bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute lymphocytic leukaemia in the elderly: characteristics and outsome with the vincristine‐adriamycin‐dexamethasone (VAD) regimen
Authors: Kantarjian Hagop M. , O'Brien Susan , Smith Terry , Estey Elihu H. , Berran Miloslav , Preti Alejandro , Pierce Sherry , Keating Michael J. 
Published: March 2008

To analyse the pretreatment characteristics, responseto therapy, and overall prognosis of elederly patients with acute lymphocytc leukaemia (ALL). 268 consecutive adults with newly‐diagnosed ALL who received the vincristine‐adria‐mycin‐dexamethasone (VAD) regimens were reviewed; Pretreatment fharacteristics, response to VAD therapy, and overall outcomewere analysed in patients 60 years or older, and compared to younger patients.Fifty‐two patients (19%) were 60 years or older. Compared with younger patients, elderly patients with ALL had a significantly worse performance status at presentation (P < 0.001); higher incidences of FAB L2 morphology (P=0.03). thrombocytopenia (P < 0.01), hypoalbuminaemia (P < 0.001) and renal dysfunction (P=0.03); and trends for worse anaemia (P = 0.06) and a higher rate of myeloid markeers positivity (P= 0.06). With VAD induction therapy, elderly patients had a lower CR rate than younger patients following two induction courses (CR rate 58% rate 58% v 82%; P < 0.01), and overall (CR rates 65% v 90%; P <).01). The response rate to VAD chemotherapy, however, appeared superior to the 30–35% CR rates reported from other series in elderly ALL patients. The lower CR rate was due to both higher induction mortality (P = 0.02) and more resistant disease (P < 0.01). The longterm CR rate was 20% in elderly patients achieving CR, but the overall survival was poor (< 10% at 3 years). There were strong associations between older age and other poor prognostic features. However, multivariate analyses identified older age to be an independent poot prognostic factor for response to chemotherapy. In summary, elderly patients with ALL have an appreciable CR rate with the VAD regimens. Patients achieving CR may have durable remissions. The myelosuppression‐associated mortality in both remission induction and maintenance may be reduced with the addition of growth factors in both treatment phases, and by using standard maintenance therapy without consolidation‐intensification phases.
A novel β‐thalassaemia mutation in the 5’untranslated region of the β‐globin gene
Authors: Athanassiadou Aglaia , Papachatzopoulou Adamandia , Zoumbos Nicholas , Maniatis George M. , Gibbs Richard 
Published: March 2008

Summary. A thymidine deletion at position +10 of the 5’untranslated region of the β‐globin gene was detected in a β‐thalassaemia intermedia patient carrying a βd́; 39 stop codon mutation on the other chromosome; this new mutation, +10(‐T), was detected by automated fluorescent DNA sequencing and verified by dot‐blot allele‐specific hybridizations.The +10(‐T) mutation is a ‘silent carrier’, is associated with a reduced amount of steady‐state β‐globin mRNA, and establishes a connection between the 5’untranslated region of the β‐globin gene and the regulation of its expression.
Retroviral‐mediated gene transfer into human myeloma cells
Authors: Björkstrand Bo , Dilber M. Siracl , Smith C. I. Edvard , Gaharton Gösta , Xanthopoulos Kleanthis G. 
Published: March 2008

Summary. We have studied retroviral‐mediated gene transfer into human myeloma cells, Bone marrow cells were obtained from four patients with advanced myeloma, where was heavily infiltrated with myelomatous plasma cells. Myloma cells were isolated by immunomagnetic separation, using the high‐affinity B‐B4 monoclonal antibody. Following separation, cells were transduced with the LN retroviral vector, which carries the gene for neomycin phosphotransferase, by incubation in cell‐free supernatant with or without a growth‐factor combination of IL‐3, IL‐6 and SCF. After infection, the cells were cultured for 9 d in RPIMI‐1640 and 10% FCS. either in the presence or absence of the neomycin analogue G418.Transduction efficiency was 1.5–3.8%, when compared to the number of cells at initiation of the culture, and 5.0–50.0% when compared to the mumber of surviving infected cells cultured without G418. The gene transfer rate was similar whether or not growth factors were present durig the retorviral infectoin.Theses preclinical data provide evidence that retroviral‐mediated gene transfer into human myeloma cells is feasible, and form part of the basis for current clinical studies of gene marking of bone marrow or peripheral blood progenitor cells before autologous stem cell transplatation in multiple myeloma.
Short‐term myeloid growth factor mediated expansion of bone marrow haemopoiesis| studied by localized magnetic resonance proton spectroscopy
Authors: Jensen Karl Erik , Hansen Per Boye , Larsen Vibeke Andreé; , Johnsen Hans E. , Nielsen Helle , Karle Hans , Henriksen Ole 
Published: March 2008

Summary. Previously we have shown that short‐term myeloid growth factor priming of haemopoiesis prior to bone marrow harvest increased the yield of myeloid progenitors in the graft. The present study is intended to investigate the expansion of haemopoiesis by volume selective proton magnetic resonance spectroscopy (MRS).Six patients were treated with daily subcutaneous injections of recombinant human granulocyte colonystimulating factor (rhG‐CSF, n = 2) or granulocytemacrophage colony‐stimulating factor (rhGM‐CSF, n = 4) for 5d before marrow harvest. MRS investigations were performed prior to treatment (day 0), day 5 and day 12. Spectroscopic examinations were performed with the stimulated echo acquisition mode (STEAM) method on a 1.5T clinical whole‐body imaging unit. A cubic volume of interest (VOI) was selected in the bone marrow of the left iliac bone.The patients responded with a rise in blood absolute neutrophil count from median 3.3 × 109/1 (range 1.3–7.3 × 109/1) before to 15.6 × 109/1 (range 6.8–22.0 x l09/ 1) after treatment. Concomitantly an increase in bone marrow cellularity and myeloid: erythroid ratios documented the stimulation of myelopoiesis. During priming, the light‐density cell proliferation rate in marrow samples increased from median 21.9 (range 4–5–31) x103 cpm to 54–7 (range 13–9–94) x103 cpm and the total number of myeloid progenitors enumerated as day 7/14 GM‐CFUs per volume aspirated marrow increased from median ll/8 x l03 (range 4.0–87.5/2.2–103.0) to 64/76 x l03 (range 28.4–1180.6/23.2–2850.0). MRS detected a significant increase in bone marrow ‘relative water content’ day 12, 1 week after myeloid growth factor treatment was stopped, from median 30.5% (range 16–45) to 79% (range 56–93). In parallel, haemopoiesis was detected in new areas of femur.In conclusion, the non‐invasive MRS method may be a useful and reliable in vivo examination for expansion of haemopoiesis and a correspondent reduction of fat tissue inbone marrow after priming with recombinant human haemopoietic growth factors.
Expression of shared idiotypes by paraproteins from patients with monoclonal gammopathy of undetermined significance
Authors: Kampe Carsten E. , Hart Sarah , Miller Richard A. , Lichtenstein Alan , Kyle Robert A. , Berenson James R. 
Published: March 2008

SummaryWe have previously demonstrated the expression of shared idiotypes by the paraproteins from approximately one‐quarter of patients with multiple myeloma (MM). We have now investigated whether similar cross‐reactivity is expressed in the paraproteins of patients with monoclonal gammopathy of undetermined significance (MGUS), using a panel of 32 monoclonal antibodies (MAB) generated against follicular B cell lymphomas. The paraproteins from 76/409 (19%) patients with MGUS reacted with at least one of 23 different anti‐idiotypic antibodies used in this study. 18 MABs demonstrated reactivity with more than one patient's paraprotein. Moreover, 10 MABs reacted frequently (with 5–22 paraproteins). Over half (41/76) of the reactive patients’ paraproteins reacted with more than one MAB from this panel. This frequency of anti‐idiotypic reactivity was similar to that of previously studied patients with myeloma, chronic lymphocytic leukaemia (CLL), and follicular B‐cell lymphomas. There was no correlation between specific anti‐idiotypic reactivity and the propensity to develop serious disease (MM, macroglobulinaemia, amyloidosis, or other lymphoproliferative disorders) in patients with MGUS. These results suggest that MGUS is derived from cells producing antibodies that are similar to those of other B‐cell malignancies and that the pattern of idiotype expression is irrelevant to malignant potential.
Subgroup and cost‐benefit analysis of the Finnish multicentre trial of clodronate in multiple myeloma
Authors: Laakso Markku , Lahtinen Reino , Virkkunen Pekka , Elomaa Inkeri 
Published: March 2008

SummaryOsteolytic lesions and pathological fractures are the major problems in the clinical management of multiple myeloma. We previously reported the main results of a randomized, controlled multicentre trial in 350 Finnish patients with multiple myeloma. All patients received standard melphalan‐prednisolone treatment and were randomized to receive either clodronate 2.4 g daily or a placebo for 24 months. The proportion of patients with progression of osteolytic bone lesions was twice as high in the placebo group as in the clodronate group (24.0%v 12.0%, P= 0.026). The purpose of the present study was to investigate factors associated with the progression of osteolytic lesions and to identify subgroups of patients who would benefit most from clodronate treatment. In univariate logistic regression analysis, including treatment (placebo, clodronate), sex, age, pain index, serum calcium and creatinine, myeloma stage, number of osteolytic lesions at baseline, and number of vertebral fractures at baseline as independent variables and the progression of osteolytic lesions as a dependent variable, only the treatment with a placebo was associated with the progression of osteolytic bone lesions. Separate analyses with respect to the progression of osteolytic bone lesions were carried out in the following subgroups: male v female, ± 64 v > 64 years, stage I v stage II‐III myeloma, no osteolytic lesions at baseline versus osteolytic lesions at baseline, no vertebral fractures at baseline versus vertebral fractures at baseline, and a 50% treatment response to cytotoxic drugs versus no treatment response to cytotoxic drugs. The treatment with clodronate delayed the progression of osteolytic lesions similarly in these subgroups, with the exception of a subgroup of patients who did not have a 50% treatment response to cytotoxic drugs. The treatment with clodronate did not significantly increase treatment costs. We conclude that the treatment effect of clodronate seems to be independent of sex and age of the patients, the stage of myeloma, and the severity of bone lesions at diagnosis, but not of treatment response to cytotoxic drugs.
Parvovirus B19 as a cause of acquired chronic pure red cell aplasia
Authors: Frickhofen N. , Chen Z. J. , Young N. S. , Cohen B. J. , Heimpel H. , Abkowitz J. L. 
Published: March 2008

SummaryParvovirus B19 infection causes chronic anaemia in immunodeficient individuals by selective suppression of erythropoiesis. The bone marrow morphology is character‐istic of pure red cell aplasia (PRCA). To determine the frequency of B19‐induced PRCA we retrospectively analysed a series of 57 PRCA patients. B19 DNA was present in serum of eight patients (14%) and could be extracted from bone marrow aspirate slides from five of these patients. Recent exposure to the virus was confirmed by the presence of anti‐B19 IgM in sera from four and by the finding of giant pronormoblasts in marrow aspirates from five of the B19 DNA‐positive patients. The sensitivities of anti‐B19 IgM and of giant pronormoblasts were only 50% and 63%, respectively; specificites were 90% and 92%. Unexpectedly, PRCA in two B19 DNA‐positive patients remitted after antilymphocyte globulin or cyclosporin A therapy, suggesting that the clinical course of B19‐induced PRCA may be indistinguishable from other forms of PRCA. As therapy with immunoglobulin is uniformly effective for treatment of B19‐associated anaemia, our data suggest that all patients with acquired PRCA should be evaluated for evidence of B19 infection. B19 DNA analysis is the most reliable method to demonstrate infection.
GM‐CSF in the treatment of Fanconi's anaemia
Authors: Kemahli Abri , Canatan Duran , Uysal Zümrüt , Akar Nejat , Cin Sükrü , Arcasoy Ayten 
Published: March 2008

SummaryWe have used recombinant human (rh) GM‐CSF in two 12‐year‐old Fanconi's aplastic anaemia patients. They had not received any previous therapy except blood transfusions. Each patient was given three 21 d courses of rh‐GM‐CSF, the first two at a dose of 3.5μg/kg/d and the third at 7 μg/kg/d s.c. There were significant increases in WBC and absolute neutrophil counts after the first week of rh‐GM‐CSF which lasted as long as the treatment was continued. Following the cessation of treatment, WBC and ANC dropped rapidly. We conclude that rh‐GM‐CSF can be used in FAA, especially in severely neutropenic cases.
Familial thrombophilia and activated protein C resistance: thrombotic risk in pregnancy?
Authors: Cook G. , Walker Isobel D. , McCall Frances , Conkie J. A. , Greer I. A. 
Published: March 2008

SummaryAn abnormal anticoagulant response in vitro to activated protein C (aPC) has been proposed as an aetiological factor in familial thrombophilia. It is postulated that this phenomenon is due to an inherited molecular defect of factor V resulting in poor inactivation by aPC. We conducted a family study when the proband presented in her second pregnancy with superficial phlebitis, a history of deep venous thrombosis and a family history of venous thromboembolic disease. No abnormality of antithrombin activity, protein C activity or deficiency of protein S were demonstrated in the family members tested. The proband had aPC ratios below the laboratory range on three consecutive occasions. In addition, her mother, who had a history of recurrent DVTs and a pulmonary embolus, and also an asymptomatic nulliparous sister, both had aPC resistance ratios below the laboratory range on consecutive samples. Further information about the combined risk of aPC resistance and pregnancy is needed before guidance on the management of affected women can be formulated.
The plasma concentration of soluble Fc‐gamma RIII is related to production of neutrophils
Authors: Huizinga T. W. J. , Haas M. de , Oers M. H. J. van , Kleijer M. , Viléa H. , Wouw P. A. van der , Moulijn A. , Weezel H. van , Roos D. , Borne A. E. G. Kr.von dem 
Published: March 2008

Summary. FcγRIII (the CD16‐antigen), a low‐affinity receptor for IgG, is expressed by neutrophils, natural killer lymphocytes and macrophages. A soluble form of FcγRIII has been identified in human plasma. This soluble form of FcγRIII (sFcγRIII) originates from release by neutrophils. In the present study we show by transfusions of plasma that contains sFcγRIII of one allotype (NA1‐FcγRIII) in recipients homozygous for the other allotype (NA2‐FcγRIII) that the clearance of sFcγRIII is about 0.7 ml/min. Because the concentration of sFcγRIII was found to be constant in a small cohort of donors followed for about 1‐5 years, the half‐life of NA1‐sFcγRIII is about 1.8 d, assuming a one‐compartment model.The plasma concentration of sFcγRIII depended mainly on the production of neutrophils in the bone marrow, and was not influenced by shifts of neutrophils from one pool to another (storage, marginating or circulating pool). Because FcγRIII is only expressed on mature neutrophils, this implies that the concentration of sFcγRIII depends on production of mature neutrophils.
Minor myeloid component in Ph chromosome‐positive acute lymphoblastic leukaemia: correlation with cytogenetic pattern and implication for poor response to therapy
Authors: Cuneo Antonio , Demuynck Hilde , Ferrant Augustin , Louwagie Andries , Doyen Chantal , Stul Michel , Cassiman Jean‐Jacques , Cin Paola Dal , Negrini Massimo , Carli Maria Gretel , Boogaerts Marc , Michaux Jean‐Louis , Castoldi Gianluigi , Berghe Herman van den 
Published: March 2008

SummaryMorphological, immunological and cytogenetic features were studied in 27 adults presenting with Ph chromosome‐positive acute lymphoblastic leukaemia (ALL), in correlation with clinical outcome.Twenty patients (group 1) were diagnosed as having typical ALL according to the FAB criteria supported by immunological findings. Less than 1% blast cells with azurophilic granules were detected in all cases. Myeloid cytochemistry, i.e. peroxidase and Sudan black‐B stain, was negative in all cases. A minor phenotype deviation consisting of the expression of the CD13 myeloid‐associated marker was detected in two patients.In seven patients (group 2) a diagnosis of ALL with a minor myeloid component was made because of the presence of a majority of lymphoid blasts and of 5‐15% blast cells with morphological cytochemical and immunological features of the myeloid lineage.Abnormal metaphases were found in 6/20 (30%) patients in group 1, compared with 7/7 (100%) patients in group 2.All patients were treated by antilymphoid regimens: however, complete remission was achieved in 17/20 (85%) patients in group 1 versus 1/7 (14.3%) patients in group 2. Median survival was 16 months, range <1‐120+ in group 1 and 9 months, range <1‐15 in group 2.It is concluded that morphological, immunological and cytogenetic studies allow for the recognition of two cytological subsets of Ph+ ALL. The presence of a minor myeloid component in otherwise typical Ph chromosome‐positive ALL may be associated with a distinct cytogenetic pattern and poor responses to antilymphoid therapy.
Trisomy 12 is uncommon in typical chronic lymphocytic leukaemias
Authors: Criel A. , Wlodarska I. , Meeus P. , Stul M. , Louwagie A. , Hoof A. Van , Hidajat M. , Mecucci C. , Berghe H. Van den 
Published: March 2008

SummaryThe incidence of trisomy 12 was studied by conventional chromosome analysis in 111 patients referred as B‐cell chronic lymphocytic leukaemia (B‐CLL). Fluorescent in situ hybridization (FISH) was also applied in 34 of those patients with either a normal karyotype or no analysable mitoses. By karyotyping, trisomy 12 was present in 11.7% (13/111), whereas additional FISH increased the incidence to 14.4% (16/111). When subdividing our cases in either typical CLL (n= 90), fulfilling the FAB classification criteria, or atypical CLL (n= 21), with one or more variations from those criteria, the incidence of +12 by metaphase analysis was 3% and 48%, respectively. Additional FISH increased the incidence to 4% and 57%. The most common aberration in atypical CLL was FMC7 positivity (n= 11), followed by CD5 negativity (n= 8), strong surface immunoglobulin staining (n= 7) and atypical morphology (n = 6). Trisomy 12 could only be demonstrated in a small proportion of neoplastic cells in all positive cases. By FISH and/or karyotyping, all available samples at diagnosis of the disease were positive.
Clinicopathological spectrum of haemophagocytic syndrome in Epstein‐Barr virus‐associated peripheral T‐cell lymphoma
Authors: Yao Ming , Cheng Ann‐Lii , Su Ih‐Jen , Lin Ming‐Tseh , Uen Wu‐Ching , Tien Hwei‐Fan , Wang Chiu‐Hwa , Chen Yao‐Chang 
Published: March 2008

SummaryHaemophagocytic syndrome (HS) is frequently observed in Epstein‐Barr virus‐associated peripheral T‐cell lymphoma (EBV‐PTCL) and represents a major cause of death. In this communication we have further analysed the spectrum of HS in 12 patients with EBV‐PTCL. The patients could be divided into three groups according to the time of onset of HS during the clinical course of PTCL. Group I patients (four cases) had HS as the initial clinical manifestation. All four patients were initially suspected to have malignant histiocytosis (MH) but a MH‐like PTCL was later diagnosed. Group II patients (six cases) developed HS at the time of lymphoma relapse. Four of them belonged to the angioinvasive type PTCL. Group III patients (two cases) developed HS at clinical remission; both were angioinvasive type PTCL. Nine patients had serological evidence suggesting active EBV infection. The clinical course after the onset of HS was generally fulminant in each group with a median survival of only 44 d despite combination chemotherapy and/or empirical therapy with high‐dose immunoglobulin and corticosteroids in six patients. In conclusion, HS represents a severe complication of EBV‐PTCL. Although most patients develop HS at a time of active lymphoma, the syndrome may occur when the lymphoma is in remission. Because of the poor outcome, early diagnosis and a new modality of treatment for HS associated with EBV‐PTCL should be pursued in future.
The progression of HCV‐associated liver disease in a cohort of haemophilic patients
Authors: Telfer Paul , Sabin Caroline , Devereux Helen , Scott Fiona , Dusheiko Geoffrey , Lee Christine 
Published: March 2008

SummaryWe have studied morbidity and mortality related to hepatitis C virus infection in haemophilic patients treated at our centre. 11/255 HCV seropositive patients have developed hepatic decompensation. 20 years after first exposure to lyophilized clotting factor concentrate the risk of hepatic decompensation is estimated to be 10.8% (95% CI 3.8‐17.8%). There is a significantly increased risk associated with HIV infection, and also with increased age. For HIV seropositive patients the rates of decline in CD4 lymphocyte count and the development of p24 antigenaemia are significant risk factors for hepatic decompensation. Cirrhosis was seen in 9/19 HIV seropositive patients at post mortem. There was an association of cirrhosis with increased age but not with CD4 count, p24 antigenaemia or AIDS. In conclusion, HCV infection is associated with serious liver disease in haemophilic patients, but so far this has been restricted to a minority of those at risk. HIV coinfection accelerates progression to hepatic decompensation, and we speculate that this is probably due to enhanced HCV replication in the presence of immune deficiency.
An echistatin‐like Arg‐Gly‐Asp (RGD)‐containing sequence in the heavy chain CDR3 of a murine monoclonal antibody that inhibits human platelet glycoprotein IIb/IIIa function
Authors: Deckmyn Hans , Stanssens Patrick , Hoet Bernard , Declerck Paul J. , Lauwereys Marc , Gansemans Yannick , Tornai Istvan , Vermylen Jos 
Published: March 2008

SummaryWe describe the production and biochemical characterization of the first GPIIb/IIIa‐inhibiting monoclonal antibody that contains an RGD sequence in the CDR3 region of the heavy chain. Monoclonal antibodies obtained by immunizing mice with human platelets were screened using consecutive ELISAs based on human platelets and immunoaffinity‐purified glycoprotein (GP) IIb/IIIa coated on microtitre plates. Out of 30 monoclonal antibodies reacting with GPIIb/IIIa, one, MA‐16N7C2, potently inhibited platelet aggregation induced by ADP, thrombin, arachidonic acid, collagen, U46619, adrenaline and platelet‐activating factor, whereas ristocetin‐induced aggregation was unaffected.MA‐16N7C2 (IgG2a) bound ˜ 4 times faster to activated than to resting platelets, with a Kdcalc of 6.6 nm and of 17.5 nm, respectively. Equilibrium binding studies to non‐activated platelets showed a Kd of 18.2 nm with 41 x 103 binding sites per platelet. The antibody recognized GPIIb/IIIa only as a Ca2+ ‐dependent complex. MA‐16N7C2 blocked fibrinogen and von Willebrand factor binding to GPIIb/IIIa in a competitive manner with a Ki of 8.5 nm and 13.2 nm, respectively. Sequence analysis revealed a RGD‐containing sequence with homology to disintegrins, in the CDR3 region of the heavy chain.That this RGD‐containing sequence could be involved in the interaction of the antibody to GPIIb/IIIa was finally indicated by showing that the binding is completely and competitively inhibited by echistatin.