References of "British journal of haematology"
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See detailA novel mutation in the CUB sequence of matriptase-2 (TMPRSS6) is implicated in iron-resistant iron deficiency anaemia (IRIDA).
JASPERS, Aurélie ULg; CAERS, Jo ULg; LE GAC, Gerald et al

in British Journal of Haematology (2013), 160(4), 564-565

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See detailPRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies.
Duhoux, Francois P; Ameye, Genevieve; Montano-Almendras, Carmen P et al

in British Journal of Haematology (2012), 156(1), 76-88

The PRDM16 (1p36) gene is rearranged in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21), sharing characteristics with AML and MDS with MECOM (3q26.2) translocations ... [more ▼]

The PRDM16 (1p36) gene is rearranged in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21), sharing characteristics with AML and MDS with MECOM (3q26.2) translocations. We used fluorescence in situ hybridization to study 39 haematological malignancies with translocations involving PRDM16 to assess the precise breakpoint on 1p36 and the identity of the partner locus. Reverse-transcription polymerase chain reaction (PCR) was performed in selected cases in order to confirm the partner locus. PRDM16 expression studies were performed on bone marrow samples of patients, normal controls and CD34(+) cells using TaqMan real-time quantitative PCR. PRDM16 was rearranged with the RPN1 (3q21) locus in 30 cases and with other loci in nine cases. The diagnosis was AML or MDS in most cases, except for two cases of lymphoid proliferation. We identified novel translocation partners of PRDM16, including the transcription factors ETV6 and IKZF1. Translocations involving PRDM16 lead to its overexpression irrespective of the consequence of the rearrangement (fusion gene or promoter swap). Survival data suggest that patients with AML/MDS and PRDM16 translocations have a poor prognosis despite a simple karyotype and a median age of 65 years. There seems to be an over-representation of late-onset therapy-related myeloid malignancies. [less ▲]

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See detailCHIC cells: a novel ALK+ cell line derived from a relapsed anaplastic large cell lymphoma
Thielen, Caroline ULg; Bisig, Bettina ULg; Gofflot, Stéphanie ULg et al

in British Journal of Haematology (2011), 152

Since the initial description of anaplastic large cell lymphoma (ALCL) as a proliferation of large CD30+ lymphoid cells, the morphological spectrum of ALCL positive for anaplastic lymphoma kinase (ALCL ... [more ▼]

Since the initial description of anaplastic large cell lymphoma (ALCL) as a proliferation of large CD30+ lymphoid cells, the morphological spectrum of ALCL positive for anaplastic lymphoma kinase (ALCL, ALK+) has expanded, and beyond the common pattern most frequently encountered, several variants have been identified, including the lymphohistiocytic and the small cell patterns (Swerdlow et al, 2008). Only ten ALK+ ALCL cell lines are currently available, and most were derived from tumours demonstrating the common type morphology (Drexler & MacLeod, 2004). We have established a novel cell line (CHIC) from the cerebrospinal fluid of a 32-year-old man with relapsing/refractory ALK+ ALCL with a t(2;5)(p23;q35) translocation whose initial tumour exhibited lymphohistiocytic features. This cell line is now made available to the scientific community. In addition to multiple in vitro applications, the tumourigenic capacity of these cells represents a useful property for in vivo drug testing. [less ▲]

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See detailEVI1-mediated down regulation of MIR449A is essential for the survival of EVI1 positive leukaemic cells.
De Weer, An; Van der Meulen, Joni; Rondou, Pieter et al

in British Journal of Haematology (2011), 154(3), 337-48

Chromosomal rearrangements involving the MECOM (MDS1 and EVI1 complex) locus are recurrent genetic events in myeloid leukaemia and are associated with poor prognosis. In this study, we assessed the role ... [more ▼]

Chromosomal rearrangements involving the MECOM (MDS1 and EVI1 complex) locus are recurrent genetic events in myeloid leukaemia and are associated with poor prognosis. In this study, we assessed the role of MECOM locus protein EVI1 in the transcriptional regulation of microRNAs (miRNAs) involved in the leukaemic phenotype. For this, we profiled expression of 366 miRNAs in 38 MECOM-rearranged patient samples, normal bone marrow controls and MECOM (EVI1) knock down/re-expression models. Cross-comparison of these miRNA expression profiling data showed that MECOM rearranged leukaemias are characterized by down regulation of MIR449A. Reconstitution of MIR449A expression in MECOM-rearranged cell line models induced apoptosis resulting in a strong decrease in cell viability. These effects might be mediated in part by MIR449A regulation of NOTCH1 and BCL2, which are shown here to be bona fide MIR449A targets. Finally, we confirmed that MIR449A repression is mediated through direct promoter occupation of the EVI1 transcriptional repressor. In conclusion, this study reveals MIR449A as a crucial direct target of the MECOM locus protein EVI1 involved in the pathogenesis of MECOM-rearranged leukaemias and unravels NOTCH1 and BCL2 as important novel targets of MIR449A. This EVI1-MIR449A-NOTCH1/BCL2 regulatory axis might open new possibilities for the development of therapeutic strategies in this poor prognostic leukaemia subgroup. [less ▲]

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See detailIn vivo ribosomal RNA turnover is down-regulated in leukaemic cells in chronic lymphocytic leukaemia
Defoiche, Julien; Zhang, Yan; Lagneaux, Laurence et al

in British Journal of Haematology (2010), 151

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See detailEnteroviral meningoencephalitis as complication of Rituximab therapy in a patient treated for diffuse large B-cell lymphoma
Servais, Sophie ULg; Caers, Jo ULg; Warling, Odette et al

in British Journal of Haematology (2010), 150(3), 379-381

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See detailValproate synergizes with purine nucleoside analogues to induce apoptosis of B-chronic lymphocytic leukaemia cells.
Bouzar, Amel ULg; Boxus, Mathieu ULg; Defoiche, Julien et al

in British journal of haematology (2009), 144(1),

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See detailMatched unrelated donor stem cell transplant in 131 patients with follicular lymphoma : an analysis from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation
Avivi, Irit; Montoto, Silvia; Canals, Carme et al

in British Journal of Haematology (2009), 147

Matched unrelated donor stem cell transplantation (MUD-SCT) provides the only curative option for patients with follicular lymphoma (FL) who fail conventional therapies and do not have a siblong donor ... [more ▼]

Matched unrelated donor stem cell transplantation (MUD-SCT) provides the only curative option for patients with follicular lymphoma (FL) who fail conventional therapies and do not have a siblong donor. The purpose of this study was to analyse the outcome of patients with FL treated with MUD-SCT included in the European Group for Blood and Marrow Transplantation registry. 131 patients treated with reduced-intensity conditioning (RIC, n=87) or conventional myeloablative (CONV, n=44) MUD-SCT between 2000 and 2005 were included. Median time from diagnosis to MUD-SCT was 47 months and the median number of previous therapeutic regimens was 4 (previous autograft : 47%). RIC recipients were significantly older, with a longer interval from diagnosis to MUD-SCT and had failed a previous autograft more frequently than CONV recipients. Non-relapse mortality (NRM) was 24% and 30% at 100-d and 1-year, respectively. After a median follow-up of 36 months, 17% of the patients developed disease progression, the 3-year progression-freee survival (PFS) being 47%. Three-year overall survival (OS) for the whole series was 51%. On multivariate analysis, RIC regimens were associated with at lower NRM and a significantly longer PFS and OS. This retrospective study demonstrated that MUS-SCT results, even in heavily pre-treated populations, in a meaningful PFS and OS [less ▲]

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See detailReduction of B cell turnover in chronic lymphocytic leukaemia.
Defoiche, Julien; Debacq, Christophe; Asquith, Becca et al

in British Journal of Haematology (2008), 143(2), 240-7

Whether chronic lymphocytic leukaemia (CLL) is a latent or a proliferating disease has been intensively debated. Whilst the dogma that CLL results from accumulation of dormant lymphocytes is supported by ... [more ▼]

Whether chronic lymphocytic leukaemia (CLL) is a latent or a proliferating disease has been intensively debated. Whilst the dogma that CLL results from accumulation of dormant lymphocytes is supported by the unresponsiveness of leukaemic cells to antigens and polyclonal activators, recent in vivo kinetic measurements indicate that B lymphocytes do divide at significant rates in CLL. However, an important and still unanswered question is whether CLL cells proliferate faster or slower compared with their normal counterparts. This report addressed directly this point and compared B-cell kinetics in CLL subjects and healthy controls, using a pulse-chase approach based on incorporation of deuterium from 6,6-(2)H(2)-glucose into DNA. We confirmed that B cells proliferated at significant levels in CLL but found that the proliferation rates were reduced compared with healthy subjects (mean 0.47 vs. 1.31%/d respectively, P = 0.007), equivalent to an extended doubling time of circulating B cells (147 d vs. 53 d). In conclusion, CLL B cells proliferate at reduced levels compared with healthy controls. CLL is thus characterized by an aberrant B-cell kinetics with a decrease in cell turnover, an observation that may impact on elaboration of efficient therapeutic strategies. [less ▲]

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See detailThe involvement of osteopontin and its receptors in multiple myeloma cell survival, migration and invasion in the murine 5T33MM model
Caers, Jo ULg; Günthert, Ursula; De Raeve, Hendrik et al

in British Journal of Haematology (2006), 132((4)), 469-77

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See detailHaematopoetic stem cell transplantation for refractory autoimmune cytopenia.
Passweg, J. R.; Rabusin, M.; Musso, M. et al

in British Journal of Haematology (2004), 125(6), 749-55

This study describes the outcome of patients receiving haematopoietic stem cell transplantation (HSCT) to treat severe refractory autoimmune cytopenia. The registry of the European Group of Blood and ... [more ▼]

This study describes the outcome of patients receiving haematopoietic stem cell transplantation (HSCT) to treat severe refractory autoimmune cytopenia. The registry of the European Group of Blood and Marrow Transplantation holds data on 36 patients receiving 38 transplants, the first transplant was autologous for 27 and allogeneic for nine patients. Patients had autoimmune haemolytic anaemia (autologous: 5; allogeneic: 2), Evans's syndrome (autologous: 2; allogeneic: 5); immune thrombocytopenia (autologous: 12), pure red cell aplasia (autologous: 4; allogeneic: 1), pure white cell aplasia (autologous: 1; allogeneic 1), or thrombotic thrombocytopenic purpura (autologous: 3). Patients had longstanding disease having failed multiple prior treatments. Among 26 evaluable patients mobilized for autologous HSCT, three died of treatment-related causes, one died of disease progression, seven were non-responders, six patients had transient responses and nine had continuous partial or complete remission. Of the seven evaluable patients receiving allogeneic HSCT, one died of treatment-related complications, one with transient response died of progressive disease and five had a continuous response. Autologous and allogeneic HSCT may induce a response in a subset of patients with autoimmune cytopenia of long duration albeit at the price of considerable toxicity. [less ▲]

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See detailOnce-weekly epoetin beta is highly effective in treating anaemic patients with lymphoproliferative malignancy and defective endogenous erythropoietin production.
Cazzola, Mario; Beguin, Yves ULg; Kloczko, Janusz et al

in British Journal of Haematology (2003), 122(3), 386-93

Epoetin beta, three-times weekly (t.i.w.), is effective in reversing anaemia in lymphoproliferative disorders. The current study investigated whether an epoetin beta dose of 30,000 IU given subcutaneously ... [more ▼]

Epoetin beta, three-times weekly (t.i.w.), is effective in reversing anaemia in lymphoproliferative disorders. The current study investigated whether an epoetin beta dose of 30,000 IU given subcutaneously once weekly (q.w.) was at least as effective as 10,000 t.i.w. administration in anaemic patients with lymphoproliferative malignancy and defective endogenous erythropoietin (Epo) production. Overall, 241 anaemic patients with multiple myeloma, low-grade non-Hodgkin's lymphoma or chronic lymphocytic leukaemia, all with serum Epo values </= 100 mU/ml, were randomized to receive the q.w. (n = 119) or t.i.w. (n = 122) regimen for 16 weeks. The primary efficacy criterion, i.e. the time-adjusted area under the haemoglobin-time curve from weeks 5-16, was comparable between the q.w. and t.i.w. groups [difference = - 0.20 g/dl (90% confidence interval - 0.52-0.11)]. Moreover, response rates were high and similar in both arms (72%vs 75%, q.w. and t.i.w. groups respectively). Baseline serum Epo was predictive of response: the lower serum Epo, the higher the likelihood of response (P = 0.002). Thus, epoetin beta administered q.w. is an effective and convenient treatment for anaemia in patients with lymphoproliferative disorders. Tailoring this treatment modality to subjects with defective endogenous Epo production represents a rational use of epoetin from both a medical and a community perspective. [less ▲]

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See detailTandem high-dose therapy (HDT) for multiple myeloma: recombinant human erythropoietin therapy given between first and second HDT allows second peripheral blood stem cell transplantation without red blood cell transfusion.
Baron, Frédéric ULg; Frere, Pascale ULg; Fillet, Georges ULg et al

in British Journal of Haematology (2003), 123(1), 103-5

We evaluated the ability of recombinant human erythropoietin (rHuEpo) therapy, given before high-dose therapy (HDT), to allow autologous peripheral blood stem cell transplantation (PBSCT) without red ... [more ▼]

We evaluated the ability of recombinant human erythropoietin (rHuEpo) therapy, given before high-dose therapy (HDT), to allow autologous peripheral blood stem cell transplantation (PBSCT) without red blood cell (RBC) transfusions. Eleven multiple myeloma patients underwent tandem HDT and autologous PBSC, receiving 500 U/kg/week rHuEpo from d 30 after initial transplant. Haemoglobin levels were 9.5 +/- 1.1 g/dl and 12.5 +/- 0.9 g/dl at the first and second transplant respectively (P < 0.001). RBC transfusions were required for 10/11 patients for the first transplant versus 1/11 for the second (P < 0.001). To conclude, a short course of rHuEpo therapy before HDT facilitates the performance of an autologous transplant without RBC transfusions. [less ▲]

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See detailBone Sialoprotein Mrna and Protein Expression in Human Multiple Myeloma Cell Lines and Patients
Bellahcene, Akeila ULg; Van Riet, I.; de Greef, C. et al

in British Journal of Haematology (2000), 111(4), 1118-21

Bone sialoprotein (BSP) is a glycoprotein essentially found in mineralizing connective tissues. We have recently demonstrated that BSP is ectopically expressed by carcinomas that metastasize to bone with ... [more ▼]

Bone sialoprotein (BSP) is a glycoprotein essentially found in mineralizing connective tissues. We have recently demonstrated that BSP is ectopically expressed by carcinomas that metastasize to bone with high frequency. Multiple myeloma (MM) is characterized by the localization of tumour plasma cells in the bone marrow. In this study, BSP expression was evaluated in human myeloma cell lines and in bone marrow aspirates and one ascites fluid from MM patients. BSP was detectable in conditioned media of MM cell lines. Using FACS analysis and in situ hybridization, we demonstrated that tumour cells from all MM patients and cell lines analysed express BSP at both the protein and the mRNA level. [less ▲]

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See detailClinical course and predictive factors for cyclosporin-induced autologous graft-versus-host disease after autologous haematopoietic stem cell transplantation.
Baron, Frédéric ULg; Gothot, André ULg; Salmon, Jean ULg et al

in British Journal of Haematology (2000), 111(3), 745-53

The administration of cyclosporin A (CyA) after autologous haematopoietic stem cell transplantation (HSCT) induces a systemic autoimmune syndrome mimicking graft-vs.-host disease (GVHD). This syndrome ... [more ▼]

The administration of cyclosporin A (CyA) after autologous haematopoietic stem cell transplantation (HSCT) induces a systemic autoimmune syndrome mimicking graft-vs.-host disease (GVHD). This syndrome, termed autologous GVHD has notable anti-tumour activity in animal studies. We intended to induce autologous GVHD with CyA in patients undergoing an autologous HSCT. We prospectively studied 118 patients with miscellaneous malignancies undergoing an autologous HSCT with low-dose CyA to characterize the clinical syndrome, its frequency and clinical course, and to determine the factors affecting its incidence. Patients received CyA from d -1 through to d 28, first starting at 2 mg/kg intravenously and then orally as soon as feasible. The dose was adjusted to achieve pre-dose blood levels around 100 ng/ml. A skin biopsy was performed when a skin rash was observed. Thirty-three percent of the patients developed clinical GVHD: clinical stage 1 in 21 patients, stage 2 in seven patients, and stage 3 in three patients. Although total body irradiation (TBI) or high-dose cyclophosphamide were previously thought to be needed, autologous GVHD occurred in five out of 12 patients (42%) after a preparative regimen with high-dose melphalan alone. Autologous GVHD was significantly more frequent in patients older than 33 years, in patients who had received high doses of granulocyte-macrophage colony forming units (CFU-GM) and in those with a diagnosis of myeloid malignancy, compared with those with lymphoid malignancies or solid tumours. A significant negative association was also found with HLA-DR6. In lymphoma patients, GVHD occurred more frequently in advanced disease than in first or second complete remission (CR1-2) patients. All other factors studied were not predictive for GVHD. In conclusion, CyA-induced GVHD is reproducibly and safely induced with doses of CyA adapted to achieve blood levels around 100 ng/ml. In retrospective analysis, there was no survival advantage for patients with GVHD. Phase III trials with this approach are needed to evaluate its anti-tumoral effect. [less ▲]

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See detailA quantitative study of peripheral blood stem cell contamination in diffuse large-cell non-Hodgkin's lymphoma: one-half of patients significantly mobilize malignant cells.
Jacquy, C.; Soree, A.; Lambert, Frédéric ULg et al

in British Journal of Haematology (2000), 110(3), 631-7

Autologous transplantation using peripheral blood stem cells (PBSCs) collected after chemotherapy, followed by growth factor administration (ASCT), is increasingly used in the treatment of non-Hodgkin's ... [more ▼]

Autologous transplantation using peripheral blood stem cells (PBSCs) collected after chemotherapy, followed by growth factor administration (ASCT), is increasingly used in the treatment of non-Hodgkin's lymphoma (NHL). However, quantitative data regarding contaminating malignant cells in the harvests are still scarce. We prospectively investigated 37 diffuse large-cell lymphomas (DLCLs) in complete remission (CR) that were treated according to multicentric protocols at our centre. DNA was extracted from the diagnostic lymph node. The complementarity-determining region (CDR) III was sequenced and a patient-specific oligomer synthesized. Contamination was evaluated semiquantitatively by polymerase chain reaction (PCR) and was confirmed by a limiting dilution analysis. PBSCs collected at regeneration after administration of granulocyte colony-stimulating factor (G-CSF), steady-state bone marrow (BM) and peripheral blood samples at CR were compared. DNA was available in 37 patients, from which 22 rearrangements could be sequenced. Patients (n = 15) who had both the required follow-up samples and a suitable clonal marker were investigated. In two cases, the patient-specific PCR assay set up at diagnosis later gave false-negative results in samples in which clonal DNA was still detectable by other sets of primers. PBSC contamination was highly variable: 7 out of 15 patients showed a PBSC/BM ratio of NHL cells greater than 1 log, whereas 8 out of 15 patients showed no difference and could vary from one apheresis to another. Eight ASCTs were performed, five of which used highly contaminated PBSCs: four patients relapsed early, three with disseminated lymphoma. Thus, 50% of DLCLs in CR seem to mobilize significantly malignant cells at regeneration under G-CSF. Considering the higher numbers of cells reinfused, this translates into a much higher number of lymphoma cells reinfused when compared with autologous bone marrow transplantation (ABMT). However, their clonogenic potential remains unknown and, despite concerning observations in certain cases, it is still unclear whether this has an impact upon the outcome of ASCT. [less ▲]

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See detailDeletion of the 5'-ABL region: a recurrent anomaly detected by fluorescence in situ hybridization in about 10% of Philadelphia-positive chronic myeloid leukaemia patients.
Herens, Christian ULg; Tassin, Françoise ULg; Lemaire, Véronique ULg et al

in British Journal of Haematology (2000), 110(1), 214-6

Inclusion of the BCR-ABL ES probe in routine cytogenetics led to the identification of a subgroup of Philadelphia positive (Ph+) chronic myeloid leukaemia patients characterized by a 5'-ABL deletion. This ... [more ▼]

Inclusion of the BCR-ABL ES probe in routine cytogenetics led to the identification of a subgroup of Philadelphia positive (Ph+) chronic myeloid leukaemia patients characterized by a 5'-ABL deletion. This anomaly was observed in 5/51 cases (9.8%). Cytological and clinical data suggest that the 5'-ABL deletion may be associated with dysplastic features of polymorphonuclear cells and metamyelocytes and a short chronic phase duration. [less ▲]

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See detailEffective treatment of Jo-1-associated polymyositis with T-cell-depleted autologous peripheral blood stem cell transplantation.
Baron, Frédéric ULg; Ribbens, Clio ULg; Kaye, O. et al

in British Journal of Haematology (2000), 110(2), 339-342

A patient with Jo-1 antibody-associated polymyositis (Jo-1 PM) had a Karnofsky score of 40% and severe muscle, liver and lung damage that was refractory to standard therapy. The female patient received an ... [more ▼]

A patient with Jo-1 antibody-associated polymyositis (Jo-1 PM) had a Karnofsky score of 40% and severe muscle, liver and lung damage that was refractory to standard therapy. The female patient received an autologous T-cell-depleted haematopoietic stem cell transplant (HSCT) after myeloablative conditioning. The transplant procedure was complicated by severe adult respiratory distress syndrome (ARDS) and adenovirus-associated haemorrhagic cystitis as well as cytomegalovirus (CMV) reactivation. The patient's creatinine phosphokinase (CPK) and alanine transaminase (ALT) values were normal on day 21. The patient's strength has improved remarkably and her dyspnoea is subjectively improved. At 15 months after the transplant, the patient was well with a Karnofsky score of 80% and had been off any therapy, including steroids, for 14 months. [less ▲]

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See detailSoluble transferrin receptor as a potential determinant of iron loading in congenital anaemias due to ineffective erythropoiesis.
Cazzola, M.; Beguin, Yves ULg; Bergamaschi, G. et al

in British Journal of Haematology (1999), 106(3), 752-5

Congenital anaemias due to ineffective erythropoiesis may be associated with excessive iron absorption and progressive iron loading. We investigated whether the soluble transferrin receptor (TfR) level ... [more ▼]

Congenital anaemias due to ineffective erythropoiesis may be associated with excessive iron absorption and progressive iron loading. We investigated whether the soluble transferrin receptor (TfR) level was related to the degree of iron overload in 20 patients with thalassaemia intermedia, six patients with congenital dyserythropoietic anaemia type II (CDA II) and four patients with X-linked congenital sideroblastic anaemia (XLSA). All but two patients had increased serum ferritin levels (median 601 microgram/l, range 105-2855 microgram/l). Multiple regression analysis showed that 62% (P < 0.0001) of the variation in serum ferritin was explained by age and by changes in soluble TfR. [less ▲]

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