Showing papers by "Jerome Tamburini published in 2013"
TL;DR: It is shown that glutamine removal inhibits mTORC1 and induces apoptosis in AML cells, and that l-ases upregulate glutamine synthase expression in leukemic cells and that a GS knockdown enhances l-ase-induced apoptotic response in someAML cells.
238 citations
TL;DR: A 70 mg dose of RAD001 at d1 and d7 of an induction chemotherapy regimen for AML has acceptable toxicity and may improve treatment, and strong plasma inhibition of P-p70S6K was observed after RAD001 administration.
Abstract: The mTORC1 signaling pathway is constitutively activated in almost all acute myelogenous leukemia (AML) patients. We conducted a phase Ib trial combining RAD001 (everolimus), an allosteric inhibitor of mTORC1, and conventional chemotherapy, in AML patients under 65 years of age at first relapse (clinical trial NCT 01074086). Increasing doses of RAD001 from 10-70 mg were administrated orally on days 1 and 7 (d1 and d7) of a 3+7 daunorubicin+cytarabine conventional induction chemotherapy regimen. Twenty-eight patients were enrolled in this trial. The treatment was well tolerated with <10% toxicity, mainly involving the gastrointestinal tract and lungs. In this phase Ib trial, the RAD001 maximum tolerated dose was not reached at 70 mg. Sixty-eight percent of patients achieved CR, of which 14 received a double induction. Eight subsequently were intensified with allogeneic-stem cell transplant. Strong plasma inhibition of P-p70S6K was observed after RAD001 administration, still detectable at d7 (d7)at the 70 mg dosage. CR rates in patients with RAD001 areas under or above the curve median were 53% versus 85%. A 70 mg dose of RAD001 at d1 and d7 of an induction chemotherapy regimen for AML has acceptable toxicity and may improve treatment.
53 citations
TL;DR: Thirteen patients who had refused a blood transfusion for religious reasons were treated by autologous stem cell transplantation without a blood product transfusion at the Institution between 2005 and 2012, with no significant bleeding complications observed.
Abstract: Thirteen patients who had refused a blood transfusion for religious reasons were treated by autologous stem cell transplantation (ASCT) without a blood product transfusion at our Institution between 2005 and 2012. The study protocol was approved by the Ethics Review Committee (ccp Ile-deFrance, Paris, France). The patients included eight males and five females with multiple myeloma (MM, n = 8), Hodgkin lymphoma (HL, n = 3) and non-Hodgkin lymphoma (NHL, n = 2) (Table I). The median age was 51 (range, 19 4–64 6) years at diagnosis and 51 8 (range, 21 6–65 2) years at ASCT. The conditioning regimens before transplantation were as follows: 140 mg/m2 melphalan (n = 1); 200 mg/m2 melphalan (n = 7) and BEAM (BCNU 300 mg/m2 day 1, etoposide 200 mg/m2 days 2–4, cytarabine 200 mg/m2 days 2–4 and melphalan 140 mg/m2 day 5) (n = 5). The mean number of CD34+ immature haematopoietic cells infused was 6 8 9 10 CD34+/kg (range, 2 5–11 28). The median delay between diagnosis and transplant was 9 3 (range, 4 9–46 3) months. Before and after the procedure, all patients received erythropoietin (EPO). After transplantation, 77% (10/13) of the patients received 4 lg/kg of the thrombopoietin receptor (TPO-R) agonist romiplostim (Nplate ; Amgen, Thousand Oaks, CA, USA) for a median of 1 (0–2) injections, along with a single injection of 6 mg pegylated granulocyte colonystimulating factor (G-CSF) pegfilgrastim (Neulasta ; Amgen, Thousand Oaks, CA, USA) at day +2. In addition, 30% (4/ 13) of our patients were treated with romiplostim before transplantation (4 lg/kg 8 d before conditioning in three patients and 15 and 8 d before in one patient) (Table I). The blood tests at the time of cell transplant were (mean values) haemoglobin 135 g/l (range, 101–153); platelets 377 5 (range, 153–860) 910/l, and neutrophils 3 71 (range, 1–11 5) 910/l. The mean duration of neutropenia (<0 5 9 10/l) and thrombocytopenia (<10 9 10/l) was 4 5 (range, 3–8) and 2 8 (range, 0–15) days, respectively. The mean haemoglobin level consistently remained over 110 g/l. Figure 1 illustrates the course of the neutrophil count, haemoglobin level and platelet count. No significant bleeding complications were observed. The median follow-up was 39 5 months (range, 10 5–157) post-diagnosis and 28 months (2–149) post-transplantation. Five patients relapsed, at a median of 28 (range, 20 5–51) months. Two MM patients and one HL patient died from disease progression.
10 citations
TL;DR: Methods for measuring the activity and predicting the efficacy of such compounds are warranted for evaluating individual responses to treatment, particularly in a context of widespread preclinical and clinical studies of protein kinase inhibitors in patients with heterogeneous myeloid malignancies.
Abstract: Protein kinase inhibitors have proved to be effective and well tolerated in special form of malignant diseases in which targeted kinases play a central role in the development and progression of the malignant clone. In addition, the development of acquired drug resistance, due to new mutations or clonal evolution, during treatment is common. Methods for measuring the activity and predicting the efficacy of such compounds are warranted for evaluating individual responses to treatment, particularly in a context of widespread preclinical and clinical studies of protein kinase inhibitors in patients with heterogeneous myeloid malignancies.
9 citations
TL;DR: Using HT, this association yielded in a high response rate and a low toxicity, and a prospective study with longer follow-up will help determining the true benefit of such strategy.
Abstract: AIM: To assess the feasibility of the combination of helical tomotherapy® (HT) and a concurrent systemic targeted therapy in patients with solitary plasmacytoma (SP) with the aim to decrease toxicity while improving therapeutic efficacy.
METHODS: Six patients with biologically, histologically, and radiologically confirmed SP were treated using HT and a systemic targeted treatment concomitantly. Total dose was 40 Gy/20 fractions. Four patients received 4 cycles of concurrent lenalidomide-dexamethasone combination and two patients were treated with concomitant bortezomib-dexamethasone. All toxicities were described using the Common Terminology Criteria for Adverse Effects v3.0.
RESULTS: Five patients had a bone tumor and one patient had an isolated pancreatic mass. Five patients presented with pain, one had neurologic symptoms related to medullary compression, which was treated by an emergency surgery. Median age was 59.5 years (range, 50-74 years). All patients had initial positron emission tomography-computed tomographys, three patients had total body bone magnetic resonance imaging examination, and three patients had computed tomodensitometry scans. The toxicity profile was excellent with no higher than grade 1 toxicity. Four of the six patients experienced a partial radiological response, four had complete response on positions emission tomography and 5/6 patients experienced a complete relief of their symptoms 4 mo after treatment. At a median follow-up of 18 mo, 5/6 patients were controlled clinically, radiologically, and biologically.
CONCLUSION: Using HT, we could deliver a highly conformal irradiation concurrently with a molecularly targeted therapy. This association yielded in a high response rate and a low toxicity. A prospective study with longer follow-up will help determining the true benefit of such strategy.
5 citations
TL;DR: Sustained Leukemia-Free State and Molecular Response to Sorafenib in a Patient With Chronic Myelomonocytic Leukemia in Transformation Driven by Homozygous FLT3-ITD Malignant Hematopoiesis
Abstract: Sustained Leukemia-Free State and Molecular Response to Sorafenib in a Patient With Chronic Myelomonocytic Leukemia in Transformation Driven by Homozygous FLT3-ITD Malignant Hematopoiesis Olivier Kosmider, Nicolas Chapuis, Sophie Kaltenbach, Romain Coriat, Pascaline Boudou Rouquette, Lise Willems, Virginie Chesnais, Isabelle Radford-Weiss, Valerie Bardet, Patrick Mayeux, Jerome Tamburini, Michaela Fontenay, Didier Bouscary
3 citations
TL;DR: This case high lights an ethical dilemma between the respect of patients’ wishes and the appropriate manage ment of a life-threaten condition by transfusion.
1 citations