bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic and prognostic significance of serum measurements of lactoferrin, lysozyme and myeloperoxidase in acute myeloid leukemia (AML): Recognition of a new variant, high‐lactoferrin AML
Authors: Öberg G. , Dahl R. , Ellegaard J. , Sundström C. , Vaeth M. , Venge P.
Published: July 2010

92 patients with acute myeloid leukemia were classified according to the FAB classification (M1 n = 20, M2 n = 43, M3 n = 1, M4 n = 19, M5a n = 2, M5b n = 2, and M6 n = 5 patients). Serum measurements of lactoferrin (LF), myeloperoxidase (MPO) and lysozyme (LYS) were performed before the start of treatment. LF was significantly lower in M1 when compared with M2 but not as compared to M4, MPO was significantly higher in M2 and M4 than in M1, but comparable MPO levels were found in M2 and M4. LYS was significantly elevated in M2 in comparison with M1, and in M4 when compared to both M1 and M2. Polymorphonuclear granulocytes (PMNs) in M1 were significantly reduced when compared with M2 and M4, whereas mononuclear cells were significantly increased in M4 in comparison with both M1 and M2. FAB classification did not generate any prognostic information. When the patients were, instead, subdivided according to LF levels we found prognostically significant differences. Of patients below 100 μg/1, 44% went into remission as compared to 77% with LF from 101 to 400 μg/1. In patients with LF levels above 400 μg/1 the remission frequency was only 14%. Multivariate statistical analysis on the data further suggested that lactoferrin may be used as an independent prognostic indicator. We conclude that although determination of the serum‐levels of lactoferrin, lysozyme and myeloperoxidase in certain cases may be valuable as a supplement to the morphological examination of acute myeloid leukemia, it is evident that none of the three determinations can be used alone to distinguish between the FAB groups. However, we suggest that lactoferrin may be used as a prognostic indicator and may even be used to recognize a new variant of AML with a particularly poor prognosis ‐high lactoferrin AML.
Myelo‐monocytic differentiation potential of the CALLA‐positive Nairn 6M1 cell line
Authors: Lau B. , Jäger G. , Lippl U.
Published: July 2010

Nairn 6M1 cells, derived from an acute lymphoblastic leukemia of the non‐T, non‐B type, are known to possess characteristics of early B‐lymphocytes. In order to determine whether these cells are able to differentiate along the granulocyte‐monocyte pathway, they were cultured in diffusion chambers, and classified according to morphological, cytochemical and immunological criteria. On the basis of this characterization, Nairn 6M1 cells positively labeling with monoclonal anti‐human granulocyte or monocyte‐specific antibodies were observed in all cases. These immunological changes were accompanied by the appearance of cells positive for the naphthyl‐AS‐D‐chloroacetate esterase reaction. However, no changes in the blast‐like appearance of the cultured cells were seen. From these data, we conclude that Nairn 6M1 cells already committed to the B‐cell lineage retain their capacity to develop cellular markers of the granulocyte‐monocyte series.
Splenectomy in patients with malignant lymphoma presenting with massive splenomegaly
Authors: King D. J. , Dawson A. A. , Thompson W. D.
Published: July 2010

6 patients with massive splenomegaly but no peripheral adenopathy were diagnosed by splenectomy as having lymphoma; and were found to have widespread disease. Despite the seriousness of their illness at presentation, all have survived for a median time of 101.5 months and reached complete remission.
Cytogenetic studies in 69 patients with myelodysplastic syndromes (MDS)
Authors: Weh Hans Josef , Calavrezos Alexander , Seeger Doris , Kuse Rolf , Hossfeld Dieter Kurt
Published: July 2010

Cytogenetic studies were performed in 69 patients with myelodysplastic syndromes classified according to the FAB proposals. Overall incidence of chromosomal anomalies was 48% with 5q‐, +8, 12p‐,‐7/7q‐ being the aberrations most often found. The 12p‐ chomosome showed a close correlation with a prior exposure to mutagenic agents and CMML. Although there were no group‐specific cytogenetic anomalies, FAB classification strongly influenced their incidence. They were lower (36%) in RA/RA‐S than in RAEB/RAEB‐T/CMML (53%). Chromosomal anomalies were significantly more often found in patients with a prior exposure to carcinogenic agents (80%) than in unexposed patients (33%). The presence of chromosomal anomalies did not predict a higher risk of leukemic transformation.
Blood clonal B cell excess at diagnosis in multiple myeloma: Relation to prognosis
Authors: Österborg Anders , Nilsson Bo , Bjorkholm Magnus , Holm Goran , Johansson Bo , Lindemalm Christina , Petterson Dagny , Åhre Anders , Mellstedt Håkan
Published: July 2010

112 patients with multiple myeloma have been studied at diagnosis for the presence of blood clonal B‐cell excess (CBE), defined as a ratio between k+ and λ+ lymphocytes outside the normal range (0.9‐3.5). 48 patients (43%) had CBE. The increase in light chain‐bearing lymphocytes was always that of the M component light chain isotype. The proportions of patients exhibiting CBE were the same in different stages. The response frequency was not influenced by the presence of CBE. However, patients with CBE had a shorter remission duration time (p < 0.001) and total survival (p < 0.05) than those without CBE. This was also noticed when each clinical stage was analyzed separately. Moreover, survival was shorter in patients with a large fraction of CBE than in those with a small one. Cox regression analysis revealed that CBE was a much stronger predictor of remission duration than age, clinical stage and renal dysfunction. CBE and response to initial treatment independently were the best factors to indicate survival. It is suggested that analysis of CBE should be included in the clinical characterization of untreated patients with multiple myeloma.
Peripheral blood lymphocyte response to recombinant and non‐recombinant interleukin 2 in previously treated patients with Hodgkin's disease, long‐time off‐therapy
Authors: Mantovani G. , Coiana A. , Massidda A. , Locci F. , Loy M. , Piludu G. , Piras M. C. , Macció A. , Del Giacco G. S.
Published: July 2010

13 patients with Hodgkin's disease (HD) previously treated, 9 of whom were long‐time (more than 2 yr) off‐therapy, were studied for peripheral blood lymphocyte response to interleukin 2 and for lymphocyte subpopulations by means of in vitro cultures and monoclonal antibodies. The aim of the study was to ascertain the role played by interleukin 2 in the impaired cell‐mediated immunity of HD patients. The results show a response of peripheral blood mononuclear cells of HD patients to either the T cell‐specific polyclonal mitogens PHA and Con A or to the T cell‐dependent, although B cell‐specific, PWM, most significantly decreased compared to the normal response. As far as the interleukin 2 involvement in HD is concerned, our study suggests: 1) an impaired endogenous interleukin 2 production by T lymphocytes, 2) a most probable deficiency of the interleukin 2 receptor (Tac) expression and 3) a decrease of the number and/or of the function of NK cells no longer responsive in vitro to interleukin 2. The phenotypic analysis of peripheral blood mononuclear cells showed a slight decrease of total T cells (T3 +), of the helper/inducer subset (T4 +) and of the T4 + /T8 + cells ratio. Our data seem to support the rationale for a therapeutical approach with interleukin 2 in controlled clinical trials also in HD patients, according to the experiments in progress in solid tumor patients.
Protein loss during acute graft‐versus‐host disease: Diagnostic and clinical significance
Authors: Guiot H. F. L. , Biemond J. , Klasen E. , Gratama J. W. , Kramps J. A. , Zwaan F. E.
Published: July 2010

In 31 consecutive patients who received an allogeneic bone marrow transplantation the loss of proteins during the period at risk for acute graft‐versus‐host disease (aGVHD) was studied in order to determine whether the quantity of protein loss could be used for grading the severity of aGVHD. It was shown that the grade classified on the basis of the severity of skin rash, the quantity of diarrhea and the seriousness of cholestasis, correlated with serum albumin loss, intestinal plasma loss (expressed by the intestinal α1‐antitrypsin clearance) and the occurrence of inflammatory cells (leukocytes) in feces. The quantity of albumin lost by intestinal route accounted for only one third of the total albumin loss. To investigate whether the remaining part of it could be explained by capillary leakage elsewhere in the body, leakage of antileukoprotease from the tissue of the respiratory tract into the blood was measured. It was shown that the serum concentration of this proteinase inhibitor correlated with albumin loss. This means that capillary leakage also occurs in the lung during aGVHD. In conclusion, the loss of proteins can be used as a parameter of the severity of aGVHD once the proper diagnosis has been established. It appears that a combination of the current ‘familiar’ grading system and SAL yields a more objective classification system with a greater prognostic value.
Chronic myelomonocytic leukemia following refractory anemia with sideroblasts: Report of two cases
Authors: Bursztyn B. , Douer D. , Ramot B.
Published: July 2010

We report 2 patients with idiopathic refractory sideroblastic anemia who developed chronic myelomonocytic leukemia 1 to 5 yr later. This observation supports the decision of the FAB cooperative group to include both conditions in the category of myelodysplastic syndrome.
Simultaneous transient erythroblastopenia and agranulocytosis: IgG‐mediated inhibition of erythrogranulopoiesis
Authors: Hanada Takashi , Ehara Takao , Nakahara Satoko , Suzuki Toshiyuki , Nagasawa Toshiro , Takita Hitoshi
Published: July 2010

We report a case of simultaneous transient erythroblastopenia and agranulocytosis recovering spontaneously. In vitro study using autologous bone marrow cells after recovery demonstrated IgG‐mediated inhibition of both erythropoiesis and gran‐ulopoiesis but not megakaryopoiesis. The inhibitory activity disappeared shortly after remission. These findings suggest that IgG‐mediated inhibition of hematopoiesis may be pathogenetic for transient bone marrow failure of the patient.
Success of bone marrow transplantation in congenital Diamond‐Blackfan anaemia: A case report
Authors: Wiktor‐Jedrzejczak Wieslaw , Pojda Cezary Szczylik Zygmunt , Kansy Maksymilian Siekierzynski Jerzy , Klos Miroslaw , Ratajczak Mariusz Z. , Pejcz Jerzy , Jaskulski Dariusz , Gornas Pawel
Published: July 2010

A 6‐yr‐old girl with congenital corticosteroid‐resistant pure red cell aplasia was treated with bone marrow transplant from her HLA‐identical, MLC‐unreactive sister in November 1984 following conditioning with busulfan and cyclophosphamide. Full engraftment was obtained and the patient at 21 months post‐transplant is in excellent clinical condition maintaining normal red cell counts. We conclude that BMT should be considered as a therapy for at least the most severe cases of Diamond‐Blackfan anaemia resistant to corticosteroids. Successfull outcome of this therapy provides an argument for the stem cell origin of this disorder.
Co‐expression of T3 and surface immunoglobulin in neoplasms of ‘early’ B cells: A report of 2 cases
Authors: Haegert David G. , Smith John L
Published: July 2010

Chronic lymphocytic leukaemia (CLL) and well‐differentiated lymphocytic lymphoma (WDLL) characteristically express surface membrane immunoglobulin (SIg) and react with monoclonal antibodies (Mabs) directed against a marker present on most normal T cells, namely Tl. These SIg‐positive B cells are usually negative for other T cell markers including T3 (CD3) which is expressed in all normal T cells. We report 2 cases, 1 CLL and 1 WDLL, in which the peripheral lymphocytes not only expressed monotypic SIg but also reacted with the T3‐specific Mabs UCHTI and OKT3 by indirect immunofluorescence or immunoperoxidase staining. False‐positive staining by both UCHTI and OKT3 was excluded by showing that lymphocytes sensitized with an irrelevant mouse Mab did not stain with second layer antibodies and that lymphocytes stained with second layer antibodies alone were always completely unreactive. Also, in 1 case the determinants demonstrated by both anti‐Ig and UCHTI were re‐expressed after capping and shedding, i.e. appeared to be endogenous. The B cell origin of the CLL lymphocytes was supported by the finding of CK gene rearrangement in the absence of Tß gene rearrangement. It seems therefore that neoplasms of ‘early’ B cells may show bidirectional differentiation and co‐express markers that are believed to be T‐specific.
Expression of a B‐lymphoid differentiation antigen (CD 19) on acute non‐lymphoblastic leukaemia cells
Authors: Campos Lydia , Guyotat Denis , Gentilhomme Odile , Treille Daniele , Fiere Denis , Germain Daniel
Published: July 2010

The expression of CD 19 (B4) surface antigen was investigated in 41 cases of acute myeloid leukaemia (AML), and 8 cases of acute undifferentiated leukaemia (AUL). Diagnosis was carried out by usual cytological and cytochemical means, and leukaemias were classified according to the FAB classification. CD 19 antigen is thought to be expressed on B lymphoid cells only. However, 2 cases out of 9 FAB M1, M2 and M3 subtypes were weakly stained (20 to 25%) by B4 antibody; 7 out of 11, and 17 out of 18 cases of M4 and M5 subtypes were markedly stained (25 to 70% of cells). 3 cases of AUL were also stained. Moreover, B4 expression was often correlated with expression of monocyte‐associated antigens, as recognized by CRIS6, My9, KiM1 and UCHM1 antibodies. It is concluded that B4 antigen is probably expressed before B differentiation and is retained in early stages of monocytic differentiation.
Drug‐induced skin reactions in patients with acute non‐lymphocytic leukaemia
Authors: Verhagen C. , Stalpers L. J. A. , de Pauw B. E. , Haanen C.
Published: July 2010

The incidence of drug‐induced skin rashes and related factors were analysed in a retrospective study of 151 patients with acute non‐lymphocytic leukaemia (ANLL). 91 (60%) developed a drug‐related toxicodermia to one or more drugs during remission, induction and maintenance therapy. The incidence of rashes was mainly confined to the blastic stage of leukaemia and occurred significantly less often during remission. Patients with acute myeloid leukaemia, FAB classification M1, M2 and M3 (M1‐3) developed skin reactions more often than those of types M4 and M5 (M4‐5). Women suffered more frequently from drug‐induced skin lesions than men. The incidence of drug‐associated rashes was significantly higher in patients with ANLL than in the general population for: Allopurinol (16%), co‐trimoxazole (14%), miconazole (28%), and ketoconazole (18%). The incidence for the penicillins (12%) and cephalosporins (3%) conformed to the upper limit as reported for the general population. Additional toxic effects of combined therapy could not explain the differences observed and a dearrangement of the immunesystem during the blastic stage of leukaemia is suggested.
Participation and interactions of neutrophil elastase in haemostatic disorders of patients with severe infections
Authors: Seitz R. , Wolf M. , Egbring R. , Radtke K.‐P. , Liesenfeld A. , Pittner P. , Havemann K.
Published: July 2010

The prognosis of septicaemia depends on the occurrence of complications such as shock and coagulation defects. The damage to haemostasis is usually explained by the action of the main coagulation and fibrinolysis enzymes, thrombin and plasmin. This paper presents data concerning the role of a third protease, granulocytic elastase. 82 patients who had been admitted to our hospital with suspected septicaemia were examined. Septicaemia was proven in 22 patients by the growth of microorganisms in blood cultures, and was clinically diagnosed in 9 patients. The plasma levels of neutrophil elastase‐like protease complexed to a1antitrypsin (a1AT‐ELP) were measured by zone immunoelectrophoresis assay (ZIA). The a,AT‐ELP values were significantly increased in the 31 septic as compared to the 51 non‐septic patients. In patients with complicated septicaemia, negative correlations of a1AT‐ELP with factor XIII and the coagulation inhibitor antithrombin III were demonstrable. Among the patients with septic complications, the 3 who survived exhibited a dramatic decrease of a1AT‐ELP, whereas in the other 16 patients who died the levels remained elevated. It might be of therapeutic significance that in 9 patients receiving fresh plasma and AT Ill‐concentrate substitution for DIC the a1AT‐ELP levels dropped, whereas they remained high in the other septicaemia patients. There were no correlations between a1AT‐ELP and the a2antiplasmin‐plasmin complexes (a2AP‐Pl), but strong correlations with signs of coagulation. The data suggest an interaction of coagulation and elastase release, probably involving the Hageman factor.
Familial malignant blood disease in the county of Jämtland, Sweden
Authors: Eriksson Mikael , Bergström Ingmar
Published: July 2010

In a material of 942 patients with malignant hematological disease, encompassing all diagnosed cases in the county of Jämtland in Sweden during a 22‐yr period, 36 families with multiple cases of such disease were found. Approximately 5% of the patients have at least one close relative who also suffers from a malignant hematological disease. An especially strong familial occurrence was found in the group of chronic lymphoproliferative diseases and it is concluded that this tendency comprises all diseases in the group, i.e. chronic lymphocytic leukemia, multiple myeloma and malignant lymphoma. In some families several cases of acute leukemia were present, and suggestions concerning immunological disturbances are made. In the group of chronic myeloproliferative diseases familial factors do not seem to play an important. part, with the possible exception of polycythemia vera. Both heredity and common environmental agents must be considered as possible etiologic factors.
Defective spectrin dimer self‐association in thalassemic red cells
Authors: Lamchiagdhase Pornvaree , Wilairat Prapon , Sahaphong Somphong , Bunyaratvej Ahnond , Fucharoen Suthat
Published: July 2010

The relative proportions of spectrin tetramer and dimer forms extrated from red cell membranes in a low ionic strength buffer at 4°C were determined for 15 normal subjects, 27 subjects with α‐thalassemia (7 α‐thalassemia trait, 9 Hb H disease (α‐thal 1/α‐thal 2) and 11 Hb H with Hb Constant Spring (CS), 23 subjects with β‐thalassemia (6 β‐thalassemia trait, 5 homozygous β‐thalassemia, 11 β°‐thalassemia with Hb E and 1 β +‐thalassemia with Hb E), 6 subjects with Hb E (2 homozygous and 4 carriers) and 1 subject with combined α‐thal 1/Hb CS and Hb E (AE Bart's disease). In all subjects (except carriers of Hb E and 1 splenectomized case of β°‐thal/Hb E) spectrin dimer forms were elevated when compared to levels in normal controls, but there were no significant differences between carrier and disease forms. Conversion of spectrin dimers to tetramers at 30° C was reduced in the thalassemic subjects with disease but was within normal range for thalassemic carriers.
Chemotherapy of progressive hairy‐cell leukaemia
Authors: Cold Søren , Brincker Hans
Published: July 2010

5 patients with hairy‐cell leukaemia were treated with chemotherapy. 3 of them received multiple courses of CHOP (cyclophosphamide‐doxorubicin‐vincristine‐prednisolone); 1 patient received cyclophosphamide monotherapy for 6 months. The 5th patient developed a Mikulicz's syndrome after splenectomy and was initially treated with cyclophosphamide monotherapy, then received 1 course of CHOP, and finally 9 courses of intermediate‐dose methotrexate. 1 complete remission (45 months+) and 3 partial remissions (75 +, 68, 32+ months) were observed, while 1 patient had progressive disease. Our results indicate that chemotherapy may be a valuable alternative to alpha‐interferon in the treatment of hairy‐cell leukaemia progressing after splenectomy.
HIV seroconversion in Swedish haemophiliacs: Relation to type and dosage of factor concentrate
Authors: Berntorp E. , Hansson B. G. , Böttiger B. , Jarevi G. , Wedbäck A. , Nordenfelt E. , Nilsson I. M.
Published: July 2010

Human immunodeficiency virus (HIV) seroconversion among 40 Swedish haemophilia A patients has been investigated by retrospective sera testing. 22/40 patients had developed HIV antibodies before 1983, i.e., when heat‐treatment of American factor concentrates was introduced. All patients had received American and Swedish factor concentrates, thus no case of seroconversion was seen among patients treated exclusively with non‐heat‐treated Swedish concentrates. Of 79 patients with severe or moderate haemophilia, all of whom had received both American and Swedish concentrates, the 36 seropositives were compared with the 43 seronegatives. The total number of units received did not differ between the two groups, though the seropositive group had received significantly more American concentrate. Two batches of concentrate were proved to have been infected. 29 seropositive and 13 seronegative patients had been treated with at least one of these batches. As expected, and unlike most of the seronegative patients, patients in the seropositive group generally had abnormal lymphocyte subsets.
T lymphocyte subpopulations in chronic lymphocytic leukemia of B cell type in relation to immunoglobulin isotype(s) on the leukemic clone and to clinical features
Authors: Kimby E. , Mellstedt H. , Nilsson B. , Björkholm M. , Holm G.
Published: July 2010

Total blood T lymphocytes and subpopulations (OKT4+ and OKT8 + cells) were studied in 59 patients with B cell chronic lymphocytic leukemia (B‐CLL). In 48 previously untreated patients, total T lymphocytes were higher as compared to healthy controls (p < 0.001). T‐cells and OKT8+ cells were significantly increased in patients in advanced clinical stage and with progressive disease in comparison to patients with low stage and indolent disease. High numbers of OKT8+ lymphocytes were also seen in patients with a dominance of μ heavy chains on the leukemic clone. Moreover, in this patient group the OKT8+ subpopulation correlated with total B cells (r = 0.68, p < 0.001) while in patients with a μδ phenotype no such correlation was seen. After successful cytostatic therapy there was a reduction in total numbers of both OKT4+ and OKT8+ cells, in particular, with a concomitant increase in OKT4/OKT8 ratios.
Clinical signification of natural killer activity in B‐cell chronic lymphocytic leukemia
Authors: Alvarez‐Mori Melchor , Casas Juan , Laguna Rafael , Jordá Julia , Durantez Alberto
Published: July 2010

The natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) and lymphocytes with the capacity to form stable rosettes with neuraminidase‐treated sheep red blood cells (E+) was studied in 28 previously untreated patients (11 at stage 0, 10 at stage I and 7 at stages II and III, according to Rai's classification) and 7 treated patients with B‐cell chronic lymphocytic leukemia (B‐CLL), all of them at stage 0 according to Rai's classification after treatment, and in 15 healthy controls. The mean NK activities of PBMC and E+ lymphocytes from untreated patients were significantly decreased (p < 0.001) when compared with those of PBMC and E+ lymphocytes, respectively, from healthy controls. However, PBMC and E+ cells from treated patients demonstrated NK activity similar to that of the corresponding cellular populations of controls (p > 0.05). Furthermore, there were no significant differences among the NK activities of E+ lymphocytes from untreated B‐CLL patients in the different clinical stages 0, I, II and III, according to Rai's classification (p > 0.05). These results demonstrate that the very low or undetectable levels of NK activity present in PBMC and E+ cell populations from previously untreated patients with B‐CLL, regardless of the clinical stage of the disease, can be modified by systemic therapy with alkylating agents. Moreover, the NK activity of PBMC and E+ lymphocytes from some treated patients that have achieved the stage 0 according to Rai's classification after chemotherapy can be found within the range of the lytic activity shown by PBMC and E+ cells from normal donors.
Interleukin‐2 can induce proliferation of leukemic B‐cells in prolymphocytic leukemia
Authors: Panayotides Panos , Porwit Anna , Lenkei Rodica , Reizenstein Peter
Published: July 2010

In a case of prolymphocytic leukemia (PLL), receptors for interleukin‐2 (IL‐2R) were demonstrated by immunofluorescence with a monoclonal antibody against IL‐2R. Highly purified leukemic B‐cells, cultured in vitro with recombinant IL‐2 (r‐IL‐2), responded to IL‐2 with a marked increase of DNA‐synthesis. Both spontaneous and r‐IL‐2‐induced proliferation of leukemic cells were totally abrogated by the anti‐IL‐2R monoclonal antibody.
Terminal stage lymphoproliferative disorders treated with low dose cytosine arabinoside
Authors: Stentoft Jesper , Jensen Mogens Krogh
Published: July 2010

5 heavily pretreated patients with chronic lymphocytic leukaemia or non‐Hodgkin lymphoma resistant to alkylating agents were treated with low‐dose cytosine arabinoside (ARA‐C). 3 of the patients showed a clinical and laboratory improvement lasting from 8 to more than 20 months. Low dose ARA‐C may be therapeutically effective in terminal stages of lymphoproliferative disorders.
Review of clinical and haematological response to low‐dose cytosine arabinoside in acute myeloid leukaemia
Authors: Shtalrid Mordechai , Lotem Joseph , Sachs Leo , Berrebi Alain
Published: July 2010

15 patients with acute myeloid leukaemia (AML) were treated with low‐dose cytosine arabinoside (LD ARA‐C). 2 patients had complete remissions, which lasted for 8 and 3 months, and 5 patients had a partial remission. 46% of the patients thus responded to LD ARA‐C. This included 1 responding patient who had not previously responded to therapy with 6‐mercaptopurine, thioguanine, or vinblastine. The 2 patients with complete remission did not show LD ARA‐C‐induced hypoplasia of bone marrow, although 1 had hypoplastic AML before therapy. Leukaemic cells from 1 patient showed in vivo maturation from M1 to M3 after LD ARA‐C treatment. The present results, together with the published data, indicate that: a. LD ARA‐C treatment, although it may have some toxic effects, is an effective treatment for some patients with AML, especially those with hypoplastic AML; b. Response to LD ARA‐C can be obtained after one or several courses of treatment; c. LD ARA‐C‐induced remissions are sometimes obtained even in patients who fail in more conventional treatments; d. LD ARA‐C‐induced remissions can be achieved without bone marrow hypoplasia, and induction of hypoplasia by itself does not always result in complete remission; e. LD ARA‐C can induce in vivo maturation of leukaemic cells. It is suggested that induction of remission in AML patients by LD ARA‐C may result from either differentiation of leukaemic blast cells, cytotoxicity to leukaemic blasts, or both mechanisms acting together.
Glutathione reductase activity and its relationship to pyridoxine phosphate activity in G6PD deficiency
Authors: Anderson B. B. , Clements J. E. , Perry G. M. , Studds C. , Vullo C. , Salsini G.
Published: July 2010

Per cent stimulation of GR activity by FAD in vitro and PNP oxidase activity were measured in G6PD deficiency, heterozygous β‐thalassaemia and controls. It is confirmed that, in contrast to the high stimulation of GR by FAD commonly found in thalassaemia indicating red‐cell deficiency of FAD, and shown here to be greater in the Italian subjects, GR is usually saturated with FAD in G6PD deficiency, leading to high in vitro activity. Unexpectedly, on the other hand, low FMN‐dependent PNP oxidase activity due to red‐cell deficiency of FMN, confirmed by response to oral riboflavin, was found in the majority of subjects with G6PD deficiency, similar to that found in heterozygous β‐thalassaemia. Whereas this is explained in thalassaemia by an inherited slow red‐cell metabolism of riboflavin to FMN, it is suggested that in G6PD deficiency an increased rate of red‐cell metabolism of FMN to FAD leads to the low FMN and high FAD. When G6PD deficiency occurs with heterozygous β‐thalassaemia, GR is usually saturated with FAD as in G6PD deficiency alone, unless there is an inherited, very slow red‐cell metabolism of riboflavin to FMN. The part played by GR in haemolytic crises in G6PD deficiency is discussed.
A rosette receptor assay with haem‐microbeads. Demonstration of a haem receptor on K562 cells
Authors: Majuri R. , Gräsbeck R.
Published: July 2010

A rosette assay was developed for the detection of haem receptor‐bearing cells. Indicator particles were prepared by covalent binding of haem to acrylic microbeads. The new method was tested on K562 human erythroleukaemia cells, known to take up haem. In tests on several batches, 80–90% of the K562 cells were rosetted with haemmicrobeads whereas mature erythrocytes were haem receptor‐negative. Rosette formation was inhibited in a dose‐dependent manner by micromolar concentrations of free haemin but not by albumin or transferrin. Uncoated microbeads or albumin‐coated microbeads did not attach to K562 cells but transferrin‐coated microbeads rosetted 50–70% of them. Diferric transferrin inhibited these rosettes, but haemin had no effect.
Expression of CD 25 (Tac antigen) in lymphoid leukemias and non‐Hodgkin lymphomas
Authors: Faure Gilbert C. , Bene Marie‐C. , Bolle‐Ghanal Marie‐H.
Published: July 2010

A monoclonal antibody to IL2 receptor Tac/CD25 antigen was included in the phenotyping panel of 92 leukemic proliferations. Spontaneous expression of this molecule was observed in one disorder of T‐phenotype only, but in 75% of B‐chronic lymphocytic leukemia (CLL) and on cells from B‐cell leukemic lymphomas. These findings provide further evidence for a non‐T‐cell restriction of IL2 receptor and raise the question of multiple gene derepression in hematologic disorders of B‐lineage.
(3H)ouabain binding to leukaemic cells and intralymphocytic sodium content in chronic lymphocytic leukaemia; no evidence for alterations of the Na+/K+‐pump
Authors: Berntorp Erik , Berntorp Kerstin
Published: July 2010

The number of specific (3H)ouabain binding sites and dissociation constants (Kd) were determined by Scatchard analysis of values for leucocytes from patients with B‐cell chronic lymphocytic leukaemia (CLL), chronic myeloid leukaemia (CML), acute blastic leukaemia (AL) and healthy subjects. CLL lymphocytes and normal B‐cells bound significantly less (3H)ouabain than did normal T‐lymphocytes. CML granulocytes showed the same binding characteristics as normal granulocytes, while blast cells from AL patients bound significantly more (3H)ouabain than did normal granulocytes or B‐cells. The increased binding capacity in blast cells might, at least partly, reflect their larger cell size. A decrease in Kd values was only found in CLL lymphocytes, as compared with normal B‐cells. Intralymphocytic sodium content in CLL lymphocytes was significantly increased, as compared with that in T‐cell‐enriched normal lymphocytes. (3H)ouabain binding did not show any relationship to different prognostic variables in CLL. The present data mainly argue against altered Na+/K+‐ATPase enzyme activity as an indicator of malignancy.
Plasma fibronectin levels during daily plasmapheresis
Authors: Wahlin Anders , Holm Jan , Hansson Mona , Berghem Lars
Published: July 2010

Plasma fibronectin concentrations were studied in 10 patients with multiple myeloma. After plasma exchange for 3 d (2.5‐3 1 plasma daily) the plasma fibronectin decreased to about 50% of the initial level. Resynthesis of fibronectin seemed to increase during 3 d of plasmapheresis, and was sufficient to normalize plasma fibronectin concentration. The plasma fibronectin concentration reached the initial level within 2 d after interrupting plasmapheresis in spite of concurrent cytotoxic treatment. The patients studied showed no signs of infection.
Multiple myeloma: Light chain isotype suppression—A marker of stable disease at presentation
Authors: Wearne Alaine J. , Joshua Douglas E. , Young Graham A. R. , Kronenberg Harry
Published: July 2010

Prognosis in multiple myeloma (MM) is related to the establishment of an immunologically and kinetically characteristic plateau phase. Patients who present with this state may not benefit from immediate chemotherapy. We assessed 20 patients with MM who were staged according to the Salmon and Durie classification at diagnosis and monitored throughout the course of their disease. Patients with a lambda paraprotein and a kappa/lambda lymphocyte ratio in the blood greater than 4.0 were considered to demonstrate light chain isotype suppression (LCIS). Similarly, patients with a kappa paraprotein and a kappa/lambda ratio of less than 0.55 were also considered to have LCIS (1). 14 patients had LCIS; of these, 6 were classified as stage IA, 2 as stage IB, 3 as stage IIA, and 3 as stage IIIA. 6 patients did not have LCIS; 3 were classified as stage IIA, 1 as stage IIIA and 2 as stage IIIB. 10 patients with LCIS were assessed for treatment benefit following administration of melphalan and prednisone, as defined by a fall in the serum paraprotein level of > 50% over 6 months. In 8 patients the serum paraprotein levels did not fall, and the patients remained in good health without clinical deterioration. Thus LCIS at presentation may indicate patients in whom treatment can be safely deferred or in whom aggressive therapy is not indicated.
Treatment of multiple myeloma with an intensive 5‐drug combination or intermittent melphalan and prednisone; a randomised multicentre trial
Authors:   Finnish Leukaemia Group, Palva I. P. , Ahrenberg P. , Ala‐Harja K. , Almqvist A. , Apajalahti J. , Hallman H. , Hänninen A. , Ilvonen M. , Isomaa B. , Järvenpää E. , Järventie G. , Kilpi H. , Koistinen S. , Korpi E. , Koivunen E. , Kätkä K. , Lahtinen R. , Laitinen A. , Lehtinen M. , Mäkelä H. , Nyländen P. , Oivanen T. , Pelliniemi T‐T. , Pulli T. , Rajamäki A. , Rosengård S. , Timonen T. , Waris E. , Wasastjerna C. , Vilpo J.
Published: July 2010

In a randomised multicentre trial a combination of methylprednisolone, vincristine, CCNU, cyclophosphamide and melphalan (MOCCA) was compared with intermittent melphalan and prednisone (MP) as primary treatment in multiple myeloma. In the MP arm the refractory or relapsed patients were treated with regimen MOCCA. The MOCCA arm produced a response rate of 75% among 64 patients and the MP arm a respone rate of 54% among 66 patients. The median surival was 41 months in the MOCCA arm and 45 months in the patients primarily randomised to the MP arm. The initial response to MOCCA improved the survival, while this effect was not statistically significant in the MP arm. The results show that the median surivival does not increase if aggressive chemotherapy is employed as the first line treatment in multiple myeloma.
Changes in serum ferritin following surgical trauma
Authors: Zdravkovic D.
Published: July 2010

A statistically significant increase in serum ferritin values was found in 14 male patients already 1 d after uniform operative trauma and, on the 3rd d following operation, the last day of observation period values were still increased. Moreover, in all patients a highly significant fall in plasma iron of acute onset was found. The hypoferremia was already seen on the day after operation. Serum transferrin was also found to be significantly reduced after operation.
Familial erythrophagocytic lymphohistiocytosis: Surface marker analysis using monoclonal antibodies
Authors: Ishii Eiichi , Hara Toshiro , Ohga Shouichi , Ueda Kohji , Suda Masahiro , Nakamura Junji , Yanagi Tadamichi , Tsuji Yoshiro
Published: July 2010

Surface marker analysis of atypical cells, present at elevated levels in the peripheral blood of a 2‐yr‐old patient with familial erythrophagocytic lymphohistiocytosis (FEL), was performed with monoclonal antibodies. The atypical cells expressed T11, T8, Ia and LeuM2 antigens, markers of suppressor/cytotoxic T lymphocyte and monocyte. The monoclonal antibody‐defined surface markers were thus distinguishable from those of other lymphoproliferative disorders clinically resembling FEL.
Lack of prognostic significance of T‐lymphocyte subset counts in B‐cell chronic lyrnphocytic leukaemia
Authors: Geisler Christian H. , Larsen Jørgen K. , Plesner Torben , Hansen Mads , Hansen Mogens Mørk
Published: July 2010

In the 50 newly diagnosed, unselected, untreated B‐CLL patients, the absolute numbers of blood T cells, T‐helper cells, and T‐suppressor/cytotoxic cells were determined by flow cytometric counting of mononuclear cells labelled with the monoclonal antibodies Leu5 (T cells), Leu3a (T‐helper cells), and Leu2a (T‐suppressor/cytotoxic cells). These estimations and the serum concentrations of IgG, IgA, and IgM were correlated to clinical stage (International Workshop System) and pretreatment observation time. For all patients together, the mean counts of Leu5 +, Leu3 +, and Leu2 + cells were significantly increased compared with the mean counts in 12 healthy controls (Mann‐Whitney). In patients with advanced disease (stage B + C), both T‐subset mean cell counts were significantly increased, whereas in patients with early‐stage disease (stage A), although some high T‐helper cell counts were noted, only the T‐suppressor/ cytotoxic mean cell count increase reached significance. Thus a trend was observed of a more frequent T‐suppressor/cytotoxic cell predominance in early‐stage disease, which is the opposite of the findings in most other prognostic studies. However, there was no significant difference in pre‐treatment observation time according to T‐helper: T‐suppressor cell ratio below vs. above 1.0, irrespective of stage, whereas according to clinical stage, the pretreatment observation time in stage A was highly significantly longer than in stage B + C (logrank test). Thus, no independent prognostic significance of T‐subset counts was found as judged by pretreatment observation time. No correlation was found between the occurrence of hypogammaglobulinaemia, T‐subset ratios or T‐subset counts. In 24 patients, the number of Leu7+ cells (natural killer/ cytotoxic cells) were also counted and found significantly increased compared with normal values.
Timing of the haematologic diagnosis of Ph+ chronic myeloid leukaemia
Authors:   The Italian Cooperative Study Group on chronic myeloid leukaemia
Published: July 2010

The timing of the diagnosis of chronic myeloid leukaemia (CML) can depend on many factors, including chance and disease characteristics. This can influence the computation of survival length and can have implications on the assessment of risk at the date of diagnosis. From a series of 635 cases of Ph+ CML, we selected 83 patients with information on blood counts over a period of 36 to 3 months before the diagnosis, and we estimated the time over which a haematologic diagnosis could or should have been anticipated. This time ranged between 24 and 3 months for all cases, and between 13 and 5.5 months for 50% of cases. These values correspond to between 31 and 13% of the median value (42 months) of survival duration that is usually calculated from the date of diagnosis. The length of the diagnostic latency was independent of the assessment of the risk at diagnosis, suggesting that risk definition is not merely a function of an early or of a late diagnosis. The median doubling time of leucocytes from first abnormal count to diagnosis was 4.2 months.
Quantitation of urinary methylmalonic acid by gas chromatography mass spectrometry and its clinical applications
Authors: Ho Chao‐Hung , Chang Hui‐Chin , Yeh Sheau‐Farn
Published: July 2010

Urine methylmalonic acid (MMA) concentrations were detected in 79 Chinese patients by gas chromatography mass spectrometry (GC/MS), using a selected ion monitoring program. 10 of the 79 patients were found to have cobalamin deficiency. Their urine MMA amounts were all elevated with a mean value 1376 ng/μl (11.66 mmol/l), ranging from 40.46 to 3900 ng/μl (0.34‐33.05 mmol/l). The remaining 69 cases were found to be unrelated to cobalamin deficiency. Their mean urine MMA was 3.62 ng/μl (30.0 μmol/l), ranging from 0–17.47 ng/μl (0–148.0 μmol/l). In this study, we found that urine MMA detected by GC/MS was a simple, rapid, convenient, specific and sensitive method for the diagnosis of cobalamin deficiency. The urine MMA concentrations in cases not due to cobalamin deficiency would not exceed 20 ng/μl (169.5 μmol/l), whereas in cobalamin deficiency the urine MMA levels always exceeded 20 ng/μl, or were even much higher. No overlapping of the results of urine MMA between these 2 groups of patients could be seen in our study. Detection of urine MMA is useful in the demonstration or exclusion of cobalamin deficiency in any suspect patients.
An IgG κ‐monotypic anti‐Pr1hassociated with fresh varicella infection
Authors: Northoff H. , Martin A. , Roelcke D.
Published: July 2010

The first cold agglutinin occurring in an adult patient with fresh varicella infection is described. The antibody caused a hemolytic crisis. It had anti‐Pr1hspecificity. It belonged to the rare cold agglutinins of the IgG class and was a κ‐monotypic (monoclonal) antibody.
Neutropenia associated with large granular lymphocytes responsive to corticosteroids in vitro and in vivo
Authors: Platanias Leonidas , Raefsky Eric , Young Neal
Published: July 2010

We describe a patient with neutropenia associated with increased circulating large granular lymphocytes (LGL). Absolute neutropenia was accompanied by the absence of myeloid precursor cells in the bone marrow. No myeloid progenitor cells (CFU‐C) could be detected by in vitro colony culture. The peripheral blood was also remarkable for the presence of a population of large granular lymphocytes demonstrable by conventional staining. These cells in flow microfluorometry studies expressed antigens Leu 4 (T‐cell antigen receptor), Leu 7 (natural killer cell marker), Leu 2 (suppressor cell marker), and HLA‐DR (activation marker); they lacked Leu 1 (a pan‐T cell antigen), Leu 3 (helper cell marker) and Tac (interleukin 2 receptor). Hematopoietic colony formation in vitro improved with addition of corticosteroids to the culture medium or elimination of the LGL population with complement‐mediated cytotoxicity. Anti‐neutrophil antibodies were present prior to and following therapy. Clinically, administration of prednisone resulted in a normalization of the total white blood cell count and absolute polymorphonuclear cell number, an increase into the normal range of the number of CFU‐C, and elimination of the LGL population. In this case of steroid‐responsive LGL‐associated neutropenia, laboratory studies suggested direct suppression of myelopoiesis by steroid‐responsive LGL.
Intravenous gammaglobulin therapy for thromboneutropenic neonates of mothers with systemic lupus erythematosus
Authors: Hanada Takashi , Saito Kenji , Nagasawa Toshiro , Kabashima Teizo , Nakahara Satoko , Okuyama Akihiko , Takita Hitoshi
Published: July 2010

i.v. IgG therapy was used to treat thromboneutropenia in 2 male neonates of mothers with SLE. The mothers of both neonates were thrombocytopenic but not neutropenic during the last 3 months of their pregnancies. Anti‐platelet and anti‐neutrophil IgG directed against platelets and neutrophils from the neonates were detected in the sera of both mothers. The platelet and neutrophil counts increased significantly with i.v. IgG therapy in both neonates, i.v. IgG therapy is a safe and effective regimen for passive immune thromboneutropenia.
Hereditary sideroblastic anaemia and autosomal inheritance of erythrocyte dimorphism in a Dutch family
Authors: Hogervorst G. D. van Waveren , van Roermund H. P. C. , Snijders P. J.
Published: July 2010

Size distribution curves of red blood cells were used to detect the presence of microcytes in peripheral blood of members of a Dutch family with hereditary side‐roblastic anaemia. 22 of 49 members of this family have a bimodal erythrocyte volume distribution curve and a dimorphic blood picture. The pattern of inheritance of this morphological abnormality is clearly autosomal. It is suggested that the study of red blood cell size distribution curves may add valuable information on the pattern of inheritance in other families with hereditary sideroblastic anaemia.
IgA multiple myeloma coexistent with atypical adult T‐cell leukemia
Authors: Tagawa Shinichi , Okamoto Yuji , Inada Eiichi , Hakura Akira , Kitani Teruo
Published: July 2010

We report a 65‐yr‐old male with adult T‐cell leukemia (ATL) who developed multiple myeloma (MM) concomitantly. Skin lesions and peripheral leukocytosis were noted during the 5‐yr observation period. There was abnormal lymphocytosis with indented or lobulated nuclei in the peripheral blood and in the bone marrow. The neoplastic cells reacted with monoclonal antibodies, OKT3, OKT4, OKIa1 and anti‐Tac. His serum was positive for the antibodies to ATL‐associated antigens. Human T‐cell leukemia virus (HTLV) proviral DNA was detected in the leukemic cells. Thus, a diagnosis of ATL was made. There was IgA (k) paraprotein in his serum, and Bence‐Jones protein (k) in urine samples. Fine needle aspiration revealed pathologic flaming plasma cells. Multiple osteolytic lesions appeared on his skull 5 yr after the initial examination. Thus, a diagnosis of MM concomitant with ATL was made.
Pathophysiological classification of acquired bone marrow failure based on quantitative assessment of erythroid function
Authors: Cazzola Mario , Bergamaschi Gaetano , Huebers Helmut A. , Finch Clement A.
Published: July 2010

Bone marrow failure encompasses a broad spectrum of disorders including aplastic, dysmyelopoietic and myelophtisic anemias. In the present study, these anemias were characterized according to the degree of erythroid proliferation and efficiency of erythropoiesis. Total erythropoietic activity was evaluated in 43 patients by measuring the erythron transferrin uptake (ETU). It averaged 20% of basal (range 3–43%) in 13 patients with severe aplastic anemia, 75% of basal (range 60–103%) in 3 patients with extensive bone marrow infiltration by neoplastic cells, 131 % of basal (range 50–217%) in 16 patients with refractory anemia, and 452% of basal (range 63–720) in 11 patients with idiopathic refractory siderobastic anemia. Respective efficiencies of erythropoiesis were 74% in aplastic anemia, 70% with bone marrow infiltration, 46% in refractory anemia, and 14% in sideroblastic anemia. Based on the ETU, patients could be categorized into absolute marrow failure, relative marrow failure, and adequate erythropoietic response to anemia. This simple determination of proliferating activity of the erythroid marrow can provide useful information on the pathophysiology of marrow failure and a basis for the selection of therapeutic approaches.
Zinc status in polycythaemia
Authors: Simmer K. , Pearson T. C. , Wheeler M. J. , Thompson R. P. H.
Published: July 2010

Zinc and iron status have been measured in three groups of polycythaemic patients managed by venesection: polycythaemia rubra vera, secondary polycythaemia and idiopathic erythrocytosis. Zinc status was assessed from the concentration of zinc in polymorphonuclear cells (PMN) and plasma. The mean PMN zinc value was lower than that of age‐matched controls (polycythaemics 57.5 ± 2.3 ±g/1010 PMN, n = 26; controls 68.9 ± 5.2 μg/1010 PMN, n = 9; means ± SEM, p < 0.05). The difference was most marked in polycythaemia rubra vera; the patients were iron‐deficient. The reduced PMN zinc levels may indicate that polycythaemic patients managed by repeated venesection are zinc‐deficient. This may contribute to some nonspecific symptoms of polycythaemia and to recurrent infections in the hypoxic patients.