bluuebunny/crossref_metadata_2025 huggingface dataset:
Myelodysplastic syndromes: Analysis of clinical and prognostic features in 96 patients
Authors: van der Weide M. , Sizoo W. , Nauta J. J. P. , Krefft J. , Langenhuijsen M. M. A. C.
Published: July 2010

In a retrospective study of 96 patients with a myelodysplastic syndrome the FAB classification, Bournemouth score and other parameters were correlated with leukaemic transformation and survival. Diagnosis was refractory anaemia (RA) in 7 patients, acquired idiopathic sideroblastic anaemia (AISA) in 2, chronic myelomonocytic leukaemia (CMML) in 31, refractory anaemia with excess of blasts (RAEB) in 34 and RAEB in transformation (RAEB‐t) in 22. Median survival for all patients was 37 weeks (RA and AISA 103, CMML 67, RAEB 35, RAEB‐t 27). Scoring according to the Bournemouth criteria showed significant differences in survival between groups A, B and C. Of the separate variables, only percentage of bone marrow blasts and haemoglobin level were prognostically significant. A modified scoring system based upon these two variables was even more discriminative. It proved to be particularly useful in CMML, a subtype with a wide range of survival times. Leukaemic transformation was seen in 39% (RA and AISA 0%, CMML 30%, RAEB 39%, RAEB‐t 75%).
High doses of natural α‐interferon (α‐IFN) in the treatment of multiple myeloma — A pilot study from the Myeloma Group of Central Sweden (MGCS)
Authors: Åhre A. , Björkholm M. , Österborg A. , Brenning G. , Gahrton G. , Gyllenhammar H. , Holm G. , Johansson B. , Juliusson G. , Järnmark M. , Killander A. , Lerner R. , Lockner D. , Nilsson B. , Simonsson B. , Stalfelt A‐M. , Strander H. , Svedmyr B. , Svedmyr E. , Udén A‐M. , Wadman B. , Wedelin C. , Mellstedt H.
Published: July 2010

α‐interferon (α‐IFN) is a biological response modifier with a dose‐dependent activity. The present study on the treatment of patients with multiple myeloma with high doses of natural α‐IFN was designed to meet this dose‐dependent concept. 50 previously untreated patients with IgA and BJ myelomas and a s‐Creatinine ≤ 200 μmol/l entered the study. Various treatment schedules were tested. The initial plan was to give the patients 30 × 106 U α‐IFN daily. This dosage, however, gave unacceptable toxicity. Step‐by‐step decreasing dose schedules were given to the patients, 10 × 106 U of α‐IFN daily for 7 consecutive d repeated every 3rd week was found to be the maximal tolerable dose that could be given to most patients. 36% (95% confidence levels: 22%‐50%) of the patients responded: 41% of the IgA myelomas and 23% of BJ myelomas. Median time to response was 1.5 months and median response duration was 20 months. Impaired general condition and central nervous system and gastrointestinal‐related toxicity were the main adverse reactions. Hematological side‐effects were mild.
Low serum levels of carotenoids in sickle cell anemia
Authors: Natta Clayton , Stacewicz‐Sapuntzakis Maria , Bhagavan Hemmige , Bowen Phyllis
Published: July 2010

Serum carotenoids, tocopherols and retinol were analyzed in patients with sickle cell anemia (SCA) and in control subjects. The data show the following: the serum levels of the major carotenoids, alpha and beta carotene, cryptoxanthin, lycopene lutein, alpha tocopherol and retinol were significantly lower in SCA patients. These findings reflect an additional abnormality of the antioxidant system in SCA patients. Gamma tocopherol, on the other hand, was significantly elevated, consistent with the previously reported reciprocal relationship between serum alpha and gamma tocopherols. Thus, these data taken together with the earlier findings on the lower levels of plasma alpha tocopherol and ascorbic acid suggest that the entire antioxidant system may be compromised in SCA patients. This may contribute in part to the phenotypic expression of the condition.
Haematological abnormalities in a 75‐year‐old population. Consequences for health‐related reference intervals
Authors: Nilsson‐Ehle H. , Jagenburg R. , Landahl S. , Svanborg A. , Westin J.
Published: July 2010

A representative sample (n = 486) of a 75‐year‐old population was studied, and probands with defined laboratory aberrations were re‐investigated. Anaemia was present in 6% of the men and 3% of the women; in 17/22 anaemic subjects a cause was found. The prevalence of plasma cobalamin concentrations < 130 pmol/l was 6%, of iron deficiency approximately 6%. Divergencies in white blood cell and platelet counts were rare. The observed haematological aberrations were almost always caused by disease. Reference intervals for haematological components were calculated in the total study group and two reference sample groups after exclusions based on anamnestic and/or laboratory screening criteria or anamnestic criteria and/or verified disease. The lower reference limits for B‐Hb and P‐B12 in a group obtained after exclusions based on anamnestic and screening data were considered to be minimum values for healthy subjects. The WHO criteria for anaemia were applicable.
Immunological typing of acute leukemias: Immunoenzymatic staining of fixed cells compared with immunofluorescence staining of unfixed cells in suspension
Authors: Ly Bernt , Beiske Klaus , Larsen Nanneke
Published: July 2010

A panel of 14 monoclonal antibodies (McAb) against hematopoietic cell surface antigens was applied on mononuclear blood or bone marrow cells from 40 cases of acute leukemia in order to compare immunoenzymatic staining (IE) (alkaline phosphatase) of fixed cells with immunofluorescence staining (IF) of unfixed suspended cells. According to the immunological results, 25 cases were phenotyped as ALL and 15 cases as AML. Cases with blast crisis secondary to chronic myelogeneous leukemia (CML‐BC) were not represented in this series. In all ALL cases the two methods gave an identical antigenic distribution. In 20 our of 21 cases of non‐T‐cell ALL, a B‐cell progenitor origin was demonstrated by a positive staining reaction with the anti‐CD 19 McAb AB1 or HD37, and in 10 cases additionally with the anti‐CD20 McAb B1 or 1F5. In contrast to the results obtained with IF, IE revealed a poor preservation of the AB1 epitope on CD19, whereas the HD37 epitope was equally well demonstrated by both methods. In 15 cases of AML the distribution of positive versus negative cells with IE or IF was identical for all McAb except J5 (anti‐CALLA) (CD10) and Bl (CD20). Thus, 10/15 AML cases expressed CALLA with IE compared to 2/15 with IF. The corresponding figures for Bl were 5/15 and 0/15, respectively. Accordingly, normal myeloid precursor cells were CALLA‐positive with IE but negative with IF. The discrepancy probably reflects the fact that, whereas both intracytoplasmatic and membrane‐bound antigens are exposed in IE, only the latter are in IF. If the alteration of antigenic accessibility after fixation is considered, IE can safely be used for immunophenotyping of acute leukemia.
High‐risk AML evidenced by a monoclonal antibody
Authors: Avnstrøm S. , Ralfkiær E. , Hansen N. E. , Nissen N. I.
Published: July 2010

A monoclonal antibody has been raised against a surface membrane antigen present on leukemic myeloblasts. In 52 consecutive patients with acute myeloid leukemia treated in a standardized fashion with intensive chemotherapy the immunologic subclass with respect to this antigen was correlated to the clinical outcome. We found the expression of this antigen to predict a poor prognosis, when measured as survival of CR‐patients and as survival after 1st relapse.
Heterogeneity of in vitro growth pattern of megakaryocyte progenitors (CFU‐M) in myeloproliferative disorders
Authors: Hamaguchi Hiroyuki , Takano Naoto , Sakamaki Hisashi , Enokihara Hideo , Saito Kenji , Furusawa Shimpei , Shishido Hideo
Published: July 2010

In groups of 26 patients with myeloproliferative disorders (MPD), 8 with chronic myelogenous leukaemia (CML); 8 with polycythaemia vera (PV); 10 with essential thrombocythaemia (ET); and 6 patients with reactive thrombocytosis (RT), we studied the growth characteristics of bone marrow CFU‐M in agar culture. The bone marrows from all the patients with MPD formed so called endogenous CFU‐M colonies, in the absence of PHA‐LCM, that increased in a dose‐dependent manner with the addition of increasing concentrations of normal human AB‐citrated plasma (NH‐ABCP), while the bone marrows from all the patients with RT and from healthy controls formed few or no endogenous CFU‐M colonies. In MPD, the endogenous CFU‐M growth was enhanced by normal T cells in a dose‐dependent fashion, and was decreased with the depletion of T cells from the marrow cells. These results suggest that the formation of endogenous CFU‐M colonies is caused by hypersensitivity of CFU‐M in MPD to NH‐ABCP, which may contain a small amount of Meg‐CSF, and/or by in vitro T cell stimulation. Among MPD, the endogenous CFU‐M growth in ET was significantly lower than that of other MPD patients; however, the total number of ET CFU‐M grown in the presence of PHA‐LCM was the highest. These data show that the bone marrow CFU‐M in MPD are heterogeneous with respect to in vitro growth pattern or sensitivity to exogenous Meg‐CSF.
Immunological phenotype of lymphoid cells in regenerating bone marrow of children after treatment for acute lymphoblastic leukemia
Authors: van den Doel L. J. , Pieters R. , Huismans D. R. , van Zantwijk C. H. , Loonen A. H. , Broekema G. J. , de Waal F. C. , Veerman A. J. P.
Published: July 2010

Bone marrow samples from 8 children treated for acute lymphoblastic leukemia (ALL) were investigated at cessation of cytostatic treatment and during 18 months thereafter. The course of the percentage of lymphoid cells and characterization of these cells by means of monoclonal antibodies, peanut agglutinin (PNA) binding and S‐phase determination are shown. The percentage of lymphocytes rises in the first 1.5 months, followed by a non‐significant decline. The percentage of cells in S‐phase is higher at 0 months than at 6, 15 and 18 months. The percentage of T‐cells does not change significantly. In the first 1.5 months a sudden rise in the percentage of common‐ALL‐antigen (cALLA)‐positive lymphocytes occurs. The number of B‐cells rises to a peak at 6 months. PNA positivity increases to a maximum at 3 months and is correlated with positivity for markers of the B‐cell lineage. The percentages of B‐cells, cALLA‐positive, and PNA‐positive lymphocytes do not change significantly after they reach their maximum values and are still high at 18 months. Our results show that after cessation of chemotherapy for ALL a lymphoid cell regeneration occurs in the bone marrow consisting of cells of the B‐cell lineage; many of these are cALLA‐positive, but are discernible from their malignant counterparts by PNA‐positivity.
Erythrocyte abnormalities in a hypoalphalipoproteinemia syndrome resembling fish eye disease
Authors: Godin D. V. , Garnett M. E. , Hoag G. , Wadsworth L. D. , Frohlich J.
Published: July 2010

Erythrocyte membrane (EM) abnormalities in a 16‐yr‐old boy with hypoalphalipoproteinemia resembling fish eye disease (FED‐LS) were investigated. The proband's erythrocytes had markedly decreased osmotic fragility with target cells observed in the peripheral film. Analysis of his EM lipids revealed normal cholesterol and phospholipid content but a marked increase in phosphatidylcholine with concomitant decreases in phosphatidylethanolamine and sphingomyelin. Of the EM enzymes examined, acetylcholinesterase and superoxide dismutase activities were decreased while those of Na+‐K+ ATPase, catalase and glutathione reductase were normal. 51Cr erythrocyte survival in the patient was slightly decreased. The observed changes in a number of structural and functional properties of erythrocytes in this disorder are indistinguishable from those previously described in homozygotes for familial lecithin:holesterol acyltransferase (LCAT) deficiency. Thus, it is possible that in both of these disorders an abnormality of plasma LCAT activity causes, either directly or indirectly, functional and structural changes in the erythrocyte membrane.
‘Auto’‐immune neutropenia after allogeneic bone marrow transplantation unresponsive to conventional immunosuppression but resolving promptly after splenectomy
Authors: Koeppler H. , Goldman J. M.
Published: July 2010

A 32‐year‐old male presented with isolated neutropenia 6 months after allogeneic bone marrow transplantation for CML from his HLA‐matched brother. The presence of granulocyte‐specific IgM and IgG antibodies in the patient's serum indicated an immune‐mediated basis for the neutropenia. A variety of manoeuvres to suppress antibody production or to reduce peripheral destruction, including high‐dose intravenous immunoglobulins 400 mg/kg (total 24 g) on 5 consecutive days, prednisolone 80 mg for 10 d and plasmapheresis on 3 consecutive d, failed to raise the neutrophil count. Splenectomy, however, resulted in a prompt and sustained rise of neutrophils to normal values.
Bone marrow transplantation for myeloblastoma
Authors: Quabeck K. , Beelen D. W. , Mahmoud H. K. , Saver H. G. , Graeven U. , Schaefer U. W. , Schmidt C. G. , Hossfeld D. K.
Published: July 2010

A 20‐yr‐old man with bulky mediastinal and retroperitoneal tumour masses identified as myeloblastoma is described. After a partial remission was induced by aggressive chemotherapy, mediastinal irradiation and retroperitoneal tumour resection, the patient received an allogeneic marrow graft from his HLA‐identical sister. The conditioning regimen consisted of high‐dose busulfan and cyclophosphamide. The patient has a well‐controlled secondary chronic graft‐versus‐host disease. He is in unmaintained complete remission and in good general condition at 20 months post‐transplantation.
Phenotypic heterogeneity of B‐ and T‐cell differentiation antigens in B‐CLL
Authors: Merle‐Beral Hélène , Blanc Catherine , Chastang Claude , Debre Patrice
Published: July 2010

Peripheral blood from 38 B‐CLL patients was studied by now cytometry with 25 clustered or non‐clustered monoclonal antibodies (moAbs) in order to characterize the cell surface phenotype of lymphoid cells. All moAbs chosen detected B or CD1–8 T‐cell differentiation antigens or MHC class II antigens. The results showed a heterogeneity in the leukemic cell reactivity with the various moAbs and between patients. The restricted B‐cell antigens recognized by BL14, Y2955 and anti‐class II moAbs were constantly expressed in leukemic cells, while B‐cell antigens reacting with FMC7 and BL13 moAbs were variably detected. In addition to CD5 antigens, other T‐cell markers, including several epitopes of the CD1 group, were also found to be present on the leukemic cell surface in several cases. The relationship between the various clinical and/or biological features of the disease and the cell surface phenotype was studied. Our results indicated a correlation between the lymphoid cell reactivity with M241 (CD1) and BL13 (CD21) and the severity of the disease.
Treatment of pure red cell aplasia with ciclosporin: Suppression of activated T suppressor/cytotoxic and NK‐like cells in marrow and blood correlates with haematological response
Authors: Tötterman Thomas H. , Bengtsson Mats
Published: July 2010

In pure red cell aplasia (PRCA), suppression of erythropoiesis is most probably effected by cellular and/or antibody‐mediated immune mechanisms. We have prospectively investigated the patterns of activated T‐lymphocyte subsets and natural killer (NK)‐like cells in the bone marrow (BM) and peripheral blood (PB) of 6 PRCA patients prior to and during treatment with the T‐cell selective immunosuppressive drug Ciclosporin (CS; Cyclosporin‐A). Before CS therapy, large proportions of circulating activated HLA‐DR+ T‐suppressor/cytotoxic cells (28%, 11–41; median and range), DR+ T‐helper cells (7%, 4–13) and cytoplasmic interferon‐γ+ (IFN‐γ) lymphocytes (20%, 9–33) were found in PRCA, but were barely detectable in healthy controls. Similarly, high levels of activated T cells were present in patient marrows. Initiation of CS therapy resulted in rapidly decreasing levels of activated T cells and NK cells both in PB and in BM. During follow‐up of individual patients, an inverse relationship was observed between the haematological response to CS and the levels of activated T‐suppressor/cytotoxic cells, IFN‐γ+ lymphocytes (in PB and BM) and NK‐like cells (in BM). The present correlations indicate a pathogenetic role of phenotypically activated T‐suppressor/cytotoxic cells and possibly NK‐like cells in PRCA. During successful treatment with CS, these cell types are reduced in numbers but reappear in relapse. Our results also pinpoint the clinical value of monitoring activated T‐cell subsets for the prediction of immunological remission in PRCA and related disorders.
Cytotoxic immunosuppressive drug treatment strategy in pure red cell aplasia
Authors: Firkin Frank C. , Maher Darryl
Published: July 2010

Remissions occured in 2 of 5 consecutive cases of acquired pure red cell aplasia (PRCA) during an initial course of treatment with either azathioprine and prednisolone, or cyclophosphamide and prednisolone. Crossover to therapy with the alternative cytotoxic immunosuppressive agent in conjunction with continued administration of prednisolone in 3 unresponsive cases resulted in remission induction. Crossover to azathioprine was effective in 2 cases initially unresponsive to cyclophosphamde, and crossover to cyclophosphamide in 1 initially unresponsive to azathioprine. This emphasises that lack of cross‐resistance to these drugs can occur in PRCA, and that crossover to treatment with the alternative agent in refractory cases is a useful strategy which has been underutilised in reported approaches to management. Administration of the effective regimen was continued for a mean of 15 months, and this more extended period of treatment was associated with a longer mean duration of remission than reported in previous studies.
Mafosfamide (ASTA‐Z‐7654) in vitro treatment of bone marrow does not eradicate Philadelphia‐positive cells in chronic myeloid leukaemia
Authors: Mortensen B. T. , Ernst P. , Philip P.
Published: July 2010

Bone marrow from 9 patients with Ph1 + CML was treated in vitro with varying concentrations of Mafosfamide in order to test the hypothesis that selective pharmacological killing of Ph1‐positive cells in CML is feasible. A marked difference in sensitivity to Mafosfamide of CFU‐GM was observed, but at all concentrations 100% persistence of Ph1 + cells was noticed. We conclude that, in classical cases of Ph1‐positive CML, Mafosfamide purging of bone marrow will not be effective.
Alkaline phosphatase‐positive B cell lymphomas
Authors: Abe Masafumi , Nozawa Yoshihiro , Wachi Eiko , Tominaga Kunihiko , Hojo Hiroshi , Wakasa Haruki
Published: July 2010

Alkaline phosphatase (ALP) activity of 70 cases of non‐Hodgkin's lymphomas of the B‐cell type was studied. ALP activity was found in malignant lymphoma (ML), follicular, small cleaved cell (1/5 cases); ML, diffuse, small cleaved cell (3/13 cases); and mantle zone lymphoma (intermediate lymphocytic lymphoma) (2/2 cases). The ALP‐positive neoplastic cells simultaneously displayed the characteristic immunophenotype of mantle zone (MZ) B lymphocytes of secondary follicle (SIg D +, BA‐1 +, IL‐2R+ and Leu‐1+). All other B‐cell lymphomas, including ML, follicular, mixed small cleaved and large cell (9 cases); ML, follicular, large cell (4 cases); ML, mixed small and large cell (7 cases); ML, diffuse, large cell (27 cases); and ML, small noncleaved cell (3 cases), were consistently negative for ALP. The present study indicates that ALP‐positive lymphomas including follicular lymphomas and diffuse lymphomas may be neoplastic counterparts of ALP‐positive MZ B lymphocytes.
Multipotent stem cell (CFU‐S) numbers and circadian variations in aging mice
Authors: Sletvold Olav , Laerum Ole Didrik
Published: July 2010

The multipotent stem cell (CFU‐S) numbers were studied in aging female C3H mice (16, 21 and 26 months old, respectively) versus young controls (3 months old). Using the spleen colony technique, the d‐8 CFU‐S numbers were measured every 3 h during the 24‐h period at three different times of the year. Prominent circadian variations were found in young mice. The peak and trough values were significantly different also in aging mice, although the peak‐trough differences were declining. When comparing young and old mice at different times of the 24‐h period, the CFU‐S numbers were sometimes significantly different, but often not. The 24‐h mean values were consistently declining during aging. Young mice had different circadian variation patterns and 24‐h mean values when examined at different times of the year. It is concluded that the d‐8 CFU‐S numbers decline in aging mice. Conflicting reports may partly be due to neglect of physiological variations.
Cytogenetic study of 105 children with acute lymphoblastic leukemia
Authors: Heinonen Kristiina , Rautonen Jukka , Siimes Martti A. , Knuutila Sakari
Published: July 2010

Cytogenetic analysis was performed on 105 children with acute lymphoblastic leukemia (ALL). Adequate mitoses for study were obtained in 79 of the cases (71%). A normal karyotype was found in 18 patients (23%), while clonal chromosomal abnormalities were detected in 61 patients (77%). The karyotypes fell into five categories according to modal number: normal (18 patients), pseudodiploid (27 patients), hypodiploid (3 patients), hyperdiploid with 47–50 chromosomes (11 patients), and hyperdiploid with ≧ 51 chromosomes (20 patients). Structural chromosome changes were found in 50 patients (63%); translocations were encountered in 15 of these patients (19%). The chromosome most often participating in translocations was number 19. Modal number was found to be an independent prognostic factor. Modal numbers 47–50 were associated with the poorest prognosis. The hyperdiploid clone with more than 50 chromosomes and the normal karyotype had the best prognosis.
T‐cell depletion versus methotrexate as GvHD‐prophylaxis in allogeneic bone marrow transplantation for leukaemia
Authors: Wiesneth M. , Hertenstein B. , Bunjes D. , Schmeiser T. , Arnold R. , Heimpel H. , Heit W.
Published: July 2010

Graft‐versus‐host disease (GvHD) prophylaxis using methotrexate (23 patients) and T‐cell depletion of the graft (40 patients) was compared in 63 allogeneic bone marrow transplantations (BMT) for leukaemia. T‐cell depletion significantly reduced (p = 0.001) the incidence of GvHD from 68% to 11% and the GvHD‐associated mortality from 79% to 5%. Actuarial disease‐free survival for low‐risk patients (57% with T‐cell depletion and 47% with MTX) was not significantly improved, due to graft failure and possibly due to a higher leukaemic relapse rate after T‐cell depletion. Prevention of graft failure after T cell‐depleted BMT is essential and could also reduce the risk of leukaemic relapse by improved engraftment.
Expression of tartrate‐resistant acid phosphatase in B‐CLL treated with phorbol ester or phorbol ester plus calcium ionophore
Authors: Drexler Hans G. , Brenner Malcolm K. , Gignac Suzanne M. , Hoffbrand A. Victor
Published: July 2010

Cells from 3 patients with B‐chronic lymphocytic leukaemia (B‐CLL) and 1 with B‐prolymphocytic leukaemia (B‐PLL) were treated in vitro with the phorbol ester 12‐O‐tetradecanoylphorbol (TPA), the calcium ionophore A23187, or a combination of TPA and A23187. TPA induced the cells to adhere to the culture flask or to clump in dense clusters; single cells became enlarged, often with cytoplasmic elongations. Cells treated with TPA plus A23187 acquired a plasmacytoid morphology and formed regular aggregates in culture. Only TPA alone induced the expression of tartrateresistant acid phosphatase (TRAP) as documented by isoelectric focusing on horizontal thin‐layer gels. The TRAP isoenzyme was first detected after 24 h of TPA treatment; its intensity increased during further TPA exposure, being maximally expressed at 72/96 h. The results suggest that, while TPA triggers B‐CLL cells to convert to hairy cell leukaemia (HCL)‐type cells, the double stimulus which more closely imitates physiological activation initiates a ‘normal’ differentiation programme which leads to plasma cells.
Retinoic acid regulates IgG Fc receptor expression in human myelomonocytic leukemia cells and normal peripheral monocytes
Authors: Nakamura Takehiko , Hemmi Hiromichi
Published: July 2010

The regulation of IgG Fc receptor (FcγR) expression by retinoic acid (RA) in human myelomonocytic cells at different stages of maturation was studied. RA suppressed IgG‐coated erythrocyte (EA) rosette formation of myelomonocytic cells blocked at relatively late stages of differentiation such as ML‐1, U‐937, THP‐1‐T, normal monocytes, and fresh cells of patients with acute myelomonocytic leukemia. However, RA increased the percentage of EA rosetting promyelocytes of HL‐60 and of patients with acute promyelocytic leukemia and a part of myeloblasts isolated from acute myelogenous leukemia patients. Other myeloblasts including KG‐1a, KG‐1, and fresh cells from patients with acute myelogenous leukemia were not affected. A kinetic study using HL‐60 and THP‐1‐T demonstrated that an increase required at least a 48‐h exposure and that the maximum decrease required approximately 6 h. The RA effect on both cell lines was dose‐dependent. The number of FcγR of HL‐60 and THP‐1‐T treated with RA became very close, although untreated THP‐1 had almost 10 times as many as HL‐60. Kd for IgG in both THP‐1‐T and HL‐60, either untreated or treated with RA, remained unchanged. These observations indicate that one of the important roles of RA is regulation of FcyR expression in myeloid cells.
Platelet aggregation in platelet rich plasma and whole blood in 18 patients affected by idiopathic myelofibrosis*
Authors: Balduini Carlo L. , Bertolino Giampiera , Gamba Gabriella , Barosi Giovanni , Sinigaglia Fabiola , Noris Patrizia , Bisio Antonella , Ascari Edoardo
Published: July 2010

Platelet aggregation in whole blood (WB) and in platelet rich plasma (PRP) was studied in 18 consecutive patients affected by idiopathic myelofibrosis (IM). On the basis of WB studies, 22% of patients were classified as normo‐aggregating and 22% as hypo‐aggregating, while 55% had spontaneous platelet aggregation (SPA). SPA was observed also when platelets from patients were stirred in the presence of normal erythrocytes, while it never occurred when normal platelets were stirred in the presence of red cells from patients. PRP studies revealed that 33% and 66% of patients were, respectively, hypo‐ and normo‐aggregating. The most frequent abnormality in PRP was represented by defective or absent aggregation response to epinephrine.
Benign familial leukopenia and neutropenia in different ethnic groups
Authors: Shoenfeld Yehuda , Alkan Michael L. , Asaly Abid , Carmeli Yehuda , Katz Miriam
Published: July 2010

Benign hereditary leukopenia‐neutropenia has been reported in several ethnic groups, including Yemenite Jews, Blacks of South African extraction, West Indians and Arab Jordanians. The subjects with BFL were shown not to have an increased incidence of infections, and their response to infection did not differ from subjects having normal white blood cell counts. This study entails the report of two additional unrelated ethnic groups with familial neutropenia — Black Beduin and Falashah Jews. The familial nature of the phenomenon was confirmed. The suggested mechanism of this type of neutropenia is a defect in release of mature WBC from the bone marrow to the peripheral circulation. All ethnic groups thus far reported have tanned or dark skin. The significance of this common feature has still to be elucidated.
Long‐term haemopoietic injury in mice after repeated irradiation: Precursor‐cell cycling and its regulation
Authors: Tejero C. , Lord B. I. , Mason T. M. , Hendry J. H.
Published: July 2010

The cycling rate of haemopoietic stem cells (day 9 CFU‐S) and granulocyte‐macrophage colony forming cells (GM‐CFC) in mouse femora was, in response to reduced numbers, elevated at all times of sampling between 3 weeks and 10 months after 4 repeated doses of 4.5 Gy X‐rays (3 wk between doses). The level of a stimulator of CFU‐S cycling was also elevated, and this was observed in both axial and marginal regions of the marrow inside the shaft. However, the rate of production of the stimulator was low; lower than previously reported in marrow regenerating after a single dose of 4.5 Gy, indicating damage to the regulatory stromal cells. The distribution of CFU‐S across the axial and marginal zones of femoral marrow was changed from that in normal mice, where higher concentrations were found near the bone surface, to a more uniform distribution.
A case of chronic neutrophilic leukemia with original chromosomal abnormalities
Authors: Lorente Jose A. , Peña Jose M. , Ferro Teresa , Garcia‐Alegria Javier , Gonzalez Juan J. , Barbado Javier , Vazquez Juan J.
Published: July 2010

We report a new case of the unusual myeloproliferative syndrome chronic neutrophilic leukemia (CNL) that met all the criteria generally required for the diagnosis of this entity. The patient presented abnormalities in platelet function not previously reported that may explain the bleeding tendency observed in these patients. The study of neutrophil function suggested also defective mobility and intracellular bactericidal activity. The chromosomal study revealed original abnormalities consisting of multiple chromosomal ruptures and figures. The disease was controlled with busulfan. After 20 months, the patient died of sepsis. An autopsy was performed confirming the diagnosis and ruling out the existence of a cause of a leukemoid reaction, such as cancer or granulomatous disease.
Lysosomal Consept of Platelet Secretion ‐ Revisited
Authors: Polasek J.
Published: July 2010

Certain morphological and biochemical aspects of platelet secretion are discussed. Based on own experiments and review of the literature a hypothesis is forwarded that platelet secretory granules or rather storage organelles can be viewed as secondary lysosomes participating in platelet endocytosis and exocytosis. Formation of the platelet thromboplastic activity, so called PF3, is linked to the platelet storage organelles disintegration and lypolysis during their exocytosis through the platelet plasma membrane.
Intermediate‐dose (25 mg/m2) intravenous melphalan for patients with multiple myeloma in relapse or refractory to standard treatment
Authors: Petrucci M. T. , Avvisati G. , Tribalto M. , Cantonetti M. , Giovangrossi P. , Mandelli F.
Published: July 2010

Intermediate‐dose (25 mg/m2) intravenous melphalan has been evaluated in 34 multiple myeloma patients refractory to standard chemotherapies. The median time from diagnosis to entering of patients into the study was 27 months (range 7–71 months). A response was obtained in 12/34 patients (35%). 4 of 12 responding patients have relapsed and 2 of these have died; 8 responders have not relapsed and are still alive. The median duration of survival after 28 months of follow‐up has not yet been reached in the group of patients responding to treatment. However, the overall median duration of survival for the 34 patients entered into the study was 8 months. The median duration of response was 16 months. Toxicity was limited to leukopenia, thrombocytopenia, nausea and vomiting. This lack of severe toxicity allowed us to administer the drug on an outpatient basis. The response rate and the low toxicity observed in this group of patients are encouraging and suggest that intermediate‐dose intravenous melphalan is an effective and safe second line treatment for patients with multiple myeloma not responding to conventional treatment.
Immunotoxins containing saporin 6 and monoclonal antibodies recognizing plasma cell‐associated antigens: Effects on target cells and on normal myeloid precursors (CFU‐GM)
Authors: Barbieri Luigi , Dinota Angelo , Gobbi Marco , Tazzari Pier Luigi , Rizzi Simonetta , Bontadini Andrea , Lemoli Roberto Massimo , Tura Sante , Stirpe Florenzo
Published: July 2010

Monoclonal antibodies 8A and 62B1, recognizing plasma cell‐associated antigens, were covalently linked to saporin 6, a ribosome‐inactivating protein similar to the A‐chain of ricin. Both immunotoxins were tested on target human cell lines U266 and Raji, on non‐target K562 cell line and on myeloid CFU‐GM progenitors. The cloning efficiency and viability of target cells were strongly reduced by 8A‐saporin 6 and 62B1‐saporin 6 immunotoxins, with an ID50 up to 200000‐fold lower than free saporin 6, whilst the K562 non‐target cell line was unaffected. Normal human myeloid precursors (CFU‐GM) were inhibited by immunotoxins only to a limited extent. An application of this model for autologous bone marrow transplantation in multiple myeloma patients is proposed. Since no eradication of cloning target cells was achieved by a single immunotoxin, mixtures made with different antibodies could help to reach this goal.
Translocation (1;5)(q23;q33) in adult acute non‐lymphocytic leukemia
Authors: Gyger Martin , Forest Lorraine , Lussier Pauline , D'Angelo Giovanni , Desy Madeleine
Published: July 2010

Chromosome banding studies carried out on bone marrow cells from a 57‐year‐old white caucasian male with an M1 acute non‐lymphocytic leukemia (ANLL) revealed an unbalanced translocation involving chromosomes 1 and 5 [der(5)t(1;5)(q23;q33)] as part of complex abnormalities in 76% of the cells analyzed. This chromosomal abnormality is the first to be reported in an adult patient with acute non‐lymphocytic leukemia. A review of previous reports on translocations involving the juxtaposition of the 1q23 ŕ qter DNA segment to other chromosomes suggests that this new translocation may be specifically involved with abnormal myeloid proliferation.
Natural history of HIV infection in Swedish haemophiliacs
Authors: Berntorp E. , Jarevi G. , Wedbäck A. , Böttiger B. , Hansson B. G. , Nordenfelt E. , Nilsson I. M.
Published: July 2010

The longitudinal follow‐up is described of 36 anti‐HIV positive haemophiliacs who had seroconverted in the period 1980–82, and of 41 seronegative controls. Laboratory variables were followed up for a mean duration of 2.5 years (1985–87). Of the 36 seropositive patients, AIDS developed in 3, and generalised persistent lymphadenopathy in 9. The HIV‐seropositive patient group had lower CD4:CD8 ratios and CD4 counts but higher CD8 counts than the seronegative group. However, there was no deterioration in the values for the lymphocyte subsets during follow‐up. Titration on paired sera showed an increase in anti‐HIV titre with time. Testing for the presence of HIV antigen was positive in 5 patients, including 2 who later developed AIDS. We conclude that anti‐HIV positive haemophiliacs, though actively immunised, often show no symptoms even as long as 7 yr after seroconversion and that, in certain patients, the immune system may even show signs of improvement.
Reevaluation of the prognostic factors for splenectomy in chronic idiopathic thrombocytopenic purpura (ITP): A report on 181 cases
Authors: Fenaux P. , Caulier M. T. , Hirschauer M. C. , Beuscart R. , Goudemand J. , Bauters F.
Published: July 2010

From 1973 to 1986 we splenectomized 181 patients with chronic ITP after platelet kinetic studies with 51Cr or 111In. Mean age at diagnosis was 34 (range 4–79 yr). Follow‐up of at least 1 yr after splenectomy was available in every patient. 141 patients (78%) achieved remission (platelets > 100 times 109/1 by 3 months after splenectomy), of whom 9 subsequently relapsed. Among the 40 non‐responders at 3 months, 3 achieved a later remission spontaneously. Factors associated with response to splenectomy included a high post‐operative platelet count (p = 0.0001), younger age at the time of surgery (p = 0.0077) and predominantly splenic sequestration of platelets (p = 0.0002), the two latter factors being partially correlated. In a multivariate analysis, however, only post‐operative platelet count and age retained an independent prognostic significance, whereas the sequestration site of platelets had only borderline value. These results are discussed in the context of indications of platelet kinetic studies in chronic ITP, before splenectomy is considered.
Treatment of multiple myeloma with carboquone‐prednisolone
Authors: Akashi Makoto , Sakamoto Shinobu , Ohta Masatsugu , Kitagawa Seiichi , Yoshida Minoru , Saito Masaki , Takaku Fumimaro , Miura Yasusada
Published: July 2010

18 previously untreated patients with multiple myeloma were entered in a clinical study of a combination chemotherapy, carboquone (CQ) and prednisolone (P) (CQ‐P). Response was observed in 44% of patients treated with CQ‐P judged by the criteria for response to chemotherapy. The median survival time was 33 months. Serious toxic reactions seldom occurred. The results suggest that the combination of CQ‐P has efficacy in the treatment of multiple myeloma and could have a role among primary chemotherapeutic regimens for the disease. Further clinical trials should be conducted to establish a new drug combination in which CQ is included.
Isolation and characterization of a tumor necrosis factor binding protein from urine
Authors: Olsson Inge , Lantz Mikael , Nilsson Eva , Peetre Christina , Thysell Hans , Grubb Anders , Adolf Günter
Published: July 2010

Tumor necrosis factor (TNF)/cachectin can produce both beneficial and harmful manifestations. Mechanisms may operate to counteract potentially harmful effects such as shock and cachexia. The TNF binding protein (TNF‐BP), which is found at increased levels in serum and urine of patients with chronic renal failure, may play such a role. TNF‐BP was purified 1000000–fold to homogeneity from urine of patients with chronic renal failure by use of ion exchange chromatography, affinity chromatography on TNF‐Sepharose and reverese phase chromatography. The purified protein contained only one chain with an apparent Mr on sodium dodecyl sulfate‐polyacrylamide gel electrophoresis of 30000. The aminoterminal amino acid sequence D‐S‐V‐X‐P‐Q‐G‐K‐Y‐I‐H‐P‐Q‐V‐N‐S‐I‐X‐K‐T revealed no significant homologies with previously described protein sequences. TNF‐BP may act as a regulator of the bioactivities of TNF/cachectin.
Tumour imaging of indium‐111 oxine‐labelled autologous lymphocytes as a staging method in Hodgkin's disease
Authors: Grimfors G. , Schnell P.‐O. , Holm G. , Johansson B. , Mellstedt H. , Pihlstedt P. , Björkholm M.
Published: July 2010

Following indium‐111 oxine‐labelled autologous lymphocyte infusion, 39 lymphocyte scintigraphies were performed in 35 patients with Hodgkin's disease (HD). Lymphocytes were obtained after leukapheresis and Lymphoprep® gradient centrifugation and were further purified by an adherence step to eliminate monocytes. A median of 1.2 (0.2–3.7) × 109 cells were labelled with 6.7 (range 1.9–16.6) Mbq indium‐111 oxine and reinfused to the patients. Gamma camera imaging was performed with a GE 400 AT. An accumulation of radioactivity was seen at 54 of 61 sites with enlarged lymph nodes. Increased radioactivity was also seen at 16 sites with no previous clinical evidence of tumour involvement. These data seem very promising and with further methodological improvement lymphoscintigraphy may prove to be an important complement in the staging procedure and follow‐up of patients with HD.
Acute transformation of chronic myelomonocytic leukaemia: a multivariate study of predictive factors
Authors: Ribera Josep‐Maria , Cervantes Francisco , Reverter Juan‐Carlos , Montserrat Emilio , Rozman Ciril
Published: July 2010

In an attempt to determine the possible predictive value of the main clinical and haematological initial features of chronic myelomonocytic leukaemia (CMML) on the evolution of acute leukaemia, as well as the real impact of such an event on survival, 35 such patients were submitted to multiple regression analyses. At the time of the study 30 out of the 35 patients had died, with a median survival of 8.2 months for the whole series. 12 patients (34%) developed acute leukaemia, between 1.5 and 42.1 months from diagnosis of CMML, the actuarial median time of acute transformation being 29.4 months. The initial bone marrow blast cell percentage was the only factor influencing the development of acute leukaemia. On the other hand, the multivariate survival study showed that acute transformation introduced in the model as a time‐dependent variable had a clear‐cut unfavourable influence on the outcome of CMML patients, as did palpable spleen, advanced age and marked monocytosis.
Sialyltransferase activity and sialic acid levels in multiple myeloma and monoclonal gammopathy
Authors: Cohen A. M. , Allalouf D. , Bessler H. , Djaldetti M. , Malachi T. , Levinsky H.
Published: July 2010

A signficant elevation of peripheral blood mononuclear cell sialyltransferase activity (STA) was observed in 14 patients with multiple myeloma (MM), and compared to 7 patients with monoclonal gammopathy of undetermined significance (MGUS) and to 10 controls. Serum sialyltransferase was significant higher in MM patients as compared to controls. It was also higher than in MGUS patients, but the difference here was not statistically significant. STA was also determined in mononuclear bone marrow cells of 5 patients with MM (with 50 to 100% plasma cells in the bone marrow aspirate) and found to be 19 times higher than that of bone marrow mononuclear cells from 6 patients with non‐malignant disorders (with less than 1% plasma cells in the bone marrow aspirate). No significant differences were observed in peripheral blood mononuclear cell sialic acid levels between MM, MGUS and controls.
Serum from patients with various thrombopoietic disorders alters terminal cytoplasmic maturation of human megakaryocytes in vitro
Authors: Straneva John E. , Briddell Robert A. , Hui Siu L. , Hoffman Ronald
Published: July 2010

Human bone marrow was depleted of progenitors (CFU‐MK), but enriched for recognizable megakaryocytes (MK), and placed in cultures with serum from either normal donors (NABS) or patients with primary (PTS) or secondary (STS) thrombocytosis, autoimmune thrombocytopenia (ATS) or aplastic anemia (AAS). Mean MK diameters shifted during the 3–4 days of incubation. Endomitotic figures were visible and mean ploidy increased slightly during cytoplasmic maturation, where decreases in immature cells (stages 1 and 2) were accompanied by increases in the mature MK (stages 3 and 4). Cytoplasmic maturation was faster in AAS, ATS and STS than PTS or NABS; mean size and ploidy were similar in all cultures. Recognizable MK were not forced to undergo additional endoreduplication in response to stimulation. Only AAS augmented MK colony formation, which indicated that at least two humoral factors can regulate megakaryocytopoiesis at separate levels, the progenitors and morphologically recognizable MK.
Relation between occupational exposure to organic solvents and chromosome aberrations in non‐Hodgkin's lymphoma
Authors: Brandt Lars , Kristoffersson Ulf , Olsson Håkan , Mitelman Felix
Published: July 2010

Chromosome analysis of lymphoma cells was performed in 54 untreated patients with non‐Hodgkin's lymphoma (NHL). 10 patients had a history of daily occupational handling of organic solvents for at least 1 year (exposed group) and 44 patients had never (or only for shorter periods) worked with solvents (unexposed group). There were no differences between exposed and unexposed patients regarding age, clinical stage or histologic malignancy grade. The patients were assigned to three categories: Patients with 0–4, 5–9, or ≥ 10 cytogenetic events producing clonal aberrations of the lymphoma cells. The proportions of exposed patients in these categories were 2/26 (8%), 5/20 (25%) and 3/8 (38%); respectively, i.e. with increasing numbers of events there was an increasing probability of previous exposure to solvents (p = 0.035; trend analysis). 5 of 7 exposed patients (71%) with intermediate or high‐grade lymphomas displayed translocations involving the band 14q32. Such 14q+ markers were found in only 5 out of 28 unexposed patients (18%) with lymphomas of comparable malignancy grade (p = 0.01). Among unexposed patients with intermediate or high‐grade lymphoma the most common clonal aberration was 6q‐ which occurred in 10 out of 28 patients (36%). This abnormality was not observed in the exposed patients with lymphomas of corresponding malignancy grades (p = 0.08). It thus appears that the number of clonal chromosome aberrations is especially large in NHL patients with a history of occupational exposure to organic solvents. Moreover, such exposure may be associated with characteristic cytogenetic changes in the lymphoma cells.
Cyclosporin‐A therapy of pure red cell aplasia in a patient with B‐cell chronic lymphocytic leukemia
Authors: Christen Randolph , Morant Rudolf , Fehr Jorg
Published: July 2010

A 65‐year‐old woman with B‐cell chronic lymphocytic leukemia (CLL) and pure red cell aplasia (PRCA) is described. After initial chemotherapy with three different regimens over 3 months (prednisone, chlorambucil/vincristine, cyclophosphamide, bleomycin/cyclophosphamide, etoposide, prednisone), normalization of the blood lymphocyte count was observed, but lymphocyte infiltration of the bone marrow persisted and erythropoiesis remained virtually absent. Monotherapy with cyclosporin‐A (CyA) was begun. After 35 days, a marked increase in the reticulocyte count was observed, and with continuing therapy, there was a rapid increase in the hemoglobin level. Follow‐up after 13 months of uninterrupted treatment with CyA revealed remission of both CLL and PRCA. CyA should be investigated further as a therapeutic modality for PRCA in patients with CLL, and such trials might provide further clues to the pathogenesis of this peculiar association.
Human hemopoietic growth factors
Authors: Platzer Erich
Published: July 2010

Hematopoiesis is regulated by a complex network of soluble stimulators and inhibitors, as well as by cellular interactions in the bone marrow microenvironment. Progress in molecular biology and protein biochemistry has provided a number of hemopoietic growth factors that are now available in large quantities for in vitro and in vivo studies. Several of them seem to hold great promise for patients suffering from insufficient hematopoiesis of various causes. This review focusses on new developments in the understanding of hemopoietic growth factors activity, and on recent clinical data.
High‐dose ARA‐C (HiDAC) plus asparaginase in elderly patients with acute non‐lymphocytic leukemia: A pilot multicentric study by the Italian cooperative group GIMEMA
Authors: Petti M. C. , Mandelli F. , Avvisati G. , Covelli A. , Amadori S. , Liso V. , Leone G. , De Laurenzi A. , Leoni P. , Neri A. , Grignani F. , Torlontano G. , Deriu L. , Caronia F.
Published: July 2010

A multicentric prospective pilot study using three different schedules of high‐dose Ara‐C at dosage of 3 g/m2every 12 hours during 3 h of infusion was undertaken by the Italian Cooperative Group GIMEMA in order: 1. to evaluate the safety and efficacy of such treatment in previously untreated ANLL patients more than 50 years old; 2. to investigate whether the addition of a standard maintenance treatment after consolidation with 4 courses of DAT (Daunorubicin + Ara‐C + 6‐Thioguanine) could improve the duration of complete remission (CR) and the proportion of long‐term survival. Overall 43/125 evaluable patients (34.4%) achieved CR. 32/125 died during the induction phase, the remaining 50 patients (40%) failed to achieve CR. As for the toxicity, the most significant toxicity of all schedules was hematologic. No substantial neurological or cardiac toxicity was observed. The multivariated analysis of several pretreatment characteristics revealed that age more than 60 yr, male sex and presence of infections at diagnosis were the most significant adverse factors for achievement of CR. The median duration of DPS for all responders was 9 months, with relapse‐free survival at 4 yr estimated at 29%. The addition of maintenance treatment to consolidated patients had no advantages in respect to the control group, even though the statistical analysis revealed a p = 0.058. However, because of the small number of randomized patients, no conclusions can be drawn concerning the importance of maintenance treatment.