bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversible adult‐onset cyclic haematopoiesis with a cycle length of 100 days
Authors: Birgens Henrik S. , Karle Hans 
Published: March 2008

Cyclic neutropenia is the most frequent of the cyclic haematopoietic disorders characterized by its regular 21 d cyclic fluctuations in the number of blood neutrophils, and in many cases simulataneous fluctuations in the other blood cell lines.In this paper we describe a 77‐year‐old woman with a cyclic pancytopenia including all the myeloid cell lines and to some extent the lymphocytes with a constant and predictable oscillation period of about 100d. Serial bone marrow biopsies and plasma lactoferrin measurements indicated a similar fluctuating pattern in the bone marrow production of neutrophils. Serial measurements of plasma GM‐CSF concentration pointed at a simple feed‐back inhibitory system. The condition was present for at least 4 years, after which it gradually improved, although the thrombocyte count still showed a fluctuating tendency after a further 4 years of observation.The clinical consequences were mild symptoms of anaemia and a few episodes of respiratory infections occurring during pancytopenic periods.We think this is the first case described in the literature with this variant of a cyclic haematopoietic disorder. The precise pathophysiological mechanism behind this condition is obscure, but probably it is due to a regulatory disturbance at a very early step in the haematopoietic stem cell hierarchy.
Differential sensitivity of human myeloma cell lines and normal bone marrow colony forming cells to a recombinant diphtheria toxin‐interleukin 6 fusion protein
Authors: Chadwick D. E. , Jean L. F. , Jamal N. , Messner H. A. , Murphy J. R. , Minden M. D. 
Published: March 2008

Summary. The cytotoxicity of a recombinant interleukin 6 (IL‐6)‐diphtheria toxin (DT) fusion protein towards human myeloma cell lines was investigated. DAB389‐IL‐6 inhibited protein synthesis and methylcellulose colony formation by U266 myeloma cells. In the clonogenic assay, the fusion protein approached the level of cytotoxicity achieved by native DT. The specificity of killing by DAB389‐IL‐6 was demonstrated by inhibition of cytotoxicity by a molar excess of free rhIL‐6.The effect of DAB389‐IL‐6 on colony formation by six OCI‐My cell lines was assessed. Similar to U266 cells, colony growth by the OCI‐My 5 and ‐My 2 cell lines was inhibited in a simple dose dependent manner. However, a biphasic effect was observed for the IL‐6 dependent OCI‐My 4 cells: DAB389‐IL‐6 stimulated colony formation at low ( 10‐11 m) concentrations, yet was inhibitory at higher doses. Three other cell lines whose growth was not altered by IL‐6 were relatively unaffected by DAB389‐IL‐6, despite their sensitivity to native DT. Flow cytometric analysis for IL‐6 receptor expression using phycoerythrin‐conjugated IL‐6 demonstrated specific binding sites on both DAB389‐IL‐6 sensitive and certain insensitive cell lines, suggesting that other factors in addition to the expression of IL‐6 receptors are involved in killing by the fusion toxin.Despite evidence for a role of IL‐6 in myeloid cell development, normal bone marrow was insensitive to the IL‐6 fusion toxin. In cultures containing both normal bone marrow and U266 cells DAB389‐IL‐6 effectively inhibited the growth of U266 myeloma colonies but had little effect on normal bone marrow erythroid, granulocyte and mixed erythroid/granulocyte colony growth. From these experiments we conclude that DAB389‐IL‐6 is specifically cytotoxic towards a subset of IL‐6‐responsive human myeloma cell lines and may be useful, in some cases, in the selective elimination of tumour cells from mixed populations of normal and malignant cells.
Different membrane expression of CD11b and CD 14 on blood neutrophils following in vivo administration of myeloid growth factors
Authors: Hansen Per Boye , Kjærsgaard Erik , Johnsen Hans E. , Gram Jesper , Pedersen Michael , Nikolajsen Kirsten , Hansen Niels Ebbe 
Published: March 2008

Summary. During the administration of recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) or granulocyte‐macrophage CSF (rhGM‐CSF) we studied the early and late changes of membrane antigen density on neutrophils. RhG‐CSF and rhGM‐CSF both caused an early transient reduction in blood neutrophilic granulocyte‐concentration within the first 30 min after treatment followed by a marked later increase during the subsequent 24 h. During the early neutropenia quantitative flow cytometry showed an associated marked increase in the density of membrane CD11b from 169 × 103 before to 568 × 103 A.U. per cell induced by rhGM‐CSF but a non‐significant change by rhG‐CSF, suggesting that different mechanisms may be responsible for the transient neutropenia. The subsequent neutrophil granulocytosis was followed by a significantly (P<0.05) increased density of the CD14 antigen from 6.1 × 103 before to 15.9 × 103 A.U. per cell during treatment with rhG‐CSF. but not by rhGM‐CSF administration.These results demonstrate that the two cytokines may affect the function of neutrophilic granulocytes in different ways. The increased expression of CD1 1b could explain some of the side‐effects during treatment with rhGM‐CSF. The upregulation of CD14 induced by rhG‐CSF may be clinically relevant, as CD14 is an opsonic receptor for lipopolysaccharide binding proteins, acting in the defence against Gramnegative bacterial infections.
Results of Medical Research Council trial UKALL IX in acute lymphoblastic leukaemia in adults: report from the Medical Research Council Working Party on Adult Leukaemia
Authors: Durrant I. J. , Richards S. M. 
Published: March 2008

Summary. The MRC UKALL IX trial for patients with untreated ALL aged 14 years and over was open to new patients from July 1980 to April 1985. 266 patients were randomized between two induction schedules, M (involving intermediate dose rnethotrexate with folinic acid rescue) and D (involving daunorubicin). Schedule M resembled that used in the previous MRC adult ALL, trial (UKALL VI). while schedule D was somewhat more intensive. No difference in disease‐free survival was found between the treatment arms, but patients on the daunorubicin arm went into remission earlier.The overall remission rate was 8 7%, which is at least as good as in contemporary studies elsewhere: factors predictive of a lower remission rate were older age and higher WBC. For those who entered remission, WBC, age and sex were the most important prognostic factors. Time to achieve remission was not a significant factor after allowance was made for these.An historical comparison does not show any improvement over the preceding MRC adult trial, although the subsequent trial does show a modest improvement at present. Because the improved outlook seen in children is not apparent in adults, and no other randomized trial has demonstrated substantial benefit for any particular regimen, the next trial, UKALL XII, will be investigating the benefit or otherwise of bone marrow transplantation.
Long‐term follow‐up of aplastic anaemia
Authors: Narayanan M. N. , Geary C. G. , Freemont A. J. , Kendra J. R. 
Published: March 2008

Summary. Of 61 patients with aplastic anaemia (AA) diagnosed in our hospitals, 37 survived more than 2 years; actuarial survival of this latter group was 58%, with a median follow‐up of living patients of 10.2 years. Laboratory and clinical data pertaining to these long‐term survivors was scrutinized to determine the incidence of clonal disorders, which was identified in 43%. Morphological evidence of the myelodysplastic syndrome (MDS) was found in 13 (35%), including four cases of RAEB; four (11%) developed PNH. Of 23 patients studied, four showed karyotypic abnormalities, but these did not always coincide with morphological features of MDS.Although four patients now have completely normal blood and marrow morphology, and another had normal blood and marrow morphology at the time of death due to unrelated disease, the study confirms the high incidence of cytopenia and morphological abnormality, sufficient to justify a diagnosis of MDS, in patients with a history of AA. No definite survival plateau was identified. However, the natural history of MDS secondary to AA seems to be different to that of MDS arising de novo; the clinical course is relatively indolent, possibly implying a different biology.
Vitamin B12 deficiency is the primary cause of megaloblastic anaemia in Zimbabwe
Authors: Savage David , Gangaidzo Innocent , Lindenbaum John , Kiire Clement , Mukiibi Joshua M. , Moyo Alpha , Gwanzura Christine , Mudenge Boniface , Bennie Anne , Sitima John , Stabler Sally P. , Allen Robert H. 
Published: March 2008

Summary. In a study of the pathogenesis and clinical features of megaloblastic anaemia in southern Africa, we evaluated 144 consecutive Zimbabwean patients with megaloblastic haemopoiesis. Vitamin B12 deficiency was diagnosed in 86.1% of patients and was usually due to pernicious anaemia; isolated folate deficiency accounted for only 5/5% of cases. Anaemia was present in 95.8% of patients; the haemoglobin (Hb) was 6 g/dl in 63.9%. Neurological dysfunction was noted in 70.2% of vitamin B12‐deficient patients and was most striking in those with Hb values > 6 g/dl. Serum levels of methylmalonic acid, homocysteine, or both, were increased in 98.5% of patients.Vitamin B12 deficiency is the primary cause of megaloblastic anaemia in Zimbabwe and, contrary to textbook statements, is often due to pernicious anaemia. Isolated folate deficiency is less common. As reported in industrialized countries 75 years ago, anaemia is almost always present and often severe. Neurological dysfunction due to vitamin B12 deficiency is most prominent in patients with mild to moderate anaemia.
Altered surface marker expression and function of G‐CSF‐induced neutrophils from test subjects and patients under chemotherapy
Authors: Spiekermann Karsten , Emmendoerffer Andreas , Elsner Joern , Raeder Evelin , Lohmann‐Matthes Marie‐Luise , Prahst Arndt , Link Hartmut , Freund Mathias , Welte Karl , Roesler Joachim 
Published: March 2008

SummaryWe have previously reported an altered surface marker expression and chemotaxis of G‐CSF‐induced neutrophils from patients with severe congenital neutropenia. However, effects of G‐CSF and influence of the underlying disease on neutrophils could not be discerned. In this study we have evaluated the effects of G‐CSF on neutrophil phenotype and function in patients under chemotherapy and in healthy test subjects. We found a significantly enhanced expression of FcγRI, CD14 and CD54 and a decrease in the level of FcγRIII during G‐CSF treatment. In addition, motility of G‐CSF‐induced neutrophils was significantly decreased. The effects were seen in patients under cytotoxic chemotherapy and in healthy test subjects. Surface marker alterations and neutrophil motility were affected by G‐CSF administration in a dose‐dependent manner. Kinetic studies on neutrophils from healthy test subjects demonstrated that all effects could be seen after a single administration of 300 μg G‐CSF and began to appear within 4 h. Release of partially immature neutrophils from the bone marrow and indirect activation of these cells by G‐CSF are discussed as possible reasons for the findings presented. They demonstrate that G‐CSF has profound effects on neutrophil phenotype and function in vivo which might have clinical implications.
Intensive induction/consolidation therapy without maintenance in adult acute lymphoblastic leukaemia: a pilot assessment
Authors: Wernli M. , Tichelli A. , Fliedner V. von , Re G. Brun del , Chaputs B. , Fey M. F. , Fopp M. , Gmür J. , Grob J‐P. , Jacky E. , Pedrazzini A. , Schmid L. , Senn H‐J. , Tobler A. , Gratwohl A. 
Published: March 2008

Summary. Maintenance chemotherapy for up to 3 years is traditionally given to patients with acute lymphoblastic leukaemia (ALL) achieving complete remission. We questioned the value of such maintenance therapy in adult patients treated with intensive induction/consolidation. In a phase II study (SAKK 33/86) 63 patients between 17 and 72 years of age (median 27 years) with newly diagnosed ALL were treated with three intensive cycles of marrow‐ablative chemotherapy. All subtypes were included. No maintenance phase was added. 53 patients (84%) entered a complete remission (CR) and 21 (33%) continue to be in unmaintained remission for 11‐69 months (median 21 months). The disease‐free survival of patients achieving CR and completing all three cycles is 40% at 3 years, with a 95% confidence interval of ± 19%. These findings are comparable to the results of conventional studies. We conclude that maintenance therapy might not be needed in all adult ALL patients. Its value should be tested in a randomized trial. For patients failing, novel approaches are needed to improve outcome in adult ALL.
Inactivation of the retinoblastoma gene appears to be very uncommon in myelodysplastic syndromes
Authors: Preudhomme Claude , Vachee Anne , Lepelley Pascale , Vanrumbeke Mickaéul , Zandecki Marc , Quesnel Bruno , Cosson Alain , Fenaux Pierre 
Published: March 2008

Summary. Rearrangements of the retinoblastoma (RB) gene have been reported in a few cases of myelodysplastic syndromes (MDS). In addition, low or absent expression of the RB protein is found in 20‐30% of cases of acute myeloid leukaemias (AML), particularly in AML with a monocytic component (M4 or M5). We performed Southern blot analysis of the RB gene in 90 cases of MDS, including 37 cases of chronic myelomonocytic leukaemia (CMML). None of them had progressed to AML at the time of study. In 37/90 patients (including 20 CMML) Northern blot analysis, study of RB protein by immunocytochemistry on bone marrow slides, and detection of point mutations in exons 20‐24 of the RB gene was also made, using single strand conformation polymorphism analysis (SSCP).No abnormal Southern profile was found in any of the 90 patients. Northern blot and immunocytochemical study of RB protein were normal in the 37 cases studied. SSCP analysis detected a point mutation in 2/37 patients tested. Direct sequencing confirmed the mutation in each case, which involved intron 21 and intron 23, respectively, and was located outside splicing sites of the neighbouring exons.These findings suggest that abnormalities of the RB gene and its expression must be very rare in MDS, and play a minor role, if any, in the pathophysiology of those disorders, at least before progression to AML.
Prevalence of antithrombin deficiency in the healthy population
Authors: Tait R. C. , Walker Isobel D. , Perry D. J. , Islam S. I. A. M. , Daly M. E. , McCall F. , Conkie J. A. , Carrell R. W. 
Published: March 2008

Summary. In a cohort of 9669 blood donors we have identified 16 cases of congenital AT deficiency (1 in 600) by way of family studies and AT gene analysis. Two donors had type I AT deficiency (prevalence 0.21 per 1000; 95% CI = 0.03/1000 to 0.75/1000), their families displaying a symptomatic phenotype. 14 donors had a type II deficiency (prevalence 1.45 per 1000; 95% CI = 0.79/1000 to 2.43/1000): one recurring and three unique mutations. None of these type II deficiencies appeared to confer a high thrombotic risk despite many of the affected individuals having experienced potentially prothrombotic challenges. The high frequency of these relatively asymptomatic variants may reflect a selection bias in the study population. However, their existence should not only add to our understanding of structure‐function relationships of AT but may also influence our management of asymptomatic deficient individuals identified in epidemiological or presurgical screening programmes.
Scedosporium inflatum infection in immunocompromised haematological patients
Authors: Tapia Manuel , Richard Carlos , Baro Julio , Salesa Ricardo , Figols Javier , Zurbano Felipe , Zubizarreta Alberto 
Published: March 2008

SummaryWe report four cases of Scedosporium inflatum (S. inflatum) infection in severely immunocompromised haematological patients. Six well‐documented cases of S. inflatum disseminated infection in haematological patients have been reported: four in Australia and two in Spain. Their clinical and pathological characteristics are heterogenous, particularly in the Australian cases. However, the clinical and pathological profile emerging from our and other Spanish cases is homogenous and very similar to the clinico‐pathological spectrum of other disseminated mycoses, including Aspergillus and S. apiospermum. The optimal treatment of S. inflatum infection is unknown and the outcome in haematological patients is very poor. Eight patients died despite systemic antifungal treatment.
Increased expression of myeloid antigen markers in adult acute lymphoblastic leukaemia patients: diagnostic and prognostic implications
Authors: Lauria F. , Raspadori D. , Martinelli G. , Rondelli D. , Ventura M. A. , Farabegoli P. , Tosi P. , Testoni N. , Visani G. , Zaccaria A. , Gamberi B. , Cenacchi A. , Tura S. 
Published: March 2008

Summary. By applying direct immunofluorescence with a dual‐staining technique we were able to demonstrate that 20/37 (54%) patients with acute lymphoblastic leukaemia (ALL) expressed both lymphoid and myeloid antigens on the same leukaemic cells. CD13 and CD33 myeloid antigens were detected in 18/20 and in 15/20 cases respectively, and both in 13. Molecular studies confirmed that the four patients with T‐cell phenotype had molecular rearrangement of T‐cell receptor (TcR) β chain, and 26 ALL patients with ‘B‐cell’phenotype showed JH rearrangement. Two ALL patients without (ALL/My‐) and three with myeloid antigens (ALL/My+) also demonstrated bcr/abl rearrangement. Both groups of patients had similar presenting features such as age, sex, Hb level, white blood cells, platelet counts and cytogenetic features. Complete response was achieved in 16/17 (94%) ALL/My‐ patients and in 15/18 (83%) ALL/My+ patients (two deaths occurred during induction) with a mean duration of 17 and 16 months respectively and with similar survival and event‐free survival curves.Myeloid antigen expression in adult ALL patients may occur more frequently than previously reported. The presence of myeloid antigen does not identify, in our series, a higher‐risk subgroup of patients, although lack of any statistical evidence of prognostic significance needs to be confirmed in a larger case study.
John Hageman's factor and deep‐vein thrombosis: Leiden Thrombophilia Study
Authors: Koster Ted , Rosendaal Frits R. , Briet Ernest , Vandenbroucke Jan P. 
Published: March 2008

SUMMARY. Because the relationship between factor XII deficiency and venous thrombosis in unclear and study results seem contradictory, we undertook a populationbased case‐control study.Among 350 unselected patients younger than 70 years, with a first, objectively confirmed, episode of deep‐vein thrombosis and without underlying malignant disease we detected a 6% frequency (21/350 patients) of factor XII deficiency (activity level 57%). Among 350 healthy control subjects, matched for age and sex, the frequency was 5% (18 subjects). Thus there is no increase in prevalence of factor XII deficiency among thrombosis patients and no increase in thrombosis risk for subjects with low factor XII levels (mathced odds ratio 1.2 (95% CI 0.6‐2.4)). In addition, there was no relation between strata of factor XII levels and thrombosis risk. In conclusion, we do not consider factor XII to be a determinant of deep‐vein thrombosis.
Transforming growth factor‐β and megakaryocytes in the pathogenesis of idiopathic myelofibrosis
Authors: Martyré M. C. , Romquin N. , Le Bousse‐Kerdiles M. C. , Chevillard S. , Benyahia B. , Dupriez B. , Demory J. L. , Bauters F. 
Published: March 2008

Summary. Although the disease is well described, the pathogenesis of bone marrow fibrosis in idiopathic myelofibrosis still remains unclear. We previously reported elevated intraplatelet transforming growth factor‐β (TGF‐β) levels in patients with this myeloproliferative disorder, compared with healthy subjects. Here, in a series of 16 patients, we show that TGF‐β expression is also increased in patients' periperal blood mononuclear cells (PBMC): (i) at the mRNA level analysed by Northern blot hybridization and/or reverse transcription‐polymerase chain reaction (RT‐PCR): (ii) and/or at the secreted peptide level as evaluated in conditioned media from patients' mononuclear cells by a growth inhibition assay on CC164 cells.By immunostaining with a polyclonal anti‐TGF‐β1 antibody, TGF‐β was localized in morphologically heterogenous cells; these cells were characterized as megakaryocytes by labelling with a gpIIbIIIa monoclonal antibody.Thus we provide evidence that both TGF‐β and megakaryocytes are linked in the pathogenesis of idiopathic myelofibrosis.
Recovery of T‐lymphocytes for adoptive immunotherapy by lymphapheresis of HIV‐infected patients without alterations of virological, immunological or clinical parameters
Authors: Lunzen Jan VAN , Schmitz Jörn , Dengler Kathrin , Schmidt Lutz , Schmitz Herbert , Dietrich Manfred 
Published: March 2008

Summary. We performed repeated continuous flow cytaphereses (CFC) on 13 asymptomatic HIV‐1‐infected patients to study the feasibility of cell separation procedures to recover high yields of peripheral blood T‐lymphocytes for adoptive immunotherapy in HIV‐infected patients and to determine immunological and virological alterations following such procedures.A mean yield of 6.23 * 109 lymphocytes could be obtained by each cytapheresis, containing 1.82 * 109 CD4+, 3.23 * 109 CD8+ T‐lymphocytes and 8.39 * 106 CD34+ peripheral progenitor cells. The CD4/CD8 ratio (mean 0.53, SD ± 0.15) in the cell samples reflected the distribution of the lymphocyte subsets in vivo. Absolute lymphocyte counts decreased at a mean of 404/mm3 (25%) immediately after CFC but were replaced from the extravascular pool within 1 h. The CD4/CD8 ratios, p24‐antigenaemia. HLA‐DR expression and neopterin levels did not change significantly after cell separation. No alteration of the number of T‐cells with integrated proviral DNA copies (1/103 to 1/106) could be detected in peripheral T‐helper cells by PCR after lymphapheresis.We conclude that high yields of peripheral T‐lymphocytes can be obtained by continuous flow lymphapheresis for cell mediated immunotherapy, withou deterioration of virological or immunological parameters in HIV‐infected patients. The separated T‐cells are fully replaced from extravascular pools after 1 h.
Estimatetd 8‐year survival of more than 40% in a population‐based study of 79 adult patients with acute lymphoblastic leukaemia
Authors: Evensen S. A. , Brinch L. , Tjønnfjord G. , Stavem P. , Wislösff F. 
Published: March 2008

Summary. We report 11 years experience with a modified version of a chemothearpy programme in use at the MRC Leukaemia Unit from 1982 to 1984, supplemented by allogeneic bone marrow transplantation in first relapse or second or later remission from 1985. 79 consecutive patients aged 15–60 years with newly diagnosed acute lymphoblastic leukaemia (ALL) were given induction chemotherapy. This included a stadard DAT course (aunorubicin, cytarabine and thioguanine) applied as In acute myelogenous leukaemia approximately midway in the induction programme. A 3‐year rotating maintenance programme consisted of combinations of cytotoxic drugs used in the induction therapy. CNS prophylaxis did not include CNS irrasiation. Allogeneic BMT was not performed in first remission.The overall complete remision (CR) rate was 82% (65/79). 26 patients relapsed (seven first in the CNS). Seven patients underwent allogeneic BMT of whom six are alive and well with a mean observation time of 32 months (range 4–99 months) after transplantation. Three patients died in first CR. Estimated 5‐and 8‐year overall survival was 51% (95% confidence interval (CI) 39–63) and 47% (CI 33–61). For patients who reached CR, the corresponding figures were 63% (CI 50–76) and 57% (CI 41–73). Estimated disease‐free survival in the remitters was 54% (CI 40–68) at 5 years and 44% (CI 28–60) at 8 years. patient age below 25 years and white cell count below 15 * 109/1 at presentation were both found to improve the chance of overall survival.