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Biomedical subjects

J Ellegaard

Publications and source records attributed to J Ellegaard.

At least 73 records · Page 4Linked to original sources

Acute myeloid and lymphoblastic leukemia in adults. The course of the disease in 315 patients from one region, during a ten-year period.

In a ten-year retrospective singlecenter study of a nonselected patient population, we describe our experience with an unchanged chemotherapy regimen for 264 patients with acute myeloid leukemia (AML) and 51 patients with acute lymphoblastic leukemia (ALL). In the AML group, 85 patients could not receive specific antileukemic treatment because of uncontrollable bleeding, infection or organ failure, but 179 were fit for remission-induction therapy with cytarabine and daunorubicin, resulting in complete remission in 79 patients. During treatment, 54 patients died of resistant disease or complications. The median duration of survival of the patients in complete remission was 18-24 months (n = 79) compared with 1-2 months for patients in partial or no remission (n = 100). As maintenance chemotherapy, thioguanine, cytarabine and daunorubicin were given for one year. In the ALL group 50 of 51 patients received remission-induction therapy with vincristine, prednisone and Adriablastin, resulting in complete remission in 39 of the patients. The median duration of survival of the patients in complete remission was nine months (n = 39) compared with 2-3 months for patients not in remission (n = 12). Central nervous system prophylaxis with intraspinal methotrexate and cranial irradiation was given, followed by methotrexate and Purinetol for three years as maintenance chemotherapy. The remission rate for AML and adult ALL was 44% and 78%, respectively. The major Cause of death after first complete remission was leukemic relapse in boths groups, with a median survival time after relapse of 3-4 months for 48 AML and six months for 30 ALL patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

First-line diagnosis based on immunological phenotyping in suspected acute leukemia: a prospective study.

In a prospective analysis of the diagnostic value of immunophenotyping in acute leukemias (ALs), all patients admitted to a pediatric and a haematological department suspected of AL were examined consecutively with a selected panel of monoclonal antibodies (Mabs) against leucocyte differentiation antigens during an 8-month period. A total of 189 samples obtained from blood, bone marrow, spinal fluid and lymph nodes in 120 cases were all analysed blindly. The results were correlated with a routine morphological/cytochemical evaluation. Differing results were obtained in seven out of 38 cases in which the immunologically defined diagnosis was acute myeloid leukemia (AML), and in one out of 21 cases with the primary diagnosis acute lymphoid leukemia (ALL). Immunological phenotyping disclosed two cases of hybrid leukemia, one case of biphenotypic and one case of bilineal leukemia. No evidence of malignancy was found in 36 cases, 30 cases of blood and bone marrow and six cases of spinal fluids, in every case in accordance with the pathological examination. These results demonstrate that a first-line immunological evaluation of bone marrow, blood and spinal fluid from patients suspected of AL is highly capable of discriminating between different malignant and nonmalignant haematological diseases and also between various types of leukemias. The immunological methods do, however, require a sufficient amount of material which was a limiting factor in 14 out of 120 examinations, mainly from patients treated with several cycles of cytostatics. It is concluded that immunophenotyping can be used as a first-line diagnostic tool in malignant haematological diseases.

Acute Disease↗

Natural killer function following allogeneic bone marrow transplantation. Very early reemergence but strong dependence of cytomegalovirus infection.

Natural killer (NK) cell function was followed sequentially after allogeneic bone marrow transplantation (BMT) using three approaches: (1) chromium-release assay with purified mononuclear effector cells, (2) chromium-release assay with whole blood effectors, and 3) enumeration of lymphocytes bearing the NK-associated antigen NKH-1 (N901). The two latter methods enabled us to demonstrate a very early reappearance (at day 4 posttransplant) of pre-NK cells, which after interferon-alpha enhancement effectively lysed K562 cells and carried the NKH-1 antigen. During the first month NK function steadily increased, and at day 28 activated NK cells, which lysed the otherwise resistant P815 cell line, could be demonstrated concomittant with a substantial over-shoot in the proportion of NKH-1+ cells. Furthermore, the increase in NK lysis was more pronounced in patients with cytomegalovirus (CMV) infections (primary or reactivated). In contrast, the presence of graft-versus-host (GVH) disease did not associate with consistent changes in the NK parameters measured here. After the first month of increase, NK declined reaching levels near those observed in their respective bone marrow donors at day 90. These data demonstrate a surprisingly early recovery after allogeneic BMT, which can largely be related to external factors among which CMV seems to be a prime candidate.

Antigens, Differentiation↗

Analysis of leucocyte differentiation antigens in blood and bone marrow in patients with refractory anaemia (RA) and RA with sideroblasts. Prognostic implications of sequential and follow-up data.

34 patients with primary myelodysplastic syndrome (MDS), initially diagnosed as subtypes refractory anaemia (RA) and RA with ringed sideroblasts (RA-S), were followed to investigate the distribution of lymphoid and myeloid differentiation antigens in the blood and bone marrow in search of potential prognostic significance with regard to progression to RA with an excess of blasts (RAEB) or acute myeloid leukaemia, and for relations to clinical, morphological and cytogenetic findings. Patients who later progressed to RAEB had significantly decreased percentages of anti-T8 positive T-suppressor cells in the blood at diagnosis compared to those who did not (p = 0.05). Sequential analysis showed a decrease with time also in the percentages of anti-T8-positive cells (p = 0.05). In the bone marrow, progressing patients initially showed significantly increased percentages of anti-My9-positive immature myeloid cells (p less than 0.001), and the percentages of anti-My9-positive cells in the bone marrow increased with time (p less than 0.005). Analysis of the pooled data revealed a statistically significant relation between increasing percentages of anti-My9-positive cells and the frequencies of clonally abnormal (p less than 0.001) and abnormal (p = 0.004) metaphases.

Anemia, Refractory↗

Isolated gingival relapse in acute myeloid leukaemia.

A 47-yr-old man with acute myeloid leukaemia had been in complete remission for 18 months when he developed a gingival tumour. Histological examination revealed leukaemic infiltrate and, at this stage, no other signs of relapse could be demonstrated. Chemotherapy and local radiotherapy resulted in the disappearance of the mass; however, histological abnormalities persisted. First relapse of acute myeloid leukaemia presenting as a gingival tumour has not been previously reported.

Gingival Neoplasms↗

Major proteins in normal human lymphocyte subpopulations separated by fluorescence-activated cell sorting and analyzed by two-dimensional gel electrophoresis.

We have compared the overall patterns of protein synthesis of normal human lymphocyte subpopulations taken from five volunteers using high resolution two-dimensional gel electrophoresis. The lymphocytes were isolated using density gradient centrifugation, labeled with subtype-specific MoAbs, and separated to a high degree of homogeneity by FACS into CD4+ helper T cells, CD8+ suppressor T cells, CD20+ B cells, and N901 (NHK-1)+ NK cells. The four lymphocyte subpopulations were labeled with [35S]methionine for 14 hr, solubilized in lysis buffer, and analyzed by two-dimensional gel electrophoresis (IEF). Of about 1000 proteins resolved in each case, most were found to be common to all subpopulations. However, eight putative markers for B1+ (proteins 5525, Mr = 63,700; 5621, Mr = 63,700; 8311, Mr = 36,900; 2202, Mr = 36,300; 6121, Mr = 30,300; 106, Mr = 29,300; 5009, Mr = 23,000; 8012, Mr = 11,600) and one for N901+ (protein 8129, Mr = 30,400) were identified. In contrast, no major protein markers were found that could differentiate T4+ and T8+ cells from each other or from B cells and NK cells. With the exception of two B1+ markers (proteins 5525 and 5621), lower but variable levels of the other markers were observed in all cell types. All the putative protein markers have been identified in the protein database of human peripheral blood mononuclear cells (PBMCs) (see accompanying article by Celis et al.). Comparison of the overall patterns of protein synthesis of the unsorted PBMCs with those of the four subpopulations showed that the synthesis of some major PBMC proteins decreased substantially in the sorted subsets. These proteins are most likely not of monocyte origin, as these cells constituted only about 15% of the total PBMCs. Also, the inhibition does not seem to be due to the addition of the single MoAbs or to cell cycle differences. Taken together, the data provide a background for further studies of protein profiles in normal (resting or activated) and malignant hematopoietic cells.

Antigens, Differentiation↗

13-cis retinoic acid treatment of myelodysplastic syndromes.

Of eight patients with primary myelodysplastic syndrome (MDS) treated with Roacutane (13-cis retinoic acid, Roche, Basel, (13-RA)) 20 mg/m2 for 6 weeks and an additional 100 mg/m2 for 4 weeks (3 patients), 4 responded either with a slight increase in peripheral blood neutrophil count or a decrease in myeloperoxidase deficient neutrophils. In agar cultures 2 patients showed a concurrent increase in growth of day 11 colonies and clusters. In 2 of the patients a decrease in the number of immature bone marrow cells positive for the myeloid antibody anti-My7 was observed. Only minor alterations were seen in natural killer cell activity. In 4 patients showing clonal chromosomal abnormalities before treatment a disappearance of minor clonal abnormalities during treatment was observed, and in 3 chromosomal abnormalities reappeared after cessation of therapy. Even though the overall impact of 13-RA on the hematopoietic system was minor, the increase in myeloperoxidase normal granulocytes in the blood and the decrease in My7 positive cells and in clonal chromosomal abnormalities warrants further interest in this agent as a treatment modality in MDS. The side effects, especially experienced by the patients receiving 100 mg/m2, were, in spite of symptomatic treatment, of such a degree that only low dose treatment (10-20 mg/m2) administered for prolonged periods of time (3-6 months) would seem recommendable.

Adult↗

Development of the phagocytic and cidal capacity during maturation of myeloid cells: studies on cells from patients with chronic myelogenous leukaemia.

Myeloid cells from peripheral blood of patients with chronic myelogenous leukaemia were isolated and fractionated by density gradient centrifugation using Lymphoprep gradient followed by discontinuous Percoll gradients. Six fractions were obtained, each enriched in one of the morphologically identifiable types of myeloid cells from myeloblasts to polymorphonuclear neutrophils. Each of these cell types were functionally and biochemically characterized. The development of the capacities for phagocytosis and killing of yeast cells and the ability to generate a respiratory burst of phagocytosis correlated closely with the content of cytochrome b and vitamin B12-binding protein, a marker of specific granules. These results support the notion that the specific granules provide the developing neutrophil with components which are essential for its microbicidal activity.

Blood Bactericidal Activity↗

Analysis of leucocyte differentiation antigens in blood and bone marrow from patients with Waldenström's macroglobulinaemia.

Peripheral blood and bone marrow mononuclear cells from 10 patients with newly diagnosed Waldenström's macroglobulinaemia were analysed for the presence of leucocyte differentiation antigens using flow cytometry. Most patients had circulating intracytoplasmic-mu cells that were positive for the B-cell specific antigens B1, B2 and B4 and for the plasma cell antigen PCA-1. When such monoclonal cyto-mu + cells were purified by immune rosette depletion they were shown to express B1 to a much lesser extent than B2, B4 and PCA-1. In bone marrow samples cells with a similar phenotype, but with higher B1 expression were found in all patients. When the serum IgM paraprotein concentrations were compared to surface markers longitudinally from presentation and during the first courses of chemotherapy, a decreased serum IgM level was accompanied by a decrease in B1 cells in peripheral blood. These data demonstrate that WM cells possess a unique phenotype with coexpression of B-cell and plasma cell associated antigens.

Aged↗

Diagnostic and prognostic significance of serum measurements of lactoferrin, lysozyme and myeloperoxidase in acute myeloid leukemia (AML): recognition of a new variant, high-lactoferrin AML.

92 patients with acute myeloid leukemia were classified according to the FAB classification (M1 n = 20, M2 n = 43, M3 n = 1, M4 n = 19, M5a n = 2, M5b n = 2, and M6 n = 5 patients). Serum measurements of lactoferrin (LF), myeloperoxidase (MPO) and lysozyme (LYS) were performed before the start of treatment. LF was significantly lower in M1 when compared with M2 but not as compared to M4, MPO was significantly higher in M2 and M4 than in M1, but comparable MPO levels were found in M2 and M4. LYS was significantly elevated in M2 in comparison with M1, and in M4 when compared to both M1 and M2. Polymorphonuclear granulocytes (PMNs) in M1 were significantly reduced when compared with M2 and M4, whereas mononuclear cells were significantly increased in M4 in comparison with both M1 and M2. FAB classification did not generate any prognostic information. When the patients were, instead, subdivided according to LF levels were found prognostically significant differences. Of patients below 100 micrograms/l, 44% went into remission as compared to 77% with LF from 101 to 400 micrograms/l. In patients with LF levels above 400 micrograms/l the remission frequency was only 14%. Multivariate statistical analysis on the data further suggested that lactoferrin may be used as an independent prognostic indicator. We conclude that although determination of the serum-levels of lactoferrin, lysozyme and myeloperoxidase in certain cases may be valuable as a supplement to the morphological examination of acute myeloid leukemia, it is evident that none of the three determinations can be used alone to distinguish between the FAB groups.

Adult↗

A two-color flow cytometry assay for detection of hairy cells using monoclonal antibodies.

We have developed a simple two-color immunofluorescence assay equally suited for microscopy and flow cytometry detecting hairy cells (HCs) in single cell suspensions, based on the concomitant reactivities with the B cell-specific monoclonal antibody B1 (CD20) and the monocyte/HC-associated antibody SHCL-3 (CD11c). Thus, HCs can be demonstrated in peripheral blood, bone marrow, and spleen specimens from hairy cell leukemia (HCL) patients even when they constitute less than 1% of the cell suspension. Likewise, admixture experiments with normal mononuclear cells and the MOLT-4 T-acute lymphocytic leukemia (ALL) cell line demonstrated that HCs could be detected in amounts as low as 1%. The validity of this assay has been ascertained by the lack of double marker positivity in cell suspensions from B-chronic lymphocytic leukemia (CLL) and acute myelogenous leukemia (AML) patients that only expressed B1 or SHCL-3, respectively. Furthermore, other malignant blood diseases, including malignant lymphomas, acute leukemias, and chronic leukemias disclosed no double marker positive cells. In a clinical setting, this assay was used for purifying HCs (by flow cytometry) from the peripheral blood from patients with no apparent morphological evidence of circulating HC infiltration and for monitoring the effect of interferon therapy. In conclusion, this assay should be of value for both diagnosis and monitoring patients with HCL.

Antibodies, Monoclonal↗

Prognostic significance of some clinical, morphological and cytogenetic findings in refractory anaemia (RA) and RA with sideroblasts.

In 27 patients initially diagnosed as refractory anaemia (RA) or RA with sideroblasts (RA-S) according to the FAB-classification a number of clinical, morphological and cytogenetic parameters were correlated for prognostic significance. From these correlations it emerged that severe cytopenia is centrally positioned with regard to clinical course in RA and RA-S. Positive correlations were found to initial diagnosis, clonal cytogenetic abnormalities, progression to RA with an excess of blasts (RAEB) or acute myeloid leukaemia (AML), the percentage of bone marrow blast cells and prolonged half life for radioactively labeled iron. The degree of peripheral blood granulocytopenia, alone, was correlated to bone marrow hypoplasia. Moreover, the frequency of abnormal karyotypes was inversely correlated to bone marrow cellularity and proportional to the frequency of bone marrow blast cells. From these relationships it may be proposed that chromosome abnormalities are associated with prolonged blast cell generation times and inhibition of blast cell maturation resulting in reduced marrow cellularity and blast cell accumulation, and, in the peripheral blood, falling percentages of neutrophil granulocytes. With the blast cell accumulation the bone marrow cellularity again becomes hyperplastic and the preleukaemic condition is transformed into RAEB or AML.

Anemia, Refractory↗