A randomised Phase II trial of Hydroxychloroquine and Imatinib versus Imatinib alone for patients with Chronic Myeloid Leukaemia in Major Cytogenetic Response with residual disease

In chronic-phase chronic myeloid leukaemia (CP-CML), residual BCR-ABL1+ leukaemia stem cells are responsible for disease persistence despite TKI. Based on in vitro data, CHOICES (CHlorOquine and Imatinib Combination to Eliminate Stem cells) was an international, randomised phase II trial designed to study the safety and efficacy of imatinib (IM) and hydroxychloroquine (HCQ) compared with IM alone in CP-CML patients in major cytogenetic remission with residual disease detectable by qPCR. Sixty-two patients were randomly assigned to either arm. Treatment ‘successes’ was the primary end point, defined as ≥0.5 log reduction in 12-month qPCR level from trial entry. Selected secondary study end points were 24-month treatment ‘successes’, molecular response and progression at 12 and 24 months, comparison of IM levels, and achievement of blood HCQ levels >2000 ng/ml. At 12 months, there was no difference in ‘success’ rate (p = 0.58); MMR was achieved in 80% (IM) vs 92% (IM/HCQ) (p = 0.21). At 24 months, the ‘success’ rate was 20.8% higher with IM/HCQ (p = 0.059). No patients progressed. Seventeen serious adverse events, including four serious adverse reactions, were reported; diarrhoea occurred more frequently with combination. IM/HCQ is tolerable in CP-CML, with modest improvement in qPCR levels at 12 and 24 months, suggesting autophagy inhibition maybe of clinical value in CP-CML

Revealing stiffening and brittling of chronic myelogenous leukemia hematopoietic primary cells through their temporal response to shear stress

Cancer cell transformation is often accompanied by a modification of their viscoelastic properties. When capturing the stress-to-strain response of primary chronic myelogenous leukemia (CML) cells, from two data sets of CD34+ hematopoietic cells isolated from healthy and leukemic bone marrows, we show that the mean shear relaxation modulus increases upon cancer transformation. This stiffening of the cells comes along with local rupture events, detected as reinforced sharp local maxima of this modulus, suggesting that these cancer cells respond to a local mechanical stress by a cascade of local brittle failure events.Physique de la morphogenèse des plantes: propriétés dynamiques et mécaniques de la paroi des cellules du méristèm

Stability Analysis of a Model of Interaction Between the Immune System and Cancer Cells in Chronic Myelogenous Leukemia

International audienceWe describe here a simple model for the interaction between leukemic cells and the autologous immune response in chronic phase chronic myelogenous leukemia (CML). This model is a simplified version of the model we proposed in [Clapp et al., Cancer Research, 75:4053-4062, 2015]. Our simplification is based on the observation that certain key characteristics of the dynamics of CML can be captured with a three compartments model: two for the leukemic cells (stem cells and mature cells) and one for the immune response. We characterize the existence of steady states and their stability for generic forms of immunosuppres-sive effects of leukemic cells. We provide a complete co-dimension one bifurcation analysis. Our results show how clinical response to tyrosine kinase inhibitors treatment is compatible with the existence of a stable low-disease, treatment-free steady state

The BMP pathway: A unique tool to decode the origin and progression of leukemia

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Second attempt to discontinue imatinib in CP-CML patients with a second sustained complete molecular response.

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Risk factors for invasive aspergillosis in acute myeloid leukemia patients prophylactically treated with posaconazole.

International audienceInvasive aspergillosis (IA) is an important cause of morbidity and mortality in neutropenic patients with hematological malignancies. To investigate the immediate and mid-term benefits of posaconazole prophylaxis in AML patients undergoing first induction chemotherapy and to study the infection risk factors, we prospectively studied the IA incidence in these patients at our hospital between years 2007 and 2008; then we compared them to a matched control group without prophylaxis. There were 55 and 66 patients in each group respectively. At day 32 post-induction, two probable cases (3.6%) were scored in the prophylaxis group compared to 8 cases (12.1%) in the control group (4 possible and 4 probable). At day 100, it reached 7.27% and 15.5% respectively. Kaplan-Meier analysis at day 100 showed lower mortality rate in the prophylaxis group compared to the control group [3.64% (n = 2, none due to IA) and 10.61% (n = 7, four due to IA) respectively, P = 0.002]. Multivariate analysis showed age and lack of response to induction as independent infection risk factors. Posaconazole prophylaxis resulted in lower incidence of IA and significantly improved survival. Patient's age and response to induction treatment are two independent infection risk factors, and need more attention during future clinical trials linked to antifungal prophylaxis