bluuebunny/crossref_metadata_2025 huggingface dataset:
Type‐specific anti‐pneumococcal antibody subclass response to vaccination after splenectomy with special reference to lymphoma patients
Authors: Grimfors G. , Björkholm M. , Hammarström L. , Asksrgrsn J. , Smith C. I. E. , Holm G.
Published: July 2010

The IgG and IgA antibody subclass responses to pneumococcal polysaccharide antigens type 6A and 19F were studied after immunization with a 14‐valent vaccine (Pneumovax®, MSD), in 53 splenectomized patients (11 Hodgkin's disease, 13 non‐Hodgkin's lymphoma (NHL), 9 immune haemolytic anaemia or idiopathic thrombocytopenic purpura and 20 posttraumatic splenectomized patients) and 18 non‐splenectomized controls. The antibodies were mainly restricted to the IgG2 and IgA2 subclasses. NHL patients had lower pre‐vaccination values to the studied antigens and lower antibody response to vaccination than the other patient groups in which the antibody responses did not differ from those of controls. 1 vaccinated NHL patient experienced two episodes of pneumococcal septicaemia, both occurring after chemotherapy which abolished the previously normal IgG2 antibody levels to the pneumococcal antigens. It is concluded that the antibody response to 6A and 19F antigens after pneumococcal vaccination is not reduced in splenectomized patients but is impaired in immunodeficiency states associated with B‐cell lymphoma and treatment with cytostatic drugs.
Mitoxantrone and etoposide: An effective regimen for refractory or relapsed acute myelogenous leukemia
Authors: Lazzarino M. , Morra E. , Alessandrino E. P. , Orlandi E. , Pagnucco G. , Merante S. , Bernasconi P. , Inverardi D. , Bonfichi M. , Bernasconi C.
Published: July 2010

23 adult patients with refractory or relapsed acute myelogenous leukemia (AML) received salvage chemotherapy with mitoxantrone and etoposide. The regimen consisted of mitoxantrone, 10 mg/m2/d by 30‐min infusion, and etoposide 100 mg/m2/d by 30‐min infusion, given 12 h apart for 5 consecutive d. Of 23 patients treated, 13 met the criteria for highly refractory disease (6 primary resistant; 4 with early relapse during maintenance; 3 relapsed and refractory to reinduction). 10 patients had relapsed off‐therapy more than 6 months after achieving first CR. Overall, 14 patients (61%) achieved a complete remission (CR): 6/13 (46%) with refractory AML, and 8/10 (80%) with relapsed AML. 2 patients had a partial remission, 2 died in aplasia, and 5 were nonresponders. In responding patients, the median time for recovery of granulocyte count was 27 d. The most important nonhematologic side effect was oral mucositis, which was severe in 35% of cases. No signs of cardiac toxicity were observed. The median CR duration was 5 months (range, 2 to 12+ months). The combination of mitoxantrone and etoposide appears a highly effective and relatively well tolerated salvage regimen for refractory and relapsed AML. Its incorporation into first‐line induction and consolidation programs for newly diagnosed AML patients should be considered.
Circulating erythroid and megakaryocytic progenitors in polycythaemia vera and essential thrombocythaemia
Authors: Florensa L. , Besses C. , Almarcha J. , Lafuente R. , Palou L. , Pedro C. , Sans‐Sabrafen J. , Woessner S.
Published: July 2010

We studied the behaviour in culture of erythroid and megakaryocyte progenitor cells (BFU‐E, CFU‐MK) obtained from peripheral blood (PB) in 38 patients: 15 with essential thrombocythaemia, 3 with reactive thrombocytosis, 16 with polycythaemia vera and 4 with secondary polyglobulia. Clonal erythroid growth without added erythropoietin was observed in all patients with polycythaemia vera and in 5 out of 15 with essential thrombocythaemia, but in none of the patients with reactive thrombocytosis or secondary polyglobulia or in controls. When the CFU‐MK were cultured without phytohaemagglutinin‐stimulated medium (PHA‐LCM), all patients with essential thrombocythaemia and 7 out of 16 with polycythaemia vera showed circulating CFU‐MK but none of those with reactive thrombocytosis or secondary polyglobulia or controls did so. This study indicates that the growth in vitro of megakaryocyic and erythroid progenitors from such a readily available source as peripheral blood can be valuable in the diagnosis of certain borderline cases of thrombocytosis or erythrocytosis.
Use of the ferritin/alanine aspartate transaminase ratio as an iron overload marker independent of liver cell damage
Authors: Triadou P. , Regnat‐Lusinchi A. , Girot R.
Published: July 2010

To define an iron overload index independent of liver cell damage, the mean annual levels of alanine aspartate transaminase (ALAT) and serum ferritin and their ratios were determined. Ferritin/ALAT ratio values were compared between two groups of patients with acute or chronic hepatitis without iron overload, and one group of thalassaemic patients with iron overload. The two groups without iron overload exhibited ferritin/ALAT ratio values of 2 and 1.2 respectively; a ratio value higher than 10 was always observed in those patients with iron overload. The ferritin/ALAT ratio is correlated with the degree of iron overload. This ratio increases in regularly‐transfused patients without chelation treatment. It generally remains stable or decreases after initiation of iron chelation therapy. The ferritin/ALAT ratio thus appears useful in the follow‐up of patients subjected to a long‐term transfusional treatment particularly when acute or chronic lilver cell damage may interfere with iron overload by increasing serum ferritin values.
Radioprotection by murine and human tumor‐necrosis factor: Dose‐dependent effects on hematopoiesis in the mouse
Authors: Slørdal Lars , Muench Marcus O. , Warren David J. , Moore Malcolm A. S.
Published: July 2010

Tumor‐necrosis factor (TNF) has been shown to confer significant radioprotection in murine models. Herein, we demonstrate a dose‐dependent enhancement of hematological recovery when single doses of either murine or human recombinant TNF are administered prior to irradiation. In addition to its action upon leukocytes and erythrocytes, TNF also alleviates radiation‐induced thrombocytopenia in the mouse. These effects on circulating blood constituents are further reflected in increased numbers of both primitive (CFU‐S) and more differentiated (CFU‐GM, CFU‐Mega) hematopoietic progenitors in TNF‐treated animals. This suggests that TNF exerts it radioprotective effects on a pool of primitive multi‐potential hematopoietic cells.
Qualitative platelet defects in chronic myeloproliferative disorders: Evidence for reduced ATP secretion
Authors: Löfvenberg Eva , Nilsson Torbjörn K.
Published: July 2010

19 consecutive untreated patients with chronic myeloproliferative disorders and thrombocytosis were subjected to comprehensive platelet function tests including platelet aggregometry. 12 patients had essential thrombocythaemia (ET) and 7 patients had polycythaemia vera (PV). Bleeding time was normal. Arachiconic acid, collagen and ristocetin aggregation were abnormal only in a minority of patients, whereas ADP aggregation was impaired in 16 out of 19 patients. The most conspicuous findings were abolished second‐wave adrenalin aggregation, increased ADP aggregation threshold, and markedly reduced ATP secretion during collagen‐induced aggregation. This triad of qualitative platelet defects seems to be a good diagnostic marker of chronic myeloproliferative disease with thrombocytosis.
Hexose monophosphate shunt activity in erythrocytes related to cell age
Authors: Ouwerkerk Ronald , Damen Peter , de Haan Karen , Staal Gerard E. J. , Rijksen Gert
Published: July 2010

Erythrocytes were separated by age using a combination of density centrifugation and counterflow centrifugation and tested for basal activity of the hexose monophosphate shunt (HMP‐shunt) as well as the methylene blue‐stimulated maximal capacity by measuring CO2 production. No significant differences were found in basal HMP‐shunt activity, but the maximal methylene blue‐stimulated activity of old erythrocytes reached only half of the activity of the total cell population. The maximal HMP‐shunt activity showed a significant correlation with hexokinase activity, but not with glucose‐6‐phosphate dehydrogenase activity in all but the youngest cells. The sensitivity to oxidative stress was tested by measuring the kinetics of pyruvate kinase isolated from erythrocytes incubated in presence and absence of methylene blue. Pyruvate kinase kinetics were affected more in the old cell population than in the total cell population: the K0.5 for phosphoenol‐pyruvate increased four times in the unseparated cells and eight times in old cells.
Accumulation of vincristine and doxorubicin in malignant lymphocytes with different immunophenotypes
Authors: Reizenstein Peter , Kapoor Rohit , Gruber Astrid , Peterson Curt
Published: July 2010

Cellular accumulation of vincristine (VCR) and doxorubicin (DOX) was studied in 15 patients with low‐grade B‐cell malignancies. Their leukemic lymphocytes were isolated and the effect of verapamil on drug uptake was studied. The immunophenotype was characterized using anti‐IgM, ‐IgD, ‐B 1, monoclonal antibodies. The more that cells bound the IgD or B1 antibodies, the more vincristine and doxorubicin did they accumulate. The fewer the cells that bound IgM antibodies, the more drug did they accumulate.
Treatment of pure red‐cell aplasia and aplastic anaemia with Ciclosporin: Long‐term clinical effects
Authors: Tötterman Thomas H. , Höglund Martin , Bengtsson Mats , Simonsson Bengt , Almqvist Dick , Killander Andreas
Published: July 2010

6 patients with pure red‐cell aplasia were treated with Ciclosporin (Cyclosporine A; CS) alone or combined with prednisolone for a period of 9–46 (median 27) months. Prior to study, 5 cases had refractory disease, steroids were contraindicated in 1, and 4/6 patients, including 2 cases with congenital disease, had a disease duration exceeding 11 years. A complete haematological response was obtained in 5/6 subjects, and a partial response in 1. When the pre‐treatment Hb levels (mean±S.D. = 64±13 g/l, range 41–80) for all 6 PRCA patients were compared with the Hb levels after 6 months of CS therapy (104±17 g/1, 80–125), a significant improvement was registered (p < 0.005). In half of the patients, remission is maintained with CS as single drug in a dose‐dependent manner. We also treated 5 patients with refractory severe aplastic anaemia with CS (1 case) or CS plus prednisolone (4 cases) for 3–27 (median 10) months. Only 1 patient responded. In this case, a complete haematological remission was induced with CS alone, and remission has been maintained for 27 months. Side effects of CS therapy were common but were dose‐dependent and reversible, with the exception of persistent nephrotoxicity in 1 patient with pure red‐cell aplasia. Based on our present results and a survey of the literature, we conclude that CS therapy is effective and indicated in refractory pure red‐cell aplasia. In severe aplastic anaemia resistant to conventional immunosuppression, the response rate is lower, but a small proportion (around 15%) of patients may benefit from CS therapy. Longer treatment periods may, however, be needed to evaluate the role of CS in aplastic anaemia.
Immunoglobulin heavy‐chain gene rearrangement in peripheral blood mononuclear cells in non‐Hodgkin's lymphomas ‐ Correlation with kappa:lambda analysis and clinical features
Authors: Lindh Jack , Lindstrøm Anita , Lenner Per , Lundgren Erik , Roos Göran
Published: July 2010

41 patients with non‐Hodgkin's lymphomas were analysed to determine occurrence of B‐cell monoclonality in peripheral blood mononuclear cells using two different methods: determination of kappa:lambda ratio by light microscopic immunofluorescence, and heavy‐chain gene rearrangement by DNA‐technique. In 21 patients (51%) clonal heavy‐chain rearrangement was found in blood, whilst 18 of the patients (44%) showed and abnormal kappa:lambda ratio. Discordant results between the methods were observed in 5 cases. Clones with gene rearrangements suggesting blood involvement were found in 16/25 (64%) patients with low grade lymphomas, in 5/16 (31%) patients with high grade lymphoma, in 17/21 (81%) patients with bone marrow involvement, in 20/27 (74%) of stage III‐IV lymphomas and in all of the 14 patients with high lymphocyte count (≥ 5.0 times 109). The conclusion was that clonal analysis by the DNA‐technique is a more sensitive method than the kappa:lambda determination using immunofluorescence. Even though the method is time‐consuming, it could prove to be valuable in selected cases.
Sequential expression of CD34 and CD33 antigens on myeloid colony‐forming cells
Authors: Bühring Hans‐Jörg , Asenbauer Bernhard , Katrilaka Kalizia , Hummel Gabriele , Busch Friedrich W.
Published: July 2010

The expression of CD33 and CD34 antigens on human bone marrow cells was examined by fluorescence‐activated cell sorting and colony assays. A marked difference of antigen expression was observed on sorted progenitors of the granulocyte/macrophage lineage (CFU‐GM) with respect to enrichment and maturation status. Single‐color cell sorting revealed no difference of enrichment by anti‐CD33 antibody between day‐7 and d‐14 progenitors, while anti‐CD34 antibody preferentially enriched d‐14 colony‐forming units (CFU). By two‐color cell sorting it could be shown that enrichment of d‐14 CFU‐GM occurred mostly in the CD34+CD33‐ and to a lesser extent in the double‐positive fraction. In contrast, there was no difference in degree of enrichment between d‐7 and d‐14 CD34‐CD33+ CFU‐GM. From these data we conclude that, during early myelopoiesis, CD34 antigens are gradually lost while CD33 antigens are acquired.
Is the histological classification of chronic granulocytic leukaemia justified from the clinical point of view?
Authors: Rozman Ciril , Cervantes Francisco , Feliu Evaristo
Published: July 2010

By means of morphometric techniques, in 100 untreated Ph'‐positive chronic granulocytic leukaemia (CGL) patients the main features from the initial bone marrow biopsy were analyzed, with particular attention being paid to morphological and quantitative study of megakaryocytes. The number of megakaryocytes per mm2 of marrow tissue showed a mean value of 25.3 (SD±18.8), and was positively correlated with either platelet counts, blood percentage of basophils and blast cells, or spleen and liver size. Based on the number and morphological characteristics of megakaryocytes, patients were classified as having granulocytic CGL (67 cases) or the so‐called chronic megakaryocytic‐granulocytic myelosis (33 cases), but except for higher platelet counts and blood percentages of basophils and blast cells in the latter, no relevant clinical, evolutionary or prognostic differences were observed between the groups. Such results cast doubt on the validity of histological classification of CGL from the clinical point of view.
Follicular low‐grade non‐Hodgkin's lymphoma: Long‐term outcome with or without tumor progression
Authors: Ersbøll Jens , Schultz Henrik B. , Pedersen‐Bjergaard Jens , Nissen Nis I.
Published: July 2010

Long‐term outcome for 127 patients with follicular low‐grade lymphoma was investigated. Therapy included radiotherapy (n = 23), low toxicity chemotherapy with or without radiotherapy (n = 76), or more intensive chemotherapy (n = 22). 6 patients had no initial therapy. Complete remission was obtained in 67% of patients. For patients under 60 years of age median survival was 8.7 yr compared with 3.8 yr for older patients, but survival from lymphoma was identical for the two age‐groups: 75% at 5 yr, and 58% at 10 yr. The relatively low tumor mortality contrasted with a relapse‐free survival of 30% at 10 yr, and relapse 8–9 yr after first remission. Examining the disease topography and the stability of histologic subtype in 78 patients with recurrent lymphoma, two types of relapse with different prognoses were identified: 1)withtumor progression (lymphoma dissemination to atypical extranodal sites and/or histologic conversion to an intermediate/high‐grade lymphoma) seen in 56% of patients with a survival from lymphoma of 13% at 10 yr; and 2)withouttumor progression (involvement of nodal sites, and unchanged histology) seen in 44% with a survival from lymphoma of 77% at 10 yr. Actuarial risk of tumor progression was 44% at 5 yr, and 67% at 10 yr. Except from the negative impact of a large tumor burden, it was not possible to identify patients with high risk for tumor progression. More important than all pretreatment factors was poor response to initial therapy (p = 0.0001). Due to lack of reliable risk factors, it is recommended that all younger patients be treated with the intention of achieving complete remission; a significant fraction might be curable.
Cell‐mediated inhibition of granulopoiesis in vitro in patients with acute myeloid leukemia in remission
Authors: Sallerfors Bengt , Olofsson Tor
Published: July 2010

We investigated the in vitro granulopoiesis in 11 patients with acute myeloid leukemia (AML) in complete remission 3–80 months after diagnosis (median 8.5 months). 3 of the patients had subnormal levels of bone marrow‐derived CFU‐GM. 6 of 10 patients tested had defective recloning capacity of d‐7 CFU‐GM, suggesting a stem cell defect. Most patients (7/11) showed an increased colony growth of bone marrow‐derived CFU‐GM after T‐cell depletion by E‐rosetting, while readdition of isolated autologous T cells to T‐cell depleted marrow caused a dose‐dependent inhibition of colony formation; bone marrow T cells were more effective in this inhibition than peripheral blood T cells. Experiments using cells depleted of either CD4‐ or CD8‐positive cells and CD4/CD8‐enriched cell populations showed that both CD4‐ and CD8‐positive cells had the capacity to inhibit colony growth. Long‐term culture of bone marrow cells in suspension showed that the production of CFU‐GM declined at about the same rate as in normal controls. Our findings suggest that there are persisting stem cell defects in patients with AML in remission and that the cell growth regulatory systems may be altered. These abnormalities could possibly be an effect of residual damage to the hematopoietic system caused by intensive chemotherapy.
Bone marrow and tissue expression of gpIIb/IIIa, LFA‐1, Mac‐1 and gp150,95 glycoproteins
Authors: Soligo Davide , Cattoretti Giorgio , Colombi Mariangela , Polli Nicoletta , Capsoni Franco , Rilke Franco , Deliliers Giorgio Lambertenghi
Published: July 2010

Monoclonal antibodies (MAbs) against platelet glycoprotein gpIIb/IIIa and the leucocyte adhesion molecules LFA‐1, Mac‐1, and gp 150,95 α chain (CD11a,b,c) and β chain (CD18) have been tested in normal and leukaemic bone marrows, in different human tissues, and in a patient with leucocyte adhesion deficiency (LAD). The effect of these MAbs on platelet aggregation was also tested. GpIIb/IIIa showed widespread distribution, while reactivity of CD11/18 antibodies was limited to haematopoietic cells. Platelets and megakaryocytes were reactive with one CD11a (25.5.2), and with no CD11b/c or CD18 MAbs. GpIIb/IIIa was present on the platelets of the patient with LAD, whereas 25.5.2, (CD11a) bound to his platelets but not to his leucocytes. These data indicate that LFA‐1, Mac‐1, and gp150,95 are not present on human platelets, but they suggest the existence of crossreacting epitopes on gpIIb/IIIa, which is consistent with the hypothesis that these molecules belong to a supergene family of adhesion molecules.
Treatment of acute myeloid leukemia in elderly patients with oral idarubicin as a single agent
Authors: Harousseau J. L. , Rigal‐Huguet F. , Hurteloup P. , Guy H. , Milpied N. , Pris J.
Published: July 2010

Idarubicin (IDR) is a new anthracycline that can be administered orally. Oral IDR was given at a dose of 30 mg/m2 daily for 3 d in 20 patients aged 65 to 79 yr with previously untreated acute myeloid leukemia (AML). 5 patients whose marrow remained blastic at d 14 received a second course. 8 patients achieved complete remission (6 after one single course). There were: 1 early death, 4 deaths in aplasia, 7 failures. The hematologic toxicity was high. All but 1 patient had to stay in hospital and the duration of neutropenia was 12 to 34 d (median 19). Oral IDR is an effective therapy for AML in elderly patients but the total dose of 90 mg/m2 is too aggressive to be administered safely outside the hospital.
Quantitation of platelet antigens after chloroquine treatment
Authors: Langenscheidt F. , Kiefel V. , Santoso S. , Nau A. , Mueller‐Eckhardt C. , Mueller‐Eckhardt C.
Published: July 2010

The effect of chloroquine treatment on the expression of various platelet antigens was studied. For this purpose, the binding of several human platelet‐reactive antibodies (polyspecific HLA antibodies; platelet‐specific PlA1, PlA2, Baka antibodies; platelet autoantibodies) and of murine monoclonal antibodies specific for epitopes on the glycoprotein (Gp) complexes IIb/IIIa or Ib/IX were quantitated by means of a competitive enzyme‐linked immunoassay (CELIA) using fresh and stored chloroquine‐treated platelets. We found that HLA antigens were substantially removed from platelets following chloroquine treatment (confirming earlier results) while platelet‐specific antigens on the Gp complex IIb/IIIa were but little affected. Epitopes on the Gp complex Ib/IX did not show any alteration. Storage of chloroquine‐treated panel platelets known to interfere with immunofluorescence had no effect on quantitative IgG determinations by CELIA. We conclude that chloroquine treatment of platelets is practicable for platelet antibody analysis, but exerts its effect unspecifically and requires cautious interpretation.
B lymphocyte function in multiple myeloma: Analysis of T cell‐ and monocyte‐dependent antibody production
Authors: Peterson Jørgen , Drivsholm Aage , Brandt Mathilde , Ambjørnsen Anne , Dickmeiss Ebbe
Published: July 2010

T‐cell and B‐cell functions were studied in 35 patients with untreated multiple myeloma (MM) and in 16 patients with MM treated with prednisolone, melphalan and vincristine. The numbers of CD4+ T cells were normal in untreated MM patients, but markedly decreased in treated patients, whereas CD8+ cell numbers were normal in untreated and treated patients. Mitogen‐induced as well as antigen‐induced lymphocyte proliferative responses were reduced, but not further affected by treatment. The antigen‐induced proliferative responses by lymphocytes of treated, but not of untreated patients, correlated positively to the proportions of CD4+ cells among MNC. Taken together, the findings suggest selective loss of CD4+ subpopulations during cytotoxic treatment. Pokeweed mitogen (PWM)‐induced Ig production was generally low, but significantly reduced Ig production was only seen in experiments employing MM B cells and monocytes co‐cultured with irradiated T‐enriched cells. Irradiated MM T cells displayed normal helper function when co‐cultured with normal B cells stimulated with PWM. MM B cells and monocytes cultured with irradiated normal T cells produced little Ig; however, MM monocytes were not suppressive. In 2 of 3 patients with either IgG‐κ or IgA‐κ myeloma, the numbers of PWM‐stimulated B cells that produced κ chains were somewhat higher than those found among normal MNC. The impaired ability of antibody production by B cells from untreated MM patients seems to relate to intrinsic B cell defect(s) rather than to abnormal regulation by T cells or monocytes. However, disturbances in the functions of CD4+ cells may be observed in treated MM.
Interest of simultaneous ultrastructural characterization of morphology, cytochemistry and immune phenotype in a case of putative hybrid acute leukaemia
Authors: Lavabre‐Bertrand T. , Vannereau H. , Donadio D. , Escola M. J. , Taib J. , Poncelet P. , Rousset T. , Bertheault F. , Lefort G. , Senelar R. , Emberger J. M. , Navarro M.
Published: July 2010

A case of acute leukaemia is reported in which blast cells expressed some B‐related antigens (namely the CALLA antigen) and no peroxidase activity at the optical level; however, some mature granular cells contained Auer rods. Simultaneous characterization of ultrastructural morphology, cytochemistry and immune phenotype was performed. There was an apparent mutual exclusion in the expression of myeloperoxidase activity and the CALLA antigen, and a heterogeneity in the CALLA expression among the blastic population. These results disagree with the hypothesis of a true biphenotypic leukaemia and demonstrate a complete heterogeneity between the lymphoblastoid cells and the myeloid ones. The interest of such a simple combined method in a case of putative hybrid acute leukaemia is emphasized.
Spontaneous erythroid colony formation in the differential diagnosis of erythrocytosis
Authors: Partanen S. , Juvonen E. , Ikkala E. , Ruutu T.
Published: July 2010

Erythroid colony formation in vitro was studied in 80 patients with erythrocytosis. 43 of the patients had polycythaemia vera (PV), 18 patients had secondary erythrocytosis, 6 had normal red cell mass, and 13 patients were regarded as unclassified. Spontaneous erythroid colony formation, in the absence of exogenous erythropoietin in the cultures, was discovered in all patients with PV, whereas no patient with secondary erythrocytosis or with normal red cell mass showed this phenomenon. 8 of the 13 patients with unclassified erythrocytosis spontaneously formed erythroid colonies. 7 patient with unclassified erythrocytosis have been followed for 5 yr. 3 of the 4 patients with spontaneous colony growth but none of the 3 without it can now be classified as PV. Thus, spontaneous erythroid colony formation indicates PV even in early and atypical cases. Therefore, the culture of erythroid progenitors is very useful in the differential diagnosis of problematic cases with erythrocytosis.
HIV‐disease and bone marrow changes: A study of 60 cases
Authors: Mir Naheed , Costello Christine , Luckit John , Lindley Roger
Published: July 2010

We report our experience of peripheral blood and bone marrow changes in patients with HIV disease. Abnormalities were most commonly seen in patients with advanced disease. In AIDS group IV patients (CDC classification) anaemia (92%) neutropenia (85%) monocytopenia (75%) and thrombocytopenia (61%) have their highest incidence, the reason being a combination of factors such as infection, myelosuppressive drugs and HIV infection itself. Bone marrow examinations were performed most commonly for microbiological culture (25%) and the investigation of anaemia (16%). Morphological changes in the bone marrow were non‐specific and not pathognomic; however erythroid hypoplasia was found to be a distinctive feature associated with MAI infection. The procedure provided a high yield for microbiological culture, particularly in MAI infection.
Gallium scanning in the management of mediastinal Hodgkin's disease
Authors: Wylie B. R. , Southee A. E. , Joshua D. E. , McLaughlin A. F. , Gibson J. , Hutton B. F. , Morris J. G. , Kronenberg H.
Published: July 2010

Gallium‐67 scanning was performed pre‐ and post‐therapy in 25 patients with Hodgkin's disease and a mediastinal mass. At restaging after therapy, radiographs (or CT scans) did not predict the presence of active disease whereas gallium scans did with a high degree of accuracy. Gallium‐67 determined disease activity in those patients who had a residual mediastinal mass predicting outcome in 11 out of 12 patients; one had a late relapse at 7 years. In patients without a residual mass gallium scanning was again accurate, predicting outcome in 11 of 13 patients. Two patients with negative gallium scans but subsequent active disease were scanned too soon after chemotherapy. The results suggest that gallium scanning has an important role in the mangement of mediastinal Hodgkin's disease and is superior to all current methods of assessing disease activity irrespective of the presence of a residual mediastinal mass.
Effects of recombinant G‐CSF and GM‐CSF on in vitro differentiation of the blast cells of RAEB and RAEB‐T
Authors: Tohyama Kaoru , Ohmori Seiichi , Michishita Masahiro , Ueda Takeo , Ueda Yasunori , Sakoda Hiroto , Yoshida Yataro , Uchino Haruto
Published: July 2010

To evaluate the effects of recombinant G‐CSF and GM‐CSF on RAEB and RAEB‐T cells, blast cells from 6 patients were incubated in liquid culture systems with these CSFs for 7 days, and their numerical, morphological and functional changes were assessed. Both CSFs stimulated cell growth, but decreased the proportion of blast cells in 5 of the 6 cases. Karyotypic abnormalities persisted during cultivation in some cases. The CSFs also stimualted the expression of part of the esterase activities, and a positive interaction of both CSFs was seen in part. Although CSFs had no significant effects on the ability of cells to reduce NBT or to phagocytize latex particles, the results indicated that they induce partial differentiation of blast cells. It appears that such pathological cells still retain the capacity to respond to growth factors.
Genetic and other influences on red‐cell flavin enzymes, pyridoxine phosphate oxidase and glutathione reductase in families with β‐thalassaemia
Authors: Anderson B. B. , Perry G. M. , Clements J. E. , Studds C. , Fashola R. , Salsini G. , Vullo C.
Published: July 2010

In 18 β‐thalassaemia families from the Ferrara area the incidence of an inherited low flavin mononucleotide (FMN)‐dependent pyridoxine phosphate (PNP) oxidase activity, a sensitive indicator of red‐cell FMN deficiency, is higher in related members in these families than in the unrelated spouses and controls subjects without family history of thalassaemia. This suggests slower red‐cell riboflavin metabolism in thalassaemia families, which may have resulted from selection in combination with thalassaemia by malaria. However, there was a markedly higher incidence of red‐cell flavin adenine dinucleotide (FAD) deficiency in thalassaemia heterozygotes than in their normal relatives. This was indicated by higher stimulation of FAD‐dependent glutathione reductase (GR) activity by FAD and lower GR activity per red cell, and suggests a marked additive effect by thalassaemia on the red cell FAD deficiency that results from the inherited slow riboflavin metabolism. There is evidence that diversion of FAD to other FAD‐dependent enzymes might be an important factor.
Chronic B‐cell lymphocytosis
Authors: Perreault C. , Boileau J. , Gyger M. , de Bellefeuille C. , D'Angelo G. , Belanger R. , Lacombe M. , Lavallee R. , Bonny Y. , Paquin M. , Brochu S.
Published: July 2010

Persistent elevation of lymphocyte counts is usually associated with a malignant monoclonal lymphoproliferative disease. Over the last 8 years, amongst patients investigated in our center for undetermined persistent lymphocytosis, a diagnosis of malignant lymphoproliferation was excluded in 6 cases as studies of surface membrane immunoglobulin light chains showed that they presented a polyclonal expansion of their B‐lymphocyte pool. All patients were young‐to‐middle aged women presenting peculiar immunohematologic findings characterized by 1) persistent (2–7 yr) elevation of lymphocyte counts (4–14 × 109/l), 2) presence of characteristic binucleated B cells on peripheral blood smears, 3) a normal bone marrow histology, 4) a polyclonal increase of serum IgM with low‐to‐normal IgG and IgA levels. Histologic examination of the spleen in 2 patients and lymph nodes in 1 showed a benign follicular lymphoid hyperplasia. The evolution was benign in every case. We suggest that chronic polyclonal B‐cell lymphocytosis is a distinct clinicopathologic entity that should not be confused with malignant lymphoproliferative disorders.
Rearrangement of TCR gamma chain gene involving JP1 suggests early thymocyte origin of peripheral T‐cell lymphoma
Authors: Leber B. F. , Amlot P. , Hoffbrand A. V. , Norton J. D.
Published: July 2010

Peripheral T‐cell lymphomas (PTL) are morphologically and immunophenotypically heterogeneous. We have examined a series of cases to determine whether this heterogeneity is reflected at the level of developmentally specific T‐cell receptor (TCR) gene rearrangement. 4 of 5 cases had clonal rearrangements of TCR beta and gamma chain genes; one of these also had a probable DQ52‐J immunoglobulin heavy chain gene rearrangement. 2 of the 4 TCR gamma gene rearrangements involved the most 5′ J region, JP1, a characteristic of immature thymocytes. These 2 cases also had immunophenotypic features of immaturity. Taken together, our results suggest that TCR gene rearrangement is correlated with surface marker data and shows that in some cases PTL may arise from a very early stage of thymocyte maturation.
Biological properties in vitro of a combination of recombinant murine interleukin‐3 and granulocyte‐macrophage colony‐stimulating factor
Authors: Riklis Irena , Kletter Yehudith , Bleiberg Ilan , Fabian Ina
Published: July 2010

The effect of recombinant murine interleukin‐3 (rIL‐3) and recombinant murine granulocyte‐macrophage colony‐stimulating factor (rGM‐CSF) on in vitro murine myeloid progenitor cell (CFU‐C) growth and on the function of murine resident peritoneal macrophages was investigated. both rIL‐3 and rGM‐CSF are known to support the growth of CFU‐C and, when combined, were found to act synergistically to induce the development of an increased number of CFU‐C. The distribution pattern of myeloid colonies in the presence of these two growth factors was in general similar to that in the presence of rGM‐CSF alone. both rGM‐CSF and rIL‐3 enhanced the phagocytosis of Candida albicans (CA) by mature macrophages producing an increase in the percentage of phagocytosing cells as well as an increase in the number of yeast particles ingested per cell. No additive effect on the phagocytosis was observed when the two growth factors were added concurrently. rGM‐CSF, but not rIL‐3, enhanced the killing of CA by macrophages. This killing was inhibited by scavengers of oxygen radicals.
Myocardial iron grading by endomyocardial biopsy. A clinico‐pathologic study on iron overloaded patients
Authors: Barosi Giovanni , Arbustini Eloisa , Gavazzi Antonello , Grasso Maurizia , Pucci Angela
Published: July 2010

Endomyocardial biopsy was performed in 13 patients with primary or secondary iron overload. Prussian blue staining showed visible iron in the biopsy fragments of 8 out of 13 patients. Because of the inhomogeneity of iron deposition in the biopsy fragments, a semi‐quantitative myocardial iron grading system was used in which the percentage of Perls' positive cells on 4 to 6 biopsy fragments was averaged from each case. The presence of stainable iron in the myofibrils was not predictable from serum iron, transferrin saturation, serum ferritin or liver iron grading, nor from evidence of endocrine dysfunction. In patients with Perls' positive material in the myocardium, there was a significant correlation between the endomyocardial iron grade and serum iron and transferrin saturation. These results suggest that other factors besides the body iron load determine cardiac iron deposition. The fact that myocardial siderosis was documented only in patients with hepatic cirrhosis, irrespective of the hepatic iron load, suggests that severe liver damage may be a prerequisite for the accumulation of iron in the heart.
Colony formation by megakaryocyte progenitors in myelodysplatic syndromes
Authors: Juvonen E. , Partanen S. , Knuutila S. , Ruutu T.
Published: July 2010

In vitro megakaryocytic colony formation by progenitors from the bone marrow was studied in 40 myelodysplastic syndrome patients. Megakaryocytic colonies were decreased in number or absent in 30 patients; only 10 showed normal colony growth. The growth correlated to some extent with the FAB‐class. Patients with normal colony formation had either RA or RARS, but also in these two FAB‐types half of the patients showed reduced megakaryocytic colony formation. Only 1 out of 15 patients with RAEB or RAEBt had normal megakaryocyte growth. The patients with CMML did not show any megakaryocytic colonies. The growth of erythroid colonies was normal in 3 patients and reduced or absent in the others. All 3 with normal erythroid colony formation also showed normal megakaryocyte growth, and all patients with normal megakaryocyte colony formation also had normal granulocyte‐macrophage colony growth. Granulocyte‐macrophage colony and cluster formation was normal in 17 patients. Defective formation of megakaryocytic, erythroid, and granulocyte‐macrophage colonies was seen in 22 patients, compatible with a defect in a pluripotent stem cell. Megakaryocytic colony formation had no obvious correlation with any specific chromosome abnormality, and the distribution of the growth patterns was almost similar in patients with a normal and those with an abnormal karyotype.
Hodgkin's disease: Recent concepts in classification and treatment
Authors: Specht Lena , Pedersen‐Bjergaard Jens
Published: July 2010

During the last few decades prognostic classification of Hodgkin's disease has been primarily according to the Ann Arbor classification. However, this does not include prognostic subgrouping of the various stages. Consequently, many studies have investigated the prognostic significance of other clinical and laboratory characteristics. Many prognostic factors have been identified, but recent studies have shown that the total tumour burden is by far the most important prognostic factor in Hodgkin's disease, and that most of the other known prognostic factors are related to tumour burden, without independent prognostic significance.

Radiotherapy has been the standard treatment in the management of early stage disease. Adjuvant combination chemotherapy improves disease‐free but survival but until now no improvement in overall survival has been documented. Combination chemotherapy alone has been tested in too few trials to allow a final conclusion.

Advanced disease is treated with combination chemotherapy. The MOPP regimen and its modifications seem equally effective. For MOPP failures ABVD and other supposedly non‐cross‐resistant combinations seem equally effective and able to produce prolonged disease‐free survival in only about 20% of these patients. In some studies alternating regimens such as MOPP/ABVD for previously untreated patients have produced better results than MOPP alone and are currently being evaluated in larger series of patients.

For patients with disease resistant to standard chemotherapy the outlook is still poor. High dose chemotherapy and total body irradiation followed by bone marrow transplantation have shown some promise. Hopefully, in the future new biological techniques will make new types of treatment available or allow a more intensive therapy with the drug combinations currently used.
Non‐Hodgkin's lymphomas: Recent concepts in classification and treatment
Authors: Ersbøll Jens , Schultz Henrik B.
Published: July 2010

The non‐Hodgkin's lymphomas (NHL) is a heterogeneous group of tumors derived from B and T lymphocytes and their precursors. In this review we have used a classification scheme of 5 main categories: 1. Follicular lymphomas, 2a. small lymphocytic cell (CLL or immunocytomas), 2b. diffuse small cleaved cell including intermediate lymphocytic and mantle zone NHL, 3. large cell NHL, 4. early B cell (Burkitt's and non‐Burkitt's), 5. precursor cell (lymphoblastic lymphomas). Classification of non‐leukemic post‐thymic T cell NHL is still controversial. Prognostic factors are parameters of tumor burden, proliferative activity, and the condition of the patient. Actual step of tumor progression, the dose intensity of chemotherapy, and the rapidity of tumor regression may also be of importance for outcome. The optimal therapy for follicular NHL remains to be defined. However, the inevitable course of tumor progression and the fact that only achievement of CR offers the chance of a significant fraction of patients being disease‐free leads to the recommendation to treat all younger patients initially. Patients with large cell NHL regardless of stage should be treated with combination chemotherapy. The CR rates have increased with the use of more dose‐intensive regimens suggesting that prognosis for high‐risk subsets might be further improved using high‐dose chemotherapy with autologous bone marrow transplantation as first‐line therapy.
B cell chronic lymphocytic leukaemia: Recent concepts in classification and treatment
Authors: Geisler Christian , Hansen Mogens Mark
Published: July 2010

The very varying length of survival in B cell chronic lymphocytic leukaemia (B‐CLL), has stimulated the development of a number of clinical staging systems based on clinical and haematological parameters. Especially the staging systems of Rai et al and of Binet et al have won acceptance, and a combination of these systems has been proposed by the International Workshop on CLL. This system, the International Workshop System, should be used as a reference in all CLL studies with prognostic aspects.

The immunophenotype of the B cell in B‐CLL is characterized by expression of faint surface membrane immunoglobulin and a number of B cell differentiation antigens, of which CD5 and the mouse erythrocyte receptor are the most important. Normal counterparts have been identified as candidates for the leukaemic target cell. No definite prognostic value of surface membrane immunoglobulin class has yet been established in B‐CLL.

Chromosome abnormalities have been found in 30 to 50% of B‐CLL cases, trisomy 12 being the most frequent finding, followed by 14q+. The prognostic role of trisomy 12 is debated, whereas a concensus is emerging of a poor prognosis associated with multiple cytogenetic abnormalities.

In advanced B‐CLL, it has been shown that response to treatment is a prerequisite for prolonged survival. The effect of intensive therapy is currently being investigated in several studies by comparison with the effect of chlorambucil and prednisone, till now the primary standard therapy. In a Danish multicentre study, however, prolonged survival following initial treatment with CHOP has not yet been recorded, in spite of a much higher remission rate than with chlorambucil and prednisone.
Therapy‐related malignancies: A review
Authors: Pedersen‐Bjergaard Jens , Philip Preben
Published: July 2010

Although many cytostatic drugs have been shown to be both mutagenic and carcinogenic in experimental systems, only the alkylating agents have been demonstrated with certainty to induce malignancy in man. Thus, therapy with almost all alkylating agents in clinical use today results in a highly increased risk of acute nonlymphocytic leukaemia (ANLL). Other types of leukaemia are not observed in excess following cancer chemotherapy, and only one type of solid tumour has been convincingly related to treatment with cytostatic drugs: carcinoma of the urinary bladder following cyclophosphamide and the now abandoned alkylating agent chlornaphazine.

Low dose total‐body irradiation, as in the atomic bomb explosions of World War II, is known to induce ANLL, acute lymphoblastic leukaemia and chronic myelogenous leukaemia, as well as various solid tumours and multiple myeloma in man. High voltage radiotherapy, by comparison, has been found to be followed by a moderately increased risk of ANLL in only a few studies. This phenomenon has been related to cell kill rather than to malignant transformation of haematopoietic stem cells within the fields of irradiation. A moderately increased risk of various solid tumours and of non‐Hodgkin's lymphomas has been observed with a long follow up, particularly in series of patients treated for Hodgkin's disease. This excess possibly represents both radiotherapy‐induced solid tumours and a general predisposition to development of solid tumours and non‐Hodgkin's lymphomas as part of the natural history of the primary malignancy.

The risk of therapy‐related acute nonlymphocytic leukaemia (t‐ANLL) is dose‐dependent and possibly directly proportional to the total cumulative dose af alkylating agents. It increases with patient age, like the risk of de‐novo ANLL, and it levels out 7–8 years after cessation of therapy with alkylating agents. Most cases of t‐ANLL present in a preleukaemic phase with refractory cytopenia. Already at this early stage the characteristic chromosome abnormalities can be observed in the bone marrow, most often loss of the whole, or parts of the long arms, of chromosomes no 5 and/or no 7. The cytogenet‐ic abnormalities are of diagnostic, prognostic and perhaps also of pathogenetic significance for t‐ANLL.
The epipodophyllotoxin derivatives VM26 and VP16: Experimental and clinical aspects
Authors: Dombernowsky Per , Hansen Heine Høi
Published: July 2010

VM26, teniposide, and VP16, etoposide, are semisynthetic derivatives of podophyllotox‐in, a derivative of podophyllin. Podophyllin is the crude extract from the roots of two related plants, the American mandrake or may apple (podophyllum peltatum) and podophyllum emodi from India, which have been used in folk medicine throughout the ages in both American and Asian cultures.

VM26 and VP16 were introduced almost simultaneously clinically in the early 1970's but the subsequent development has differed greatly (1,2,3,4,5). VP16 has been widely studied alone and in combination in the majority of common tumour types and is highly effective in several, notably testicular and small cell lung cancers, lymphomas and acute leukaemias. Early indications of this activity focused investigator interest almost exclusively on VP16, with the result that clinical research on VM26 has lagged far behind. VM26 has tended to be used in paediatric oncology, especially for neuroblastoma, but is also active in acute leukaemias, lymphomas and in small cell carcinoma.
Multidrug resistance: Drug extrusion and its counteraction by chemosensitizers
Authors: Friche E. , Skovsgaard T. , Danø K.
Published: July 2010

Multidrug resistance involves cross‐resistance between some of the most important agents in cancer chemotherapy, including the anthracyclines and the vinca alkaloids. It is closely related to an active extrusion of the drugs from the resistant cells, which is related to an overexpression of the multidrug resistance gene encoding a membrane protein, the P‐glycoprotein, that has homologies with bacterial transport proteins. The extrusion mechanism is accessible to inhibition by several means, and particularly the use of competitive inhibition with non‐toxic analogues of the drugs has proved to be an effective way to reverse multidrug resistance in animal tumors in vivo.
Some methods and applications of flow cytometric DNA analysis in clinical and experimental oncology
Authors: Vindeløv Lars L. , Christensen Ib J.
Published: July 2010

An integrated set of methods for routine flow cytometric DNA analysis are described. The methods consist of procedures for sample acquisition, storage, standardization, staining and statistical analysis. Our experience with the methods over the past ten years is reviewed. It is concluded that only with adequate solutions to all methodological steps involved, is it possible to produce reliable end‐point results. Flow cytometric DNA analysis is a valuable research tool in clinical and experimental oncology. Final evaluation of the prognostic significance of DNA analysis in neoplastic disease awaits the results of ongoing studies.