TET2 mutations in acute myeloid leukemia (AML): results from a comprehensive genetic and clinical analysis of the AML study group.

Purpose: The tet oncogene family member 2 (TET2) gene was recently identified to be mutated in myeloid disorders including acute myeloid leukemia (AML). To date, there is increasing evidence for a functional role of TET2 mutations (TET2(mut)) in AML. Thus, we explored the frequency, gene-expression pattern, and clinical impact of TET2(mut) in a large cohort of patients with AML in the context of other AML-associated aberrations.

Evaluation of dysplasia through detailed cytomorphology in 3156 patients from the Düsseldorf Registry on myelodysplastic syndromes.

Using the Düsseldorf MDS registry with standardized cytomorphology we here describe dysplastic features in detail, concentrating on 16 different dysplastic features in the blood and 19 in the marrow in 3156 patients. The most frequent dysplastic features were megaloblastoid changes and bi- and multinuclearity in the erythropoiesis, pseudo-Pelger cells and hypogranulation in the granulopoiesis and micromegakaryoctes and mononuclear megakaryocytes in the megakaryopoiesis. The frequency of dysplastic changes did not differ significantly among the WHO types with the exception of MDS with del(5q) and CMML types.

New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge.

Purpose: The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the International Prognostic Scoring System (IPSS) in 1997, knowledge concerning the prognostic impact of abnormalities has increased substantially. The present study proposes a new and comprehensive cytogenetic scoring system based on an international data collection of 2,902 patients.

Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): a multicenter study.

Myelodysplastic syndromes (MDS) with del(5q) are considered to have a benign course of the disease. In order to address the issue of the propensity of those patients to progress to acute myeloid leukemia (AML), data on 381 untreated patients with MDS and del(5q) characterized by low or intermediate I International Prognostic Scoring System (IPSS) risk score were collected from nine centers and registries. Median survival of the entire group was 74 months.

Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies.

We aimed to determine the prognostic impact of monosomal karyotype (MK) in acute myeloid leukemia (AML) in the context of the current World Health Organization (WHO) classification and to evaluate the outcome of MK(+) patients after allogeneic HSCT. Of 1058 patients with abnormal cytogenetics, 319 (30%) were MK MK(+). MK(+) patients were significantly older (P = .

Deferasirox treatment of iron-overloaded chelation-naïve and prechelated patients with myelodysplastic syndromes in medical practice: results from the observational studies eXtend and eXjange.

EXtend and eXjange were prospective, 1-yr, non-interventional, observational, multicentre studies that investigated deferasirox, a once-daily oral iron chelator, in iron-overloaded chelation-naïve and prechelated patients with myelodysplastic syndromes (MDS), respectively, treated in the daily-routine setting of office-based physicians. No inclusion or exclusion criteria or additional monitoring procedures were applied. Deferasirox was administered as recommended in the European Summary of Product Characteristics.

Therapy-related myeloid neoplasms following treatment with radioiodine.

Background: Few data are available on therapy-related myelodysplastic syndromes and acute myeloid leukemia developing after radioiodine treatment.

Design And Methods: We retrospectively analyzed 39 patients with myeloid neoplasms following radioiodine treatment, whose data were reported to the Duesseldorf Myelodysplastic Syndromes Register (8 of 3814 patients) and five other German Myelodysplastic Syndromes centers (n=31) between 1982 and 2011. These data were compared with those from 165 patients from our Myelodysplastic Syndromes Register with therapy-related myeloid neoplasms following chemotherapy (n=90), radiation (n=30), or radiochemotherapy (n=45).

Upfront allogeneic blood stem cell transplantation for patients with high-risk myelodysplastic syndrome or secondary acute myeloid leukemia using a FLAMSA-based high-dose sequential conditioning regimen.

Patients suffering from high-risk myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) secondary to MDS (sAML) are characterized by poor response to conventional cytotoxic chemotherapy. The purpose of our prospective single-center study was to examine the safety and efficacy of an allogeneic hematopoietic stem cell transplantation (HSCT) following a sequential conditioning regimen as first-line therapy for previously untreated patients with high-risk MDS or sAML. Between November 2003 and June 2010, 30 patients (20 high-risk MDS, 10 sAML) received fludarabine (4 × 30 mg/m(2)), amsacrine (4 × 100 mg/m(2)), and Ara-C (4 × 2 g/m(2), FLAMSA).

Incidence and prevalence of myelodysplastic syndromes: data from the Düsseldorf MDS-registry.

Population-based data on patients with MDS are scarce. Here we report the incidence and prevalence of MDS based on data from the Düsseldorf MDS Registry. Cases in the city of Düsseldorf in the study period were identified from the MDS Registry.

Monitoring of minimal residual disease in NPM1-mutated acute myeloid leukemia: a study from the German-Austrian acute myeloid leukemia study group.

Purpose: To evaluate the prognostic value of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) with NPM1 mutation (NPM1(mut)).

Patients And Method: RNA-based real-time quantitative polymerase chain reaction (RQ-PCR) specific for the detection of six different NPM1(mut) types was applied to 1,682 samples (bone marrow, n = 1,272; blood, n = 410) serially obtained from 245 intensively treated younger adult patients who were 16 to 60 years old.

Results: NPM1(mut) transcript levels as a continuous variable were significantly associated with prognosis after each treatment cycle.

Coalesced multicentric analysis of 2,351 patients with myelodysplastic syndromes indicates an underestimation of poor-risk cytogenetics of myelodysplastic syndromes in the international prognostic scoring system.

Purpose: The International Prognostic Scoring System (IPSS) remains the most commonly used system for risk classification in myelodysplastic syndromes (MDSs). The IPSS gives more weight to blast count than to cytogenetics. However, previous publications suggested that cytogenetics are underweighted in the IPSS.

Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group.

Purpose: To compare low-dose decitabine to best supportive care (BSC) in higher-risk patients with myelodysplastic syndrome (MDS) age 60 years or older and ineligible for intensive chemotherapy.

Patients And Methods: Two-hundred thirty-three patients (median age, 70 years; range, 60 to 90 years) were enrolled; 53% had poor-risk cytogenetics, and the median MDS duration at random assignment was 3 months. Primary end point was overall survival (OS).

Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance.

About 40% of patients with myelodysplastic syndromes (MDSs) present with a normal karyotype, and they are facing different courses of disease. To advance the biological understanding and to find molecular prognostic markers, we performed a high-resolution oligonucleotide array study of 107 MDS patients (French American British) with a normal karyotype and clinical follow-up through the Duesseldorf MDS registry. Recurrent hidden deletions overlapping with known cytogenetic aberrations or sites of known tumor-associated genes were identified in 4q24 (TET2, 2x), 5q31.

Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndrome.

The incidence of myelodysplastic syndromes increases with age and a high prevalence of co-morbid conditions has been reported in these patients. So far, risk assessment in myelodysplastic syndromes has been mainly based on disease status. We studied the prognostic impact of comorbidity on the natural history of myelodysplastic syndrome with the aim of developing novel tools for risk assessment.

Prognostic molecular markers in myelodysplastic syndromes.

Cytogenetic findings in myelodysplastic syndromes play an important role in diagnosis, prognostication and clinical decision making. Therefore, they became an important aspect in scoring systems such as the International Prognostic Scoring System (IPSS) and the WHO-adapted Prognostic Scoring System (WPSS). Ongoing efforts to refine the categorization of karyotypes with regard to prognosis and therapeutic options will change scoring systems in the near future.

Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals low-abundance mutant clones with early origins, but indicates no definite prognostic value.

Mutations in the TET2 gene are frequent in myeloid disease, although their biologic and prognostic significance remains unclear. We analyzed 355 patients with myelodysplastic syndromes using "next-generation" sequencing for TET2 aberrations, 91 of whom were also subjected to single-nucleotide polymorphism 6.0 array karyotyping.