Biomedical subjects

Philippe Moreau

Publications and source records attributed to Philippe Moreau.

44 records · Page 3Linked to original sources

PubMed2003

HLA-G in cancer: a way to turn off the immune system.

The expression of HLA-G in cancer represents a strategy employed by tumors to avoid immune destruction. Indeed, this non-classical HLA class I molecule suppresses various immune cell functions through binding to inhibitory receptors. We here review the studies done by our group that described for the first time (i) HLA-G expression in malignancies such as melanomas, renal and breast carcinomas. (ii) the up-regulation of HLA-G gene transcription by tumor environmental factors such as cytokines and stress and by agents used in chemotherapy such as demethylating molecules, and (iii) the biological relevance of such HLA-G expression in the evasion of malignant cells from antitumor immune response.

Cell Line, Tumor↗

PubMed2003

HLA-G in transplantation: a relevant molecule for inhibition of graft rejection?

The human MHC class I molecule HLA-G has long been known as a molecule selectively expressed by cytotrophoblastic cells. By inhibiting the cytolytic function of decidual NK cells, HLA-G protects the HLA-A and -B negative semiallogeneic embryonic tissue against the mother's immune system. In the light of this immuno-suppressive function, the role of HLA-G in transplantation was investigated. We will review here recently published data on this topic, showing that expression of HLA-G affects the responsive capacity of the immune system, might directly participate in graft acceptation, and should be taken into account for the monitoring of transplantation patients.

Animals↗

PubMed2002

Recurrent 14q32 translocations determine the prognosis of multiple myeloma, especially in patients receiving intensive chemotherapy.

Recently, we have described the biological correlations associated with the main translocations involving the 14q32 chromosomal region, that is, t(14q32), in patients with multiple myeloma (MM). We have now extended the analysis to the prognostic value of these chromosomal rearrangements in 168 consecutive patients with newly diagnosed MM receiving intensive chemotherapy within clinical trials of the Intergroupe Francophone du Myelome (IFM). Patients with t(4;14) displayed a poor outcome (short event-free survival and short overall survival), whereas those with t(11;14) displayed long survival. On the other hand, patients with neither t(4;14) nor t(11;14) presented an intermediate outcome. Importantly, chromosome 13 abnormalities (C13As) significantly influence the prognosis of this latter group. In contrast, C13As affected the outcome of the other patients to a much lesser extent, either because of an almost constant association (in the t(4;14) group) or because of a lack of any significant prognostic impact (in the t(11;14) group; only one event occurred in the 10 patients with t(11;14) and C13As). Considering that t(4;14) and t(11;14) (1) are the only (so far recognized) true, recurrent t(14q32)'s, (2) are linked to specific immunoglobulin isotypes, and (3) display specific outcomes, they represent distinct entities corresponding to a specific oncogenesis and prognosis. These data emphasized the interest in analyzing these two translocations by fluorescence in situ hybridization in prospective therapeutic trials in order to consider these translocations as distinct entities.

Adult↗

PubMed2002

Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myélome 9502 randomized trial.

High-dose therapy has become a common treatment for myeloma. The objective of this study (Intergroupe Francophone du Myélome [IFM] 9502 trial) was to compare in a prospective and randomized trial the 2 most widely used conditioning regimens before autologous stem cell transplantation in newly diagnosed symptomatic patients younger than 65 years old: 8 Gy total body irradiation plus 140 mg/m(2) melphalan (arm A) versus 200 mg/m(2) melphalan (arm B). A total of 282 evaluable patients were compared--140 in arm A and 142 in arm B. Baseline characteristics and disease response to 4 cycles of the VAD regimen performed before randomization and autologous stem cell transplantation were identical in the 2 treatment arms. In arm B, hematologic recovery was significantly faster for both the duration of neutropenia and thrombocytopenia, transfusion requirements were also significantly lower, and the median duration of hospitalization was significantly shorter. In arm A, the incidence of severe mucositis was significantly increased. The median duration of event-free survival was similar in both arms (21 vs 20.5 months, P =.6), but the 45-month survival was 65.8% in arm B versus 45.5% in arm A (P =.05). This difference might be attributed in part to better salvage regimens after relapse in arm B compared with arm A. We conclude that 200 mg/m(2) melphalan is a less toxic and at least as effective conditioning regimen when compared with 8 Gy total body irradiation with 140 mg/m(2) melphalan. This regimen should be considered as the standard of care before autologous stem cell transplantation in multiple myeloma.

Adult↗

PubMed2002

Thalidomide in patients with advanced multiple myeloma: a study of 83 patients--report of the Intergroupe Francophone du Myélome (IFM).

BACKGROUND: To evaluate treatment by thalidomide and identify predictive factors of survival, event free survival and response among patients with advanced multiple myeloma treated with thalidomide as single agent therapy. PATIENTS AND TREATMENT: Patients with advanced multiple myeloma (n=83) were treated with an oral dose of thalidomide (median 400 mg/day). At start of treatment, all patients had active disease and 58 (69%) had received at least one autologous transplantation. RESULTS: With a median follow-up of 338 days (range, 247-629 days), 52 patients are alive, whereas 31 died between 8 and 150 days after the first administration of thalidomide. The response to thalidomide was considered as major in 11 patients (13%), partial in 29 patients (35%) and minor in 15 patients (18%), giving a total response rate of 66% (54 out of 83 patients). Thirteen patients had stable disease and 15 patients progressed. In multivariable analysis, age greater than 60 years, short interval between diagnosis and onset of thalidomide, requirement for red blood cell transfusion, IgA isotype, platelets' count <80 x 10(9)/l and serum albumin level <30 g/l at the start of thalidomide were associated with poor outcome. These three last factors produced a simplified prognostic model for patients with advanced myeloma and treated with thalidomide. Thus, among the 38 patients without any of these unfavorable risk features, one-year overall survival and event free survival were 87% and 78%. By contrast, the 43 patients with at least one unfavorable feature had one-year overall survival and event free survival of 40% and 32%, respectively (Log-Rank, P=0.0002 for both). Patients who received > or =34.4 g of thalidomide in the first 90 days of treatment had a better outcome than those who received <34.4 g. However, the mean received daily dose of thalidomide in the first 90 days has not been found to influence survival, event free survival or response. Short-term side effects of thalidomide were generally moderate. CONCLUSION: Thalidomide is an effective treatment for patients with advanced myeloma, in particular, who have no poor-risk features. The poor results achieved by the other patients emphasize the need for prospective protocols using thalidomide in combination, especially with dexamethasone. In addition, further studies are needed to determine the optimal thalidomide dose and duration.

Adult↗

PubMed2002

CD38 expression and secondary 17p deletion are important prognostic factors in chronic lymphocytic leukaemia.

CD38 expression and chromosomal abnormalities are novel prognostic factors in chronic lymphocytic leukaemia (CLL). However, their value remains undetermined. CD38 was evaluated in 123 patients and chromosomal aberrations in 111 cases with fluorescence in situ hybridization (FISH). CD38 expression was found in 27% of the cases. In addition, seven out of 32 CD38- patients became CD38+ during evolution of the disease. Chromosomal abnormalities included isolated 13q deletion (40%), 12q trisomy (14%), 11q deletion (without 17p deletion) (14%) and 17p deletion (7%). CD38 expression was significantly associated with Binet stages B and C, atypical morphology and 11q deletion. On univariate analysis of survival estimates, advanced Binet stages, CD38+ phenotype, atypical morphology and 11q or 17p deletions were associated with shorter event-free survival (EFS), treatment-free interval (TFI) and overall survival (OS). Multivariate analysis identified both Binet stages and CD38 as independent prognostic factors with regard to EFS and TFI. However, CD38 appeared as an independent factor for OS when restricted to Binet stage A. Chromosomal aberrations were re-evaluated during evolution in 31 cases. The 17p deletion was the most frequent new chromosomal abnormality (35%) and significantly associated with death (64%). In conclusion, CD38 expression and secondary 17p deletion are important poor prognostic indicators, especially in Binet stage A CLL.

ADP-ribosyl Cyclase↗

PubMed2002

Viewpoint on the functionality of the human leukocyte antigen-G null allele at the fetal-maternal interface.

The description of healthy individuals homozygous for the human leukocyte antigen-G (HLA-G) null allele raised doubts about the role of HLA-G in fetal-maternal tolerance. In light of recent results, we discuss this point by considering the potential activity of this null allele that might, indeed, produce functional truncated HLA-G molecules. In this context, we have recently described that, like the full-length HLA-G1, the HLA-G2, -G3, and -G4 truncated isoforms may be expressed at the cell surface and may modulate both innate and acquired immune responses.

Alleles↗

PubMed2002

Tandem high-dose therapy followed by autologous stem-cell transplantation for refractory or relapsed high grade non-Hodgkin's lymphoma with poor prognosis factors: a prospective pilot study.

We conducted a tandem autologous stem cell transplantation procedure for patients with relapsed or refractory high-grade non-Hodgkin's lymphoma (HGNHL) or with transformation of indolent lymphoma (n=15). These patients had poor prognosis factors. The procedure was well tolerated, ten patients were in complete remission. Overall survival rate is 67%.

Adult↗