes de l'Adulte.

PURPOSE: Results of a multidrug chemotherapy regimen consisting of cyclophosphamide, pirarubicin, teniposide, and prednisolone (CTVP) plus subcutaneous granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin's lymphoma (NHL) are reported. PATIENTS AND METHODS: Between January and December 1992, 46 previously untreated patients older than 69 years with intermediate- and high-grade NHL received cyclophosphamide 750 mg/m2, teniposide 75 mg/m2, pirarubicin 50 mg/m2 day 1, and prednisolone 40 mg/m2 days 1 to 3. G-CSF, 5 micrograms/kg/day, was administered from day 4 up to day 14 or when the absolute neutrophil count reached 5 x 10(9)/l. Six cycles were scheduled every 3 weeks. RESULTS: Grade 3 or grade 4 neutropenia complicated 22% and 26% of chemotherapy cycles, respectively. Fever or/and clinical infection were observed in 4% and 14% of cycles. One toxic death related to a septic shock occurred. Eight cycles (4%) were delayed with a median duration of 7 days. Administered median dose intensity was 93.5%. Objective response rate was 74% and 46% of the patients achieved a complete response. The 2-year overall survival and event-free survival rates were 47% and 28%. CONCLUSION: In comparison with a previous group of patients treated with CTVP, G-CSF allows delivery of chemotherapy with a reduced neutropenia-induced morbidity in an outpatient setting in elderly patients with aggressive NHL without modifying response rate or survival.

Aged↗

All-trans retinoic acid in adult chronic myelomonocytic leukemia: results of a pilot study.

Retinoids can inhibit the spontaneous in vitro growth of CFU-GM observed in juvenile chronic myeloid leukemia (JCML) and, when administered in vivo, have shown some clinical benefit in this disease. Because adult chronic myelomonocytic leukemia (CMML) has many features in common with JCML, we treated 10 cases of advanced adult CMML with ATRA (45 mg/m2/day). Five of them were also tested in vitro. After two patients had a rapid increase in WBC counts and clinical signs reminiscent of the 'ATRA syndrome' seen in acute promyelocytic leukemia, with fatal outcome in one of them, it was decided to add hydroxyurea (HY) to ATRA to patients with high WBC at inclusion or during ATRA treatment, and no more cases of ATRA syndrome were seen. Overall, six patients received ATRA + HY and four ATRA alone. Four patients had a minor but significant response with reduction of transfusion requirement (two cases) or increase in platelet counts (two cases). Apart from the ATRA syndrome, no other side-effect of ATRA was seen. Bone marrow mononuclear cells showed spontaneous growth of CFU-C in methylcellulose in the five patients tested in vitro, with a predominance of CFU-M. ATRA (10(-7) M) inhibited CFU-M growth in all cases, but increased CFU-G growth in one patient who developed the ATRA syndrome. No differentiation of bone marrow myeloid cells after short-term liquid culture with ATRA was observed. A decrease of CFU-C growth was observed in the four patients reevaluated during follow-up. In some cases of CMML, ATRA can improve anemia or thrombocytopenia but not other parameters. Furthermore, it can also induce hyperleukocytosis and ATRA syndrome in some patients, requiring the rapid addition of cytoreductive agents such as HY.

Aged↗

[Predictive value of intracellular accumulation of daunorubicin and P-glycoprotein expression simultaneously determined by flow cytometry in adult acute myeloid leukemias].

Multidrug resistance (MDR) phenotype expression was evaluated retrospectively in 87 patients with acute myeloid leukemia (AML), 69 with de novo AML, ten with relapsed AML and eight with AML secondary to myelodysplastic syndrome (MDS). MDR phenotype, characterized by P-glycoprotein expression (MRK16 monoclonal antibody) and decrease in intracellular daunorubicin (DNR) accumulation was determined using flow cytometry. All patients received chemotherapy including cytosine-arabinoside and anthracycline (daunorubicin, zorubicin, idarubicin) or mitoxantrone, and quinine in ten cases. The predictive value of the MDR phenotype for clinical responsiveness was studied using uni- and multivariate analyses. Univariate analysis showed that DNR accumulation (p < 10(-4)), P-glycoprotein expression (p = 10(-4)) and disease status (de novo versus recurrent AML and acute MDS) (p = 10(-4)) were predictive of clinical responsiveness. The significance of these three parameters was maintained in multivariate analysis. When de novo AML was considered, only DNR accumulation was of predictive value (p < 10(-4)) for complete response to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Predictive value for treatment outcome in acute myeloid leukemia of cellular daunorubicin accumulation and P-glycoprotein expression simultaneously determined by flow cytometry.

To evaluate the clinical relevance of multidrug resistance (MDR) phenotype, the intracellular daunorubicin accumulation (IDA) and P-glycoprotein (P-gp) expression were investigated in 87 adult patients with acute leukemia: 69 patients with de novo acute myeloid leukemia (AML), 10 with AML at relapse, and eight with secondary leukemia to myelodysplastic syndromes (MDS-AML). IDA and P-gp expression were determined by double-labeling flow cytometry analysis. Of 87 patients, 36 expressed P-gp (41%). P-gp expression was more frequently observed in AML at relapse and MDS-AML as compared with de novo AML (P = .0001). P-gp expression was significantly associated with CD34 expression (P = .0003) and chromosome 7 abnormalities (P = .027). A significantly reduced IDA was observed in P-gp+ as compared with P-gp- patients (P = .0007). Of the 87 patients, 51 achieved complete remission (CR). A reduced IDA was observed in patients in failure as compared with patients in CR (22% +/- 17% v 42% +/- 21%; P = 10(-4). Twelve of 36 P-gp+ patients as compared with 40 of 51 P-gp- patients achieved CR (33% v 78%; P = 10(-4). The prognostic value of IDA and P-gp expression was confirmed in multivariate analysis. These data suggest that the determination of IDA and P-gp expression may be useful in designing therapy for patients with AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Gelatinous transformation of the bone marrow. Apropos of 3 cases].

Gelatinous transformation of the bone marrow is a rare histological lesion usually associated with cachexia. The authors report three new cases, two in anorexia nervosa and the third in Hodgkin disease. A review of the literature underlines association with marrow cell necrosis and provides the most frequent etiologies. Pathogenesis of gelatinous transformation remains unclear and her prognostic depends on etiology.

Adolescent↗

[Acute drug-induced agranulocytosis. Clinical study apropos of 30 patients and evolution of etiologies over 2 decades].

Between 1982 and 1993, 30 patients were treated for drug-induced agranulocytosis. They did not receive cytotoxic chemotherapy nor radiotherapy during the past 6 months. There is a higher incidence in women (21 females, nine males). Mean age is 59.3 years old. The drug could be found in 25 cases including noramidopyrine five cases, antithyroid drugs four cases, non steroidal anti-inflammatories drugs four cases. Five patients died of infection during agrulocytosis. Sepsis was documented in three cases. We used hematopoietic growth factors in two cases. Neutrophils rose up to 0.5.10(9)/l between 2 to 14 days after the diagnosis and 1.10(9)/l between 3 to 16 days. Time when absolute neutrophil count was less than 0.5.10(9)/l was shorter (p = 0.008) when bone marrow was rich with maturation arrest but with few or no mature forms rather than reduction of granulocytic precursors. By comparison with a similar study made in the same institution between 1971 and 1981, there were fewer cases each year. Drugs involved were not similar: phenicols were not found, reference to noramidopyrine is less frequent. Now antithyroid drugs is becoming one of the most important etiologies.

Acute Disease↗

[Splenectomy under celioscopy].

Laparoscopic splenectomy has been extensively developed since its first description by Delaître in 1991. From May 1993 to July 1994, 12 patients underwent laparoscopic splenectomy in the "service de Chirurgie C" of the "CHU de Nancy". Six of them were successful. 6 women with a mean age of 27.7 years. The mean operating time was 2 h 30 min. For all cases, the indication was idiopathic thrombocytopenic purpura. No mortality and no morbidity was reported. One patient needed a blood transfusion. The postoperative stay ranged from 3 to 7 days. Splenectomy appears to be another procedure that may be successfully performed under laparoscopic guidance with satisfactory conditions of safety. The outcome evaluation should be continued in order to accurately define the real advantages and risks of this new technique.

Adolescent↗

Comparative evaluation of S9788, verapamil, and cyclosporine A in K562 human leukemia cell lines and in P-glycoprotein-expressing samples from patients with hematologic malignancies.

The activity of S9788, recently synthetized as a modulator of multidrug resistance (MDR), was compared with verapamil and cyclosporine A in normal sensitive and MDR K562 cell lines, then in samples from 33 patients with hematological malignancies, using flow cytometry with simultaneous detection of P-glycoprotein and determination of intracellular daunorubicin fluorescence. This technique was compared and correlated with a tritiated daunorubicin accumulation method. In K562 cell lines, S9788 exhibited a significantly higher reversing activity than verapamil and cyclosporine A, and allowed a complete restoration of the accumulation of daunorubicin when used at 5 mumol/L. In the clinical samples, the three compounds were evaluated at equimolar concentration (5 mumol/L) using concomitant exposure to daunorubicin and to the reversing agent. In P-glycoprotein-negative samples, no significant effect on intracellular daunorubicin fluorescence of any of the reversing agents was noted. In the 15 P-glycoprotein-positive samples, a significant increase in daunorubicin fluorescence, by at least one reversing agent, was seen in 10 cases, among which S9788 reversing activity was higher than that of the two other agents in seven cases. Complete reversal was only achieved in one case with S9788.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. European APL 91 Group.

We designed a multicenter randomized trial comparing chemotherapy with daunorubicin-Ara C (chemotherapy group) and all transretinoic acid (ATRA) combined to the same chemotherapy (ATRA group) in newly diagnosed APL patients aged 65 years or less. The major endpoint of the study was event-free survival (EFS) ("events" being defined as failure to achieve complete remission [CR], occurrence of relapse, or death in CR). Early termination of the trial was decided after the first interim analysis, as EFS was significantly higher in the ATRA group. At the time, 101 patients had been randomized (54 in the ATRA group and 47 in the chemotherapy group). In the ATRA group, 49 (91%) patients achieved CR, 5 (9%) had early death, and 0 had resistant leukemia, compared with 38 (81%), 4 (8%), and 5 (10%) patients, respectively, in the chemotherapy group. The difference in CR rate between the two groups was not significant. The duration of coagulopathy was significantly reduced in the ATRA group, compared with the chemotherapy group. In the ATRA group, six patients relapsed after 7 to 15.5 months. In the chemotherapy group, 12 patients relapsed after 1 to 16 months, and 2 died in CR. Kaplan-Meier EFS was estimated at 79% +/- 7% and 50% +/- 9% at 12 months, respectively, in the ATRA and the chemotherapy group (P = .001). Kaplan-Meier estimate of relapse was 19% +/- 8% and 40% +/- 12% at 12 months (P = .005). In conclusion, ATRA followed by chemotherapy increases EFS in newly diagnosed APL. These results strongly suggest that ATRA should be incorporated in the front line therapy of newly diagnosed APL.

Adolescent↗

Malignant lymphoma in the donor heart after heart transplantation.

A case of post-transplant lymphoproliferative disease (PTLD) with donor heart involvement is reported. The 49-year-old patient presented with heart failure initially ascribed to acute graft rejection. The treatment with high doses of immunosuppressive agents was unsuccessful and the outcome rapidly fatal. This case suggests that cardiac failure occurring after high doses of immunosuppressive therapy could be a sign of early PTLD in heart transplant recipients.

Biopsy↗

All-transretinoic acid followed by intensive chemotherapy gives a high complete remission rate and may prolong remissions in newly diagnosed acute promyelocytic leukemia: a pilot study on 26 cases.

We entered 26 patients with newly diagnosed acute promyelocytic leukemia (APL) in a pilot study of all-transretinoic acid (ATRA) followed by intensive chemotherapy. Median age was 46 (range 25 to 63). No patient presented with leukocytes > 10 x 10(9)/L or had the microgranular APL variant. Cytogenetic analysis (25 patients) found a t(15;17) in 24 cases. Patients were scheduled to receive ATRA (45 mg/m2/d) until complete remission, followed by an intensive daunorubicin (DNR) + Ara C course ("4 + 7" course), then three "2 + 5" DNR + Ara C courses and maintenance chemotheapy. However, the "4 + 7" course was administered in emergency if hyperleukocytosis rapidly developed to prevent leukostasis. Twenty-five patients (96%) achieved CR, 14 with ATRA alone and 11 after the addition of the "4 + 7" course on day 2 to 30 of treatment, because leukocytes rapidly increased (9 cases), because of resistance to ATRA (1 case), and development of organomegaly (1 case). The remaining patient died on day 6, from CNS bleeding. Apart from hyperleukocytosis, side effects were usually moderate. In the 11 patients who could be studied in vitro, a very good correlation was found between in vivo and vitro differentiation and proliferation of APL blasts with ATRA. Three patients were allografted after the "4 + 7" course. Four patients did not receive this course but received the subsequent "2 + 5" courses and maintenance. The remaining patients followed the scheduled protocol. Three patients relapsed after 8, 11, and 15 months (including one allografted patient). Two patients died in CR, after 6 and 17 months. The other 20 patients remained in CR after 18+ to 34+ months (median 21). Actuarial disease free interval (DFI) and event free survival (EFS) were 87% and 77%, respectively, after 18 months. These results were compared to those obtained in our previous APL 84 trial with chemotherapy alone in newly diagnosed APL (after excluding patients included in this trial who presented with hyperleukocytosis). In APL 84 trial, the CR rate was 76%, the actuarial DFI and EFS were 59% and 48% after 18 months, respectively. Differences with the pilot study of ATRA followed by chemotherapy were significant for DFI (P = .02), EFS (P = .006), but not for CR rate (P = .08). Although this is a historical comparison, these results suggest that ATRA followed by chemotherapy may prove superior to chemotherapy alone in newly diagnosed APL, by slightly increasing the CR rate, but perhaps more importantly by reducing the relapse rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗

Acute haematogenous osteomyelitis of the patella revealed by a pathological fracture in multiple myeloma.

A 57-year-old man was followed up for multiple myeloma with no lytic bone lesions. During a septicaema, he presented with a pathological fracture of the patella. Despite a poor haematological status, he received surgical treatment, which allowed diagnosis of haematogenous osteomyelitis of the patella. The outcome was favourable, with a 6-week plaster immobilization after cerclage and 4 months of intravenous antibiotic therapy. This case emphasizes the fact that one well-known cause of bone lesions may lead to an erroneous diagnosis. The successful clinical course suggests that accurate therapeutic management may be discussed in haematological malignancies when intensive-care support is available.

Acute Disease↗

Flow cytometric analysis of the cell cycle in chronic gastritis.

Flow cytometric cell cycle analysis was recorded in gastric biopsy specimens from patients with normal gastric mucosa (GM), superficial gastritis (SG) and chronic atrophic gastritis (CAG). Cell-cycle analysis showed significantly higher percentages of cells in S- and S+G2/M-phase in CAG than in SG and normal GM (P < 0.0001). Moreover, CAG with severe or moderate atrophy showed significantly higher percentages of cells in S-phase (P < 0.05) and S+G2/M-phase (P < 0.02) than CAG with mild atrophy in antrum. In fundus, even if this increase was observed, it did not reach statistical significance. Consideration of concomitant pathologic findings such as oesophagite, gastric or duodenal ulcer, duodenite or benign polyp allowed a better differentiation of CAG both in antrum and in fundus. Significantly higher S-phase was observed in CAG with severe or moderate atrophy than in CAG with mild atrophy (P < 0.05). No statistically significant results were observed in patients with normal gastric mucosa or chronic gastritis and a concomitant pathologic finding.

Cell Cycle↗

Time-variations of pretreatment peripheral blood S + G2/M-phase size determined by flow cytometry in adult acute myeloid leukaemia.

The circadian and seasonal variations of pretreatment proliferative activity of peripheral blood (PB) as PB S + G2/M-phase size was determined by flow cytometry in 61 adult patients with acute myeloid leukaemia (AML). Pretreatment PB S-phase (p less than 0.002), G2 + M-phase (p less than 0.008) and S + G2/M-phase size are statistically correlated to the time of sampling, with the highest phase size at the end of the day. Time-variations of the blast cell count are slightly significant (p = 0.049). Cytological diagnosis-related differences in S + G2/M-phase (p less than 0.003) and white blood cell count (p less than 0.04) time-variations are observed. For all patients, no seasonal variations can be drawn, but in AML 1 (p less than 0.029) and AML 4-5 patients (p less than 0.003), the circadian variations of S + G2/M are affected by the seasons. The present results suggest that time may be taken into account in the monitoring of chemotherapy in acute leukaemia.

Adult↗

Prognostic significance of peripheral blood S + G2/M phase size in adult acute non-lymphoblastic leukaemia.

Flow cytometric analysis of peripheral blood (PB) S + G2/M phase size was performed in 73 adult patients with untreated acute non-lymphoblastic leukaemia, to assess whether the results may correlate to response rate and patient prognosis. All patients were treated with the same induction chemotherapy regimen: ARA-C alone or in combination with an anthracycline antibiotic. Pretreatment PB S + G2/M phase size is significantly correlated to induction response rate (p less than 0.02), duration of response (p less than 0.02) and duration of survival. Patients with low PB S + G2/M phase size experience a longer survival, in patients over and below 50 yr (p less than 0.001). Lastly, early deaths tend to be more frequent in the high median age and high PB S + G2/M phase size group. Our study suggests that PB S + G2/M phase size has prognostic significance in obtaining response and duration of survival.

Adult↗