bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunological definition of acute promyelocyte leukemia (FAB M3): A study of 39 cases
Authors: De Rossi G. , Avvisati G. , Coluzzi S. , Fenu S. , LoCoco F. , Lopez M. , Nanni M. , Pasqualetti D. , Mandelli F.
Published: July 2010

Acute promyelocytic leukemia (FAB‐M3) is a distinct entity among acute non‐lymphoid leukemias (ANLL) with peculiar morphological, biological, clinical and prognostic features. An atypical form of M3 (M3v) could be confused with other FAB ANLL and therefore the diagnosis of this variant requires ultrastructural analysis and/or cytogenetic study and/or selective gene rearrangement studies. The immunological phenotype of blast cells in 39 APL patients was studied at diagnosis. The diagnosis of M3 FAB type was ascertained in 32 and the diagnosis of M3v in 7 cases. Using a large series of monoclonal antibodies (mAb), the APL blast cells were B and T cell antigens‐negative, HLA‐DR constantly negative, CD 13‐ and/or CD33‐positive, CD9‐positive. Among ANLL this phenotype seems to be closely related to APL both in M3 type and M3v subtype. Because the diagnosis of APL (M3 or M3v) is important in order to establish the specific therapeutic approach, the discriminant capacity of the immunological typing to identify M3 and mainly M3v (hypogranular) could be determinant for a “quick” diagnosis.
Immunophenotype of hairy‐cell leukemia
Authors: Hassan I. B. , Hagberg H. , Sundström C.
Published: July 2010

15 cases of HCL were studied with a panel of monoclonal antibodies against different leukocyte antigens. A B‐cell phenotype different from that of B‐CLL was observed (CD10‐, CD19+, CD20+, CD21‐, CD22+, CD37+, CD38‐, FMC7+, LN1+, PCA‐1+, BLy7+and CD5‐). As expected, CD11c and CD25 were positive and, in addition, a My7 and My9 positivity in varying degree was noted. 3 weeks of in vitro incubation did not significantly alter the phenotype. We conclude that HCL exhibits a unique phenotype among chronic B‐cell leukemias, which is closer to the plasma cell stage of differentiation than that of B‐CLL. The BLy7 monoclonal antibody seems to be a promising marker for HCL.
A prospective study of haemostatic parameters in relation to the clinical course of myeloproliferative disorders
Authors: Wehmeier A. , Fricke S. , Scharf R. E. , Schneider W.
Published: July 2010

Abstract:Platelet function and the clinical course of the disease were prospectively investigated in 29 patients with myeloproliferative disorders. Serial determinations (median: 5 investigations per patient within 17 months) of platelet aggregation, plasma and intraplatelet concentrations of β‐thromboglobulin (βTG) and platelet factor 4 (PF4), and of fibrino‐peptide A (FPA) plasma levels were carried out. In the chronic phase of polycythaemia vera, patients with thrombohaemorrhagic complications during the study period had higher platelet count, more severe platelet aggregation defects, and increased plasma levels of βTG and FPA compared to patients without complications. However, thrombohaemorrhagic complications were not predicted by changes in these parameters in the individual patient during the chronic disease phase. When patients with chronic myelogenous leukaemia entered blast crisis, bleeding complications were related to thrombocytopenia, impaired platelet function and low intraplatelet concentrations of βTG and PF4. Cytoreduction by chemotherapy in the chronic phase of CML did not alter βTG and PF4 plasma levels, whereas treatment of polycythaemia rubra vera by venesection favourably influenced platelet α‐granule secretion and increased intraplatelet concentrations of βTG and PF4.
Prognostic factors in multiple myeloma in a population‐based trial
Authors: Hannisdal E. , Kildahl‐Andersen O. , Grøttum K. A. , Lamvik J.
Published: July 2010

Abstract:Prognostic factors have been tested in patients with multiple myeloma treated according to a randomized trial of standard therapy versus 5‐drug combination therapy. The following population‐based study included 92 patients with a median age of 70 yr. The median survival was 31 months. The Cox regression model was used to search for predictors of survival. The cut‐off levels for blood analyses derived in earlier studies tended to select few patients in the high‐risk groups, for example only 8% of the patients had hemoglobin (Hb) ≤ 7.5 g/dl. Lytic bone lesions in the pelvis or in the long bones, or spontaneous fractures and age > 70 yr gave prognostic information in addition to anemia and impaired renal function. The MRC staging system was a better prognostic tool than the Durie & Salmon stages. Palliative treatment regimens which take quality of life into account should be considered carefully in multiple myeloma patients > 70 yr.
Bone marrow stromal elements in murine leukemia: Decreased CSF‐producing fibroblasts and normal IL‐1 expression by macrophages
Authors: Ben‐Ishay Z. , Barak V. , Shoshan S. , Prindull G.
Published: July 2010

Abstract: A study of bone marrow stromal elements in murine acute myeloid leukemia (AML) was carried out. Our previous studies had indicated marrow stromal deficiency in murine AML. In the current investigation, separate stromal cells were cultured and the results obtained have shown that, while marrow stromal macrophages are normal in leukemia and express adequate amounts of IL‐1, the fibroblasts are markedly reduced. However, if sufficient fibroblasts are pooled in vitro, they produce adequate amounts of CSF. Test of TNFα in leukemic cells CM, as possible cause of marrow stromal inhibition in leukemia, had not disclosed this cytokine. Further, it was observed that total body lethal irradiation of leukemic mice aggravates the stromal deficiency, confirming results of our previous investigations. It is concluded that bone marrow stromal deficiency in murine AML is due to decreased fibroblasts and, implicitly, reduced CSF production.
Abnormal chromatin clumping in leucocytes: A clue to a new subtype of myelodysplastic syndrome
Authors: Jaén Ana , Vallespi Teresa , Torrabadella Marta , Irriguible Dolores , Woessne Soledad , Abella Eugenia , Milla Fuensanta , Lafuente Roser
Published: July 2010

Abstract: We report 6 patients with myelodysplastic syndrome, all of whom showed a bizarre nuclear anomaly within the neutrophils that was characterized by extensive clumping of chromatin into large blocks separated by clear zones, generally associated with a lack of segmentation. Anaemia, thrombocytopenia, variable leucocyte counts with leucoerythroblastic picture, marrow hypercellularity with granulocytic hyperplasia and moderate dysplastic changes in erythroblastic and megakaryocytic lines were present at diagnosis. 2 patients had normal karyotypes and a 3 showed a deletion of chromosome 14. 5 out of 6 patients had pneumonia at diagnosis. The median survival was short (5 months) and haemorrhagic complications were the cause of death in 4 patients. The clinical features and the evolution of these and other reported cases suggest that the presence of abnormal chromatin clumping in leucocytes might be a clue to a new subtype of myelodysplastic syndrome.
Immunogenotyping with antigen receptor gene probes as a diagnostic tool in childhood acute lymphoblastic leukaemia
Authors: Fey M. F. , Tobler A. , Stadelmann B. , Hirt A. , Theilkäs L. , Khandjian E. W. , Ridolfi‐Lüthy A. , Delaleu B. , Weil R. , Wagner H. P.
Published: July 2010

Abstract: 13 cases of childhood acute lymphoblastic leukaemia (ALL) were studied combining cell surface marker analysis with immunogenotyping by Southern blot hybridisation with a panel of antigen receptor gene probes. The immunophenotypes were unequivocal: 7 patients had B‐phenotype and 6 patients T‐phenotype ALL. In several patients immunogenotypes were not fully consistent with the respective phenotypes. For example, 2 B‐cell precursor ALL had rearranged TCRβ chain genes and 2 T‐ALL rearrangement of Ig heavy‐chain genes. All cases showed clonal rearrangement or deletions within the TCRδ gene locus. TCRδ gene rearrangements might, therefore, serve as markers of clonality but not of B‐ or T‐lineage in immature lymphoid neoplasms. We conclude that in current diagnostic practice immunogenotyping is a supplement rather than an alternative to immunophenotyping by surface marker analysis.
Labelling autologous platelets with 111In tropolonate for platelet kinetic studies: limitations imposed by thrombocytopenia
Authors: Danpure H. J. , Osman S. , Peters A. M.
Published: July 2010

Abstract: An in vitro method of radiolabelling platelets with 111In tropolonate in plasma has been devised enabling imaging and cell kinetic studies to be performed in patients with thrombocytopenia (TP) using autologous, rather than donor, platelets. Platelets from 10 TP patients, with platelet counts ranging from 4–91 times 109/1, were labelled in 50% plasma with 111In tropolonate, containing the optimum tropolone concentration of 2 times 10−4 mol/l, at platelet concentrations ranging from 0.08‐4.5 times 109/ml resulting in labelling efficiencies (LE) between 51 and 86%. In 4 patients, red cells contaminated the platelets but this was corrected for by measuring the proportion of 111In on the platelets prior to injection and in the post‐injection blood samples. Platelet recovery (PR), mean platelet life‐span (MPLS) and platelet production rate (PPR) were calculated and splenic and hepatic images were taken. The results clearly show that useful clinical data can be obtained by this method even in patients with severe TP.
Clinical significance of serum pro‐collagen III in chronic myeloproliferative disorders
Authors: Najean Yves , Legrand Michèle , Poirier Odette , Senechal Alain , Arrago Jean‐Paul
Published: July 2010

Abstract: Pro‐collagen III (PC III) has been proposed as a useful value for diagnosis and follow‐up of myeloproliferative disorders. A significant difference is observed between polycythaemia vera (PV) and essential thrombocythaemias (ET) on one hand, and the pure erythrocytoses (PE) on the other hand, but a large overlap makes this test of low diagnostic value. High values are observed in primary and post‐PV myelofibrosis, but excessive PC III levels in active PV are not predictive of evolution toward myelofibrosis. PC III level is lower in myelo‐suppressed patients (32P, or hydroxy‐urea) than in active cases or in patients treated by phlebotomies. We conclude that PC III measurement is of low diagnostic value for discriminating PV and PE, does not appear to allow short‐term prediction of evolution to myelofibrosis, but may be useful to evaluate the role of treatment in delaying progression of PV toward myelofibrosis.
In vivo elaboration of CSF in acute inflammation: Proportionality to the intensity of the inflammatory stimulus and requirement of T lymphocytes
Authors: Hamood Mohamad , Chatelain Christian , Fondu Pierre , Symann Michel
Published: July 2010

Abstract: The colony‐stimulating factor(s) (CSF) that stimulates the in vitro growth of bone marrow granulocyte‐monocyte progenitors (CFU‐GM) increases in the serum of mice challenged by an aseptic abscess induced by copper rod insertion. The effect of the inflammation on the increase of serum CSF is dose‐related. The creation of 3 aseptic abscesses indeed results in a higher and longer elevation of serum CSF than 1 abscess. Serum CSF also increases in parallel with the rise in bone marrow CFU‐GM; this is consistent with the CSF playing a role in regulation of haematopoiesis in vivo. From previous studies, it appears that T lymphocytes play a central role in the regulation of haematopoiesis. In order to determine the role of T lymphocytes in the inflammation response, cyclosporin A (CyA), an inhibitor of T lymphocyte function, was given in vivo, 2 days before inflammation induction. CyA abrogates the increase in both serum CSF and CFU‐GM. Furthermore, a lower increase in serum CSF was observed in copper‐implanted nude mice. These results suggest that the CSF production induced by inflammation requires the functional integrity of T lymphocytes.
Heat production rate in blood lymphocytes as a prognostic factor in non‐Hodgkin's lymphoma
Authors: Monti M. , Brandt L. , Ikomi‐Kumm J. , Olsson H.
Published: July 2010

Abstract:The heat production rate in peripheral blood lymphocytes was evaluated by direct calorimetry in 76 untreated adults with non‐Hodgkin's lymphoma (NHL). Elevated values were recorded for 20 out of 54 patients with lymphomas of high or intermediate malignancy grade (37%) and for 1 out of 22 patients (5%) with low grade lymphomas (p = 0.01). Median survival was 39 months for patients with normal values and 8.5 months for those with elevated values (p = 0.005). In a subgroup of 38 patients with high or intermediate grade NHL stage III‐IV, 17 patients with abnormally high lymphocyte heat production rates had a significantly shorter survival than 21 patients with normal values (p = 0.01). In a multivariate analysis the prognostic impact of lymphocyte heat production was superior to histologic malignancy grade, clinical stage and age.
Endogenous BFU‐E in peripheral blood in diagnosis of polycythemia vera
Authors: Biljanovic‐Paunović L. , Ruvidić R. , Pavlović‐Kentera V.
Published: July 2010

Abstract: Erythroid progenitors (CFU‐E and BFU‐E) growth in vitro from bone marrow and peripheral blood of patients with polycythemia vera (PV) was studied using a methylcellulose culture technique. The aim of the study was to find out whether the in vitro colony formation of peripheral blood could be used in the differential diagnosis of PV. In all 25 patients studied, endogenous colonies were found in the bone marrow and peripheral blood. The parallel study of both bone marrow and peripheral blood erythroid progenitors indicates that the presence of endogenous BFU‐E in peripheral blood is a dependable test for PV. The results presented here showed that the abnormalities in PV erythroid progenitors are expressed at the level of both CFU‐E and BFU‐E, suggesting multiple changes in the erythroid progenitors. Our finding indicate that peripheral blood BFU‐E differ from bone marrow BFU‐E with regard to their dependence for further differentiation on BPA, the activity present in PHA‐LCM.
Induction and maintenance alpha‐interferon therapy in myelofibrosis with myeloid metaplasia
Authors: Barosi G. , Liberato L. N. , Costa A. , Buratti A. , DI Dio F. , Salvatore S. , Ascari E.
Published: July 2010

Abstract: In 12 patients having myelofibrosis with myeloid metaplasia (MMM), recombinant‐ α interferon (r‐αINF) was given for 16 weeks at an initial dose of 3 times 106 U/day as a cytoreductive agent. At the end of the 16th wk, Hb showed minor changes; WBC were reduced from 43 times 109/l, range 6.4–69.4, to 16 times 109/l, range 5–39 (p = 0.05); platelets decreased from 845 times 109/l, range 215–1748, to 370 times 109/l, range 96–730 (p = 0.005). 2 cases responded at the starting dose, while the effective dose was 5 times 106 U/d in the others. Minor changes in spleen size were noted, while no significant changes in bone marrow fibrosis occurred. After induction therapy, 3 patients were allocated to maintenance therapy (from 10 up to 34 months). To maintain platelet count lower than 500 times 109/l, the required r‐α‐INF dose was constantly 10 MU/wk, while the same result was not achieved in 1 case with hydroxyurea, 1 g/die. The association with hydroxyurea, 500 mg/die, allowed reduction of the r‐αINF dose to 6 MU/die in 1 other case.
Therapy of essential thrombocythemia with alpha‐interferon: Results and prospects
Authors: Lazzarino M. , Vitale A. , Morra E. , Gagliardi A. , Bernasconi P. , Torromeo C. , Inverardi D. , Burgio V. L. , Castello A. , Bernasconi C. , Mandelli F.
Published: July 2010

Abstract: Conventional treatment of symptomatic essential thrombocythemia (ET) consists of long‐term administration of myelosuppressive cytotoxic agents which, although efficacious in most cases, are associated with leukemogenic potential. Alpha‐interferon (IFN) exerts a dose‐dependent inhibitory influence on thrombopoiesis through a direct antiproliferative effect on megakaryocytic precursors. Therefore, it may provide a biologic, potentially non‐mutagenic alternative to conventional cytotoxic treatments. At daily doses ranging from 1 to 5 M.U., alpha‐IFN is efficacious in inducing a hematologic response in most patients with ET. Response to IFN is a gradual process. The median time to hematologic response varies from 1 to 3 months and a significant proportion of patients reach and maintain normal platelet counts with low doses (1–3 M.U./d). Normalization of marrow megakaryocytosis requires longer treatment (9–12 months). Also patients resistant to cytotoxic drugs may respond to alpha‐IFN, suggesting a lack of cross‐resistance between the two treatment modalities. Side‐effects, although not severe, represents a limit to the administration of adequate doses of IFN in about 25% of cases. Once hematologic response has been obtained, both low‐dose IFN and cytotoxic drugs are effective as maintenance. The full potentialities of alpha‐IFN in ET in combination with cytotoxic drugs or with other cytokines need to be further investigated.
Alpha‐2b recombinant interferon (Intron) in Hodgkin's lymphoma: Therapeutic perspective
Authors: Mazza P. , Tura S. , Bocchia M. , Zinzani P. L. , Gherlinzoni F. , Mandelli F. , Anselmo M. P. , Papa G. , Antimi M. , Gobbi P. G. , Porcellini A. , Rizzoli V. , Resegotti L. , Levis A. , Deriu L. , Chierichini A. , Ciccone F. , Fanin R. , Castoldi G. , Scapoli G. L. , Liso V. , Chisesi T. , Rancan L. , Amurri B.
Published: July 2010

Abstract: In an ongoing phase II study we are evaluating the role of alpha‐2b recombinant interferon in Hodgkin's disease; the study design includes patients with high‐risk parameters who are treated by combination chemotherapy MOPP, ABVD, MOPP + ABVD or equivalent combinations. At the end of the therapeutic program which could include also radiotherapy, patients will be randomly assigned to receive alpha‐2b interferon at 3MU/day over 3 months and then 3MU/three times/week over 9 months or no further treatment. Up to September 1989, 107 patients were randomized; evaluable patients with a minimum follow‐up of 3 months are 95, 56 in the arm of interferon and 39 in the arm of no further treatment. The results are preliminary and differences could not be disclosed between the two arms concerning either the relapse rate or the incidence of infections. Tolerance and toxicity due to alpha‐2b interferon in patients with Hodgkin's disease could be defined as acceptably good considering that mild and reversible hematological toxicity was experienced in 12 (21%) patients; objective clinical toxicity was recorded in 4 (7%) patients although 7 (12%) patients refused to continue the treatment. Definite conclusions will be drawn when 100 patients per arm become evaluable.
Interferon alpha‐2b as therapy for patients with Ph‘‐positive chronic myelogenous leukemia
Authors: Alimena Giuliana , Morra Enrica , Lazzarino Mario , Liberati Anna M. , Montefusco Enrico , Inverardi Daniela , Bernasconi Paolo , Mancini Marco , Donti Emilio , Grignani Fausto , Bernasconi Carlo , Dianzani Ferdinando , Mandelli Franco
Published: July 2010

Abstract: We treated 114 ph1+ chronic myeloid leukemia (CML) patients, 105 of whom were in chronic phase (CP) and 9 in accelerated phase (AP), with interferon alpha‐2b (IFN α‐2b) at intermittent or daily doses of 2–5 MU/m2. Of 35 previously untreated CP patients, 22 (63%) showed complete hematological response (CHR). This was significantly influenced by initial risk status. In 19 of the 22 CHR patients the median of ph1+ cells decreased from 100% to 58%. Of 36 patients pretreated for < 12 months, 19 (53%) achieved CHR. CHR rate was significantly related to IFN dose. Cytogenetic improvement was observed in 15 of the 19 patients, the median of ph1+ cells dropping from 100% to 76%, with complete suppression of the ph1 chromosome in 1 case. Of the 34 patients pretreated for > 12 months, 21 (62%) obtained CHR. Cytogenetic improvement was observed in 10 cases, the median of ph1+ cells declining from 100% to 66%. 1 of 9 AP patients obtained CHR. After a median follow‐up of 32 months for the 63 CHR patients, 49 (78%) are still in disease control: 34 on IFN therapy, 15 after bone marrow transplantation (BMT) (13 autologous and 2 allogeneic). Blastic transformation (BT) occurred in 9 of 63 (14%) CHR patients and in 24 of 51 (47%) patients with less than CHR. IFN α‐2b has proved to be an effective treatment for CML. Its combination with other treatment modalities represents an interesting and promising approach for future studies.
Splenectomy after initial therapy with alpha‐IFN in patients with hairy‐cell leukemia (HCL): a multi‐center study by the Italian Cooperative Group for HCL. Preliminary results
Authors: Damasio E. E. , Federico M. , Frassoldati A. , Lamparelli T. , Annino L. , Bernasconi C. , Chisesi T. , Foá R. , Lauria F. , Pagnucco G. , Resegotti L.
Published: July 2010

Abstract: Since December 1987, 115 patients with HCL have been enrolled in a prospective multicenter study to evaluate the role of splenectomy after an induction therapy with alpha interferon. The group of patients was divided into two categories: those younger and those older than 65 years. The schedule of treatment with IFN was, respectively, 1.8 MU/sm/daily and 1.0 MU/daily. 33 patients were treated with r‐alpha‐2a, 34 with r‐alpha‐2b, and 25 with alpha‐Ly. To date, 92 patients are fully evaluable. The response was assessed every 3 months by bone marrow trephine biopsy. Patients in CR continued IFN therapy for 3 months and, if they were still in CR, could undergo an optional splenectomy. Patients in PR continued therapy for 12 months and subsequently were randomized for splenectomy or observation only. In these preliminary results of an ongoing protocol, CR was obtained in 5 cases (6%), PR in 59 (64%), MR in 25 (27%), NR in 3 (3%). Only 2 of the 5 patients in CR underwent splenectomy and are still in CR. Of the 59 patients in PR, only 15 completed 12 months of therapy. 9 patients in Group A were randomized, 4 were splenectomized and 5 were in the observation arm. All patients were splenectomized safely and no complications occurred. These preliminary results suggest that splenectomy could be effective in consolidating the response obtained with IFN.
Interferon alpha‐2a in cutaneous T‐cell lymphoma
Authors: Vegna M. L. , Papa G. , Defazio D. , Pisani F. , Coppola G. , De Pità O. , Puddu P. , Ferranti G. , Simoni R. , Mandelli F.
Published: July 2010

Abstract: 23 newly diagnosed patients affected by cutaneous T‐cell lymphoma were treated with sub‐cutaneous interferon alpha‐2a to evaluate the therapeutic efficacy and the toxicity of this agent. IFN was administered daily with dose escalation from 3 to 18 million units for 12 weeks; thereafter, patients induced into complete (CR) or partial (PR) remission were given IFN at maximal tolerated dose 3 times weekly for 6 or 9 months. The objective tumor response was observed in 17 patients (74%): 8 (35%) were CR and 9 (39%) were PR. A 74‐yr‐old patient died because of neutropenia and sepsis at the end of induction phase, while receiving IFN at dose of 18 million units. Disease stage is the initial feature predictive of response to IFN therapy. The dose schedule of this study was well tolerated: only 3 patients developed liver toxicity, while leukopenia was evident in 6 patients. Only 2 CR patients have relapsed, 18 and 24 months from response; the remaining 6 CR patients are in continuous complete remission with a median follow‐up of 41.8 months. 6 PR patients have progressed from 8 to 17 months after response, and in the 3 PR patients not yet progressed the response duration ranges from 20 to 24 months. In conclusion, interferon alpha‐2a is a very effective agent in therapy of untreated cutaneous T‐cell lymphoma with an overall response rate of 74%.
Alpha‐2b‐interferon as single therapy for patients with chronic myeloid leukemia relapsing after T‐cell depleted allogeneic bone marrow transplantation
Authors: Arcese W. , Mauro F. R. , Screnci M. , Alimena G. , Iori A. P. , De Cuia M. R. , Coco F. Lo , Montefusco E. , Fazi P. , Mandelli F.
Published: July 2010

Abstract: 20 CML patients with hematological (5 pts) or only cytogenetic (15 pts) relapse occurring after allogeneic BMT have been treated with alpha‐2b‐interferon (IFN) at a starting dose of 5 times 106 IU/m2, subcutaneously, three times a week. All 5 patients with hematological relapse achieved hematological remission without reduction of bone marrow Ph1‐positive cells. With a median follow‐up of 43 months (range 6–48) from the hematological relapse, 3 patients are alive and 2 patients died from non‐lymphoid blast crisis. 7 out of 15 patients with only cytogenetic relapse remain in hematological remission at a median of 37 months (range 3–45) from cytogenetic relapse, with 2 patients achieving complete cytogenetic remission confirmed at the molecular level by disappearance of the bcr rearranged band. With a median follow‐up of 21 months (range 6–46), 8 patients progressed from cytogenetic to hematological relapse: 4 patients died from blast crisis and the other 4 patients are currently alive in chronic phase. For the 15 patients, the actuarial survival from BMT is 71% at 5 years.
Analytical goals for haematology tests
Authors: Fraser C. G.
Published: July 2010

Abstract:  All analytical methods can be defined in terms of their practicability and reliability performance characteristics. Desirable standards of performance, or analytical goals, are required for these, particularly for imprecision and inaccuracy. Goals for imprecision have been set using a variety of methods including reference values, opinions of clinicians, views of individuals, and data on biological variation. The last approach is currently favoured; desirable imprecision is equal to or less than one‐half of the biological within‐subject variation. If this goal is met, total variability of test results is increased by less than about 10% due to analytical variability. Valid estimates of within‐subject variability are available for the complete blood count. The goal for inaccuracy is that methods should have no bias so that results are comparable over time and geography; goals based on biological variation should be viewed and used, therefore, as goals for total error. In current practice, some of the goals cannot be met; they should be considered as targets worthy of achievement, not as inflexible criteria of acceptance or rejection of methods.
Clinically based quality goals; a NORDKEM project
Authors: Petersen P. Hyltoft , de Verdier C‐H. , Groth T. , Aronsson T.
Published: July 2010

Abstract:  The three main aspects of analytical quality are ‘goals for analytical qualtity’, ‘creation of analytical quality’, and ‘control of analytical quality’. In the NORDKEM‐project ‘medical need for quality specifications within laboratory medicine’ the aspects of analytical quality are combined. The aims is to make an appraisal of the different approaches to goal setting, and to develop a practical procedure for assessing analytical quality requirements. The goals are used to define which demands should be met by the process of establishing and maintaining the quality, and for design of internal as well as external quality assurance procedures. The project is an umbrella project with three main subprojects and several satellite projects. In this presentation a model for evaluation of influence of analytical bias and imprecision on the outcome from a diagnostic classification based on biomodal distribution is described.
Standardization and harmonization of the blood count: The role of International Committee for Standardization in Haematology (ICSH)
Authors: Lewis S. M.
Published: July 2010

Abstract:  Scientific principles of standardization were first applied in haematology in 1963 when the International Committee for Standardization in Haematology was established with a primary objective to improve the measurement of haemoglobin. Subsequently, ICSH has established Expert Panels on a wide range of haemat‐ological topics, including especially a Panel on Cytometry. The purpose of haematological standardization is to obtain precision, accuracy, specificity and harmonization of results between different laboratories in all countries and also between different instruments or methods in the same laboratory. To achieve these objectives ICSH sponsors collaborative studies by scientists from academic centres and from industry and uses a consensus procedure for establishing standards on the basis of the scientific data, followed by an educational programme to ensure that the standards are adopted worldwide.

ICSH defines material standards and standardized methods. Material standards are classified as primary international standards, certified reference materials, secondary standards and calibrators. These must be distinguished from control preparations which are intended exclusively for quality control.

Standardization of methods must also be considered at four levels: definitive, reference, selected and routine. Each has a place in practice but their roles must be clearly defined. ICSH has an established protocol for evaluation of automated blood cell counters. This defines the levels of precision and accuracy of instrument performance. It is also necessary to assess “clinical utility”. The main requirement of the practising haematologist is clinical reliability and harmonization of results for comparability. One of the major functions of ICSH is to provide an interface for collaboration between the manufacturers who develop the instruments and the users in order to achieve this goal.
Relationship of quality goals and measurement performance to the selection of quality control procedures for multi‐channel haematology analysers
Authors: Westgard J. O. , Cembrowski G. S.
Published: July 2010

Abstract:  An approach is described for selecting QC procedures based on goals for analytical quality, the performance characteristics of the measurement procedure (imprecision, bias, frequency of errors), and the performance characteristics of the control procedure (probabilities for error detection and false rejection). Performance characteristics of stable sample QC procedures and patient data QC procedures (retained patient specimens, Bull's single‐rule algorithm, Bull's multi‐rule algorithm) are compared to determine when to apply these different QC procedures to multichannel hematology ! analysers. Precise, stable methods may be controlled using Bull's single‐rule algorithm; less precise, less stable methods require Bull's multi‐rule algorithm, retained patient specimens, or stable sample QC procedures; imprecise and unstable methods are best controlled using stable sample QC procedures. “Multi‐stage” designs may employ stable samples for “startup” testing, retained patient specimens for short term monitoring, and Bull's single‐rule algorithm for long term monitoring.
Practical experience with a quality control procedure using retained patient specimens on Technicon HI and COULTER S 880
Authors: Rustad P. , Lund P. Kr.
Published: July 2010

Abstract:  External quality assessment and internal quality control in hematology is complicated by the lack of good control materials. Commercial materials do not always behave as patient blood and they are expensive. Patient specimens are unstable, but may be used either within certain time limits or as in Bull's moving average for red cell indicies.

We have used retained patient specimens for internal quality control supplemented by a commercial control material. Three patient‐specimens were run alternatively on a Technicon HI and a Coulter 880 at regular intervals. The variations for each instrument and between instrument were computed. We used the 2of32s control rule.

Our conclusion is that the Coulter 880 had an overall better performance than the Technicon H1 when using retained patient specimens. But both instruments practically met suggested analytical goals.
Quality Assurance in Clinical Laboratories. An updated supplement to a bibliography
Authors: Uldall A.
Published: July 2010

Abstract: A supplement to a bibliography (Scand J Clin Lab Invest 1987;47 suppl. 187:1–96) dealing with quality assurance in the clinical laboratory is presented. The increasing role of national and international standardizing bodies is stressed as well as implementation of rules of “good laboratory practice”. Objectively established quality goals for all services is highly needed in order to provide a rationale for the efforts dedicated to quality improvements. Quality goals for many clinical chemistry and haematology investigations are now available.
Automated differential leukocyte counts in newborn infants. Comparison of Coulter VCS and Technicon HI with manual counts
Authors: Johannessen B. , Ommundsen T. , Minde T. E. , Haneberg B. , Sandberg S.
Published: July 2010

Abstract: There was good agreement between results obtained with Coulter VCS/Technicon HI and manual counting with respect to neutrophils and eosinophils. Coulter VCS overestimates the lymphocyte percentage compared to manual counting and to HI. If, however, the percentage of so called “naked” cells are added to the percentage of manually counted lymphocytes, the agreement between VCS and the manual method is improved. The alarms given by the two instruments are of little value in detecting left shift or nucleated red blood cells.
External quality assessment of automated blood leukocyte differential counts and other simultaneous measured quantities
Authors: Uldall A. , Jacobsson L. , Rajamaki A.
Published: July 2010

Abstract:  An external quality assessment scheme (EQAS) of automated differential counts of leukocytes has been carried out using selected fresh blood specimens. The measurements were carried out one day after blood drawing because of the delay in the mail. Reference laboratories established target values for differential counts. They counted visually 600–700 cells in each specimen on smears. The concensus value among 12 laboratories for manual count of total leukocytes was used as target value, but was found on average 9% smaller than the average instrumental value. H1 results compared favorable with the target value for the differentials. The less advantageous findings on Coulter S + IV are partly explained by the age of the specimen when measured. The data indicated that better calibration of the instruments could decrease the overall variation of platelets counts and haemoglobin determinations. An EQAS involving measurement on fresh specimens is in progress.
Allergy testing using degranulation of basophils and flow cytometry
Authors: Nilsson T. A.
Published: July 2010

Abstract:  The Technicon H6000 hematology system was evaluated as a detector for the allergen‐induced basophil degranulation reaction in whole blood samples from individuals with type I allergy. Diluted standard skin prick test allergen extracts were added into heparin‐EDTA blood samples in presence and absence of free calcium ions and the H6000 basophil channel scattergram was used with a modification of the method for basophil counting. In one experiment only 250 microliters of blood was used for each allergen to be tested. The result correlated well to skin prick test and RAST results. The conclusions are that the H6000 is suitable for allergy testing using whole blood from patients, if the basophil channel is modified, and that the Technicon H1 system probably also is possible to use as a detector for basophil degranulation studies.
Improved automated differential counts of leukocytes from newborn infants using pre‐dilution of blood samples
Authors: Minde T. E. , Vallanger M. , Haneberg B. , Sandberg S.
Published: July 2010

Abstract: A method for automated differential leukocyte counting using peroxidase staining and light scatter (H1) failed to present results in more than 25% of blood samples from newborn infants. These failures were mostly seen at or below 2 weeks of age, and with high concentrations of haemoglobin F (HbF). Dilution of the blood with equal amounts of isotonic saline made the problem disappear almost completely. The results of differential counts on such diluted blood samples also compared more favourably with tradio‐tional manual counts of blood smears than did the results obtained with undiluted blood. The present method with blood diluted 1/2 is therefore recommended for routine use in newborn infants.
Coupling of HI to a central laboratory computer, automated evaluation of instrument alarms
Authors: Barth‐Magnus K.
Published: July 2010

Abstract:  Everyone who has worked with an H1 from Technicon knows that it pours out a vast number of asterisks and error flags and that the same information is hidden in different places. After comparing a great number of samples from H1 with manual methods, we found that we could reduce the number of alarms of medical significance to about 20.

So we built a microcomputer which sends the test results, the asterisks and 20 user defined alarm flags to the host computer where the verification takes place.

The verification program automatically approves of tests where no alarms, asterisks or high or low values occur. Tests with any kind of alarm or asterisk are displayed. Doubtful results are automatically deleted following specified rules, the meaning of the asterisks can be studied on a switch‐screen like on H1, and the technician can take the appropriate action, microscopy, rerun or checking H1
Changes in serum erythropoietin levels during allogeneic bone marrow transplantation
Authors: Grace R.J. , Kendall R.G. , Chapman C. , Hartley A. E. , Barnard D. L. , Norfolk D. R.
Published: July 2010

Abstract: Serial serum erythropoietin levels were measured in 10 consecutive patients undergoing allogeneic bone marrow transplantation. Observed erythropoietin levels are compared with those predicted from a large control population of anaemic patients not receiving chemotherapy. There was an initial acute rise in serum erythropoietin, peaking between days 1 and 4 after marrow transfusion, which was unrelated to changes in haemoglobin concentration. Patients maintained serum erythropoietin concentrations at around twice the predicted level for the first 2 weeks following transplantation, with a gradual fall into the expected range by wk 3. Erythropoietin levels did not change with episodes of bacterial infection or acute graft‐versus‐host disease. A patient with severe aplastic anaemia had initial successful engraftment with normalisation of erythropoietin levels, but showed a marked and amplified rise in erythropoietin 2 wk before falling peripheral blood counts indicated failure of the bone marrow graft.
Studies of in vitro megakaryocytopoiesis in adult immune thrombocytopenic purpura (ITP)
Authors: Bellucci S. , Han Z. C. , Caen J. P.
Published: July 2010

Abstract: In vitro megakaryocytopoiesis was studied in 8 patients with chronic immune thrombocytopenia (ITP). A significant increase of megakaryocyte (MK) colony formation was observed in 5/5 patients studied. Furthermore, the serum of these 8 patients was able to enhance MK colony formation by normal marrow cells. This effect was neither due to a decrease of inhibitors of megakaryocytopoiesis such as betathromboglobulin ((3TG) nor to the IgG fraction of patients' serum. In addition, the level of interleukin 6, which is above all a stimulus for MK maturation, was found within the normal range in 8/8 patients tested. These data suggest that in chronic ITP there is an increase of MK progenitor cell number which may be due to an increased level of MK colony‐stimulating activity.
In vivo evaluation of the anemia induced by azidothymidine (AZT) in a murine model of AIDS
Authors: Chow Fung‐Phing R. , Hamburger Anne W.
Published: July 2010

Abstract: Azidothymidine (AZT) induces severe anemia in patients with acquired immune deficiency syndrome (AIDS). To evaluate the mechanism of anemia in immune‐suppressed animals, a murine model of AIDS (MAIDS), caused by infection with LP‐BM5 murine leukemia virus (LP‐BM5 MuLV) was used at early and late stages of the disease. AZT‐induced anemia was dose‐ and time‐dependent. An increased percentage of erythroblasts in bone marrow was observed, with an increased ratio of early to late erythroblasts in both disease stages. Increases in splenic erythroid burst‐forming units (BFUe) were observed in early‐stage AZT‐treated mice. Mean plasma erythropoietin (EPO) levels were increased by AZT in both groups in a dose‐dependent manner and were inversely proportional to hematocrit values. These data suggest that the anemia induced by AZT stimulated a response by immature erythroid elements, but that the maturation or survival of early erythroblasts may be impaired.
Acute leukemia in professional drivers exposed to gasoline and diesel
Authors: Lindquist Ragnhild , Nilsson Bo , Eklund Gunnar , Gahrton Gosta
Published: July 2010

Lindquist R, Nilsson B, Eklund G, Gahrton G. Acute leukemia in professional drivers exposed to gasoline and diesel. Eur J Haematol 1991: 47: 98–103.

Abstract: The environmental exposure to the petroleum products gasoline, diesel, and their motor exhausts was studied in a case‐control interview of 125 patients with acute leukemia and 1 matched control per patient. Odds ratios were calculated by comparing discordant matched patient‐control pairs. An excess risk for developing acute leukemia was found for the professional drivers, and odds ratio was determined to be 3.0 (95% CI: 1.1–9.2/p<0.02). For those who were exposed for more than 5 years in their life‐time, or more than 1 yr during the 5–20 yr period prior to diagnosis, the odds ratio was 5.0 (p?<0.05). This finding remains after consideration is given to exposures to organic solvents, smoking and therapeutic x‐ray treatment. No excess risk was observed for persons professionally exposed to motor oil and machine oil without exposure to fuels and exhausts. No preferential type of acute leukemia was found to be associated with exposure to fuels and their exhausts. The results indicate an etiological relationship between the development of acute leukemia and exposure to petroleum products as fuels and exhaust.
Relationship between platelet volume and anti‐platelet autoantibodies in idiopathic thrombocytopenic purpura
Authors: Kokawa Terutoshi , Nomura Shosaku , Yasunaga Kojiro
Published: July 2010

Abstract: We used flow cytometry to explore the relationship between platelet volume and anti‐platelet autoantibodies in 71 patients with idiopathic thrombocytopenic purpura (ITP). An increase in platelet volume was found more frequently in patients with a platelet count of less than 20000/μl. Platelet volume was larger in patients without anti‐GPIIb/IIIa autoantibodies than in patients with these autoantibodies. Furthermore, the platelet count was significantly lower in patients without anti‐GIIb/IIIa autoantibodies than in the patients with these autoantibodies. There was a positive correlation between a large platelet volume in patients with a platelet count of less than 30000/μl and high platelet‐associated IgM levels. These results suggest that the platelet volume is related to the severity of thrombocytopenia in ITP.
Folate‐deficient human lymphoblasts: Changes in deoxynucleotide metabolism and thymidylate cycle activities
Authors: van der Weyden Martin B. , Hayman Ronald J. , Rose Ian S. , Brumley Jane
Published: July 2010

Abstract: Peripheral blood lymphocytes of healthy volunteers cultured with phytohaemagglutinin in folate‐deficient medium exhibit megaloblastic maturation with reduced intracellular folate content. We have employed this in vitro model for megaloblastic maturation to determine accompanying changes in cellular thymidylate cycle activities and deoxynucleotide levels. Folate‐deficient cells exhibit a two‐fold increase in thymidine kinase and thymidylate synthase activities. These increased activities were reduced to those of folate‐replete cells by co‐culture of folate‐deficient cells with thymidine. Folate deficiency was accompanied by reduced cellular levels of thymidine triphosphate (TTP) and deoxyguanosine triphosphate (dGTP). Exogenous deoxyuridine produced no increase in the reduced levels of TTP of folate‐deficient cells but effected a two‐fold increase in cellular deoxycytidine triphosphate. Exogenous thymidine increased the reduced TTP levels of folate‐deficient cells and corrected the reduced dGTP level; the increase in cellular TTP accompanying exogenous thymidine was more pronounced in folate‐deficient cells. These in vitro findings are compatible with a block in de novo thymidylate synthesis and explain in part the reported in vivo changes for the deoxynucleotide pool in megaloblastic marrow cells due to folate or vitamin B12 deficiency.
Dietary deficiency of vitamin B12 is associated with low serum cobalamin levels in non‐vegetarians
Authors: Narayanan M. N. , Dawson D. W. , Lewis M. J.
Published: July 2010

Abstract: A prospective study of 106 patients with low serum cobalamin (vitamin B12) levels showed that, in 37, it was unexplained. The dietary intake of the vitamin was assessed in these patients by questionnaire and was found to be low in 10 (37%). None of these patients was vegetarian and they were of varying age and social circumstance. Dietary deficiency may be the sole cause of a low serum cobalamin in a significant proportion of non‐vegetarians. An assessment of dietary intake should be part of the investigation of cobalamin deficiency.
Acute renal failure associated with haematological malignancies: A review of 10 years experience
Authors: Harris K. P. G. , Hattersley J. M. , Feehally J. , Walls J.
Published: July 2010

Harris KPG, Hattersley JM, Feehally J, Walls J. Acute renal failure associated with haematological malignancies: A review of 10 years experience. Eur J Haematol 1991: 47: 119–122.

Abstract: Patients with ARF and haematological malignancy (excluding myeloma), presenting to a single unit over 10 years were analyzed to see if patients likely to benefit from intensive renal supportive therapy could be identified. 31 episodes of ARF were identified in 29 patients (mean age 51 + 2.9 yr): 19 were associated with acute leukaemia (13 AML, 6 ALL); 10 with lymphoma. Acute tubular necrosis (ATN) was identified as the cause of ARF in 26 cases, with sepsis (96%) and exposure to nephrotoxic drugs (88%), especially aminoglycosides, being the commonest precipitating factors. Toxic levels of the latter were commonly documented. Patient survival was 45%. Requirement for mechanical ventilation resulted in a universally fatal outcome; age greater than 55 yr and the presence of CNS symptoms or signs were also significantly associated with a poor outcome. Non‐ATN causes (urate nephropathy or obstruction) carried a better prognosis. However, only 4 patients (14%) lived for more than 6 months following ARF. Thus, although a subgroup of patients more likely to benefit from treatment can be identified, the overall prognosis is poor and limited by that of the underlying disease. The potential benefit of avoiding nephrotoxic drugs, especially aminoglycosides, in these patients is highlighted by this study.