64 research outputs found
Emergency laparoscopic ileo-colic resection and primary intracorporeal anastomosis for Crohn’s acute ileitis with free perforation and faecal peritonitis: first ever reported laparoscopic treatment
The Effects Of High Dose Selenium Supplementation On Perioperative Systemic Inflammation In Patients Undergoing Open Heart Surgery
Beyond image defined risk factors (IDRFs): a delphi survey highlighting definition of the surgical complexity index (SCI) in neuroblastoma
Long-term survival of sorafenib-treated FLT3-ITD-positive acute myeloid leukaemia patients relapsing after allogeneic stem cell transplantation.
BACKGROUND
Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukaemia (AML) relapsing after allogeneic stem cell transplantation (allo-SCT) has a dismal prognosis with limited therapeutic options. FLT3-ITD kinase inhibition is a reasonable but palliative experimental treatment alternative in this situation. Information on long-term outcome is not available.
METHODS
We performed a long-term follow-up analysis of a previously reported cohort of 29 FLT3-ITD-positive AML patients, which were treated in relapse after allo-SCT with sorafenib monotherapy.
FINDINGS
With a median follow-up of 7.5 years, 6 of 29 patients (21%) are still alive. Excluding one patient who received a second allo-SCT, five patients (17%) achieved sustained complete remissions with sorafenib. Four of these patients are in treatment-free remission for a median of 4.4 years.
INTERPRETATION
Sorafenib may enable cure of a proportion of very poor risk FLT3-ITD-positive AML relapsing after allo-SCT
High activity of sorafenib in FLT3-ITD-positive acute myeloid leukemia synergizes with allo-immune effects to induce sustained responses
Preliminary evidence suggests that the multikinase inhibitor sorafenib has clinical activity in FLT3-ITD-positive (FLT3-ITD) acute myeloid leukemia (AML). However, the quality and sustainability of achievable remissions and clinical variables that influence the outcome of sorafenib monotherapy are largely undefined. To address these questions, we evaluated sorafenib monotherapy in 65 FLT3-ITD AML patients treated at 23 centers. All but two patients had relapsed or were chemotherapy-refractory after a median of three prior chemotherapy cycles. Twenty-nine patients (45%) had undergone prior allogeneic stem cell transplantation (allo-SCT). The documented best responses were: hematological remission in 24 patients (37%), bone marrow remission in 5 patients (8%), complete remission (with and without normalization of peripheral blood counts) in 15 patients (23%) and molecular remission with undetectable FLT3-ITD mRNA in 10 patients (15%), respectively. Seventeen of the patients without prior allo-SCT (47%) developed sorafenib resistance after a median treatment duration of 136 days (range, 56-270 days). In contrast, allo-SCT patients developed sorafenib resistance less frequently (38%) and significantly later (197 days, range 38-225 days; P=0.03). Sustained remissions were seen exclusively in the allo-SCT cohort. Thus, sorafenib monotherapy has significant activity in FLT3-ITD AML and may synergize with allogeneic immune effects to induce durable remissions.Leukemia advance online publication, 8 May 2012; doi:10.1038/leu.2012.105
P573: PHARMACOKINETIC EXPOSURE EQUIVALENCE AND PRELIMINARY EFFICACY AND SAFETY FROM A RANDOMIZED CROSS OVER PHASE 3 STUDY OF AN ORAL HYPOMETHYLATING AGENT DEC-C COMPARED TO IV DECITABINE IN AML PATIENTS
Expression of the CTLA-4 ligand CD86 on plasmacytoid dendritic cells (pDC) predicts risk of disease recurrence after treatment discontinuation in CML
Expression of the CTLA-4 ligand CD86 (B7.2) on plasmacytoid dendritic cells (pDC) predicts risk of disease recurrence after treatment discontinuation in chronic myeloid leukemia
Sorafenib as maintenance therapy post allogeneic stem cell transplantation for FLT3-ITD positive AML: Results from the randomized, double-blind, placebo-controlled multicentre sormain trial.
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