Effects of lenalidomide on the bone marrow microenvironment in acute myeloid leukemia: Translational analysis of the HOVON103 AML/SAKK30/10 Swiss trial cohort.

This translational study aimed at gaining insight into the effects of lenalidomide in acute myeloid leukemia (AML). Forty-one AML patients aged 66 or older of the Swiss cohort of the HOVON-103 AML/SAKK30/10 study were included. After randomization, they received standard induction chemotherapy with or without lenalidomide. Bone marrow biopsies at diagnosis and before the 2nd induction cycle were obtained to assess the therapeutic impact on leukemic blasts and microenvironment. Increased bone marrow angiogenesis, as assessed by microvessel density (MVD), was found at AML diagnosis and differed significantly between the WHO categories. Morphological analysis revealed a higher initial MVD in AML with myelodysplasia-related changes (AML-MRC) and a more substantial decrease of microvascularization after lenalidomide exposure. A slight increase of T-bet-positive TH1-equivalents was identifiable under lenalidomide. In the subgroup of patients with AML-MRC, the progression-free survival differed between the two treatment regimens, showing a potential but not significant benefit of lenalidomide. We found no correlation between the cereblon genotype (the target of lenalidomide) and treatment response or prognosis. In conclusion, addition of lenalidomide may be beneficial to elderly patients suffering from AML-MRC, where it leads to a reduction of microvascularization and, probably, to an intensified specific T cell-driven anti-leukemic response

Inferior outcome of addition of the aminopeptidase inhibitor tosedostat to standard intensive treatment for elderly patients with aml and high risk mds

Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation w

Integrating novel agents into multiple myeloma treatment - current status in Switzerland and treatment recommendations.

The treatment of multiple myeloma has undergone significant changes in the recent past. The arrival of novel agents, especially thalidomide, bortezomib and lenalidomide, has expanded treatment options and patient outcomes are improving significantly. This article summarises the discussions of an expert meeting which was held to debate current treatment practices for multiple myeloma in Switzerland concerning the role of the novel agents and to provide recommendations for their use in different treatment stages based on currently available clinical data. Novel agent combinations for the treatment of newly diagnosed, as well as relapsed multiple myeloma are examined. In addition, the role of novel agents in patients with cytogenetic abnormalities and renal impairment, as well as the management of the most frequent side effects of the novel agents are discussed. The aim of this article is to assist in treatment decisions in daily clinical practice to achieve the best possible outcome for patients with multiple myeloma

A european perspective on haematopoietic growth factors in haemato-oncology : report of an expert meeting of the EORTC

Contains fulltext : 25507___.PDF (publisher's version ) (Open Access

Nutritional support during the hospital stay reduces mortality in patients with different types of cancers: Secondary analysis of a prospective randomized trial.

INTRODUCTION Nutritional support in patients with cancer aims at improving quality of life. Whether use of nutritional support is also effective in improving clinical outcomes remains understudied. METHODS In this preplanned secondary analysis of patients with cancer included in a prospective, randomized-controlled, Swiss, multicenter trial (EFFORT), we compared protocol-guided individualized nutritional support (intervention group) to standard hospital food (control group) regarding mortality at 30-day (primary endpoint) and other clinical outcomes. RESULTS We analyzed 506 patients with a main admission diagnosis of cancer, including lung cancer (n=113), gastrointestinal tumors (n=84), hematological malignancies (n=108) and other types of cancer (n=201). Nutritional risk based on Nutritional Risk Screening [NRS 2002] was an independent predictor for mortality over 180 days with a (age-, sex-, center-, type of cancer-, tumor activity- and treatment-) adjusted hazard ratio of 1.29 (95% CI 1.09 to 1.54; p=0.004) per point increase in NRS. In the 30-day follow-up period, 50 patients (19.9%) died in the control group compared to 36 (14.1%) in the intervention group resulting in an adjusted odds ratio of 0.57 (95% CI 0.35 to 0.94; p=0.027). Interaction tests did not show significant differences in mortality across the cancer type subgroups. Nutritional support also significantly improved functional outcomes and quality of life measures. CONCLUSION Compared to usual hospital nutrition without nutrition support, individualized nutritional support reduced the risk for mortality and improved functional and quality of life outcomes in cancer patients with increased nutritional risk. These data further support the inclusion of nutritional care in cancer management guidelines

Dicentric translocation (9;12) presenting as refractory Philadelphia chromosome-positive acute B-cell lymphoblastic leukemia

A 66-year-old Caucasian woman presented with a Philadelphia chromosome positive common B-cell acute lymphoblastic leukemia and a dic(9;12) involving the der(9)t(9;22), a rearrangement so far not observed in acute lymphoblastic leukemia. The patient was treated for the acute lymphoblastic leukemia, but showed refractory disease and died 6 months after initial diagnosis. This case suggests that, in the combination of t(9;22) and dic(9;12), the known poor prognostic feature of t(9;22) in acute lymphoblastic leukemia may outweigh the favorable outcome reported in patients with dic(9;12)

[Distress among cancer patients and their partners in the first year after diagnosis]

Diagnosis of a malignant disease can cause serious psychological problems in patients as well as their intimate partners