Showing papers by "Jean Luc Harousseau published in 1998"

A systematic collaborative overview of randomized trials comparing idarubicin with daunorubicin (or other anthracyclines) as induction therapy for acute myeloid leukaemia

Abstract: A collaborative overview, using individual patient data, has been performed to compare idarubicin versus daunorubicin or other anthracyclines, when used with cytosine arabinoside as induction chemotherapy for newly diagnosed acute myeloid leukaemia. There were 1052 patients in five trials versus daunorubicin, 100 in one trial versus doxorubicin, and 745 in one trial versus zorubicin. In the trials of idarubicin versus daunorubicin, early induction failures were similar with the two treatments (20% idarubicin v 18% daunorubicin; P = 0.4), but after day 40 the later induction failures were fewer with idarubicin (17% v 29%; P < 0.0001). Therefore complete remission rates were higher with idarubicin (62% v 53%; P = 0.002). Among remitters, fewer of the patients allocated to idarubicin relapsed (P = 0.008) but slightly more died in remission, leading to a non-significant benefit (P = 0.07) in disease-free survival. Overall survival in these five trials was significantly better with idarubicin than with daunorubicin (13% v 9% alive at 5 years; P = 0.03). There was a trend (P = 0.006 for remission rate) for the benefit of idarubicin over daunorubicin to decrease with increasing age. There were no significant differences in outcome in the small trial comparing idarubicin versus doxorubicin, or in the large trial comparing idarubicin versus zorubicin. The induction regimens based on idarubicin achieved, in the particular circumstances of the trials reviewed here, better remission rates and better overall survival than those based on daunorubicin.

CD28, a marker associated with tumoral expansion in multiple myeloma.

Abstract: CD28 expression was thoroughly investigated on plasma cells of monoclonal gammopathy of undetermined significance, multiple myeloma (MM), and human myeloma cell lines. CD28+ plasma cells were detected in 19% of 31 monoclonal gammopathy of undetermined significance, 41% of 116 MM, and 100% of 13 human myeloma cell lines. CD28+ myeloma cells were detected in 21 of 79 (26%) MM cases at diagnosis, 13 of 22 (59%) at medullary relapse (P < 0.009), and 14 of 15 (93%) at extramedullary relapse (P = 0.05), including 10 of 10 (100%) secondary plasma cell leukemias (P = 0.05). Serial studies in individual patients confirmed the emergence of CD28+ myeloma cells with tumoral expansion and treatment failure. This was significantly correlated with the expression of CD28 ligand, i.e., CD86 (but not CD80), and with an increase in the proliferative activity (labeling index) of myeloma cells in bone marrow. Whereas the expression of CD56 defines a particular subset of myeloma patients, CD28 is the only antigen for which expression correlates with tumor progression. Our data show that an aggressive compartment of CD28+ and CD86+ myeloma cells emerges during the course of MM in vivo, indicating that CD28 could be aberrantly expressed on highly malignant (possibly mutated) myeloma cells. Conversely, a subset of proliferative plasmablasts coexpressing CD28 and CD86 could be the normal counterpart of the clonogenic myeloma stem cell because a subset of CD28+ plasma cells was observed in 6 of 6 cases of reactive plasmocytosis.