bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogeneic bone marrow transplantation for secondary leukaemia and myelodysplastic syndrome: a survey by the Leukaemia Working Party of the European Bone Marrow Transplantation Group (EBMTG)
Authors: Witte T. De , Zwaan F. , Hermans J. , Vernant J. , Kolb H. , Vossen J. , Lönnqvist B. , Beelen D. , Ferrant A. , Gmür J. , Yin J. Liu , Troussard X. , Cahn J. , Lint M. Van , Gratwohl A. 
Published: March 2008

SummaryThis retrospective survey of the EBMT Leukaemia Working Party describes 78 patients with myelodysplasia (MDS) or secondary acute myelogenous leukaemia (sAML) who received an allogeneic bone marrow transplant (BMT). The status of underlying disease at the time of transplantation was prognostic for the 2‐year disease‐free survival. Thirty‐four patients received intensive chemotherapy prior to the conditioning for BMT. The 2‐year disease‐free survival was 60% for the 16 patients transplanted in complete remission. The results were significantly less favourable for those with more advanced disease who only partially responded to prior intensive chemotherapy (2‐year diseasefree survival: 18%) while none of those who either relapsed or were resistant to chemotherapy survived BMT for 2 years. Forty‐four patients had not received any prior intensive chemotherapy. The disease‐free survival at 2 years after BMT was 58 ± 19% when a patient was transplanted for refractory anaemia (RA(S)), 74 ± 14% for refractory anaemia with excess of blasts (RAEB), 50 ± 16% for RAEB in transformation (RAEBt), and 18 ± 11% for secondary AML.Allogeneic BMT can therefore be considered as curative treatment for patients with MDS. Patients with sAML who have a histocompatible donor should be given chemotherapy intensive enough to induce complete remission. If this is achieved these individuals have a prognosis comparable to those with de novo AML in first remission after BMT.
Interleukin 2 does not promote the in vitro and in vivo proliferation and growth of human acute leukaemia cells of myeloid and lymphoid origin
Authors: Foa R. , Caretto P. , Fierro M. T. , Bonferroni M. , Cardona S. , Guarini A. , Lista P. , Pegoraro L. , Mandelli F. , Forni G. , Gavosto F. 
Published: March 2008

SummaryThe effect of recombinant interleukin 2 (IL2) on the in vitro and in vivo proliferation and growth of human acute leukaemia cells of both myeloid and lymphoid origin was investigated. In none of the 25 primary samples tested could a continuously in vitro growing cell line be obtained by adding IL2 to the culture medium. Although IL2 induced a proliferative signal in three of the 31 acute leukaemias analysed, the overall 3H‐thymidine uptake of the neoplastic cells was significantly reduced (P<0.05) in the presence of IL2. The unlikelihood of an important proliferative signal triggered by IL2 was confirmed in a semisolid clonogenic assay, which failed to document an increased colony growth in the 26 samples studied. Furthermore, using a colorimetric assay as a test for cell proliferation and survival, in seven of the 11 fresh acute leukaemia samples tested a 22–40% reduction in viability was observed in the presence of IL2, while in the remaining four, IL2 was ineffective. In order to investigate the effect of IL2 in an in vivo setting, an experimental model in heavily immunosuppressed nu/nu mice was established. In no case did IL2 promote the in vivo proliferation and growth of human myeloid and lymphoid acute leukaemia cells injected in the mice. On the contrary, with seven of the eight leukaemic cell lines which gave rise spontaneously to leukaemic masses, this could be prevented when the mice received locally 300 U of IL2 three times daily for 90 d. IL2 also blocked the growth in vivo of three fresh acute leukaemia samples (two myeloid and one lymphoid). Co‐culture experiments using leukaemic cell lines and increasing numbers of normal lymphocytes suggest that the inhibitory effect of IL2 is probably exerted via an indirect mechanism. These findings, coupled to the well‐documented ability of IL2 to generate lymphokine activated killer cells cytolytic against leukaemic blasts, further point to the potential role of immunotherapy with IL2 in the management of patients with haematological malignancies.
The common pathway for alpha‐ and gamma‐thrombin‐induced platelet activation is independent of GPIb: a study of Bernard‐Soulier platelets
Authors: Jandrot‐Perrus Martine , Rendu Francine , Caen Jacques P. , Levy‐Toledano Sylviane , Guillin Marie‐Claude 
Published: March 2008

Summary. The responses to alpha‐ and gamma‐thrombin were studied in normal and Bernard‐Soulier platelets labelled with [32P]phosphate, to investigate the relationship between thrombin binding to the platelet membrane glycoprotein Ib (GPIb) and thrombin‐induced platelet activation. For this purpose we conducted parallel studies of the kinetics of platelet aggregation, granule secretion, hydrolysis of poly‐phosphoinositides, formation of phosphatidic acid, phosphorylation of the myosin light chain (p20) and of the 43 kDa protein (p43), and thromboxane B2 formation. Like alphathrombin, gamma‐thrombin activated control platelets via all the above metabolic responses, but only after a prolonged lag. In Bernard‐Soulier platelets, alpha‐thrombin induced polyphosphoinositide hydrolysis and phosphatidic acid formation, p20 and p43 phosphorylation, thromboxane B2 formation, secretion and to a lesser extent aggregation, but only after a prolonged lag. The metabolic responses of Bernard‐Soulier platelets to gamma‐thrombin were very similar to those of control platelets.We have previously showed that GPIb which is not present in Bernard‐Soulier platelets binds alpha‐ but not gammathrombin. The present results indicate that thrombin binding to GPIb is not directly coupled either with the activation of phospholipase C specific to polyphosphoinositides, or with the activation of protein kinase C and phospholipase A2. However, thrombin binding to GPIb appears to promote an early mechanism which accelerates all the platelet responses.
‘MACHO’ chemotherapy for stage IV B cell lymphoma and B cell acute lymphoblastic leukaemia of childhood
Authors: Hann I. M. , Eden O. B. , Barnes J. , Pinkerton C. R. 
Published: March 2008

SummaryAn intensive 6‐month schedule of drugs was devised with both systemic and central nervous system activity, known by the acronym ‘MACHO’, to treat 24 newly and consecutively diagnosed children, 13 with stage IV B‐cell non‐Hodgkin's lymphoma (B‐NHL) and 11 with B‐cell acute lymphoblastic leukaemia (B‐ALL). There were three deaths from complications of chemotherapy (two infective, one biochemical). Five children with central nervous system disease at diagnosis (CNS +) received planned additional megatherapy/bone marrow transplants. Event‐free survival (EFS) at 1 year for the 11 cases of B‐ALL is 64% (95% confidence intervals [CI] 31–89%) and of 13 stage IV B‐NHL cases is 50% (95% CI 19–75%). Patients with bulky abdominal disease had a 32% EFS at 1 year (CI 13–68%) compared with 76% (CI 39–94%) for those without bulky abdominal disease. Overall EFS for eight CNS + patients is 73% at 1 year (95% CI 34–97%) compared with 48% (95% 24–74%) for those without CNS disease (CNS—). However, only two of the CNS+ cases had bulky abdominal disease (patients 10 and 12) and the difference is not significant (P<0·5).A score of 1 was given for each of the following potential prognostic features: bulky abdominal disease, pleural effusion and severe renal dysfunction within 48 h of presentation. Patients who scored 0 or I fared significantly better than those who scored 2 or 3 (EFS at 1 year 78% [CI 49–95%] versus 24% [6–65%], P<0·04). Two patients with a score of 2 survived past 6 months and another is currently well, but has not regenerated his marrow following autologous transplantation. This protocol is relatively effective for patients who have B‐ALL, but those patients who have bulky abdominal disease, often associated with severe renal dysfunction, and those with CNS disease, do not fare so well and require new approaches to therapy.
Definition of two distinct types of AIDS‐associated non‐Hodgkin lymphoma
Authors: Boyle Michael J. , Swanson Cheryl E. , Turner Jennifer J. , Thompson Ian L. , Roberts John , Penny Ronald , Cooper David A. 
Published: March 2008

Summary Non‐Hodgkin lymphoma (NHL) in a human immunodeficiency virus (HIV)‐infected person is an AIDS‐defining condition. There is both an increased incidence of NHL and a poorer prognosis for the disease in these HIV‐infected persons, compared with patients who spontaneously develop NHL.A series of 41 consecutive patients with HIV‐associated NHL treated at St Vincent's Hospital, Sydney. between 1984 and September 1989 was assessed. Of these, 36 had NHL proven on biopsy and NHL was diagnosed clinically in the other five. On histologic examination 11 had high‐grade malignant lymphoma, small non‐cleaved cell (SNCC) type, similar to Burkitt lymphoma, 18 had high‐grade lymphoma large cell immunoblastic (LCI) type, and seven could not be classified due to inadequate material for assessment.The clinical features of these two groups were compared. Those patients with LCI had advanced CD4+ immunodeficiency and poor survival (median = 6 weeks). The other group with SNCC had better preserved immune function, and longer survival (median=18 weeks). Three patients had survived longer than 3 years all of whom had SNCC lymphoma as their first AIDS‐defining illness.The clinical features and prognostic factors demonstrated in this study document heterogeneity of NHL in HIV‐infected patients and should be used as a guide to treatment of these patients, by reserving more intensive treatment for those persons with better prognostic features.
Antithrombin Vicenza, Ala 384 to Pro (GCA to CCA) mutation, transforming the inhibitor into a substrate
Authors: Caso R. , Lane D. A. , Thompson E. A. , Olds R. J. , Thein S. L. , Panico M. , Blench I. , Morris H. R. , Freyssinet J. M. , Aiach M. , And F. Rodeghiero , Finazzi G. 
Published: March 2008

Summary. Antithrombin (AT) Vicenza has been previously identified as a functionally abnormal antithrombin associated with familial thrombosis (Finazzi et al, 1985). It binds normally to heparin, but loses its affinity following interaction with thrombin: it is a poor inhibitor of thrombin. AT Vicenza was isolated from plasma by heparin–Sepharose and thrombin–Sepharose chromatography, fragmented with cyanogen bromide (CNBr) and its tryptic peptides were analysed by fast atom bombardment mass spectrometry mapping. An abnormal peptide mass 1112 was identified. Edman degradation confirmed a substitution of Ala to Pro in the sequence Ala 383–Arg 393. Polymerase chain reaction amplification of exon 6 of the gene followed by genomic sequencing, localized the mutation to codon 384, GCA to CCA. The same mutation has recently been reported in AT Charleville (Mohlo‐Sabatier el al, 1989).Sodium dodecyl‐sulphate polyacrylamide gel electrophoresis of AT Vicenza (/Charleville) under non‐reducing conditions revealed an apparent increase in mol. wt following interaction with thrombin: under reducing conditions the mol. wt was less than that of normal AT. This indicated cleavage and unfolding of the molecule. The site of cleavage was determined by incubation of AT Vicenza (/Charleville) with thrombin‐Sepharose, reduction and S‐carboxymethylation and reverse phase FPLC. A peptide was identified with the NH2‐terminal sequence beginning Ser–Leu–Asn, demonstrating the cleavage had occurred at the reactive site of the variant. It is concluded that the Ala 384 to Pro substitution transforms AT Vicenza (/Charleville) from an inhibitor into a substrate.
Teniposide, dexamethasone and continuous‐infusion cyclophosphamide in advanced refractory myeloma
Authors: Leoni Franco , Ciolli Stefania , Salti Franco , Teodori Paolo , Ferrini Pierluigi Rossi 
Published: March 2008

SummaryTwenty‐one patients with advanced refractory myeloma (nine primary unresponsive to melphalan, 12 relapsed and resistant to first‐line salvage therapy) received monthly 7 d courses of cyclophosphamide by continuous infusion, associated with teniposide and dexamethasone. Six patients died within 2 months from start of treatment, before receiving an adequate trial. Among the 15 evaluable patients, there were eight objective responses and three improvements (decrease of monoclonal protein > 50% or > 30%, respectively). After a median follow‐up of 10 months, all responding patients are alive and none of them is still relapsed. In heavily pretreated patients, ineligible for more aggressive approaches, cyclophosphamide by continuous‐infusion exerted a good antineoplastic activity without increasing toxicity.
Detection of soluble IL‐2 receptor in the serum of patients with myelodysplastic syndromes: induction under therapy with GM‐CSF
Authors: Zwierzina Heinz , Herold Manfred , Schöllenberger Susanne , Geissler Dietmar , Schmalzl Franz 
Published: March 2008

Sera of 15 healthy controls and 33 patients suffering from myelodysplastic syndromes (MDS) were investigated for soluble interleukin‐2 receptor (sIL‐2R) expression with a cell‐free enzyme‐linked immunosorbent assay (ELISA) system (T‐Cell Sciences; Cambridge, U. S. A.). The upper limit of the assay is indicated with 477 U/ml. According to the FAB classification eight refractory anaemia (RA). 15 refractory anaemia with excess of blasts (RAEB), five refractory anaemia with excess blasts in transformation (RAEBt) and five chronic myelomonocytic leukaemia (CMML) were examined. None of the patients had reported infectious episodes or been under treatment with cytotoxic agents and/or cytokines within the previous 3 months. Significant differences in sIL‐2R levels between RA (median 368 U/ml), RAEB (median 675 U/ml) and RAEBt (median 971 U/ml) and between RA and CMML (median 723 U/ml) were detected.Six patients, who had been under treatment with rhGM‐CSF for at least 2 weeks, demonstrated a three‐ to sevenfold increase of sIL‐2R expression compared to pretreatment levels. In kinetic evaluation of serum samples for 24 h, the increase of sIL‐2R expression begins within 4 h after subcutaneous application of GM‐CSF and reaches its maximum after 12 h.Our data cannot suggest whether increased sIL‐2R expression is a primary event due to involvement of lymphocytes in the malignant clone or whether it results from secondary alteration of the cytokine network. Application of GM‐CSF in MDS may result in improvement of altered lymphocyte function. As GM‐CSF induces sIL‐2R expression, a down regulation of the immune response caused by neutralization of free IL‐2 cannot be excluded.
Inducibility of lymphokine activated killer (LAK) cells in patients with acute myelogenous leukaemia in complete remission and its clinical relevance
Authors: Archimbaud Eric , Bailly Mireille , Doré Jean‐Françlois 
Published: March 2008

SummaryPeripheral blood mononuclear cells (PBMC) from 42 patients with acute myelogenous leukaemia (AML) in complete remission (CR) and from normal donors were activated into LAK cells in the presence of 1000 U/ml of recombinant interleukin‐2 (rIL‐2). Cytotoxicity of LAK cells was assayed against K562, Daudi, and Raji cell lines, and autologous and/or allogeneic thawed leukaemic blasts. Fresh unactivated PBMC from normal donors and AML patients served as controls. Mean f standard deviation (SD) percentage lysis of the different targets by patient LAK cells were: K562 61 ± 20%. Daudi 62 ± 23%, Raji 48 ± 24%, autologous blast cells 12 ± 16% and allogeneic blast cells 13 ± 10%. Lysis of the different targets by LAK cells from normal donors was similar to that achieved with LAK cells from AML patients. Overall there was a good correlation between the lysis of the different targets. There was no significant difference between the percentage lysis of autologous and allogeneic thawed blast cells, although LAK cells from seven out of the 18 patients tested were unable to lyse autologous leukaemic cells. Activity of patient LAK cells did not correlate with the initial characteristics of the patient nor with the time spent in CR before harvesting PBMC for activation. At the time of analysis, 32 patients were in continuing CR and 10 had relapsed. Multivariant analysis for prognostic factors showed that patients whose LAK cells had more lytic activity on K 562 (P=0·005) and fresh blast cell (P=0·02) targets had significantly less risk of relapse than patients with little inducible LAK cell activity. These observations are in favour of clinical trials of r‐IL2 aimed at prolonging CR in AML.
Alpha interferon raises serum beta‐2‐microglobulin in patients with multiple myeloma
Authors: Tienhaara Anri , Remes Kari , Pelliniemi Tarja‐Terttu 
Published: March 2008

SummarySerum β2‐microglobulin (β2m) levels were followed in eight patients with multiple myeloma who were treated with leucocyte alpha interferon (αIFN) 6 × 106 IU daily for 1‐2 weeks before chemotherapy. Serial measurements of serum β2m were carried out regularly during the first week on αIFN. A rise in β2m was observed in all patients, with maximum increments ranging from 29% to 185% (mean 109%). The increase in β2m was most marked in patients with elevated pretreatment levels of serum β2m and creatinine. In six patients the peak value was reached between the third and the fifth day, after which the levels decreased. In two patients serum β2m remained elevated for 3 and 4 months, respectively. A marked increase in serum β2m can be induced by αIFN in myeloma, which should be taken into consideration when using β2m for the assessment of tumour response during αIFN therapy.
Differentiation between neutrophil‐bound antibodies and immune complexes
Authors: Klaassen R. J. L. , Goldschmeding R. , Vlekke A. B. J. , Rozendaal R. , Kr. von dem Borne A. E. G. 
Published: March 2008

SummaryIt is often unknown whether neutrophil‐bound immunoglobulins (NBIg) in patients with chronic diseases consist of bound immune complexes (IC) or of anti‐neutrophil antibodies. Until now, the detection of IC in serum by the C1q‐binding test has been used to define the nature of NBIg. Here we present studies on methods for characterization of NBIg using a bivalent IC and heat‐aggregated IgG as IC models and neutrophil alloantibodies as antibody models. Heat‐aggregated IgG was readily detected in the C1q‐binding test. However, the bivalent IC, which is capable of binding to both low‐affinity Fc receptors (FcRII and FcRIII) on neutrophils, was not detected in this test. This was due to failure of the bivalent IC to bind to C1q, as was demonstrated by studies with immobilized C1q. However, the bivalent IC as well as heat‐aggregated IgG, when bound to neutrophils from healthy donors, were not or only marginally eluted from the cell surface by lowering the pH, in contrast to a number of different cell‐bound antibodies. This led to the observation that eluates, prepared from sensitized cells, showed reactivity with donor neutrophils, whereas eluates, prepared from cells to which immune complexes had bound, did not. Thus, a negative result in the C1q‐binding test does not prove that a serum does not contain neutrophil‐binding IC, but the reactivity of an eluate can distinguish between anti‐neutrophil antibodies and bound IC.
Simple in vivo bioassay for erythropoietin
Authors: Kawamura Akinori , Imai Nobuo , Kawacuchi Tsutomu , Hayakawa Takao 
Published: March 2008

SummaryA new method of in vivo bioassay for erythropoietin (EPO) is described. This method is based on the measurement of immature reticulocytes in EPO‐treated mice using an automatic microcell counter, and is simpler and more precise than the existing methods of polycythaemic mouse assay and starved rat assay.Normal mice were injected subcutaneously for 3 successive days with EPO at the doses betweeen 0 and 9·6 IU/mouse. On the following day, 20 μl of peripheral blood from each EPO‐treated mouse was collected and haemolysed with a stromatolysing agent, Quicklyser. Residual particles derived from immature reticulocytes in the stromatolysed blood cells were counted using a microcell counter (Sysmex CC‐180A) and a cell monitor (Sysmex CM‐5). The number of the residual particles increased in a dose‐dependent manner in EPO‐treated mice. The mean of correlation coefficients of five log dose‐response lines was 0·924, and the mean of precision indices was 0·138. A good correlation was also observed between the residual particle counts and reticulocyte counts obtained from smears.
Rapid identification by denaturing gradient gel electrophoresis of mutations in the γ‐globin gene promoters in non‐deletion type HPFH
Authors: Gottardi E. , Losekoot M. , Fodde R. , Saglio G. , Camaschella C. , Bernini L. F. 
Published: March 2008

Summary We have outlined a fast, non‐radioactive strategy to identify point mutations in the 5’flanking region of the γ‐globin genes using denaturing gradient gel electrophoresis (DGGE) of amplified DMA. In a sample of previously characterized carriers of non deletion‐type hereditary persistence of fetal haemoglobin (HPFH) the different point mutations in both γ gene promoters could be easily identified by DGGE of a 327 bp fragment. A 4 bp deletion at position —225 to —222 of the Aγ globin gene was unexpectedly found in several samples and shown to represent a frequent polymorphism.Analysis of a 681 bp fragment specific for the 5’region of the Aγ gene, showed that this can be used to determine the haplotype of the chromosome under study.This technique may be useful in the study of sequence variations associated with high Hb F expression in physiological and pathological conditions.
Marrow proliferation and the appearance of giant neutrophils in response to recombinant human granulocyte colony stimulating factor (rhG‐CSF)
Authors: Campbell L. J. , Maker D. W. , Tay D. L. M. , Boyd A. W. , Rockman S. , McGrath K. , Fox R. M. , Morstyn G. 
Published: March 2008

Summary.During a study of recombinant human granulocyte colony stimulating factor (rhG‐CSF) administration, 15 patients received twice daily i.v. infusions and nine patients received daily s.c. infusions of rhG‐CSF for 5 d prior to cytotoxic therapy, and then a second course subsequent to melphalan administration. There was a striking dose‐related neutrophilia and the appearance in the blood of early myeloid cells that express the intercellular adhesion molecule CD54. In addition, giant neutrophils or macropolycytes were observed in the peripheral blood of all patients. These cells were evident on the display of the Technicon H*1 as a population of large peroxidase positive cells, and using Feulgen staining these cells were shown to be tetraploid. Bone marrow kinetics studies performed on Day 4 or 5 indicated an increase in the proportion of bone marrow cells in S phase, G2 and mitosis, reflecting a proliferative response of the marrow. Large myeloid precursors and occasional binucleate promyelocytes were seen in the bone marrows done on Days 14 and 18 but not on Day 5. These findings indicate that administered G‐CSF has both quantitative and qualitative effects on myeloid cells in vivo.
Ber‐H2 (anti‐CD30)‐saporin immunotoxin: a new tool for the the treatment of Hodgkin's disease and CD30+ lymphoma: in vitro evaluation
Authors: Tazzari Pier Luigi , Bolognesi Andrea , Totero Daniela de , Falini Brunangelo , Lemoli Roberto M. , Soria Marco R. , Pileri Stefano , Gobbi Marco , Stein Harald , Flenghi Leonardo , Martelli Massimo F. , Stirpe Fiorenzo 
Published: March 2008

Summary.An immunotoxin containing an anti‐CD30 monoclonal antibody (Ber‐H2) and saporin, a ribosome‐inactivating protein type 1, is described. It specifically inhibits protein synthesis by Hodgkin derived target cell lines with a very high efficiency (IC50 ranging from 5 × 10–12 M to 5.10∼14 M, assaporin), while irrelevant immunotoxins do not. Present results suggest that this immunotoxin could be used for in vivo therapy as well as for ex vivo bone marrow purging in Hodgkin's disease and CD304+ lymphomas.