bluuebunny/crossref_metadata_2025 huggingface dataset:
Perioperative use of recombinant human erythropoietin in patients refusing blood transfusions. Pathophysiological considerations based on 5 cases
Authors: Wolff M. , Fandrey J. , Hirner A. , Jelkmann W.
Published: July 2010

Abstract: The efficacy of the administration of recombinant human erythropoietin (rHuEPO) in the treatment of anaemia in critically ill surgical patients refusing red cell transfusions requires further documentation. Herein, we report the outcome of 5 consecutive severely anaemic Jehovah's Witness patients (lowest haemoglobin concentration 27 g/l), who were discharged from the hospital in good condition after treatment. RHuEPO (50–280 U/kg body weight) was daily administered to 4 of the patients, who either exhibited preoperative anaemia or developed postoperative anaemia refractory to endogenous EPO probably due to inflammation. RHuEPO treatment was followed by a steep rise in reticulocytes and haemoglobin concentration. The fifth patient, who exhibited no signs of systemic inflammation following emergency hemicolectomy, was also treated with intravenous iron, but not with rHuEPO. His blood haemoglobin concentration rose from 27 g/l to 92 g/l in 3 wk. These observations indicate that the administration of rHuEPO is justified in the management of life‐threatening anaemia, although only on a humanitarian basis, because there is no predictor for the possible spontaneous recovery.
Iron status in young Danes. Evaluation by serum ferritin and haemoglobin in a population survey of 634 individuals aged 14–23 yr
Authors: Milman Nils , Ulrik Charlotte Suppli , Graudal Niels , Jordal Robert
Published: July 2010

Abstract: Iron status was assessed by serum ferritin and haemoglobin in a population survey comprising 634 randomly selected urban Danes (312 males, 322 females) 14–23 yr old. At all ages, males had significantly higher serum ferritin and haemoglobin values than females. Males: median serum ferritin displayed a steady increase with age from 33 to 109 μg/l (rs=0.53, p<0.0001). The prevalence of absent mobilizable body iron stores (serum ferritin <13 μg/l) was 3.5% at 16–17 yr of age, gradually declining to 0% at 22–23 yr. None of the males had iron deficiency anaemia (serum ferritin <13 μg/l and haemoglobin <129 g/l). Females: median ferritin values displayed a slight increase with age from 28 to 39 μg/l (rs=0.19, p<0.001). The prevalence of absent iron stores was 12.5% at 16–17 yr of age, declining to 6.6% at 22–23 yr. The prevalence of iron deficiency anaemia (serum ferritin <13 μg/l and haemoglobin <121 g/l) was 4.7% at 16–17 yr of age, declining to 1.3% at 22–23 yr of age. Compared with surveys in other parts of Scandinavia, young Danes had slightly higher serum ferritin levels, and a lower prevalence of iron deficiency.
Assessment of erythropoiesis following renal transplantation
Authors: Beshara S. , Birgegård G. , Goch J. , Wahlberg J. , Wikström B. , Danielson B. G.
Published: July 2010

Abstract:Ten patients, who received cadaveric kidneys, were followed for 24 wk with serial measurements of serum erythropoietin (S‐Epo), transferrin receptor (S‐TfR) and iron variables. The mean pretransplant creatinine clearance was 8.2 (range 0–22) ml/min and the mean haemoglobin (Hb) level was 99±18.6 (range 66–124) g/l. Nine patients demonstrated a gradual increase in S‐Epo levels, which reached a peak, and was accompanied by a parallel increase in S‐TfR levels with a median lag period of 3 wk between both peaks. Hb correction followed the S‐TfR peak after a second lag period (median 7 wk). Elevated S‐Epo and S‐TfR did not result in correction of anaemia in 1 patient due to impaired graft function. Within4months, S‐Epo levels reached the normal range while TfR levels were higher than normal. Follow‐up of iron status demonstrated the development of iron deficiency in 5 patients, which was corrected spontaneously. Improvement in erythropoiesis after renal transplantation seems to occur by means of expansion of the erythroid marrow, as detected by increasing S‐TfR levels, subsequent to a S‐Epo peak. This expansion precedes Hb normalization. A nonuraemic environment is probably a prerequisite for the correction of anaemia but not for the increase in S‐Epo or S‐TfR levels. Iron deficiency may occur after transplantation due to an increase in iron utilization.
Amplification of multiple regions of chromosome 12, including 12q13–15, in chronic lymphocytic leukaemia
Authors: Merup Mats , Juliusson Gunnar , Wu Xiushan , Jansson Monika , Stellan Birgitta , Rasool Omid , Röijer Eva , Stenman Göran , Gahrton Gösta , Einhorn Stefan
Published: July 2010

Abstract: Trisomy 12 is a frequent abnormality in chronic lymphocytic leukaemia (CLL). The biological importance of trisomy 12 is still poorly understood but it has been suggested that one or several genes are duplicated leading to malignant transformation. We present a case with amplification of 12q13–22 found in a clinically aggressive relapse of CLL. A smaller region, 12q13–15, was amplified most frequently and a YAC containing the MDM2 gene gave the highest number of signals. Additionally, in a subclone an amplicon containing at least 5 copies of a cosmid from 12q23–24 was detected. The case shows that small duplications of chromosome 12, not revealed by cytogenetic analysis, may occur in CLL. Also, it shows that cytogenetic clonal evolution can occur in CLL without morphological evidence of blast transformation. Our results indicate that the 12q13–15 region carries an important gene for CLL progression.
Some correlations between light transmission changes and some commonly used in vitro assays for the assessment of platelet concentrates
Authors: Järemo Petter
Published: July 2010

Abstract: This study aims to relate the duration of light transmission changes (LTCs) through platelet concentrates (PCs) to the results of a panel analytical procedures, many of which have correlated with platelet in vivo viability. LTCs of 16 PCs stored in Pl‐732 containers were studied over 10 d. On d 1, platelet counts and total PC ATP content were determined. On d 7, determination of the following parameters was carried out: pH, bicarbonate, the rate of oxygen consumption, the dispersion of the size distribution, the total platelet ATP content, the extent of shape change (ESC), the osmotic reversal reaction and extracellular lactate dehydrogenase (LDH) level. In addition, the rate of lactate production was determined over storage. A second series consisting of 18 PCs stored in Pl‐146 containers was monitored over 7 d. Mean platelet volume (MPV) was determined on d 3 and 7 and ESC was analysed on d 3. LTCs correlated significantly with pH, bicarbonate, the rate of oxygen consumption, increased platelet size distribution and decreased ESC. In addition, significant correlations were found when comparing LTCs with MPV(s). This study demonstrates that LTCs are closely related to parameters reflecting platelet metabolism.
Recovery of drug sensitivity by MS‐209, a new multidrug resistance‐reversing agent, on acute myelogenous leukaemic blasts and K562 cells resistant to adriamycin cell line
Authors: Wang Y. H. , Motoji T. , Motomura S. , Shiozaki H. , Tsuruo T. , Mizoguchi H.
Published: July 2010

Abstract:The efficacy of MS‐209, a quinoline derivative synthesized as a new multidrug resistance (MDR)‐reversing agent, was studied on blast cells from 33 acute myelogenous leukaemia (AML) patients and on the human myelogenous leukaemia K562 cell line resistant to adriamycin (K562/ADM). By the addition of MS‐209, the intracellular daunorubicin (DNR) contents which had been found to be low in P‐gp‐positive AML blasts and in K562/ADM were significantly enhanced to the level of P‐gp‐negative blasts and that of sensitive K562. The intracellular rhodamine (Rh123) contents also increased in P‐gp‐positive blasts and K562/ADM cells with MS‐209. A leukaemic blast colony assay also demonstrated the effect of MS‐209, i.e. a high D10value for DNR of P‐gp‐positive blasts was reduced to the D10level similar to that observed in P‐gp‐negative blasts by the addition of MS‐209. The greater DNR sensitivity reversing effect of MS‐209 was observed in blasts with higher P‐gp positivity. These findings suggest the potential usefulness of MS‐209 in overcoming MDR in AML patients, especially those with high P‐gp expression. This study clarified the relationship between the clinical outcome of the patients and the P‐gp positivity, intracellular DNR content and DNR drug sensitivity of leukaemic progenitors.
Effects of in vivo administration of G–CSF on neutrophil functions in healthy volunteers
Authors: Höglund M. , Håkansson L. , Venge P.
Published: July 2010

Abstract: The aim of the present study was to investigate the in vivo effects of granulocyte colony‐stimulating factor (G–CSF) on neutrophil (PMN) function. G–CSF was administered once daily as s.c. injection for 6 d (d1–6) to healthy male volunteers. PMN migration (modified Boyden chamber), chemiluminescence (CL), adherence to nylon fibers and phagocytosis of IgG‐ and IgG‐C3‐coated particles were investigated before (d1), during (d2, d5) and 3 wk after G–CSF 7.5–10 μg/kg/d (n=12). PMN surface expression of adhesion‐ and Fcγ‐receptors was measured on d1, d5, d8 and 3 wk after G–CSF 3–5 μg/kg (n=12). Results obtained after G–CSF were compared to baseline using Wilcoxon's signed rank test. G–CSF induced PMNs showed a significantly (p<0.05) decreased chemokinetic response (d5) as well as a reduced chemotaxis towards zymosan activated serum, FMLP and IL‐8, respectively. Chemotaxis was reduced both at d2 and d5. Neutrophil adherence, phagocytosis and luminol‐enhanced CL increased, whereas G–CSF had no effect on lucigenin‐enhanced CL. G–CSF (3–5 μg/kg) caused an enhanced expression of CD11b, CD18, CD35, CD64 (FcγRI) and CD32 (FcγRII), respectively. We conclude that neutrophils produced in response to G–CSF have a reduced chemotaxis but an enhanced adherence and phagocytic capacity. G–CSF in vivo does not stimulate the respiratory burst.
Molecular cytogenetics of childhood acute myelogenous leukaemias
Authors: Leblanc Thierry , Berger Roland
Published: July 2010

Abstract: Chromosome abnormalities of childhood acute myeloblastic leukaemia, observed at least in 70–80% of cases, are presently recognized as important parameters for diagnostic, prognostic and follow‐up purposes. These abnormalities are numerical, structural or both numerical and structural. They are also classified in “primary” abnormalities, usually more or less related with one subtype of leukaemia, and “secondary” abnormalities thought to appear in a second time. Chromosome abnormalities of childhood acute myeloblastic leukaemia (AML) are not basically qualitatively different from those of adult AML. The main difference lies in the incidence of the various types of abnormalities, and these differences appear to be more marked for age extremes such as infants and elderly patients. In total, 3 common abnormalities are more frequently observed in childhood than in adult AML: t(8;21) in AML‐M2, monosomy 7 in AML‐M4, der(11q) in AML‐M5. In addition, molecular rearrangements associated with chromosomal abnormalities are dependent on the type of rearrangement and not on age. As in adult AML, the prognostic value of chromosome abnormalities has been diversely evaluated; some anomalies seem to be related to a shorter survival than others independent of the various therapeutic protocols used. In the present work, chromosome abnormalities of childhood AML have been reviewed according to cytologic subtypes as well as to some clinical settings. Special attention has been paid to abnormalities frequently or exclusively encountered in children.
Cytotoxic T‐lymphocytes recognizing P‐glycoprotein in murine multidrug‐resistant leukemias
Authors: Azuma Eiichi , Masuda Shinichi , Qi Jiang , Kumamoto Tadashi , Hirayama Masahiro , Nagai Masataka , Hiratake Shinya , Umemoto Masakazu , Komada Yoshihiro , Sakurai Minoru
Published: July 2010

Abstract:A multidrug‐resistant murine lymphoid leukemia P388/ADR overexpresses P‐glycoprotein (P‐gp), an active transporter that pumps cytotoxic drugs out of cells and a product of mdr1 gene. Cytotoxic T lymphocytes (CTL) that showed cytotoxicity against P388/ADR were generated from mixed lymphocyte tumor cell culture. CTL do not kill drug‐sensitive parental P388 (P388/parent) that does not express P‐gp. Monoclonal antibody against P‐gp inhibited cytotoxic activity. Similar results were obtained in another multidrug‐resistant cell line P388/VP‐16. Cytotoxic activity was mediated by Thyl+ CD4 CD8+ T‐cells. When P388/ADR was treated with murine IL‐4, expression of P‐gp was downregulated. Monoclonal antibody against interleukin‐4 (IL‐4) abrogated the IL‐4‐induced suppression of P‐gp. Cytolytic activity of CTL against IL‐4‐treated P388/ADR was dose dependently inhibited. These results suggest that P‐gp is immunogenic and can be a target of CTL in this murine leukemia model.
Infradiaphragmatic Hodgkin's disease: the Swedish National Care Programme experience
Authors: Kälkner Karl Mikael , Enblad Gunilla , Gustavsson Anita , Starkhammar Hans , Branehög Ingemar , Lenner Per , Glimelius Bengt
Published: July 2010

Abstract: A Swedish national care programme has provided guidelines for staging, treatment and follow‐up of all patients with Hodgkin's disease (HD) since 1985. Between January 1985 and December 1992, 920 patients were reported and followed prospectively. Of a total of 533 patients with stage I and II disease, 484 presented with supradiaphragmatic HD and 49 (9%) with infradiaphragmatic HD. The median follow‐up time was 4.3 yr (3.3–10 yr). Significant differences in average age (45±21 yr and 55±19 yr), male: female ratio (1.1 : 1 and 2.8 : 1) and B‐symptoms (25% and 47%) were observed in patients with supra‐ and infradiaphragmatic HD, respectively. Forty‐six patients with infradiaphragmatic HD were treated with a curative intention and 40 (87%) achieved a complete response. Eleven (28%) of the 40 patients have recurred and 8 patients have died of HD. Complete response rates and recurrence frequencies did not differ from those observed in patients with supradiaphragmatic HD. Mortality was, however, significantly higher (p=0.001) in the infradiaphragmatic group; this was due mainly to poorer effects of salvage treatment in an elderly population. In this population‐based study, patients with peripheral disease in stage IA respond well to inverted Y irradiation alone, whereas it appears to be important to give stage II patients chemotherapy or a combined modality treatment in order to avoid unacceptably high recurrence rates.
Effects of thrombopoietin (c‐mpl ligand) on growth of blast cells from patients with transient abnormal myelopoiesis and acute myeloblastic leukemia
Authors: Hirai Hideyo , Shimazaki Chihiro , Yamagata Noboru , Goto Hideo , Inaba Tohru , Kikuta Takehisa , Sumikuma Toshiya , Sudo Yoshikazu , Ashihara Eishi , Fujita Naohisa , Hibi Shigeyoshi , Imashuku Shinsaku , Ito Etsuro , Nakagawa Masao
Published: July 2010

Abstract: Thrombopoietin (TPO) is a ligand for c‐mpl that promotes both proliferation and differentiation of megakaryocytes in vivo and in vitro. We investigated the expression of c‐mpl transcripts and the effects of recombinant human TPO (rhTPO) on the proliferation and differentiation of human leukemic cell lines or fresh samples obtained from 32 patients with transient abnormal myelopoiesis (TAM) or acute myeloblastic leukemia (AML). Cells were cultured with TPO alone or combined with rh interleukin‐3 (IL‐3) or stem cell factor (SCF). Expression of c‐mpl was verified in 6 of 13 cases tested. All but one of the cases that showed c‐mpl expression responded to TPO. Blasts from all cases of TAM or French–American–British (FAB) subtype M7 showed growth responses to TPO with higher sensitivity than cells of other FAB subtypes and these responses were increased by addition of rhIL‐3 or rhSCF in some cases. Responses of cells of other FAB subtypes varied. In addition, increased expression of platelet‐specific surface antigens on MO7E cells after incubation with rhTPO was observed. These data suggest that TPO may be involved in the abnormal proliferation and differentiation of human leukemic cells, especially of M7 and TAM cells, considered to be of megakaryocytic lineage.
Poor survival in t(8;21)(q22;q22)‐associated acute myeloid leukaemia with leukocytosis
Authors: Billström Rolf , Johansson Bertil , Fioretos Thoas , Garwicz Stanislaw , Malm Claes , Zettervall Olle , Mitelman Felix
Published: July 2010

Abstract: Twenty‐nine consecutive cases with a t(8;21)(q22;q22) in the bone marrow (BM) karyotype were retrospectively studied concerning clinical, morphological and cytogenetic data. All had been diagnosed as acute myeloid leukaemia (AML), 27 FAB subtype M2 and two M1, comprising 5% of all cytogenetically analysed AML during 18 yr. Auer rods were the most consistent t(8;21)‐associated morphological finding and were demonstrated in 92% of the reviewed BM specimens, whereas BM eosinophilia was seen in only 24%. The median age was 53 yr, and 30% of the patients were >60 yr old. Twenty‐four patients had received induction chemotherapy; 22 of these (91%) entered a complete remission (CR). The median survival time in treated patients was 18 months. Leukocytosis at diagnosis (>20×109/l) was significantly (p=0.01) associated with shorter survival time. All four children are still in first CR after 9–80 months. Seven cases (25%) developed granulocytic sarcomas, discovered either at diagnosis (n=4) or at first relapse (n = 3). Secondary chromosome abnormalities were found in 62% of the cases, most often loss of a sex chromosome. The presence of such secondary aberrations did not correlate with any morphological or clinical characteristics, including survival. This first Scandinavian study of AML with t(8;21) corroborates the previous findings that these AMLs are characterized by distinct morphological features, a high frequency of CR and a striking tendency to develop extramedullary leukaemic manifestations. Leukocytosis at diagnosis indicates a less favourable prognosis.
Serum thrombopoietin and interleukin 6 concentrations in tumour patients and response to chemotherapy‐induced thrombocytopenia
Authors: Heits F. , Katschinski D. M. , Wilmsen U. , Wiedemann G. J. , Jelkmann W.
Published: July 2010

Abstract: The relation between the number of platelets in blood and the concentrations of immunoreactive thrombopoietin (TPO), interleukin 6 and interleukin 11 (IL‐6, IL‐11) was studied in the sera of 32 normal subjects, of 29 untreated tumour patients and of 6 tumour patients following chemotherapy with ifosfamide, carboplatin and etoposide (ICE). Platelet counts, TPO and IL‐6 concentrations were higher than normal in blood of tumour patients before chemotherapy. However, no statistical relation existed between these variables. Following chemotherapy, the number of circulating platelets decreased reaching a nadir at d 10–13, while the serum concentration of TPO increased concomitantly. Circulating IL‐6 did not increase during chemotherapy‐induced thrombocytopenia. IL‐11 was not detectable in any serum. Thus, the reactive thrombocytosis in tumour patients could be related to elevated TPO and IL‐6 levels. In contrast to circulating TPO, however, neither serum IL‐6 nor IL‐11 levels increase significantly in thrombocytopenia following myelosuppressive chemotherapy.
How does interferon exert its cell growth inhibitory effect?
Authors: Grandér Dan , Sangfelt Olle , Erickson Sven
Published: July 2010

Abstract: The interferons (IFNs) have become accepted therapy in a range of haematological and non‐haematological malignancies. The mechanism behind IFN's antitumour action is, however, unclear. Interferons (IFNs) are capable of modulating a variety of cellular responses. One prominent effect of IFNs is their cell growth inhibitory activity, which has also been suggested to be of major importance in their antitumour action. In the present review we will discuss the cellular events leading to a decreased number of cells following IFN treatment, the molecular mechanisms underlying these phenomena, and the importance of these effects in a clinical perspective.
Analysis of low and high grade B‐cell lymphoma subtypes using semi‐nested PCR and two primer sets
Authors: Essop M. F. , Blakolmer K. , Close P. M. , Manuel Y. E. , Cornelius S.
Published: July 2010

Abstract: Immunoglobulin gene rearrangements in B‐cell lymphoma subtypes may not always be detected by PCR if only one primer set is applied. We therefore analysed a range of low and high grade B‐cell lymphoma subtypes for monoclonality using PCR, to determine appropriate primer selection strategies for routine diagnostic use. Semi‐nested PCR was performed on 70 unequivocal B‐cell lymphoma cases using paraffin‐embedded tissue (PET). Consensus primers directed at the framework 3 (Fr3) and framework 2 (Fr2) regions of the immunoglobulin heavy chain (IgH) gene were used to detect monoclonality. Monoclonality was found in 77% of cases using primer Fr3, 58% using Fr2, and in 93% of cases when data were combined for both primers. In 89% of the 38 low grade and 97% of the 31 high grade B‐cell lymphomas monoclonality could be detected when combining both primers. Fr3 gave superior results in most of the lymphoma subtypes analysed. We conclude that both Fr3 and Fr2 are useful, in a routine histopathology laboratory, for detecting monoclonality in most B‐cell lymphoma subtypes. Certain subtypes, however, are sometimes not targeted by these primers and therefore require additional analyses.
Inhibition of superoxide production and chemotaxis by methotrexate in neutrophils primed by TNF‐α or LPS
Authors: Okuda Akiro , Kubota Masaru , Watanabe Kenichiro , Sawada Machiko , Koishi Seiji , Kataoka Akihiro , Usami Ikuya , Lin Ying Wei , Furusho Kenshi
Published: July 2010

Abstract: We have demonstrated recently that methotrexate (MTX) inhibits superoxide generation and chemotaxis induced by N‐formylmethionyl‐leucyl‐phenylalanine (fMLP) in neutrophils primed by granulocyte colony‐stimulating factor (G–CSF). To extend these observations, we examined the in vitro effect of MTX on fMLP‐stimulated superoxide generation and chemotaxis in neutrophils primed by either tumor necrosis factor α (TNF‐α) or bacterial lipopolysaccharide (LPS). MTX inhibited superoxide generation and chemotaxis more efficiently in TNF‐α‐or LPS‐primed neutrophils than in unprimed neutrophils. When either hypoxanthine or guanosine was added to the culture medium, the effects of MTX were partially counteracted. Furthermore, MTX caused a significant inhibition of both superoxide production induced by phorbol 12‐myristate‐13‐acetate and chemotaxis induced by interleukin 8 in G‐CSF‐primed neutrophils. These results may support the hypothesis that neutrophils primed by different stimuli are more susceptible to the inhibitory effects of MTX on superoxide generation and chemotaxis irrespective of chemoattractants. Such an effect can be partly attributed to the perturbation of purine nucleotide biosynthesis.
Cell proliferation, bcl‐2, c‐myc, p53 and apoptosis as indicators of different aggressiveness in small lymphocytic lymphoma (SLL)
Authors: Palestro G. , Ponti R. , Chiusa L. , Chiarle R. , Geuna M. , Novero D. , Freilone R. , Pich A.
Published: July 2010

Abstract: Cell proliferation activity, by MIB1 mAb, expression of bcl‐2, c‐myc and p53 gene proteins and apoptotic index (AI) were assessed in. 54 cases of SLL and compared to the morphological subtypes of this disorder, defined by Lennert on the basis of amount and distribution of small and larger activated lymphocytes as diffuse, tumor‐forming and pseudofollicular subtypes (DS, TFS, PFS). MIB1 scores showed significant differences between DS, PFS and TFS (5.5%, 16.61% and 24.14%, respectively; p<0.0001). Worth noting, the MIB1 score did not differ significantly when comparing DS with the diffuse areas of PFS, or TFS with the pseudofollicles of PFS. The mean bcl‐2 gene protein score was displayed to a high extent in all subtypes, but less extensively by larger activated lymphocytes that, conversely, expressed c‐myc. MIB1 score correlated negatively with bcl‐2 and positively with c‐myc protein scores. These findings suggest that lymphocytes protected from apoptosis by bcl‐2 would be exponed to cell activation and growth acceleration provided by c‐myc. This condition would account for a different aggressiveness of morphologically activated subtypes, such as TFS and PFS with larger pseudofollicles. The survival analysis, performed in 23 cases, showed a trend of association of cell proliferation and c‐myc expression with a more aggressive progression of the disease. Overexpression of p53 and apoptosis were found only in a minority of cases, unrelated to the subtypes. In conclusion, cell growth fraction, bcl‐2 and c‐myc assessement may be of help in predicting the aggressiveness of different subtypes of SLL. This approach should be most conveniently applied to PFS, which represents a continuum between DS and TFS, in order to distinguish, in this heterogeneous subtype, more indolent from more aggressive disorders.
Bone marrow patterns in patients with aplastic anaemia and myelodysplastic syndrome: observations with magnetic resonance imaging
Authors: Kusumoto Shuya , Jinnai Itsuro , Matsuda Akira , Murohashi Ikuo , Bessho Masami , Saito Masanobu , Hirashima Kunitake , Heshiki Atsuko , Minamihisamatsu Masako
Published: July 2010

Abstract: Bone marrow magnetic resonance imaging (MRI) was obtained in 48 patients with myelodysplastic syndrome (MDS) (35 cases) or aplastic anaemia (AA) (13 cases). The lower thoracic and lumbar spine were evaluated on sagittal plane using a 1.5 Tesla superconducting MR unit with a surface coil. Pulse sequence of STIRs (TR 2000 msec, TI 160 msec, TE 20 msec) were applied. Four distinct patterns of signal intensity (SI) on the STIR images were classified as follows: pattern 1, homogeneously low SI; 2, marginally high SI; 3, heterogeneously high SI; 4, homogeneously high SI. In all 13 patients with AA, STIR images initially revealed pattern 1. In 25 of 35 cases with MDS patients, the STIR images were initially classified as pattern 3. The STIR images of 6 AA and 5 MDS patients with a clinical response to treatment showed pattern 2 similar to that of normal marrow distribution. The STIR images of MDS patients showed an abnormal distribution of SI. Significant signal changes in the STIR images can be observed in successive examinations of the patients, thus facilitating follow‐up of the disease and treatment. MRI of the bone marrow provides a noninvasive means of grossly examining a large fraction and is a useful technique in patients with aplastic anaemia or myelodysplastic syndrome.
Activation of the interleukin‐10 gene in the human T lymphoma line HuT 78: identification and characterization of NF‐κ B binding sites in the regulatory region of the interleukin‐10 gene
Authors: Mori Naoki , Prager Diane
Published: July 2010

Interleukin‐10 (IL‐10) is a pleiotropic cytokine which has potent inhibitory effects on macrophages and T cells, and contributes to the regulation of proliferation and differentiation of B cells. Resting HuT 78, a T‐cell line derived from a Sezary lymphoma, produced significant amounts of IL‐10 compared with another T‐cell line, Jurkat. To elucidate the mechanisms by which the IL‐10 is expressed, we have analyzed their activity in human T‐cell lines. We report here evidence that members of the family of transcription factors nuclear factor‐κ B (NF‐κ B)/Rel can specifically recognize 3 identical sequences located in the 5′‐regulatory region of IL‐10 gene in resting HuT 78 cells, whereas Jurkat cells expressed high levels of NF‐κ B consisting of p65 and p50 only upon activation with tumor necrosis factor‐α (TNF‐α). In HuT 78 cells, p50 was the major component in the NF‐κ B complexes. Exogenous TNF‐α and the monoclonal antibody to TNF‐α did not affect IL‐10 production and constitutive NF‐κ B binding levels in HuT 78 cells. This study is the first demonstration of a role for NF‐κ B in the IL‐10 gene expression, and suggests that its expression does not require TNF‐α. These novel findings may account for the specific IL‐10 gene expression in T cells.
Increase of CD34 positive cells in polycythaemia vera
Authors: Andréasson Björn , Swolin Birgitta , Kutti Jack
Published: July 2010

Abstract: The purpose of the present work was to evaluate the proliferative character of polycythaemia vera (PV). Therefore, in 15 patients with different stages of PV we assessed the level of CD34 positive (CD34+) cells in peripheral blood and bone marrow, erythroid colony growth of bone marrow cells and plasma erythropoietin (EPO). The mean concentration of CD34+ cells in blood was significantly increased in PV patients (9.0±11.2×103/mL) compared to healthy controls (2.0±1.7×103/mL). In aspirated bone marrow no such difference between PV and control subjects was present. Six patients with splenomegaly and/or requirement for chemotherapy had significantly higher mean blood levels of CD34+ cells compared to the remaining PV patients. All PV patients presented EPO independent erythroid colonies. Three PV patients with anaemia and long disease duration had high EPO levels.
Mobilization of CD34+ cells by glycosylated and nonglycosylated G‐CSF in healthy volunteers — a comparative study
Authors: Höglund M. , Smedmyr B. , Bengtsson M. , Tötterman T. H. , Cour‐Chabernaud V. , Yver A. , Simonsson B.
Published: July 2010

Abstract: In vitro studies indicate that lenograstim (glycosylated G–CSF) is more potent than filgrastim (nonglycosylated G–CSF) on a weight for weight basis. However, such a difference has not yet been shown in vivo. The primary objective of this trial was to compare the efficacy of equivalent doses (μg) of lenograstim and filgrastim in mobilizing CD34+ cells. Thirty‐two healthy male volunteers, median age 27 yr (19–44 yr), were randomized to receive either lenograstim 10 μg/kg followed by filgrastim 10 μg/kg or vice versa with a washout period of a minimum 4 wk. Both drugs were administered as s.c. injections once daily for 5 d (d 1–5). CD34+ cells were mobilized with a similar kinetics, peaking at median d 6 (5–6) for both drugs. A significant difference in favour of lenograstim was shown for peak number of CD34+ cells/μl blood (104±38 vs. 82±35, mean±l SD, p<0.0001, paired t‐test, n=30) and number of CFU‐GM/μl blood at d 6 (14.6±8.4 vs. 10.2±4.6, p<0.0001), respectively. There was no difference in the d 6 number of CD3+ cells. Both drugs were generally well tolerated and did not differ with respect to number of adverse events. In conclusion, lenograstim 10 μg/kg/d mobilizes PBPC more efficiently than the identical dose of filgrastim, indicating a difference in in vivo potency between the two G–CSFs.
Acquired pure red cell aplasia in Japan
Authors: Mamiya Shigeo , Itoh Toshihiro , Miura Akira B.
Published: July 2010

Abstract: We reviewed the clinical features of 150 patients with acquired pure red cell aplasia (PRCA) in Japan. There were 35 patients with acute type and 115 with chronic type PRCA. Of the acute PRCA patients, 17 had human parvovirus B19 infection. Drug‐induced PRCA was demonstrated in 7 patients. Of the 115 patients with chronic PRCA, 51 patients were classified as primary and 64 cases were associated with miscellaneous diseases such as thymoma, a variety of hematological disorders and collagen diseases. Among the hematological disorders, PRCA was most frequently seen in granular lymphocyte proliferative disorders (GLPD). The erythroid colony growth patterns from bone marrow were variable. The serum erythropoietin level was high in most patients. Various kinds of treatment were tried for the chronic PRCA cases. Cyclosporin A (CyA) was the most effective form of treatment and the response rate was 82% (31/38). Twenty‐three of 37 patients (62%) responded to bolus methylprednisolone therapy. The largest number of patients were treated with oral prednisolone, and the therapy was effective in 27 of the 55 (49%). The response rate to cyclophosphamide was only 29% (5/17), but in combination with prednisolone, half of the patients (7/14) responded to the therapy. CyA is recommended as the first‐line therapy for acquired chronic PRCA.
Five putative drug resistance parameters (MDR1/P‐glycoprotein, MDR‐associated protein, glutathione‐S‐transferase, bcl‐2 and topoisomerase IIα) in 57 newly diagnosed acute myeloid leukaemias
Authors: Lohri Andreas , van Hille Benoît , Bacchi Marisa , Fopp Markus , Joncourt Franzisca , Reuter Jürgen , Cerny Thomas , Fey Martin F. , Herrmann Richard
Published: July 2010

Abstract:Using a modified quantitative reverse transcriptase (RT) PCR assay in 57 patients with acute myeloid leukaemia (AML) from a Swiss Phase III multicentre study (SAKK 30/85), we measured the m‐RNA expression of the genes from the multidrug resistance gene 1 (MDR1), the multidrug resistance associated protein (MRP), glutathione‐S‐transferase (GST) π, bcl‐2 and topoisomerase (topo) IIα. P‐glycoprotein (p‐gp) was measured by Western blot, and GST activity by functional assays. To analyse progression‐free (PFS) and overall survival (OS), parameters were prospectively divided into “low” and “high” groups, according to their median values (exceptions: MDR1 and p‐gp). Median follow‐up was 60 months. Results: MDR1‐ and MRP mRNA levels correlated with each other (r= 0.54, Spearman), FABM4/M5 and extramedullary disease. “Low” bcl‐2‐mRNA predicted longer PFS: 22 months vs. 7 months (median,p= 0.02, log rank), and longer OS: 64 months vs. 14 months (p= 0.06). “Low” topo Hoc predicted poorer outcome: median PFS 9 vs. 19 months (p= 0.03); median survival 12 months vs. “not reached” (p= 0.03). An improved outcome tendency, albeit nonsignificant, was seen in p‐gp‐negative patients. In a Cox model adjusted for age, performance status, presence of Auer rods, FAB type and clinical response, bcl‐2 and topo IIα mRNA levels retained their predictive values.
2‐Chlorodeoxyadenosine (cladribine)‐related eosinophilia in patients with lymphoproliferative diseases
Authors: Robak T. , Błasińska‐Morawiec M. , Krykowski E. , Hellmann A. , Lewandowski K. , Dmoszyńska A. , Adamczyk‐Cioch M. , Kazimierczak M. , Trepińska E. , Dwilewicz‐Trojaczek M. , Kuratowska Z. , Skotnicki A. B. , Nowak W. S. , Zdziarska B. , Urasiński I.
Published: July 2010

Abstract: Eosinophilia and allergic skin reactions are uncommon events after 2‐chlorodoxyadenosine (2‐CdA, cladribine) administration. A multicentre retrospective analysis of eosinophilia in 360 patients treated with 2‐CdA for lymphoid malignancies has been made. B‐cell chronic lymphocytic leukaemia (B‐CLL) was diagnosed in 153, hairy cell leukaemia (HCL) in 68, low‐grade non‐Hodgkin's lymphoma (LGNHL) in 119, high‐grade NHL in 2 and Waldenström's macroglobulinaemia (WM) in 18 patients. 2‐CdA was administered at a dose 0.12 mg/kg/d in 2‐h intravenous infusion for 5 consecutive d. The courses were repeated monthly. Patients with HCL received 1 cycle of 2‐CdA, with NHL 2 – 6 (mean 3.5) cycles and with B‐CLL 3 – 6 (mean 5) cycles. Twenty patients (5.5%), including 5 with HCL, 6 with LGNHL, 7 with B‐CLL and 2 with WM, developed peripheral blood eosinophilia. The mean values of absolute eosinophil count were 0.78×109/l (0.58 – 1.06×109/l), 0.71×109/l (0.52 – 1.3×109/l), 85 (0.56 – 1.82×109/l) and 0.75 (0.74 – 0.76×109/l), respectively. Eosinophilia occurred in 13 patients after 1 course, in 4 after 2 courses, and in 5 after ≥3 courses of the therapy. In 17 cases it resolved spontaneously. Allergic skin lesions with pruritus were noticed in 3 patients simultaneously with an increase in eosinophil count. All of them required antihistaminic drugs and/or corticosteroids. One patient with B‐CLL experienced repeated episodes of eosinophilia. The highest incidence of 2‐CdA‐induced eosinophilia was noticed in patients with MW (11.1%) and HCL (7.4%) who received only 1 cycle of this drug and entered a complete remission. This side effect was less frequently observed in LGNHL and B‐CLL, i.e. in 5.0% and 4.6% of cases, respectively. The mechanism of 2‐CdA‐induced eosinophilia is not clear. It has been postulated that massive tumour cell lysis may trigger a release of IL‐5 and probably other cytokines. The allergic mechanism of 2‐CdA‐induced eosinophilia is also possible, especially in patients with simultaneous skin reactions.
Cardiac function during iron chelation therapy in adult non‐thalassaemic patients with transfusional iron overload
Authors: Jensen P. D. , Olsen N. , Bagger J. P. , Jensen F. T. , Christensen T. , Ellegaard J.
Published: July 2010

Abstract: It is well‐documented that iron chelation by desferrioxamine protects/improves the cardiac function in blood transfusion‐dependent children suffering from ß‐thalassaemia. In patients who do not become dependent upon blood transfusion until adulthood (ANT‐patients), iron chelation by desferrioxamine may affect the cardiac function in unknown ways, presumably because age‐related changes in the heart may cause iron chelation to affect the cardiac function in different ways. We therefore followed the left ventricular ejection fraction (LVEF) by multigated radionuclide angiography in 16 iron‐loaded ANT‐patients during iron chelation alone and after increasing the efficacy of chelation by vitamin C supplementation. During 12 months of iron chelation the mean LVEF fell significantly from 63.3% to 58.0% (p = 0.04). Individual changes in LVEF did not correlate significantly with age but with the pretreatment liver iron concentration. After initiation of vitamin C supplementation, the mean LVEF increased from 55.9% to 65.3% (p = 0.01). Our data suggest that in ANT‐patients prolonged desferrioxamine treatment without vitamin C supplementation may be associated with reduced LVEF, whereas vitamin C supplementation seems to benefit the cardiac function. Similar findings have not been described in ß‐thalassaemia and may hence be specific for ANT‐patients. However, our findings have to be confirmed by controlled studies.
Distribution and incidence rates of lymphoid neoplasms according to the REAL classification in a single institution. A prospective study of 940 cases
Authors: Salar A. , de Sevilla A. Fernández , Romagosa V. , Domingo‐Claros A. , González‐Barca E. , de Sanjosé S. , Pera J. , Servitje O. , Grañena A.
Published: July 2010

Abstract: Recently, a new classification system for lymphoid neoplasms, known as the REAL classification, has been proposed. Our aim is to know the distribution of lymphoid neoplasms according to this schema and compare it with the Updated Kiel classification. We also estimate incidence rates of lymphoid neoplasms in our area. From January 1993 to November 1996, 940 patients were diagnosed of lymphoid neoplasm in our center. Histologic material was prospectively classified according to both the REAL and the Updated Kiel classifications. According to the REAL classification, distribution of all cases of lymphoid neoplasms was as follows: 73.6% B‐cell neoplasm, 9.4% T‐cell neoplasms, 9.6% Hodgkin's disease and 7.4% unclassifiable. Considering only non‐Hodgkin's lymphomas (NHL), 87.2% of cases could be categorized according to the REAL and 77.7% with the Updated Kiel classification. These figures differed due to unrecognized categories in the Kiel schema. Annual incidence rate per 100,000 inhabitants was 20.1 for lymphoid neoplasms, and NHL alone was 9.0. In conclusion, the REAL classification allowed us to categorize more cases of NHL than did the Updated Kiel classification, fundamentally because of the inclusion of some recently described entities.
Production of recombinant human GM‐CSF‐EPO hybrid proteins: in vitro biological characterization
Authors: Coscarella A. , Carloni C. , Liddi R. , Mauro S. , Novelli S. , Mele A. , Masella B. , Valtieri M. , De Santis R.
Published: July 2010

Abstract: Selective lineage differentiation depends upon the combined action of several colony‐stimulating factors. Here we describe 3 human granulocyte‐macrophage colony‐stimulating factor‐erythropoietin (GM‐CSF‐EPO) hybrid proteins generated by recombination of the relevant cDNAs. The expression vector containing the murine cytomegalovirus (mCMV) promoter and dihydrofolate reductase (DHFR) gene was used for the expression of the hybrid genes in Chinese hamster ovary (CHO) cells. Purified hybrid proteins from CHO transfectant cultures induced proliferation of both EPO and GM‐CSF dependent cell lines. The clonogenic test, performed on purified human hematopoietic precursor cells, indicates that the hybrid proteins are more efficient at inducing erythroid differentiation compared with the equimolar mixture of GM‐CSF and EPO.
Prognostic factors of hemophagocytic syndrome in adults: analysis of 34 cases
Authors: Kaito K. , Kobayashi M. , Katayama T. , Otsubo H. , Ogasawara Y. , Sekita T. , Saeki A. , Sakamoto M. , Nishiwaki K. , Masuoka H. , Shimada T. , Yoshida M. , Hosoya T.
Published: July 2010

Abstract: Hemophagocytic syndrome (HPS) presents with fever, pancytopenia, liver dysfunction and increase in hemophagocytic histiocytes in various organs. Although there are two major classifications of HPS in adults, malignant and reactive histiocytosis, it is often very difficult to distinguish between these disorders. We analyzed the laboratory data of patients with HPS to evaluate prognostic factors. Of 34 patients, 14 survived, and 20 died. The median age of survivors was 29.6 ± 11.5 yr significantly younger than those who died (54.7 ± 17.8 yr). Twenty patients had no obvious underlying disease, the other 13 had hematological malignancies or viral infections. Comparison of laboratory data revealed that nonsurvivors had significantly lower Hb and platelet values on admission. During treatment, worsening of anemia and thrombocytopenia, increase of transaminase and biliary enzymes were similarly more prominent. Risk factors associated with death were: age over 30 yr, presence of disseminated intravascular coagulation, increased ferritin and β2‐microglobulin, anemia accompanied by thrombocytopenia and jaundice. Our data suggests that patients with HPS and any of these risk factors should be treated aggressively with sufficient chemotherapy and supportive care.
Identification of an arginine452 to histidine substitution in the erythroid 5‐aminolaevulinate synthetase gene in a large pedigree with X‐linked hereditary sideroblastic anaemia
Authors: Edgar A. J. , Losowsky M. S. , Noble J. S. , Wickramasinghe S. N.
Published: July 2010

Abstract:  The coding region of the erythroid 5‐aminolaevulinate synthetase gene (ALAS2) from a large pedigree with pyridoxine‐responsive X‐linked hereditary sideroblastic anaemia was examined for mutations. In three affected males from this pedigree, single strand conformational polymorphism (SSCP) analysis showed anomalous migration of a PCR product spanning exon 9. Sequencing of amplified genomic DNA from one of these affected males revealed a guanine to adenine transition at nucleotide 1407 of the cDNA sequence in exon 9 of the gene. This mutation results in the loss of an HhaI restriction enzyme digest site. An HhaI digest assay demonstrated the presence of this mutation in other affected males but not in unaffected males and unrelated individuals. The point mutation results in an arginine to histidine substitution at amino acid residue 452. The arginine residue is conserved in both the erythroid and housekeeping ALAS genes in all known vertebrate sequences. This arginine is located in the middle of a predicted alpha‐helix.
Clonal CD8+ and CD52– T cells are induced in responding B cell lymphoma patients treated with Campath‐1H* (anti‐CD52)
Authors: Österborg A. , Werner Å. , Halapi E. , Lundin J. , Harmenberg U. , Wigzell H. , Mellstedt H.
Published: July 2010

Abstract:  Five patients with non‐Hodgkin's lymphoma (NHL) and 4 patients with chronic lymphocytic leukaemia (CLL) were treated with the CDR‐grafted (rat × human) monoclonal antibody (mAb) Campath‐1H (anti‐CD52). Tumour regression was noted preferentially in peripheral blood and in the bone marrow but lymph nodes were less affected. Normal blood B and T cells were profoundly reduced in all patients whereas CD16+ NK cells and CD14+ monocytes decreased marginally. In all responding CLL patients CD52‐negative T but not B cells appeared during treatment and persisted for several months (4–19+) during unmaintained follow‐up. Clonal T cells defined as a predominance of a single T cell receptor (TCR) V gene usage, in one case verified by TCR CDR3 fragment analysis and nucleotide sequencing, emerged within the CD52–/CD8+ cell population during Campath‐1H therapy in 2 CLL patients, both achieving a long‐lasting remission. The increase in CD8+ T cell expansions (up to 23‐fold) during unmaintained remission and follow‐up suggest that the clonal CD8+ cells may represent regulatory T cells controlling the growth of the tumour B cell clone. Clonal T cells might thus be a target for an immune therapeutic intervention in B cell tumours.
Administration of high doses of recombinant human erythropoietin to patients with β‐thalassemia intermedia: a preliminary trial
Authors: Bourantas K. , Economou G. , Georgiou J.
Published: July 2010

Abstract:  Four patients (1 male, 3 female, age range 16–56 yr) with β‐thalassemia intermedia were given high doses of recombinant human erythropoietin (rHuEpo), iron sulfate and folic acid in an attempt to improve their anemia. The dose schedule was: rHuEpo, 500 U/kg 3 times weekly, iron sulfate, 300 mg/d and folic acid, 5 mg/d. All patients were red blood cell transfusion‐dependent. Hematological data and fetal hemoglobin (HbF) were assayed every 2 wk. XmnI polymorphism and β‐thalassemia mutations were identified by PCR. All patients showed a moderate to high increase in hemoglobin values (mean value: 2.5 g/dl) and in 1 patient HbF levels also increased; 3 patients became red blood cell transfusion‐independent and 1 patient was able to extend the intervals between transfusions significantly. No side effects were observed during rHuEpo therapy.
High‐dose methylprednisolone for children with acute lymphoblastic leukemia and unfavorable presenting features
Authors: HiçsÖnmez G. , Gümrük F. , Zamani P. V. , Tuncer M. A. , Yetgin S. , Gürgey A. , Atahan L. , Özsoylu S.
Published: July 2010

Abstract:  In an attempt to improve treatment outcome high‐dose methylprednisolone (HDMP, 20–30 mg/kg, once a day orally) was used instead of a conventional dose of steroid (2 mg/kg/d, in 3 divided doses) in children with acute lymphoblastic leukemia (ALL) with increased risk factors. HDMP combined with cytotoxic agents (vincristine and l‐asparaginase) resulted in an improved complete remission rate (94%) in 48 newly diagnosed children with ALL compared to 81% in 86 historical controls receiving standard dose steroid combined with the same treatment regimen. The bone marrow relapse rate was lower in patients who received HDMP (31%) than in controls (56%). Treatment was discontinued in 56% of 48 patients receiving HDMP and in 35% of 86 controls. The difference was significant (p<0.05). The 5‐yr continuous complete remission rate was significantly greater in patients received HDMP compared with the control patients (60% vs. 43%, p<0.05). HDMP treatment was well tolerated without significant adverse effects. Moreover, during induction therapy the duration of leukopenia (< 2 × 109/L) was shorter in patients receiving HDMP. We conclude that HDMP combined with other antileukemic agents increased the CR rate and prolonged the duration of remission in children with ALL who had increased risk factors. However, the optimal dosage of HDMP and its role in maintenance therapy should be determined in future, randomized studies.