A A van de Loosdrecht

Prediction of treatment-related toxicity and outcome with geriatric assessment in elderly patients with solid malignancies treated with chemotherapy: a systematic review

INTRODUCTIONnThe number of older patients with cancer is increasing. Standard clinical evaluation of these patients may not be sufficient to determine individual treatment strategies and therefore Geriatric Assessment (GA) may be of clinical value. In this review, we summarize current literature that is available on GA in elderly patients with solid malignancies who receive chemotherapy. We focus on prediction of treatment toxicity, mortality and the role of GA in the decision-making process.nnnDESIGNnWe conducted a systematic search in PubMed. Studied populations needed to fulfill the following criteria: 65 years or older, diagnosis of solid malignancy, treatment with chemotherapy, submission to GA, either designed to study prediction of treatment toxicity or mortality or to evaluate the role of GA in the decision-making process.nnnRESULTSnOur search provided 411 publications. Thirteen met the predefined criteria. These studies revealed: (i) up to 64% of elderly patients suffer from severe toxicity caused by polychemotherapy, (ii) Nutritional status, functionality and comorbidity are often associated with worse outcome, (iii) GA reveals (unknown) geriatric problems in more than 50% of elderly patients with cancer and (iv) 21%-53% of chemotherapy regimens are being modified based on GA.nnnCONCLUSIONSnIn geriatric oncology, an accurate predictive test to guide anticancer treatment in order to prevent serious toxicity is needed. The value of GA in predicting toxicity and mortality in older patients with cancer undergoing treatment with chemotherapy has not been proven. It may be valuable in revealing geriatric problems but current evidence for its usefulness to guide treatment decisions in this setting is limited. However, we are convinced that GAs should be carried out to optimize treatment strategies in elderly patients with cancer to improve treatment efficacy and minimize toxicity.

Azacitidine results in comparable outcome in newly diagnosed AML patients with more or less than 30% bone marrow blasts

The efficacy of azacitidine has been demonstrated in acute myeloid leukemia (AML) patients with 20-30% bone marrow (BM) blasts, but limited data is available on patients with ≥30% blasts. We analyzed 55 newly diagnosed AML patients, treated with azacitidine. The overall response rate was 42%. Median overall survival (OS) was 12.3 months. We confirmed poor-risk cytogenetics, therapy-related AML, performance score ≥2, and white blood cell count ≥15×10(9)/L as independent adverse predictors for OS. The BM blast percentage, however, had no impact on OS (P=0.55). In conclusion, administration of azacitidine is effective in AML patients with 20-30% and >30% BM blasts.

Identification of CD14 as a predictor for leukemic dendritic cell differentiation in acute myeloid leukemia

Identification of CD14 as a predictor for leukemic dendritic cell differentiation in acute myeloid leukemia

TNF-alpha receptor 1 expression on acute myeloid leukemic blasts predicts differentiation into leukemic dendritic cells.

TNF- α receptor 1 expression on acute myeloid leukemic blasts predicts differentiation into leukemic dendritic cells

Central diabetes insipidus preceding acute myeloid leukemia with t(3;12)(q26;p12)

A 52-year-old woman presented with polyuria and polydipsia. A diagnosis of central diabetes insipidus (DI) was made, which turned out to be the first sign of acute myeloid leukemia (AML). Cytogenetic analysis revealed a balanced translocation between chromosome 3 and 12 t(3;12)(q26;p12). The patient was treated with standard induction chemotherapy and vasopressin. Before consolidation chemotherapy could be administered, deep venous thrombosis was diagnosed and leukemia relapsed. Rescue chemotherapy was started. This is the first report of an association between AML with t(3;12) and DI. Its possible pathogenesis is discussed with a review of the literature.

Flt-3 internal tandem duplication hampers differentiation of AML blasts towards leukemic dendritic cells

Flt-3 internal tandem duplication hampers differentiation of AML blasts towards leukemic dendritic cells

Improved risk stratification by the integration of the revised International Prognostic Scoring System with the Myelodysplastic Syndromes Comorbidity Index

Myelodysplastic syndromes (MDS) comprise bone marrow failure diseases with a diverse clinical outcome. For improved risk stratification, the International Prognostic Scoring System (IPSS) has recently been revised (IPSS-R). This single-centre study aimed to validate the IPSS-R and to evaluate prior prognostic scoring systems for MDS. We retrospectively analysed 363 patients diagnosed with MDS according to the FAB criteria between 2000 and 2012. The IPSS, MD Anderson Risk Model Score (MDAS), World Health Organisation (WHO)-classification based Prognostic Scoring System (WPSS), refined WPSS (WPSS-R), IPSS-R and MDS-Comorbidity Index (MDS-CI) were applied to 222 patients considered with primary MDS following the WHO criteria and their prognostic power was investigated. According to the IPSS-R, 18 (8%), 81 (37%), 50 (23%), 43 (19%) and 30 (13%) patients were classified as very low, low, intermediate, high and very high risk with, respectively, a median overall survival of 96 (95% Confidence interval (CI) not reached), 49 (95% CI 34-64), 22 (95% CI 0-49), 19 (95% CI 11-27) and 10 (95% CI 6-13) months (p<.000). The IPSS-R showed improved prognostic power as compared to the IPSS, MDAS, WPSS and WPSS-R. Furthermore, the MDS-CI refined the risk stratification of MDS patients stratified according to the IPSS-R. In conclusion, accounting for the disease status by means of the IPSS-R and comorbidity through the MDS-CI considerably improves the prognostic assessment in MDS patients.

CD40-targeted adenoviral GM-CSF gene transfer enhances and prolongs the maturation of human CML-derived dendritic cells upon cytokine deprivation.

Vaccination with autologous leukaemia-derived dendritic cells (DC) presents an adjuvant treatment option for chronic myeloid leukaemia (CML). Here, we show that high-efficiency CD40-targeted adenoviral gene transfer of GM-CSF to CML-derived DC induces long-lived maturation in the absence of exogenous cytokines and may thus ensure protracted stimulation of CML-specific T cells upon vaccination.

Minimal residual disease detection defined as the malignant fraction of the total primitive stem cell compartment offers additional prognostic information in acute myeloid leukaemia

Introduction:u2002 Immunophenotypic detection of minimal residual disease (MRD) in bone marrow (BM) of acute myeloid leukaemia (AML) patients is of high prognostic relevance. Standard MRD percentage is assessed as a percentage of total white blood cells (WBCs) and is therefore highly dependent on WBC count. Peripheral blood (PB) contains more than five times lower MRD percentages. Therefore, PB in BM aspirates cause dilution of the MRD cells, possibly leading to false‐negative results for BM MRD. The latter is avoided when relating the fraction of malignant primitive cells, identified by aberrant marker expression [aberrant primitive cells (aPC)], to the total population of primitive cells. Such a fraction may in addition reflect an important biological parameter.

Erythropoiesis-stimulating agents significantly delay the onset of a regular transfusion need in nontransfused patients with lower-risk myelodysplastic syndrome

The EUMDS registry is an unique prospective, longitudinal observational registry enrolling newly diagnosed patients with lower‐risk myelodysplastic syndrome (MDS) from 17 European countries from both university hospitals and smaller regional hospitals.