Immunophenotypic measurable residual disease (MRD) in acute myeloid leukemia: Is multicentric MRD assessment feasible?

Flow-cytometric detection of now termed measurable residual disease (MRD) in acute myeloid leukemia (AML) has proven to have an independent prognostic impact. In a previous multicenter study we developed protocols to accurately define leukemia-associated immunophenotypes (LAIPs) at diagnosis. It has, however, not been demonstrated whether the use of the defined LAIPs in the same multicenter setting results in a high concordance between centers in MRD assessment.

The feasibility and efficacy of subcutaneous plerixafor for mobilization of peripheral blood stem cells in allogeneic HLA-identical sibling donors: results of the HOVON-107 study.

Background: Plerixafor (PFX) mobilizes CD34+ cells into circulation by disrupting the CXCR4 binding of the hematopoietic stem cell in its bone marrow niche.

Study Design And Methods: in the prospective HOVON-107 study (www.hovon.

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.

Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML.

Clofarabine has demonstrated antileukemic activity in acute myeloid leukemia (AML) but has yet to be critically evaluated in younger adults in the frontline with standard chemotherapy. We compared 2 induction regimens in newly diagnosed patients ages 18 to 65 with acute myeloid leukemia (AML)/high-risk myelodysplastic syndromes, that is, idarubicine-cytarabine (cycle I) and amsacrine-cytarabine (cycle II) without or with clofarabine (10 mg/m on days 1-5 of each of both cycles). Consolidation involved chemotherapy with or without hematopoietic stem cell transplantation.

Plerixafor for stem cell mobilization: the current status.

Purpose Of Review: Nowadays, plerixafor is approved for patients who fail to mobilize sufficient CD34⁺ cells for an autologous stem cell transplantation. Plerixafor is effective in the majority of these patients, who otherwise could not be treated adequately. We discussed in this review the current status of the optimal use of plerixafor in different clinical diagnoses and settings.

Evaluation of Dutch guideline for just-in-time addition of plerixafor to stem cell mobilization in patients who fail with granulocyte-colony-stimulating factor.

Background: Plerixafor in combination with granulocyte-colony-stimulating factor (G-CSF) is approved for the use of stem cell collection in patients who fail to mobilize on G-CSF. In 2009 the Stem Cell Working Party of the Dutch-Belgian Cooperative Trial group for Hematology Oncology (HOVON) composed a guideline for the use of plerixafor. According to this guideline it is recommended to add plerixafor to G-CSF in patients with circulating CD34+ cell counts of fewer than 20 × 10(6) /L on 2 consecutive days accompanied by increasing white blood cells.

High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study.

Purpose: Half the patients with acute myeloid leukemia (AML) who achieve complete remission (CR), ultimately relapse. Residual treatment-surviving leukemia is considered responsible for the outgrowth of AML. In many retrospective studies, detection of minimal residual disease (MRD) has been shown to enable identification of these poor-outcome patients by showing its independent prognostic impact.

Addition of bevacizumab to chemotherapy in acute myeloid leukemia at older age: a randomized phase 2 trial of the Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and the Swiss Group for Clinical Cancer Research (SAKK).

An urgent need for new treatment modalities is emerging in elderly patients with acute myeloid leukemia (AML). We hypothesized that targeting VEGF might furnish an effective treatment modality in this population. Elderly patients with AML were randomly assigned in this phase 2 study (n = 171) to receive standard chemotherapy (3 + 7) with or without bevacizumab at a dose of 10 mg/kg intravenously at days 1 and 15.

Cytarabine dose for acute myeloid leukemia.

Background: Cytarabine (ara-C) is an important drug in the treatment of acute myeloid leukemia (AML). High-dose cytarabine (2000 to 3000 mg per square meter of body-surface area) is toxic but results in higher rates of relapse-free survival than does the conventional dose of 100 to 400 mg per square meter. Intermediate dose levels have not been thoroughly evaluated.

Clinical effectiveness of leucoreduced, pooled donor platelet concentrates, stored in plasma or additive solution with and without pathogen reduction.

Pathogen reduction (PR) of platelet products increases costs and available clinical studies are equivocal with respect to clinical and haemostatic effectiveness. We conducted a multicentre, open-label, randomized, non-inferiority trial comparing the clinical effectiveness of buffy-coat derived leukoreduced platelet concentrates (PC) stored for up to 7 d in plasma with platelets stored in platelet additive solution III (PASIII) without and with treatment with amotosalen-HCl/ultraviolet-A (UVA) photochemical pathogen reduction (PR-PASIII). Primary endpoint of the study was 1-h corrected count increment (CCI).

Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique.

Mixed-lineage leukaemia (MLL)-partial tandem duplications (PTDs) are found in 3-5% of adult acute myeloid leukaemia (AML), and are associated with poor prognosis. In adult AML, MLL-PTD is only detected in patients with trisomy 11 or internal tandem duplications of FLT3 (FLT3-ITD). To date, studies in paediatric AML are scarce, and reported large differences in the frequency of MLL-PTD, frequently utilising mRNA RT-PCR only to detect MLL-PTDs.

Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype.

Purpose: To investigate the prognostic value of various cytogenetic components of a complex karyotype in acute myeloid leukemia (AML).

Patients And Methods: Cytogenetics and overall survival (OS) were analyzed in 1,975 AML patients age 15 to 60 years.

Results: Besides AML with normal cytogenetics (CN) and core binding factor (CBF) abnormalities, we distinguished 733 patients with cytogenetic abnormalities.

Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new partner gene.

Chromosome rearrangements are found in many acute leukemias. As a result, genes at the breakpoints can be disrupted, forming fusion genes. One of the genes involved in several chromosome aberrations in hematological malignancies is NUP98 (11p15).

Criteria for defining a complete remission in acute myeloid leukaemia revisited. An analysis of patients treated in HOVON-SAKK co-operative group studies.

Complete remission (CR) in patients with acute myeloid leukaemia (AML) is the primary endpoint for the evaluation of induction treatment and treatment strategies. However, the choice and application of the criteria for a haematological CR can often become a subject of debate because of regeneration more than 5% blasts may be present at the time of response evaluation; platelet and neutrophil recovery may be incomplete and marrow cellularity can vary. This study examined the individual parameters for CR in 1250 adult patients with de novo AML treated according to three successive study protocols.

Prognostic index for adult patients with acute myeloid leukemia in first relapse.

Purpose: The treatment of acute myeloid leukemia (AML) in first relapse is associated with unsatisfactory rates of complete responses that usually are short lived. Therefore, a clinically useful prognostic index can facilitate therapeutic decision making and evaluation of investigational treatment strategies at relapse of AML.

Patients And Methods: A prognostic score is presented based on the multivariate analysis of 667 AML patients in first relapse among 1,540 newly diagnosed non-M3 AML patients (age 15 to 60 years) entered onto three successive Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer Research Collaborative Group trials.

Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia.

Background: Sensitization of leukemic cells with hematopoietic growth factors may enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML).

Methods: In a multicenter randomized trial, we assigned patients (age range, 18 to 60 years) with newly diagnosed AML to receive cytarabine plus idarubicin (cycle 1) and cytarabine plus amsacrin (cycle 2) with granulocyte colony-stimulating factor (G-CSF) (321 patients) or without G-CSF (319). G-CSF was given concurrently with chemotherapy only.

Transfusion of pooled buffy coat platelet components prepared with photochemical pathogen inactivation treatment: the euroSPRITE trial.

A nucleic acid-targeted photochemical treatment (PCT) using amotosalen HCl (S-59) and ultraviolet A (UVA) light was developed to inactivate viruses, bacteria, protozoa, and leukocytes in platelet components. We conducted a controlled, randomized, double-blinded trial in thrombocytopenic patients requiring repeated platelet transfusions for up to 56 days of support to evaluate the therapeutic efficacy and safety of platelet components prepared with the buffy coat method using this pathogen inactivation process. A total of 103 patients received one or more transfusions of either PCT test (311 transfusions) or conventional reference (256 transfusions) pooled, leukoreduced platelet components stored for up to 5 days before transfusion.

High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients.

The proto-oncogene EVI1 encodes a DNA binding protein and is located on chromosome 3q26. The gene is aberrantly expressed in acute myeloid leukemia (AML) patients carrying 3q26 abnormalities. Two mRNAs are transcribed from this locus: EVI1 and a fusion of EVI1 with MDS1 (MDS1-EVI1), a gene located 5' of EVI1.

Minimal residual disease quantification in patients with acute myeloid leukaemia and inv(16)/CBFB-MYH11 gene fusion.

We have designed a real-time CBFB-MYH11 reverse transcription polymerase chain reaction (RT-PCR) assay to quantify minimal residual disease (MRD) in patients with inv(16)-positive acute myeloid leukaemia (AML). Six patients were followed for a median of 17.5 months after diagnosis during which 120 evaluable samples were analysed.