Bart J Biemond

University of Amsterdam, Amsterdamo, North Holland, Netherlands

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Publications (80)469 Total impact

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    ABSTRACT: Venous thromboembolism (VTE) is a frequent complication in patients with acute lymphoblastic leukemia (ALL). A significant proportion of patients develop cerebral venous thrombosis (CVT). To investigate risk factors for and the clinical course of CVT in ALL patients, we describe all cases of CVT which occurred in a well-defined cohort of 240 adults, treated for newly diagnosed ALL in the HOVON (Dutch-Belgian Hemato-Oncology Cooperative Group)-37 study. We conducted a nested case-control study to explore the relevance of early symptoms and risk factors for CVT in ALL patients. Nine of 240 patients developed CVT (4%). CVT occurred during or shortly after L-asparaginase therapy (in 8 cases) and shortly after intrathecal methotrexate injections (in all cases) during cycle I of remission induction treatment. CVT was associated with prior headache and seizures. In 5 of 9 patients with CVT, headache before the diagnosis of CVT occurred within 3 days after lumbar puncture and initially had a postural character. CVT is relatively common in adult ALL patients. Our data suggest that CVT in adult ALL patients results from the additive effects of multiple risk factors, with a particular role for asparaginase and the effects of lumbar punctures for intrathecal therapy. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 04/2015; 138(7). DOI:10.1016/j.jstrokecerebrovasdis.2015.03.041 · 1.99 Impact Factor
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    ABSTRACT: Patients with sickle cell anemia (SCA) are at a high risk to develop cerebral damage. Most common are silent cerebral infarctions (SCIs), visible as white matter hyperintensities (WMHs) on MRI in a patient without neurological deficits. The etiology of SCIs remains largely unclear. In addition, patients are at an increased risk for overt stroke, which is associated with large vessel disease. This classification based on the presence or absence of neurological deficits may not be the most fitting for research purposes, as it does not match the different underlying pathology. A classification based on imaging findings may therefore be a more straightforward approach for research purposes. We explored the feasibility to identify imaging features of SCIs in young, asymptomatic patients with SCA using ultra high-field 7 Tesla (7T) MRI. 7T MRI has a high resolution, which offers a unique chance to investigate small subclinical brain lesions in detail. To explore the superiority of 7T in identifying imaging abnormalities, we compared our results with 3T MRI. Ten young, neurologically asymptomatic patients with SCA underwent 7T and 3T MRI; 10 healthy, age-matched controls underwent 7T MRI. We used existing neuroimaging standards to classify the brain lesions. We scored 7T and 3T scans separately, blinded for all other results. Using 7T MRI, we identified more patients with intracerebral lesions (9/10 vs. 5/10), a higher total count of WMHs (203 vs. 190, p = 0.016) and more lacunes (5 vs. 4) compared to 3T MRI. Abnormalities seen on 7T, which could not be identified on 3T, were cortical hyperintensities (in 3/10) and a different aspect of irregular WMHs, closely associated with cortical hyperintensities in a patient with large vessel stenosis. In 7 controls, a total of 13 WMHs were present. Using 7T MRI, we identified more intracerebral lesions compared to 3T, and found several abnormalities not visible on 3T. 7T MRI in SCA seems of particular interest to study the cortical involvement and the relation between WMHs and the cortex. We found some imaging features that are thought to be representative for small vessel disease, including WMHs, lacunes and prominent perivascular spaces; to understand whether small vessel disease plays a role in SCA requires further research. © 2015 S. Karger AG, Basel.
    Cerebrovascular Diseases 03/2015; 39(3-4):181-189. DOI:10.1159/000373917 · 3.70 Impact Factor
  • American Journal of Hematology 01/2015; 90(4). DOI:10.1002/ajh.23944 · 3.48 Impact Factor
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    ABSTRACT: The preferred type of post-remission therapy (PRT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1) is a subject of continued debate, especially in patients at higher risk of non-relapse mortality (NRM), including patients >40 years of age. We report results of a time-dependent multivariable analysis of alloHSCT (n=337) versus chemotherapy (n=271) or autologous HSCT (n=152) in 760 patients aged 40 and 60 years with AML in CR1. Patients receiving alloHSCT showed improved survival (OS) as compared to chemotherapy (respectively 57±3% vs 40±3% at 5 years, P<0.001). Comparable OS was observed following alloHSCT and autoHSCT in patients with intermediate risk AML (60±4% vs 54±5%). However, alloHSCT was associated with less relapse (HR 0.51, P<0.001) and better RFS (HR 0.74, P=0.029) as compared to autoHSCT in intermediate risk AMLs. AlloHSCT was applied following myeloablative conditioning (n=157) or reduced intensity conditioning (n=180), resulting in less NRM, but comparable outcome with respect to OS, RFS, and relapse. Collectively, these results show that alloHSCT is to be preferred over chemotherapy as PRT in patients with intermediate and poor risk AML aged 40-60 years, while autoHSCT remains a treatment option to be considered in patients with intermediate risk AML.Leukemia accepted article preview online, 27 November 2014. doi:10.1038/leu.2014.332.
    Leukemia 11/2014; 29(5). DOI:10.1038/leu.2014.332 · 9.38 Impact Factor
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    ABSTRACT: - Copyright © 2014, Ferrata Storti Foundation.
    Haematologica 11/2014; 100(3). DOI:10.3324/haematol.2014.110213 · 5.87 Impact Factor
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    ABSTRACT: Introduction:Many patients with sickle cell disease (SCD) have a reduced exercise capacity and abnormal lung function. Cardiopulmonary exercise testing (CPET) can identify causes of exercise limitation.Methods:44 consecutive SCD patients (27 HbSS, 11 HbSC, and 6 HbS-beta thalassemia) with a median age (interquartile range) of 26 (21-41) years underwent pulmonary function tests, CPET, chest x-ray and echocardiography to further characterize exercise limitation in SCD.Results: Peak oxygen uptake (V'O2-peak), expressing maximum exercise capacity, was decreased in 83% of the studied patients. V'O2-peak correlated with hemoglobin levels (R=0.440, P=0.005), forced vital capacity (FVC) (R=0.717, P<0.0001). Cardiothoracic ratio on chest x-ray inversely correlated with FVC (R=-0.637 P<0.001). According to criteria for exercise limitation, the patients were limited in exercise capacity due to anemia (n=17), cardiovascular dysfunction (n=2), musculoskeletal function (n=10), pulmonary ventilatory abnormalities (n=1), pulmonary vascular exercise limitation (n=1) and poor effort (n=3).Conclusion: In the present study we demonstrate that anemia is the most important determinant of reduced exercise tolerance observed in SCD patients without signs of pulmonary hypertension. We found a strong correlation between various parameters of lung volume and cardiothoracic ratio and we hypothesize that cardiomegaly and relative small chest size may be important causes of the impairment in pulmonary function, i.e. reduced long volumes and diffusion capacity, in SCD. Taking into account anthropomorphic differences between SCD patients and controls could help to interpret lung function studies in SCD better.
    American Journal of Hematology 08/2014; 89(8). DOI:10.1002/ajh.23752 · 3.48 Impact Factor
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    ABSTRACT: In adult patients with sickle cell disease two distinct subphenotypes have previously been defined: patients with the viscosity-vaso-occlusion subphenotype (VVO) suffer mainly from vaso-occlusive pain crises and have a relatively high hemoglobin concentration. Patients classified as the hemolysis-endothelial dysfunction subphenotype (HED) suffer from stroke and pulmonary hypertension and have an elevated concentration of lactate dehydrogenase. However, this classification is not possible in children due to low rates of complications. We used laboratory markers to classify children into the two subphenotypes, and measured vWF and vWF propeptide as markers of endothelial dysfunction. We included 106 children with sickle cell disease (mean age 8.7years), 74 (70%) with HbSS/HbSβ° genotype and 32 (30%) with HbSC/HbSβ(+) genotype. vWF and vWF propeptide were significantly elevated in patients with sickle cell disease; this was more pronounced in patients with the HbSS/HbSβ° genotype. Patients with the HED subphenotype had higher levels of vWF propeptide, and a trend towards higher levels of vWF compared to those with the VVO subphenotype. We demonstrated that even young children in a stable clinical condition show signs of persistent endothelial dysfunction. A prospective study should demonstrate whether elevated levels of vWF and its propeptide are associated with an increased risk of complications specific for the HED subphenotype.
    Thrombosis Research 10/2013; 132(6). DOI:10.1016/j.thromres.2013.10.006 · 2.43 Impact Factor
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    ABSTRACT: 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. Most studies focus on molecular markers or analyze data in retrospect. This study establishes the value of immunophenotypically assessed MRD in the context of a multicenter clinical trial in adult AML with sample collection and analysis performed in a few specialized centers. In adults (younger than age 60 years) with AML enrolled onto the Dutch-Belgian Hemato-Oncology Cooperative Group/Swiss Group for Clinical Cancer Research Acute Myeloid Leukemia 42A study, MRD was evaluated in bone marrow samples in CR (164 after induction cycle 1, 183 after cycle 2, 124 after consolidation therapy). After all courses of therapy, low MRD values distinguished patients with relatively favorable outcome from those with high relapse rate and adverse relapse-free and overall survival. In the whole patient group and in the subgroup with intermediate-risk cytogenetics, MRD was an independent prognostic factor. Multivariate analysis after cycle 2, when decisions about consolidation treatment have to be made, confirmed that high MRD values (> 0.1% of WBC) were associated with a higher risk of relapse after adjustment for consolidation treatment time-dependent covariate risk score and early or later CR. In future treatment studies, risk stratification should be based not only on risk estimation assessed at diagnosis but also on MRD as a therapy-dependent prognostic factor.
    Journal of Clinical Oncology 09/2013; 31(31). DOI:10.1200/JCO.2012.45.9628 · 18.43 Impact Factor
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    ABSTRACT: Activated polymorphonuclear neutrophils play an important role in the pathogenesis of vaso-occlusive painful sickle cell crisis. Upon activation polymorphonuclear neutrophils can form neutrophil extracellular traps. Neutrophil extracellular traps consist of a meshwork of extracellular DNA, nucleosomes, histones and neutrophil proteases. Neutrophil extracellular traps have been demonstrated to be toxic to endothelial and parenchymal cells. This prospective cohort study was conducted to determine neutrophil extracellular trap formation in sickle cell patients during steady state and painful crisis. As a measure of neutrophil extracellular traps, plasma nucleosomes levels were determined and polymorphonuclear neutrophil activation was assessed measuring plasma levels of elastase-α1-antitrypsin complexes in 74 patients in steady state, 70 patients during painful crisis, and 24 race-matched controls using Enzyme Linked Immunosorbent Assay. Nucleosome levels in steady state sickle cell patients were significantly higher compared to levels in controls. During painful crisis levels of both nucleosomes and elastase-α1-antitrypsin complexes increased significantly. Levels of nucleosomes correlated significantly to elastase-α1-antitrypsin complex levels during painful crisis, (Sr = 0.654, P < 0.001). This was seen in both HbSS/HbSβ0-thalassemia (Sr=0.55, P<0.001) and HbSC/HbSβ+-thalassemia patients (Sr=0.90, P=<0.001) during painful crisis. Levels of nucleosomes showed a correlation with length of hospital stay and were highest in patients with acute chest syndrome. These data support the concept that neutrophil extracellular trap formation and neutrophil activation may play a role in the pathogenesis of painful sickle cell crisis and acute chest syndrome.
    Haematologica 08/2013; 98(11). DOI:10.3324/haematol.2013.088021 · 5.87 Impact Factor
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    ABSTRACT: Tyrosine kinase inhibitors treatment in responding chronic myeloid leukaemia (CML) patients is generally continued indefinitely. In this randomised phase II trial, we investigated whether CML patients in molecular response(4.5) (MR(4.5), quantitative reverse-transcription polymerase chain reaction (RQ-PCR)) after previous combination therapy with imatinib and cytarabine may discontinue imatinib treatment safely. Thirty-three patients from the HOVON 51 study with an MR(4.5) for at least 2 years who were still on imatinib treatment were randomised between continuation of imatinib (arm A, n=18) or discontinuation of imatinib (arm B, n=15). After a median follow up of 36 months since randomisation, 3 patients (17%) in arm A and 10 patients (67%) in arm B had a molecular relapse. All 3 relapsing patients in arm A had also stopped imatinib after randomisation. All but one relapsing patient relapsed within 7 months after discontinuation of imatinib. The molecular relapse rate at 12 and 24 months after randomisation was 0% and 6% (arm A) and 53% and 67% (arm B) respectively. As-treated analysis revealed 56% and 61% relapses at 1 and 2 years since cessation in patients who discontinued imatinib, in contrast to 0% of patients who continued imatinib. All evaluable patients remained sensitive to imatinib after reinitiation and regained a molecular response. Our data suggest that discontinuation of imatinib is safe in patients with durable MR(4.5).
    European journal of cancer (Oxford, England: 1990) 07/2013; 49(15). DOI:10.1016/j.ejca.2013.06.018 · 4.82 Impact Factor
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    ABSTRACT: During febrile neutropenia in only 30 to 60 percent an infectious agent is identified. This diagnostic gap could hypothetically be reduced with the broad implementation of molecular detection techniques like PCR, which has revolutionized the detection of infectious diseases during the last two decades. We performed a longitudinal prospective study (N = 81) of neutropenic patients to assess the role of respiratory viruses in neutropenic fever and to determine the clinical relevance of blind screening for these viruses. Respiratory viruses were recovered in 14% of the patients prior to neutropenia. In 13% of neutropenic patients without fever and in 19% of those with fever, a respiratory virus was detected. Comparing different sample types; nasal swabs performed significantly better (16/117 = 43%), than throat swabs (6/106 = 6%). Throat gurgles did not show significant differences from the latter sample types. Blind diagnostic screening for respiratory viruses before or during neutropenia is not useful. Nasal swabs are sensitive and practical option for screening on respiratory viruses.
    Virology Journal 06/2013; 10(1):212. DOI:10.1186/1743-422X-10-212 · 2.09 Impact Factor
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    ABSTRACT: The differential diagnosis of chest pain in a patient with sickle cell disease is difficult and may encompass several serious conditions, including chest syndrome, pulmonary embolism and infectious complications. In this manuscript we provide an overview on the various underlying diseases that may cause chest pain in patients with sickle cell disease and provide clues for a proper diagnostic workup.
    The Netherlands Journal of Medicine 06/2013; 71(5):265-269. · 2.21 Impact Factor
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    ABSTRACT: BACKGROUND: The aim of this study was to investigate the effects of red blood cell (RBC) transfusion on the hemorrheologic properties and microcirculatory hemodynamics in anemic hematology outpatients receiving 2 to 4 RBC units of either “fresh” (leukoreduced storage for less than 1 week) or “aged” (leukoreduced storage for 3‐4 weeks) RBCs.STUDY DESIGN AND METHODS: Measurements were performed before and 30 minutes after RBC transfusion in hematology outpatients. Leukoreduced RBC suspensions were stored in saline‐adenine‐glucose‐mannitol (SAGM) additive solution. Whole blood viscosity was measured using Couette low‐shear viscometry, RBC deformability and aggregability were measured using laser‐assisted optical rotational cell analysis, and microcirculatory density and perfusion were assessed using sidestream dark field imaging.RESULTS: One group of patients (n = 10) received a median (interquartile range) of 3 (2‐3) RBC bags that were stored for 7 (5‐7) days (fresh) and the other group of patients (n = 10) received 3 (3‐3) RBC bags that were stored for 23 (22‐28) days (aged). After transfusion of fresh versus aged RBCs, hematocrit increased to 32 ± 3% versus 31 ± 2% (p 2 versus 18.7 ± 1.9 mm/mm2 (p = 0.595), respectively.CONCLUSION: Storing leukoreduced SAGM‐suspended RBCs for 3 to 4 weeks did not affect their ability to improve hemorrheologic properties and microcirculatory hemodynamics in our small group of anemic hematology outpatients. Larger studies are needed to confirm this finding.
    Transfusion 06/2013; 53(6). DOI:10.1111/j.1537-2995.2012.03905.x · 3.57 Impact Factor
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    Tijdschrift voor kindergeneeskunde 02/2013; 81(1). DOI:10.1007/s12456-013-0073-3
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    Tijdschrift voor kindergeneeskunde 02/2013; 81(1). DOI:10.1007/s12456-013-0105-z
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    ABSTRACT: Treatment of acute lymphoblastic leukaemia (ALL) is frequently complicated by venous thromboembolism (VTE). The efficacy and optimal approach of VTE prevention are unclear, pa rticularly in adult patients. We assessed the effect of thromboprophylaxis on symptomatic VTE incidence in cycle 1 of ALL treatment in adult patients. Secondly, we explored potential etiologic factors for VTE and the clinical impact of VTE on ALL outcome. We retrospectively assessed symptomatic VTE incidence and use of thromboprophylaxis in 240 adults treated for newly diagnosed ALL in the Dutch-Belgian HOVON-37 multicentre study (1999-2005). Potential etiologic factors were explored by analysis of patient and disease characteristics, impact of VTE on ALL outcome by analysis of complete remission and overall survival rates. Symptomatic VTE was observed in 24 of 240 patients (10%). Thromboprophylaxis differed by centre (prophylactic fresh frozen plasma (FFP) supplementation or no thromboprophylaxis) and was applied only during L-asparaginase in cycle 1. VTE incidence was significantly lower with FFP supplementation than without FFP (6% vs. 19%; adjusted odds ratio [OR] 0.28; 95% confidence interval [CI] 0.10-0.73). FFP did not influence antithrombin or fibrinogen plasma levels. Patients with VTE in cycle 1 had a significantly poorer complete remission rate (adjusted OR 0.18; 95% CI 0.07-0.50), particularly patients with cerebral sinus thrombosis (adjusted OR 0.17; 95% CI 0.04-0.65). Our study suggests that prophylactic FFP supplementation effectively reduces symptomatic VTE incidence during ALL treatment in adults. This should be confirmed in a randomised controlled trial.
    Thrombosis and Haemostasis 01/2013; 109(4). DOI:10.1160/TH12-11-0845 · 5.76 Impact Factor
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    ABSTRACT: An urgent need for new treatment modalities is emerging in patients with elderly AML. We hypothesized that targeting VEGF might furnish an effective treatment modality in AML. Elderly patients with AML or RAEB and an IPSS of 1.5 or higher were randomly assigned in this Phase II study (n=171) to receive standard chemotherapy (3+7) with or without bevacizumab at adose of 10 mg/kg iv in 60 minutes at days 1 and 15. In the second cycle patients received cytarabine 1000 mg/m(2) twice daily on days 1- 6 plus or minus bevacizumab. The primary endpoint was CR. The CR rates in both arms were not different (65%). The EFS at 12 months was 33% for the standard arm vs 30% for the bevacizumab arm and at 24 months 22% vs 16% (p=0.42). The frequencies of severe AEs (SAE) were higher in the bevacizumab arm (63) as compared to the control arm (28; p=0.043), but the percentages of death or life threatening SAEs were lower in the bevacizumab arm (60% vs 75% of SAEs). Although it is feasible the addition of bevacizumab to standard chemotherapy does not improve the therapeutic outcome of AML at older age. (NTR904 www.trialregister.nl).
    Blood 10/2012; DOI:10.1182/blood-2012-04-420596 · 10.43 Impact Factor
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    ABSTRACT: To determine to what extent allogeneic hematopoietic stem-cell transplantation (alloHSCT) quantitatively reduces relapse in acute myeloid leukemia with monosomal karyotype (MK-AML) compared with alternative postremission therapy and how it compares with other cytogenetic subcategories. Of 2,560 patients (younger than age 61 years) without core-binding factor abnormalities including 305 patients with MK-AML receiving first-line induction treatment, 1,975 patients (77%) achieved remission, and 1,588 received consolidation in the first complete remission (CR1) after two induction cycles. Consolidation treatment of 107 patients with MK-AML consisted of alloHSCT (n = 45), chemotherapy (n = 48), or autologous HSCT (n = 14). The 5-year overall survival after start of consolidation was 19% for patients with MK-AML who received alloHSCT and 9% for those who received chemotherapy or autoHSCT (P = .02). Relapse-free survival (RFS) at 5 years was 17% versus 7% (P = .003). Cox regression analysis was performed with alloHSCT as a time-dependent covariate. Hazard ratios (HRs) associated with alloHSCT for relapse and RFS were 0.30 (95% CI, 0.24 to 0.37; P < .001), and 0.52 (95% CI, 0.43 to 0.62; P < .001), respectively. HRs were similar in MK-AML and the other cytogenetic subgroups. AlloHSCT, applied as consolidation in CR1, is associated with a significant reduction of relapse and improvement of survival in MK-AML, with the same relative reduction of relapse or death as in other cytogenetic risk categories.
    Journal of Clinical Oncology 05/2012; 30(17):2140-6. DOI:10.1200/JCO.2011.39.6499 · 18.43 Impact Factor
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    ABSTRACT: Asplenic patients are at risk for pneumococcal sepsis. Patients with hyposplenic function, such as associated with sickle cell disease (SCD), are also at risk. However, tests to assess splenic function are either unavailable or lacking standardization. The aim of this study was to compare different methods for determining splenic function. Eighteen patients with SCD (i.e., 10 heterozygous (SC) and 8 homozygous (SS) SCD patients), and eight splenectomized patients were compared to 10 controls. All subjects underwent spleen scintigraphy, after which functional splenic volumes (FSV) were calculated. FSV was compared to immunological function and B cell-subsets, as well as phagocytic function represented by the presence of Howell Jolly bodies (HJB) and percentages of pitted red cells (PIT). Heterozygous SCD (SC) patients had increased splenic volumes, but diminished FSV, homozygous SCD (SS) patients were asplenic. Splenectomized and SS patients had a strongly reduced phagocytic and immunological function. SC patients had reduced anti-polysaccharide responses without an increase in PIT. FSV correlated significantly with phagocytic and immunological function. HJB were indicative of splenic dysfunction, HJB absence was not indicative of normal functioning splenic tissue. Although visualizing HJB is methodologically advantageous to PIT, both are valid biomarkers of splenic dysfunction. The amount of non-switched memory B cells is strongly correlated to FSV.
    American Journal of Hematology 05/2012; 87(5):484-9. DOI:10.1002/ajh.23154 · 3.48 Impact Factor
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    ABSTRACT: The clinical value of chemotherapy sensitization of acute myeloid leukemia (AML) with G-CSF priming has remained controversial. Cytarabine is a key constituent of remission induction chemotherapy. The effect of G-CSF priming has not been investigated in relationship with variable dose levels of cytarabine. We randomized 917 AML patients to receive G-CSF (456 patients) or no G-CSF (461 patients) at the days of chemotherapy. In the initial part of the study, 406 patients were also randomized between 2 cytarabine regimens comparing conventional-dose (199 patients) versus escalated-dose (207 patients) cytarabine in cycles 1 and 2. We found that patients after induction chemotherapy plus G-CSF had similar overall survival (43% vs 40%, P = .88), event-free survival (37% vs 31%, P = .29), and relapse rates (34% vs 36%, P = .77) at 5 years as those not receiving G-CSF. However, patients treated with the escalated-dose cytarabine regimen benefited from G-CSF priming, with improved event-free survival (P = .01) and overall survival (P = .003), compared with patients without G-CSF undergoing escalated-dose cytarabine treatment. A significant survival advantage of sensitizing AML for chemotherapy with G-CSF was not apparent in the entire study group, but it was seen in patients treated with escalated-dose cytarabine during remission induction. The HOVON-42 study is registered under The Netherlands Trial Registry (www.trialregister.nl) as #NTR230.
    Blood 03/2012; 119(23):5367-73. DOI:10.1182/blood-2011-11-389841 · 10.43 Impact Factor

Publication Stats

1k Citations
469.00 Total Impact Points

Institutions

  • 2007–2015
    • University of Amsterdam
      • • Faculty of Medicine AMC
      • • Department of Medical Microbiology
      • • Department of Cardiology
      Amsterdamo, North Holland, Netherlands
  • 2005–2015
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Hematology
      • • Academic Medical Center
      Amsterdamo, North Holland, Netherlands