401 research outputs found
The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis
To determine whether MDR1 reversal by the addition of the P-glycoprotein
(P-gp) inhibitor PSC-833 to standard induction chemotherapy would improve
event-free survival (EFS), 419 untreated patients with acute myeloid
leukemia (AML) aged 60 years and older were randomized to receive 2
induction cycles of daunorubicin and cytarabine with or without PSC-833.
Patients in complete remission were then given 1 consolidation cycle
without PSC-833. Neither complete response (CR) rate (54% versus 48%; P =
.22), 5-year EFS (7% versus 8%; P = .53), disease-free survival (DFS; 13%
versus 17%; P = .06) nor overall survival (OS; 10% in both arms; P = .52)
were significantly improved in the PSC-833 arm. An integrated P-gp score
(IPS) was determined based on P-gp function and P-gp expression in AML
cells obtained prior to treatment. A higher IPS was associated with a
significantly lower CR rate and worse EFS and OS. There was no significant
interaction between IPS and treatment arm with respect to CR rate and
survival, indicating also a lack of benefit of PSC-833 in P-gp-positive
patients. The role of strategies aimed at inhibitory P-gp and other
drug-resistance mechanisms continues to be defined in the treatment of
patients with AML
No impact of high-dose cytarabine on the outcome of patients transplanted for acute myeloblastic leukaemia in first remission
Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib
Monitoring of single cell signal transduction in leukemic cellular subsets has been proposed to provide deeper understanding of disease biology and prognosis, but has so far not been tested in a clinical trial of targeted therapy. We developed a complete mass cytometry analysis pipeline for characterization of intracellular signal transduction patterns in the major leukocyte subsets of chronic phase chronic myeloid leukemia. Changes in phosphorylated Bcr-Abl1 and the signaling pathways involved were readily identifiable in peripheral blood single cells already within three hours of the patient receiving oral nilotinib. The signal transduction profiles of healthy donors were clearly distinct from those of the patients at diagnosis. Furthermore, using principal component analysis, we could show that phosphorylated transcription factors STAT3 (Y705) and CREB (S133) within seven days reflected BCR-ABL1(IS) at three and six months. Analyses of peripheral blood cells longitudinally collected from patients in the ENEST1st clinical trial showed that single cell mass cytometry appears to be highly suitable for future investigations addressing tyrosine kinase inhibitor dosing and effect. (clinicaltrials. gov identifier: 01061177)Peer reviewe
Relationships between erythron and spleen in blood diseases
Thèse d'agrégation de l'enseignement supérieur (Faculté de médecine) -- UCL, 198
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