Prevalence of malnutrition in adult patients previously treated with allogeneic hematopoietic stem-cell transplantation.

INTRODUCTION: Malnutrition is common after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and is a well-known prognostic factor for survival. The nutritional status of patients in a long term after allo-HSCT is less well documented. The main objective of this study was to evaluate the prevalence of malnutrition in adult patients who underwent allo-HSCT more than one year ago. Secondary objectives were to assess body composition, muscle strength, and factors associated with malnutrition. PATIENTS & METHODS: All allo-HSCT patients admitted into the University Hospital of Clermont-Ferrand between 1st January 1985 and 31st December 2012 were screened. Clinical and biological nutritional assessments included anthropometric measurements, serum nutritional proteins, body composition assessed by bioelectrical impedance, and upper-limb muscle strength (MS) measured by dynamometry. Hematological and nutritional data during and after hospital stay for allo-HSCT were retrospectively collected. RESULTS: Eighty four allo-HSCT patients (52% men; mean age 54.4 ± 12.5 years) were enrolled. Average follow-up after allo-HSCT was 56.4 ± 47.5 months. Prevalence of malnutrition at the end of follow-up was 20%. Compared to well-nourished patients (WN group), undernourished patients (UN group) at the end of follow-up were significantly more likely to be undernourished (50% vs. 21%, p = 0.04) at hospital admission, and to have a Nutritional Risk Index of <97.5 (47% vs. 20%, p = 0.004). Compared to a reference population, mid-arm muscle circumference and MS were significantly more likely to be decreased in the UN group than in the WN group (35.3% vs. 8.9%, p = 0.017; 24% vs. 3%, p = 0.005, respectively); fat-free mass index and appendicular skeletal muscle mass index were decreased in 30.5% and 36.6% of all patients, respectively, with no difference between UN and WN groups. Chronic graft-versus-host disease was more frequent, although not significantly in the UN group (76% vs. 52%, p = 0.071). In multivariate analyses, the presence of malnutrition at hospital admission for allo-HSCT trended towards an increased risk of longer-term malnutrition (OR = 3.60 [0.95; 13.67], p = 0.06). CONCLUSION: Malnutrition is a frequent consequence of allo-HSCT, and may occur several months or years after allo-HSCT, particularly if malnutrition existed before allo-HSCT. Our findings support the need for specialized nutritional care for both before and after allo-HSCT. Furthermore, assessment of muscle mass may be a pertinent parameter of malnutrition in this instance.

[PI3K-AKT-mTOR pathway: Description, therapeutic development, resistance, predictive/prognostic biomarkers and therapeutic applications for cancer]. / La voie de signalisation PI3K-AKT-mTOR: description, développement thérapeutique, résistances, marqueurs prédictifs/pronostiques et applications thérapeutiques en cancérologie.

Among many cancer cells signaling pathways, PI3K-AKT-mTOR plays a major role in growth, proliferation and cellular survival. This is a complex pathway activated either by an extracellular way (receptors with tyrosine kinase activity) or by an intracellular way with transformed or overexpressed proteins involved in the signal transduction. To date, there are many applications of mTOR inhibitors in oncology with an expanding development rapidly. However, resistances appear to mTOR inhibitors which lead to 2nd generation mTOR inhibitors development. A better knowledge of predictive and prognostic biomarkers will allow to specify the group of patients who may benefit from these treatments and help to the choice.

[Pazopanib for treatment of renal cell carcinoma and soft tissue sarcomas]. / Intérêt du pazopanib dans le traitement des cancers du rein et des sarcomes des tissus mous.

The role of angiogenesis in the physiopathology of renal cell carcinoma is fundamental. Strategies targeting angiogenesis have been developed including VEGF and VEGFR inhibitors for the treatment of metastatic renal cell carcinoma (mRCC), in first and second line. Pazopanib is an angiogenesis inhibitor targeting VEGF receptor, PDGF receptor and c-KIT receptor. This treatment is a treatment option recommended for patients with mRCC, would be in first line or after cytokines failure. Pazopanib has been recently approved for patients with metastatic soft tissue sarcoma, after failure of at least one line of chemotherapy.

[Gemtuzumab ozogamicin for treatment of acute myeloid leukemia]. / Intérêt du gemtuzumab ozogamicin dans les leucémies aiguës myéloïdes.

Gemtuzumab ozogamicin (GO) is a humanized monoclonal antibody anti-CD33 conjugated with calicheamicin and was indicated for acute myeloid leukemia (AML) patients. It was initially approved in 2000 by FDA thank to promising results from a phase II trial including elderly relapsing AML patients. Numerous studies evaluated this treatment as salvage and frontline therapy in various regimens including associations with intensive chemotherapy. Based on the results from a randomized phase III trial, this agent was withdrawal because of no evidence for its benefit in terms of survival associated with excessive toxicity. Other phase III trials were then reported and show potentially better efficacy/toxicity profile. We review here the results of main trials interesting this agent, which is so far only available in a compassionate ATU program in France for the treatment of relapsing CD33+ AML patients.