bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased levels of circulating interleukin‐6 in patients with hodgkin's disease
Authors: Gause Angela , Scholz Rotraud , Klein Sigrid , Jung Wolfram , Diehl Volker , Tesch Hans , Hasenclever Dirk , Pfreundschuh Michael 
Published: February 2007

AbstractExpression of interleukin‐6 (IL‐6) and IL‐6 receptors has been demonstrated in Hodgkin and Reed‐Sternberg (H and RS) cells in vitro and in vivo. In order to evaluate the clinical significance of IL‐6 serum levels in patients with Hodgkin's disease (HD), we tested the sera of 56 untreated patients with HD by means of a sensitive sandwich ELISA. While IL‐6 was only rarely detectable in healthy controls or patients with non‐Hodgkin's lymphoma, 32 of 56 patients (57 per cent) had detectable IL‐6 levels (range 12–32pg/ml). The rates of detectable IL‐6 levels and the median levels were not correlated with age, sex, histological subtype, stage or the presence of B‐symptoms, nor with any of a wide spectrum of laboratory parameters tested, including erythrocyte sedimentation rate, total leukocyte and lymphocyte counts, serum levels of soluble CD8, CD25 or CD30. The rates of complete remissions and freedom from treatment failure were not different in IL‐6‐negative and IL‐6‐positive patients. Except in one of 23 follow‐up sera taken after therapy, IL‐6 was no longer detectable even for patients who suffered from progressing disease, suggesting that the neoplastic H and RS cells are not the major source of circulating IL‐6.
The biological and clinical significance of the KI‐67 growth fraction in multiple myeloma
Authors: Drach Johannes , Gattringer Claus , Glassl Herta , Drach Doris , Huber Heinz 
Published: February 2007

AbstractWe tested the significance of the Ki‐67 plasma cell growth fraction in 49 bone marrow samples from 42 patients with multiple myeloma (MM). As a new approach to study myeloma cell proliferation, strong positivity of the CD38 antigen as plasma cell related feature was simultaneously evaluated with nuclear Ki‐67 expression in a flow cytometric double immunofluorescence assay. Mean Ki‐67 values were significantly higher in MM at relapse (22·4 per cent ± 10·4) as compared with MM at diagnosis (11·9 per cent ± 8·4, p < 0·005) and plateau‐phase (10·0 per cent ± 5·5, p < 0·001), respectively. Serial observations in six patients confirmed this change in cell kinetic behaviour during the course of the disease. Elevated Ki‐67 values correlated significantly with stage III (versus stage I, p < 0·05), beta‐2‐microglobulin serum levels > 6 (p < 0·001), plasmablastic morphology (p < 0·001), and diploid myeloma cell DNA‐content (p < 0·005). No correlation was found between Ki‐67 and immunoglobulin isotypes as well as immunophenotypic features (expression of CD10, CD33, and CD56) of myeloma cells. Clinically, six of seven patients with Ki‐67 > 14 per cent at diagnosis had an unfavourable course (primary resistant disease or early relapse), and three of four patients with elevated Ki‐67 values at plateau‐phase relapsed within 3 months. Our results demonstrate the usefulness of Ki‐67 in determining proliferative activity in MM and emphasize its value in the evaluation of the risk profile of MM patients.
Detection of immunoglobulin gene rearrangement in B‐cell lymphomas by polymerase chain reaction gene amplification
Authors: Liang Raymond , Chan Vivian , Chan T. K. , Wong Thomas , Todd David 
Published: February 2007

AbstractThis is a report on our attempt to use polymerase chain reaction (PCR) to detect rearrangement of the immunoglobulin gene in the tissue specimens obtained from 30 patients with non‐Hodgkin's lymphomas. There were 20 B‐cell lymphomas and 10 T‐cell. All 20 B‐cell lymphomas but none of the 10 T‐cell lymphomas had JH rearrangement by Southern analysis. Two pairs of primers (V670/OL‐4 and VH26/OL‐4) were designed to amplify the CDR3 region of the immunglobulin gene heavy chain. The PCR analysis was positive using either one or both pairs of primers in 11 of the the 20 cases (55 per cent) of B‐cell lymphomas which all had positive rearrangement by Southern analysis. The two pairs of primers seemed to produce complementary results as the specimens may be positive to one pair but negative to the other. The false negative rate of 45 per cent is however much higher than the respective figures of 18 per cent and 0 per cent observed in our patients with acute lymphoblastic leukemia and chronic lymphocytic leukemia in a previous study. Peripheral blood and bone marrow biopsy specimens obtained at the time of initial diagnosis were available from 10 patients with B‐cell lymphomas whose lymph node biopsy specimens at the time of diagnosis were positive by both Southern analysis and PCR. All these peripheral blood and marrow specimens had no microscopic evidence of involvement by lymphoma cells and JH rearrangement was not detected by Southern analysis. However, rearranged bands identical to that of the lymph node biopsy specimen were detected by PCR in the peripheral and marrow blood of one of them. This PCR technique has been shown to have a sensitivity of 0·1 per cent in our previous report and may be more useful than morphology alone or Southern analysis in detecting minimal lymphomatous involvement in the peripheral blood and bone marrow at the time of initial diagnosis. Further clinical correlation is required to confirm the finding.
Proliferation in non‐hodgkin's lymphomas as determined by immunohistochemical double staining for Ki‐67
Authors: Tominaga Kunihiko , Yamaguchi Yoshiko , Nozawa Yoshihiro , Abe Masafumi , Wakasa Haruki 
Published: February 2007

AbstractThe authors have studied proliferation (growth fractions) in non‐Hodgkin's lymphomas (NHL) using an immunohistochemical double staining technique with the monoclonal antibody (MoAb), Ki‐67, in order to clarify the relationships between histologic type, proliferation and prognosis. The percentages of Ki‐67 positive (Ki‐67+) cells in B cell lymphomas were higher for diffuse lymphomas than for follicular lymphomas and increased in order from small to large cell types. In addition, the percentage of Ki‐67+ cells in B cell lymphomas inversely correlated with survival in months (n = 33 r = ‐0·54 p < 0·01). These results indicate that the percentage of Ki‐67+ cells in B cell lymphomas correlates with histologic type and prognosis. Although the prognosis of T cell lymphomas is considered worse than that of B cell lymphomas, the percentage of Ki‐67+ cells was lower, in general, in T cell lymphomas than in B cell lymphomas. These data indicate that proliferation in T cell lymphomas does not correlate with survival.
‘Aggressive’ low grade lymphocytic lymphomas can be identified by flow cytometric s‐phase determinations
Authors: Lindh J. , Jonsson H. , Lenner P. , Roos G. 
Published: February 2007

AbstractForty‐five patients with low grade non‐Hodgkin's lymphomas were studied with respect to the fraction of S‐phase cells in fresh tumour material by flow cytometric analysis. Patients with stage I lymphomas were treated with radiotherapy, patients with stage II‐IV lymphomas with Prednimustine (SterecytR). Patients with lymphocytic lymphomas of CLL type were only treated if they had symptoms. Median S‐phase fraction in the samples was 2‐0 per cent. A significantly shorter survival was found for patients with lymphocytic lymphomas with S‐phase fractions >2·0 per cent compared with cases showing lower S‐phase fractions. No significant difference in survival was found in the subgroups of immunocytic or follicular and follicular diffuse centroblastic/centrocytic lymphomas. In a Cox multivariate analysis, in which also age, constitutional symptoms, stage and morphology were included, the fraction of S‐phase cells was found to be a statistically significant, prognostic parameter for low grade lymphomas, mainly due to the result in the subgroup of lymphocytic lymphomas.
In vitro differentiation of a hodgkin's disease derived cell line
Authors: Klein S. , Jones D. B. , Tesch H. 
Published: February 2007

AbstractWe have examined the Hodgkin's disease derived cell line Co in terms of its capacity to differentiate in vitro. Co cells show the characteristics of immature T cells and express CD3 molecules in the cytoplasm. On activation with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) these cells express the CD3 antigen and the T cell receptor αβ (TCRαβ) on the cell surface. Surface expression of the activation marker CD25 (IL2 receptor) was also greatly increased, whereas CD4 and CD8 levels were not altered. Supernatants of TPA‐stimulated Co cells contained the cytokines IL2, IL3, IL4 and IL8, whereas these cytokines were not detected in the supernatants of untreated cells. Different subclones of the Co cell line differed in their response to TPA with respect to the induced CD3 and TCR expression. Our data demonstrate that a Hodgkin's disease derived cell line can be induced to differentiate in vitro from a pre‐T cell phenotype towards a more mature T cell. It is possible that similar processes may occur in Hodgkin's disease in vivo.
The management of acute myelogenous leukemia in the elderly: Ten‐year experience in 118 patients
Authors: Bassan Renato , Buelli Maurizio , Viero Piera , Minotti Clara , Barbui Tiziano 
Published: February 2007

AbstractThis retrospective study was undertaken to analyse the survival pattern of 118 consecutive, unselected patients with acute myelogenous leukemia (AML) aged between 60 and 82 years observed at a single centre over a 10‐year period (1981–1991). Thirty‐two per cent of cases had an antecedent hematological disorder (AHD), and 7 per cent had a secondary AML. Forty patients (39 per cent) were managed with palliative intent with short courses with oral hydroxyurea ±6‐thioguanine. In contrast to 78 patients (61 per cent) selected for remission‐induction treatment, these were significantly older (P< 0·0001), had a greater incidence of AHD (P<0·039) and of hypoplastic AML (P<0·017), and an inferior amount of blast cells in the bone marrow (P<0·003). Patients undergoing remission‐induction chemotherapy were managed with DAT‐like chemotherapy, high‐dose cytosine arabinoside (HD‐ara‐C), and mitoxantrone‐based regimens. The complete response (CR) rate was 29 per cent. Response was higher with the two most intensive HD‐araC and mitoxantrone‐etoposide‐araC programmes (P<0·026), and correlated favourably with no AHD (P<0·04) and lower blast cell count in the peripheral blood (P <0·02). Overall survival of responders was longer than in palliation and nonresponder groups (P<0·025 and P<0·001, respectively). In the active treatment group, survival correlated with performance status (P<0·005) and blast cell count (P<0·05). Infection was the main cause of morbidity during active treatment, accounting for most induction failures (60 per cent), followed by haemorrhage (12 per cent) and resistant disease (12 per cent). These results from an unselected series represent an improvement over those obtained by us in previous years (1971–1980), and show that intensive treatment programmes are applicable to the elderly with AML and that prolonged disease‐free survival is possible for some. Improving further CR rate and duration will depend equally on the optimization of supportive care measures and the introduction of more effective therapeutic modalities.
Large cell lymphoma with initial presentation in the bone marrow
Authors: Wong K. F. , Chan J. K. C. , Ng C. S. , Chu Y. C. , Li L. P. K. , Chan C. H. 
Published: February 2007

AbstractThis report describes 14 cases of large cell lymphoma with initial presentation as marrow involvement in the absence of peripheral lymphadenopathy. The disease affected mainly the middle‐aged and elderly, with male predominance. Most patients presented with swinging fever and peripheral blood cytopenia. Reactive hemophagocytic syndrome was a common finding, causing significant morbidity and mortality. Peripheral lymphadenopathy was absent (by case selection), but involvement of the liver, spleen and paraaortic lymph nodes could be demonstrated in some cases. However, in some patients, the involvement was apparently restricted to the bone marrow. Involvement of the bone marrow was often subtle, and could be missed on casual examination. Immunohistochemical studies on eight cases showed that four exhibited a B‐cell phenotype. three a T‐cell phenotype and one a non‐T non‐B phenotype. The prognosis was poor, with survival being measured in days to weeks in most patients.
Accumulation of p53 protein correlates with tumour proliferative activity in EBV positive Burkitt's lymphoma
Authors: Lehtinen Tuula , Isola Jorma , Aine Risto , Alavaikko Martti , Lehtinen Matti 
Published: February 2007

Abstractp53 tumour suppressor gene is often found mutated in Burkitt's lymphoma (BL) cell lines and tumours. We analysed 35 BL tumours for the accumulation of p53 protein, and correlated the results with DNA flow cytometric data on the proliferative activity (SPF), and data on the presence or absence of Epstein‐Barr virus (EBV) DNA. More than one‐third (37 per cent) of the tumours showed accumulation of p53, which was considered to be consistent with mutation of the p53 gene. Tumours that were positive both for EBV DNA and p53 had significantly higher mean SPF than corresponding EBV DNA negative and/or p53 negative tumours. The proportions of tumour cells with accumulation of p53 appeared to correlate with tumour SPF only in EBV DNA positive BLs. However, there was no apparent association between accumulation of p53 and the presence or absence of EBV DNA. These findings are suggestive of multiple pathways in BL tumour progression.
A pilot study of chlophepp‐B—A weekly regimen for patients with untreated advanced or recurrent hodgkin's disease
Authors: Smith G. M. , Wright D. , Child J. A. , Simmons A. V. , Norfolk D. R. , Barnard D. L. , Parker D. , Parapia L. 
Published: February 2007

AbstractTwenty‐five patients with either previously untreated advanced Hodgkin's disease (HD) or with relapsed disease were treated with an intensive weekly chemotherapy regimen (ChlOPhEPP‐B) in which the myelo‐suppressive combinations of epirubicin and chlorambucil, and procarbazine and etoposide alternated at two‐week intervals, interspersed with vincristine and prednisolone and then vincristine, prednisolone and bleomycin in a four‐week cycle. Of the previously untreated patients (n=14), 12 (86 per cent) showed a complete response (CR); in the previously treated patients (n=11), CR was achieved in five (46 per cent). Toxicity was predictable and not evidently more severe than with more standard regimens. Neutropenia leading to treatment delay and/or dose reduction was seen in 11 patients (44 per cent) but severe neutropenia (WHO grade 4) was documented in only six patients (24 per cent) for a cumulative total of nine treatment weeks (1‐8 per cent of the total treatment time). Dose reductions for neutropenia were applied in relation to 11 of the 379 weekly treatment points (2·9 per cent). Delays in treatment, for any reason, averaged 3·65 weeks per patient. The study demonstrated the feasibility of a more intensive weekly multidrug schedule. This approach may be applicable in the treatment of advanced HD and represents a further option in the strategy of treating relapsed disease.
Prognostic significance of karyotype analysis in children with acute lymphoblastic leukemia
Authors: Ankathil Ravindran , Stephen J. , Vasudevan D. M. , Kusumakumary P. , Pillai G. Rajasekharan , Nair M. Krishnan 
Published: February 2007

AbstractChromosome studies, using bone marrow samples of 26 pretreated children (below 15 years of age) with Acute Lymphoblastic Leukemia were carried out to explore the potentialities of applying chromosomal findings as a prognostic indicator in these patients. Abnormal karyotype was identified in 15 patients (57·6 per cent). The chromosomes frequently involved in non‐random numerical abnormalities were Nos. 8, 18 and 21. Structural chromosome changes observed consisted of deletion 6q‐ and translocation t (4; 11).After karyotype analysis, patients were grouped into subsets on the basis of the karyotype pattern observed. They were followed up to evaluate their prognosis and survival period. Patients showing hyperdiploid clone with greater than 51 chromosomes had the best prognosis. Patients with normal karyotype and patients with deletion of the long arm of chromosome 6 showed intermediate prognosis whereas patients showing t (4; 11), trisomy 8, trisomy 18, trisomy 21, and hypodiploid karyotype were associated with worst prognosis. Thus, karyotype analysis before treatment helps to classify ALL patients as poor, intermediate and good prognosis groups and on this basis therapy can be designed accordingly.
Identification of some marker chromosomes in acute leukemias by fluorescence in situ hybridization
Authors: Shi Guangping , Weh Hans Josef , Hossfeld Dieter K. 
Published: February 2007

AbstractFour patients with acute leukemia are presented in whom conventional karyotypic analysis had revealed complex numerical and structural changes including unidentifiable (marker) chromosomes. It is demonstrated that the application of fluorescence in situ hybridization (FISH) may contribute to the identification of such anomalies.
Pharmacokinetics of high dose methylprednisolone and use in hematological malignancies
Authors: Patel P. M. , Selby P. J. , Graham M. A. , Viner C. , Newell D. R. , McElwain T. J. 
Published: February 2007

AbstractThe pharmacokinetics of oral and intravenous high dose methylprednisolone (Solu‐medrone, Upjohn) were compared in patients with hematological malignancies. The aim of the study was to determine the oral bioavailability of high dose methylprednisolone and to establish whether this is a feasible and more convenient route of administration. The plasma pharmacokinetics were described by a one‐compartment open model with peak plasma levels of 6·9 ± 2·5 μg/ml. Total area under the plasma concentration versus time curve was similar by either route. Mean relative oral bioavailability was generally high (91 ± 27 per cent).Retrospective analysis of 34 patients with chronic lymphocytic leukemia (CLL), non‐Hodgkin's and Hodgkin's lymphoma treated with high dose methylprednisolone showed 11 responses including two complete remissions among nine patients with CLL. There was significant improvement in platelet counts in thrombocytopenic patients and treatment was well tolerated and toxicity was relatively low. High dose methylprednisolone may therefore be a useful palliative treatment for hematological malignancies, particularly where marrow suppression is a problem.
Evidence of colony suppressor activity and deficiency of hematopoietic growth factors in hairy cell leukemia
Authors: Gasché Christoph , Reinisch Walter , Schwarzmeier Josef D. 
Published: February 2007

AbstractThe cause of myelosuppression in hairy cell leukemia (HCL) has been ascribed to a reduction of the circulating progenitor cell (CPC) compartment and to suppression of hematopoiesis by TNF‐α. The present study was performed to evaluate the inhibitory effect of hairy cells (HCs) and a possible lack of hematopoietic growth factors on the number of autologous CPCs in vitro. In initial experiments the number of circulating BFU‐E, CFU‐GM and CFU‐mix in HCL patients was found decreased. Monocytopenia but not the number of circulating HCs correlated to the degree of colony reduction in our patients. This pointed to a lack of colony stimulating factors (CSFs) in HCL. Actually, the growth of BFU‐E, CFU‐GM, and CFU‐mix improved upon the addition of IL‐3 and GM‐CSF in HCL patients but not in healthy donors. To test the suppressive role of HCs in our assay system, cultures were performed after removal of autologous HCs. The results showed that in HC‐depleted cultures the numbers of BFU‐E, CFU‐GM, and CFU‐mix were significantly higher. This inhibitory effect of HCs could partially be neutralized by the addition of monoclonal antibodies against TNF‐α. When the assays were performed with the removal of HCs and the addition of CSFs normal progenitor cell counts were detected in most patients. We conclude that HCs mediate the inhibition of colony growth in part by TNF‐α. Monocytopenia is related with a deficiency of CSFs in this disease. The reduced colony growth in HCL, therefore, is due to both the inhibitory effects of HCs and the deficiency of CSFs. We suppose that the CPC‐compartment is actually preserved in this disease.
CORRELATION OF IMMUNOLOGICAL SURFACE ANTIGENS WITH SURVIVAL IN DIFFUSE LARGE CELL LYMPHOMA
Authors: Pilkington G. , Juneja S. , Tan L. , Matthews J. , Quirk J. , Lee G. , Ironside P. , Cooper I. , Jose D. 
Published: February 2007

AbstractThe prognostic value of immunophenotyping lymphomas with a panel of monoclonal antibodies (Mab) to various lymphoid antigens was assessed by studying 47 cases of diffuse large cell lymphoma. Cell suspensions were analysed by flow cytometry after labelling by indirect immunofluorescence. Thirty‐eight cases were demonstrated to be of B cell and nine of T cell phenotype. Univariate analysis demonstrated that survival was significantly longer in patients expressing higher levels of HLA‐DR (p=0·01) and normal levels of CD8 (p=0·04) but was not significantly associated with any of the other antigens. Our results support the possible value of HLA‐DR in determining the prognosis of patients with diffuse large cell lymphoma.
The management of chronic lymphocytic leukemia at a single centre over a 24‐year period: prognostic factors for survival
Authors: Karmiris T. , Rohatiner A. Z. S. , Love S. , Carter M. , Ganjoo R. K. , Amess J. , Norton A. J. , Lister T. A. 
Published: February 2007

AbstractOver a 24‐year period, 137 patients were referred for management of newly diagnosed chronic lymphocytic leukemia. One hundred and nineteen patients have been reviewed in terms of response to therapy and prognostic factors for survival; 18 patients were excluded either because lymph node biopsy was not compatible with the diagnosis of CLL (11 patients), or because the lymphocyte count at presentation was < 5 × 109/1 (seven patients).Patients were staged retrospectively according to both the Rai and Binet Classifications. Forty‐eight per cent (57/119) were deemed not to be in need of any treatment at presentation, 36 per cent (43/119) have never received any specific therapy. The majority of patients received chlorambucil alone, at a dose of 10 mg daily given for 6 weeks, followed by a 2‐week interval, followed by three, 2‐week cycles. The overall response rate (complete + partial remission) was 38 per cent.In terms of survival, there was a trend in favour of patients who responded to treatment in comparison with those who did not but this did not reach statistical significance (P=0.07). Correlation with stage were highly significant, the median survivals for patients with stage A, B and C disease (Binet) were 12.5, 8 and 3.5 years respectively. On univariate analysis, the absolute lymphocyte count at presentation was the most significant prognostic factor for survival, patients presenting with an absolute lymphocyte count above 50 × 109/1 having a less favourable prognosis (P=0.002). However, on multivariate analysis, older age, a low hemoglobin, low platelet count, and the presence of lymphadenopathy and fever at presentation correlated adversely with survival.Overall, 40 patients died as a consequence of CLL or from disease‐related causes, 34/40 dying of infection. Twenty‐one patients developed second cancers.With a median follow‐up of 13 years, these results confirm that the two staging systems can separate patients into prognostic groups, however in practice, there is heterogeneity of outcome within stage. New approaches are urgently needed.