Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes: the HOVON89 trial.

A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint.

Similar efficacy outcomes with peripheral blood stem cell versus bone marrow for autologous stem cell transplantation in acute myeloid leukemia: Long-term follow-up of the EORTC-GIMEMA randomized AML-10 trial.

We report here the long-term follow-up of the only prospective randomized trial of autologous hematopoietic stem cell transplantation (auto-HSCT) with peripheral blood stem cells (APBSCT) versus auto-HSCT with bone marrow (ABMT) in acute myeloid leukemia (AML) patients in first remission (CR). We observed that among patients alive and still in CR 5 years after planned auto-HSCT, approximately 10% of the patients died in the following 10 years. This stresses the need for long-term close surveillance of AML patients after auto-HSCT.

A framework for the clinical implementation of optical genome mapping in hematologic malignancies.

Optical Genome Mapping (OGM) is rapidly emerging as an exciting cytogenomic technology both for research and clinical purposes. In the last 2 years alone, multiple studies have demonstrated that OGM not only matches the diagnostic scope of conventional standard of care cytogenomic clinical testing but it also adds significant new information in certain cases. Since OGM consolidates the diagnostic benefits of multiple costly and laborious tests (e.

Genome Mapping Nomenclature.

Background: Genome Mapping Technologies (optical and electronic) use ultra-high molecular weight DNA to detect structural variation and have application in constitutional genetic disorders, hematological neoplasms, and solid tumors. Genome mapping can detect balanced and unbalanced structural variation, copy number changes, and haplotypes. The technique is analogous to chromosomal microarray analysis, although genome mapping has the added benefit of being able to detect and ascertain the nature of more abnormalities in a single assay than array, karyotyping, or FISH alone.

10-day decitabine versus 3 + 7 chemotherapy followed by allografting in older patients with acute myeloid leukaemia: an open-label, randomised, controlled, phase 3 trial.

Background: Many older patients with acute myeloid leukaemia die or cannot undergo allogeneic haematopoietic stem-cell transplantation (HSCT) due to toxicity caused by intensive chemotherapy. We hypothesised that replacing intensive chemotherapy with decitabine monotherapy could improve outcomes.

Methods: This open-label, randomised, controlled, phase 3 trial was conducted at 54 hospitals in nine European countries.

Next-generation cytogenetics: Comprehensive assessment of 52 hematological malignancy genomes by optical genome mapping.

Somatic structural variants (SVs) are important drivers of cancer development and progression. In a diagnostic set-up, especially for hematological malignancies, the comprehensive analysis of all SVs in a given sample still requires a combination of cytogenetic techniques, including karyotyping, FISH, and CNV microarrays. We hypothesize that the combination of these classical approaches could be replaced by optical genome mapping (OGM).

Prognostic and predictive performance of R-ISS with SKY92 in older patients with multiple myeloma: the HOVON-87/NMSG-18 trial.

The standard prognostic marker for multiple myeloma (MM) patients is the revised International Staging System (R-ISS). However, there is room for improvement in guiding treatment. This applies particularly to older patients, in whom the benefit/risk ratio is reduced because of comorbidities and subsequent side effects.

Survival Improvement over Time of 960 s-AML Patients Included in 13 EORTC-GIMEMA-HOVON Trials.

We report the outcomes of secondary acute myeloid leukemia (s-AML) patients included in one of 13 European Organisation for Research and Treatment of Cancer (EORTC) collaborative AML trials using intensive remission-induction chemotherapy. Among 8858 patients treated between May 1986 and January 2008, 960 were identified as having s-AML, either after MDS (cohort A; = 508), occurring after primary solid tumors or hematologic malignancies other than MDS (cohort B; = 361), or after non-malignant conditions or with a history of toxic exposure (cohort C; = 91). Median age was 64 years, 60 years and 61 years in cohort A, B and C, respectively.

Impact of the type of anthracycline and of stem cell transplantation in younger patients with acute myeloid leukaemia: Long-term follow up of a phase III study.

We provide a long-term evaluation of patients enrolled in the EORTC/GIMEMA AML-10 trial which included a total of 2157 patients, 15-60 years old, randomized to receive either daunorubicin (DNR, 50 mg/m ), mitoxantrone (MXR, 12 mg/m ), or idarubicin (IDA, 10 mg/m ) in addition to standard-dose cytarabine and etoposide for induction chemotherapy and intermediate dose cytarabine for consolidation. Younger patients who reached complete remission with complete (CR) or incomplete (CRi) recovery were then scheduled to receive an allogeneic hematopoietic stem cell transplantation (HSCT). That was if they had a HLA-identical sibling donor; in all other cases, an autologous HSCT had to be administered.

Ring sideroblasts in AML are associated with adverse risk characteristics and have a distinct gene expression pattern.

Ring sideroblasts (RS) emerge as result of aberrant erythroid differentiation leading to excessive mitochondrial iron accumulation, a characteristic feature for myelodysplastic syndromes (MDS) with mutations in the spliceosome gene SF3B1. However, RS can also be observed in patients diagnosed with acute myeloid leukemia (AML). The objective of this study was to characterize RS in patients with AML.

HER2, chromosome 17 polysomy and DNA ploidy status in breast cancer; a translational study.

Breast cancer treatment depends on human epidermal growth factor receptor-2 (HER2) status, which is often determined using dual probe fluorescence in situ hybridisation (FISH). Hereby, also loss and gain of the centromere of chromosome 17 (CEP17) can be observed (HER2 is located on chromosome 17). CEP17 gain can lead to difficulty in interpretation of HER2 status, since this might represent true polysomy.

Impact of induction regimen and allogeneic hematopoietic cell transplantation on outcome in younger adults with acute myeloid leukemia with a monosomal karyotype.

Monosomal karyotype confers a poor prognosis in patients with acute myeloid leukemia. Here, we determined the impact of the type of remission-induction chemotherapy and the impact of having a donor in younger acute myeloid leukemia patients with a monosomal karyotype included in two phase III trials. In the first trial patients were randomized to receive either daunorubicin, mitoxantrone, or idarubicin in addition to standard-dose cytarabine and etoposide for induction chemotherapy.

Cytogenetic clonal heterogeneity is not an independent prognosis factor in 15-60-year-old AML patients: results on 1291 patients included in the EORTC/GIMEMA AML-10 and AML-12 trials.

Unlabelled: The presence of cytogenetic clonal heterogeneity has been associated with poor prognosis in patients with acute myeloid leukemia (AML). Here, we reassessed this association. The study cohort consisted of all patients with an abnormal karyotype randomized in the EORTC/GIMEMA AML-10 and AML-12 trials.

Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial.

The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical cytotoxic agents prior and thalidomide after HDM (VAD arm) in multiple myeloma (MM) patients aged 18-65 years. Here, the long-term follow-up and data on second primary malignancies (SPM) are presented. After a median follow-up of 96 months, progression-free survival (censored at allogeneic transplantation, PFS) remained significantly prolonged in the PAD versus VAD arm (hazard ratio (HR)=0.

Clonal evolution in myelodysplastic syndromes.

Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5-11 years).

Genomic array as compared to karyotyping in myelodysplastic syndromes in a prospective clinical trial.

Karyotyping is considered as the gold standard in the genetic subclassification of myelodysplastic syndrome (MDS). Oligo/SNP-based genomic array profiling is a high-resolution tool that also enables genome wide analysis. We compared karyotyping with oligo/SNP-based array profiling in 104 MDS patients from the HOVON-89 study.

Cytogenetic Nomenclature and Reporting.

A standardized nomenclature is critical for the accurate and consistent description of genomic changes as identified by karyotyping, fluorescence in situ hybridization and microarray. The International System for Human Cytogenomic Nomenclature (ISCN) is the central reference for the description of karyotyping, FISH, and microarray results, and provides rules for describing cytogenetic and molecular cytogenetic findings in laboratory reports. These laboratory reports are documents to the referring clinician, and should be clear, accurate and contain all information relevant for good interpretation of the cytogenetic findings.

Implementation of erythroid lineage analysis by flow cytometry in diagnostic models for myelodysplastic syndromes.

Flow cytometric analysis is a recommended tool in the diagnosis of myelodysplastic syndromes. Current flow cytometric approaches evaluate the (im)mature myelo-/monocytic lineage with a median sensitivity and specificity of ~71% and ~93%, respectively. We hypothesized that the addition of erythroid lineage analysis could increase the sensitivity of flow cytometry.

Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma.

The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging.

Guidelines for genomic array analysis in acquired haematological neoplastic disorders.

Genetic profiling is important for disease evaluation and prediction of prognosis or responsiveness to therapy in neoplasia. Microarray technologies, including array comparative genomic hybridization and single-nucleotide polymorphism-detecting arrays, have in recent years been introduced into the diagnostic setting for specific types of haematological malignancies and solid tumours. It can be used as a complementary test or depending on the neoplasia investigated, also as a standalone test.