PubMed Health⌕ Search

Biomedical subjects

T Lamy

Publications and source records attributed to T Lamy.

53 records · Page 3Linked to original sources

Multidrug resistance in B-cell chronic lymphocytic leukemia.

Multidrug resistance (MDR) was investigated in peripheral blood cells isolated from 40 patients with B cell chronic lymphocytic leukemia (B-CLL) and from 7 healthy volunteers, using a flow cytometric assay that detects cellular efflux of the fluorescent dye rhodamine 123 (Rh 123), which has been demonstrated to be transported from the cell by the P-glycoprotein pump. The proportion of B leukemic cells effluxing Rh 123 and thus displaying MDR was low (14 +/- 17%) in B-CLL and in only 4 cases did the contingent of B leukemic cells showing MDR represent more than 30% of the total leukemic cells. In contrast, a higher proportion of cells effluxing Rh 123 (44 +/- 13%) was demonstrated in normal B lymphocytes. No statistical correlation was found between the number of leukemic B cells displaying MDR and clinical parameters or previous treatment. These results clearly suggest that MDR activity is usually low in B-CLL.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Multi-drug resistance (MDR) activity in acute leukemia determined by rhodamine 123 efflux assay.

We prospectively analyzed MDR functional activity by the Rh123 efflux assay in 84 de novo acute leukemias. Thirty of the 60 AML cases (50%) showed a positive dye efflux (in more than 10% of blast cells). In 19 cases, the dye efflux was superior to 30%. Twenty-four of the 30 efflux positive cases were CD34+ and could be studied in double staining. The mean percentage of effluxing CD34+ blast cells was 54%. There was a high correlation between CD34 expression and MDR activity (P < 10(-4)), MDR activity and PgP expression (P < 10(-6)). All the efflux negative samples were PgP negative. Nine efflux positive cases were PgP negative. Five of the 24 ALL were efflux positive. MDR activity did not correlate with FAB subtype (with the exception of AML3: 1/6 was efflux positive), age, white blood cell count or LDH level. Forty-seven AML patients were treated with conventional chemotherapy including cytarabine and an anthracycline. Thirty-one (66%) entered complete remission (CR). CR rate was statistically lower for efflux positive as compared to efflux negative patients, 46 vs 87% (P = 0.003), for PgP+ as compared to PgP- patients, 40 vs 78% (P = 0.01), for CD34+ as compared to CD34- patients, 45 vs 84% (P = 0.005). There was no correlation between P110 expression (32 AML cases studied) and FAB subtype, MDR status and clinical outcome. Two years survival was 20% for efflux positive patients as compared to 54% for efflux negative patients (P < 0.07), 15% for PgP+ vs 54% for PgP- patients (P < 0.04). The finding of efflux+/PgP- cases suggests the existence of other membrane efflux pumps. Rh123 efflux assay is straightforward in routine and could be included in MDR screening because of its potential interest in clinical outcome in AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Improvement of hematologic recovery after high-dose intensification using peripheral blood progenitor cells (PBPC) mobilized by chemotherapy and GM-CSF.

We have tested the efficiency of GM-CSF to mobilize peripheral blood progenitor cells (PBPC) and evaluated the hematological reconstitution after GM-CSF primed-PBPC infusion following myeloablative therapy. Twenty three patients suffering from hematological malignancies were included in this study. Starting 24 hours after completion of a standard dose chemotherapy including vindesine, cyclophosphamide, adriblastine, prednisone, (VCAP), 5 micrograms/kg sub-cutaneous daily dose GM-CSF was given for a median time of 14 days followed by three consecutives cycles of leukapheresis. Fifteen of these 23 patients underwent GM-CSF primed-PBPC autotransplantation following high dosed intensification regimen. PBPC collection and hematopoietic recovery were compared with a 15 patients control group who did not receive GM-CSF. No marrow or growth factors were administered after PBPC reinfusion in the two groups. VCAP/GM-CSF mobilization induced significantly higher yields of CFU-GM (3.8 fold) than did VCAP mobilization alone, 19 x 10(4)/kg (2-73) vs 5 x 10(4)/kg (2-27), (p < 0.005). The median number of days to achieve 1.10(9)/l neutrophils, platelet count > 20.10(9)/l and > 50.10(9)/l was significantly lower in the GM-CSF group than in the control group, respectively 13 vs 19 days (p = 0.04), 15.5 vs 27 days (p < 0.02), 19 vs 51 days (p < 0.01). When compared with the control group, transfusion requirements and median of hospital stay were both significantly decreased for the patients receiving GM-CSF primed-PBPC. Our study confirms that infusion of GM-CSF primed-PBPC as a sole source of hematopoietic support improves hematopoietic reconstitution following myeloablative therapy.

Adult↗

P-glycoprotein (P-170) and CD34 expression in adult acute myeloid leukemia (AML).

We investigated the prognosis value of CD34 and P-170 expression in blast cells of adult patients affected by de novo acute myeloid leukemia (AML). CD34 antigen was analyzed by indirect immunofluorescence (IFI) and alkaline phosphatase-labeled streptavidin biotine (AP-LSAB) in 62 patients (median age: 51 years). P-170 expression was determined by AP-LSAB in 51 cases using JSB1 and C219 monoclonal antibodies. All patients were treated with conventional chemotherapy induction regimen. Follow-up was from 6 to 79 months. Complete remission (CR) rate was not statistically different between CD34+ and CD34- patients (67 vs. 84%, p = 0.2). The duration of CR and survival were not influenced by CD34 expression. Karyotype abnormalities were more frequent among MDR+ patients (65 vs. 21%, p < 0.01). CR rate was statistically lower in MDR+ patients as compared to MDR- patients (63 vs. 96%, p = 0.01). Median disease-free survival (DFS) was shorter for MDR+ patients but the difference was not significant (5 vs. 10 months, p = 0.09). Patients who were positive for both parameters CD34 and P-170, had a poor prognosis with a 50 vs. 100% CR rate for CD34/P-170 negative patients, (p = 0.002), a lower median DFS (3 vs. 12 months, p = 0.01) and overall survival (OS) (3 vs. 14.5 months, p = 0.01). Results of cytogenetic analysis did not influence CR rate but the relapse rate was higher, although not significant, for the patients with unfavorable karyotype (63 vs. 33%). The seven CD34+/MDR+ patients with poor prognosis karyotype had a statistically lower CR rate, median DFS and OS than the 7 CD34-/MDR- patients with normal or favorable karyotype (CR: 29% vs. 100%, p = 0.02), (DFS: 3 vs. > 12 months, p = 0.01), (OS: 4 vs. > 12 months, p = 0.02). Our data indicate that P-170 but not CD34 expression is predictive for a lower CR rate. The identification of a bad prognosis subgroup of CD34+/MDR+ AML patients (and especially those with poor prognosis karyotype) has to be confirmed on larger series using uniform methodology.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Benefit of prophylaxis by intravenous systemic vancomycin in granulocytopenic patients: a prospective, randomized trial among 59 patients.

We have tested the benefit of prophylaxis by intravenous systemic vancomycin among 59 neutropenic patients in a randomized trial. Vancomycin was delivered on day zero of chemotherapy until the resolution of neutropenia in the prophylactic group (vanco+). Empiric antibiotic therapy (piperacillin, ofloxacine) was identical for all patients. The number of days with fever > 38.5 degrees C was significantly higher in the control (vanco-) group than in the vanco+ group (7.4 vs. 3.7, p < 0.02). Zero gram-positive infections occurred in the vanco+ group versus 9 in the vanco- group (p < 0.002). The mean number of days of empiric antibiotic therapy was reduced in the vanco+ group (11.3 vs. 16.3, p = 0.12). However, no benefit was noted between the two groups with regard to mortality or the severity of the infections. The selection of resistant microorganisms after systemic treatment with vancomycin is of potential risk. Such a prophylactic antibiotic regimen does not seem to be justified.

Adult↗

Splenectomy in idiopathic thrombocytopenic purpura: its correlation with the sequestration of autologous indium-111-labeled platelets.

We present a retrospective analysis of 111In-platelet sequestration studies in 111 patients with the clinical diagnosis of idiopathic thrombocytopenic purpura (ITP). Fifty-one of these patients underwent splenectomy, independent of the results of the 111In-platelet studies to determine if these isotopic results could accurately predict a beneficial response to splenectomy. Between January 1984 and June 1990, 111 patients who presented with ITP were subjected to a study of autologous 111In-labeled platelets through autotransfusion. The platelet sequestration site was splenic (81%), mixed (12%), or hepatic (7%). Fifty-one patients with persistent drug-resistant thrombocytopenia underwent splenectomy regardless of the isotopic results: 33 patients beyond 6 mo after diagnosis and 18 with high hemorrhagic risks before this delay. The follow-up median duration was 2.9 yr. Thirty-three of the 38 patients with splenic sequestration showed a normalized platelet count, as opposed to 2 of the 13 with mixed or hepatic sequestration (p < 0.001). In addition, platelet survival extended beyond 8 days in six patients, with no apparent sequestration site. The platelet isotopic study performed with this technique appears to be indicated in ITP: it guides clinicians in their decision to perform splenectomy and relates to a more central mechanism certain thrombocytopenias that are inappropriately categorized as ITP.

Adolescent↗

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↗

Lung abscess due to Pseudallescheria boydii in the course of acute leukaemia. Report of a case and review of the literature.

We report a case of lung infection by Pseudallescheria boydii, which appeared during therapeutic aplasia in a patient with acute leukaemia. The association of sudden chest pain and fever with negative blood cultures and haemoptysic expectoration first suggested a diagnosis of pulmonary aspergillosis, in particular because evidence of lung abscesses appeared very rapidly and large mycelial filaments were found on direct examination of the expectoration. Pseudallescheria boydii was identified by culture. Investigations in vitro of the effects of antimycotics showed that the micro-organism was resistant to amphotericin B and sensitive to imidazoles. The clinical and radiological outcome after treatment with ketoconazole was favourable.

Adolescent↗

Home treatment of febrile neutropenia: an empirical oral antibiotic regimen.

Between May 1988 and November 1989, 68 consecutive febrile courses supervening after polychemotherapy for lymphoma outpatients (median age 50 years) were treated by the combination of oral Pefloxacin/Amoxicillin Clavulanic acid. In terms of median data, neutropenia appeared on d9 [d1-d17], and lasted 5 days [2-9] with a PMN nadir observed at 0.104 x 10(9) [0-0.5 x 10(9)/l], while fever rose on d10 [1-24]. In 59 cases (87%), fever and/or focal symptoms disappeared within 3 days, after which treatment was maintained for 7 days. Nine failures were observed, of which 2 were due to abandonment of treatment, 2 to vomiting and 5 to persistence of the original symptoms. Meti Susceptible-Staphylococci were found in blood samples from 2 patients, one of whom, with grade IV lymphoma that had proved resistant to chemotherapy, died. The treatment was found to be effective and well tolerated, offering a good alternative to hospitalization during a transient chemotherapy-induced neutropenia.

Adolescent↗

[Agranulocytosis and connectivitis different from Felty's syndrome: 4 cases. Success of cyclosporin in a case].

Four cases of chronic agranulocytosis in patients with systemic diseases different from Felty's syndrome are reported. Two patients had primary Sjögren's syndrome (confirmed in one, suspected in the other), one had systemic lupus erythematosus and the last patient had an unclassifiable connective tissue disease. Only one severe infection was recorded. The pathophysiological mechanisms involved are discussed. There is a strong suspicion that the cytopenia is of immune origin. Corticosteroid therapy was effective in all four patients. One patient who could not tolerate corticosteroids was successfully treated with cyclosporin A.

Adult↗

[Occurrence of non-Hodgkin's lymphoma in chronic myeloid leukemia].

The authors report the case of a 42-year old woman who developed chronic myelocytic leukemia with Philadelphia chromosome followed, 21 months later, by malignant follicular lymphoma with small cleaved cells and giant cells. This case is comparable to the other associations of acute or chronic myelocytic and lymphocytic blood diseases previously published. Several pathogenic theories are reviewed. They involve chemotherapy with alkylating drugs (but the diagnosis is sometimes simultaneous), cellular oncogens or, more probably, a clonal abnormality of the stem cell sequentially or concomitantly expressed in the cells of both lineages; unfortunately, in the absence of Philadelphia chromosome this theory has not yet been demonstrated on lymphoma cells.

Adult↗