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PubMed1980

Ultrastructure of blastic crisis in osteomyelofibrosis. A report of 2 cases with some unusual features.

The clinical and morphological findings are presented in two patients suffering from myelofibrosis and osteomyelosclerosis which terminated in an acute blastic crisis. Clinical follow-up data and light microscopy of the bone marrow however, revealed a chronic megakaryocytic-granulocytic myelosis (CMGM) with progression into myelofibrosis during the course of disease. In one patient the blastic transformation involved predominantly basophils, and in the other, neutrophils, with an accompanying abnormal proliferation of megakaryocytes in both cases. Electron microscopy of this cell population demonstrated remarkable atypicalities of the neutrophilic, basophilic and megakaryocytic cell lines. These abnormalities consisted of a nuclear-cytoplasmic asynchrony and a partial arrest of maturation, sometimes resulting in bizarre cell forms. Our investigations support the hypothesis of a mixed cellularity type of myelosis with a gradual and insiduous progression into osteomyelofibrosis/-sclerosis and a potential blastic crisis. In the evolution of blastic crisis all cell lines may be transformed, but with predominance of one population - basophils and neutrophils in our two cases - in addition to atypicalities of megakaryocytes.

Acute Disease↗

PubMed1976

Detection of methionine in pernicious anemia megaloblasts and other types of erythroid precursors.

Utilizing a bacterial-agar overlay technic incorporating the methionine-requiring bacterium Leukonostoc mesenteroides, little or no bacterial growth was seen surrounding the megaloblasts and proerythroblasts of eight patients who had severe untreated pernicious anemia. Similarly, scant bacterial growth was observed in five cases of chronic erythremic myelosis (DiGuglielmo syndrome). Heavy bacterial growth, indicating ample amounts of methionine, was seen in two cases of autoimmune hemolytic anemia, and in two cases of severe untreated folate-deficiency anemia. The results are consistent with the "methyltetrahydrofolate trap" hypothesis in pernicious anemia, in which a defect in the methylcobalamin-dependent methyltransferase leads to reduced amounts of methionine. These studies also suggest that a similar methyltransferase defect does not occur in folate deficiency or autoimmune hemolytic anemia. The generation of methionine, as estimated by the present technic, may also be defective in chronic erythremic myelosis.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed1983

An immunohistochemical study of hemoglobin A, hemoglobin F, muramidase, and transferrin in erythroid hyperplasia and neoplasia.

The bone marrow biopsy specimens of 35 patients with benign and malignant erythroid hyperplasias were examined for the presence of hemoglobin A, hemoglobin F, muramidase (lysozyme), and transferrin, using an indirect immunoperoxidase method (PAP) on Zenker's-fixed paraffin-embedded bone marrow biopsy specimens and particles. Five cases of each of the following entities were studied: erythroleukemia and erythremic myelosis, acute granulocytic leukemia with maturation (FAB M2), polycythemia rubra vera, myeloproliferative syndrome in childhood, megaloblastic anemia (B12 and folate deficiency), erythroid hyperplasia (regenerating bone marrow and hemolytic anemia), and Ph' chromosome positive chronic granulocytic leukemia. Hemoglobin A was present in both the early and late erythroid precursors in all conditions. Hemoglobin F was the predominant hemoglobin in early erythroblasts of pernicious anemia and in both early and late erythroid elements in erythroleukemia and erythremic myelosis. Small quantities of hemoglobin F were present in a few isolated clusters in other conditions. Staining for hemoglobin F may be useful in identifying immature erythroid precursors and in distinguishing some cases of dysplastic erythroid hyperplasia from neoplasia. Additionally, these findings suggest that the maturational switch in hemoglobin synthesis operates with distinct pathways under different conditions.

Bone Marrow↗

PubMed1984

Cytochemical detection of erythroblastic enzymes in acquired dyserythropoiesis.

We have studied the amount and intracellular distribution of erythroblastic alkaline and acid phosphatase, nonspecific esterase, and N-acetyl-beta-glucosaminidase in 50 patients with acquired dyserythropoiesis. 19 morphologically normal bone marrow smears served as controls. Alkaline phosphatase was found in all controls (mean 9.4% of erythroblasts). The percentage of positive erythroblasts in pathological conditions varied greatly from absence to over 70%. Acid phosphatase and N-acetyl-beta-glucosaminidase were positive in pernicious anaemia and in acute erythremic myelosis. Nonspecific esterase was only detected in a case of erythremic myelosis. This case also showed a faint metachromasia with the dye azure A.

Acetylglucosaminidase↗

PubMed1992

[Diagnosis of chronic myeloproliferative diseases based on bone marrow biopsy].

The bone marrow biopsies and laboratory data of 248 patients with untreated chronic myeloproliferative disorders have been evaluated according to the Hannover Classification. 47.6 per cent of the cases were classed as primary or basic diseases, including chronic myeloid leukaemia common type, chronic myeloid leukaemia megakaryocytic type, chronic megakaryocytic-granulocytic myelosis, polycythaemia vera and essential thrombocythaemia. In 52.4 per cent of the biopsies the advanced stages of the primary diseases like increase of fibers and loss of differentiation were noted; the increase of fibers in myeloid leukaemia megakaryocytic type and in chronic megakaryocytic-granulocytic myelosis, and loss of differentiation in chronic myeloid leukaemia common type were frequently noted. In 14.1 per cent of the cases the advanced myelofibrosis and blast cell accumulations obscured the histological features of the primary disease, therefore these cases were placed in the unclassifiable group. The cases without increase of fibers and loss of differentiation accounted for only 4 per cent of the unclassifiable category. Leucocyte and platelet count as well as haematocrit values showed considerable overlapping and scattering and were generally lower in cases which developed myelofibrosis.

Bone Marrow↗

PubMed1977

Presence of complement-fixing antibodies against antigens of Gross virus-induced rat lymphoma and normal rat thymus in sera of patients with some forms of malignancies.

Presence of complement-fixing antibodies against soluble antigen(s) of Gross virus-induced rat lymphoma W/Fu(C58NT)D was determined in sera of 180 healthy donors, in sera from 100 healthy pregnant women and in sera obtained from 139 patients with acute myelosis, acute lymphadenosis, acute undifferentiated leukosis, chronic myelosis, chronic lymphadenosis and Hodgkin's disease. Antibodies against soluble complement-fixing antigen from W/Fu(C58NT)D rat lymphoma were found in 33 (5).5%) out of 64 sera of patients with acute leukemia, in 15 out of 60 sera of patients with Hodgkin's disease, in 17 (9.4%) out of 180 healthy donors and in 22 (22.0%) out of 100 sera from healthy pregnant women. None of 15 sera from patients with chronic leukemia were positive. Titers of complement-fixing antibodies in positive sera remained unchanged after absorption with pooled lymphocytes from healthy human donors. Some selected positive sera reacted also with a soluble antigen prepared from normal rat thymus. Nature of complement-fixing antibodies detected and of corresponding antigens is discussed.

AKR murine leukemia virus↗

PubMed1979

[Acute mature myelocytic leukemia as a form of the myeloproliferative syndrome].

On the basis of five observations of adult patients with the clinical feature of mature cellular leukaemia which proved to be therapy-refractory and which was characterized by a rapid course is referred to the necessity of the differentiation of such cases from the classical myeloic leukaemia. The cardinal symptoms of this type of disease, which probably is identified with the cases described in literature as atypical chronic myelosis, as paraneutrophil leukaemia or as acute myelofibrosis, and also shows common features with the juvenile chronic myelosis, are, apart from the mature cellular differential blood picture a short life expectancy (less than 1 year), an initial thrombocytopenia, a normal or increased activity of the alkaline granulocyte phosphatase, the lack of Ph1-chromosome as well as the bad therapeutic reaction to busulfan. The observation of the simultaneously existing fibroses of the bone marrow as well as of the final increase of immature blasts induced the classification of the clinical picture as a special form of the myeloproliferative syndrome.

Acute Disease↗

PubMed1979

[Determination of serum vitamin B12 in hematologic diseases].

By means of a test set of the Isocommerz (GDR) determinations of vitamin B12 in the serum were carried out according to the principle of the competitive protein binding. The normal values lie between 200 and 1,000 pg/ml serum. Clearly decreased levels of vitamin B12 are found in the pernicious anaemia, in other megaloblastic anaemias and in disturbances of the resorption after resection of the stomach. Increased values can be stated in the untreated chronic myelosis and in the blast episode. Under Busulphan-therapy a significant decrease of the values of vitamin B12 develops. The method seems to be practically important for the well-timed recognition of deficiency conditions of vitamin B12 in beginning pernicious anaemia, in disturbances of intestinal resorption after resection of the stomach and for the observation of the course of the chronic myelosis.

Acute Disease↗

PubMed1981

[Megakaryocytic pseudomyelosis with severe thrombocytosis].

A 66-year-old female patient complained of loss of body weight and fatigue. The clinical examination revealed a thrombocytosis with a maximum count of 3.200 . 10(9) platelets and a leukocytosis with maximally 25 . 10(9) white cells in the peripheral blood. The bone marrow showed a large increase of megakaryocytes. Under the diagnosis of megakaryocytic myelosis a chemotherapy with 186 mg busulfan was performed. In the course of this treatment the clinical picture of a sepsis occurred which could not be controlled by antibiotics. The patient died four months after her admission to the clinic. The essential findings in autopsy were a caseous tuberculosis of the lymph nodes with haematogenic generalization which appeared as a septic tuberculosa gravissima ("typhobacillosis" Landouzy). The bone marrow was atrophic. Spleen liver and lymph nodes were without evidence for a myeloproliferative disorder. Thus, the initial diagnosis had to be changed to a megakaryocytic pseudomyelosis with massive thrombocytosis as a reaction to the tuberculous infection. The differential diagnosis of megakaryocytic myelosis, other disorders of the myeloproliferative syndrome, and the reactive thrombocytosis are discussed.

Aged↗

PubMed1983

The value of bone marrow biopsy in chronic myeloid leukaemia.

Seventy-six patients with chronic myeloid leukaemia (CML) could be subdivided by core biopsy into chronic granulocytic leukaemia (CGL, n = 24) and chronic megakaryocytic granulocytic myelosis (CMGM, n = 52). By pure clinical definition 59 patients were grouped as classical CML and 17 showed a course which we termed atypical myelosis. The most reliable criteria for distinguishing between the classical and atypical forms were ALP-Index, peripheral leukocyte and platelet count and the estimated number of megakaryocytes in the bone marrow. The classical myeloses consisted of 40 per cent CGL and 60 per cent CMGM whereas the atypical consisted of CMGM only including all stages of fibrosis. Fibrosis was at the time of bone marrow biopsy found in 20 per cent of classical CML and in about 50 per cent of atypical myeloses. In classical CML Philadelphia chromosome could be detected in all the patients with CGL and in 50 per cent of those with myelofibrosis. Atypical myeloses did not exhibit Philadelphia chromosome. In 70 per cent of the cases it was possible to distinguish between CGL and CMGM by peripheral blood findings and bone marrow cytology.

Adult↗

PubMed1981

[Compartment analysis in the diagnosis of iron metabolism disorders].

The principle of the ferrokinetics according to the catenary model and to the multilocular system of Pollycove and Mortimer is described in short. The most important results of the investigation of the iron metabolism of 15 patients with chronic myelosis, 31 with osteomyelofibrosis and 68 with chronic liver diseases according to the catenary model are reported. According to the multicompartment model the ferrokinetic investigations of 18 patients with chronic liver disease as well as of one patient each with chronic myelosis and panmyelopathy were evaluated. An increased depot iron metabolism and a decreased effective erythropoiesis could particularly clearly stated in the latter patient. The statements to various parameters according to the two model demonstrations are compared.

Adult↗

PubMed1982

Erythroleukemia: a study of 15 cases and literature review.

Out of a total of 185 cases of acute leukemia at our institution from 1967 to 1978, fifteen cases (8.1%) were identified as erythroleukemia or erythremic myelosis. The symptoms at presentation were often related to anemia (10/15 cases); the presenting hemoglobin value was lower than 10.0 gm/100 ml. Nucleated red cells were present in the peripheral blood and reticulocyte response was inappropriate to the degree of anemia. Marrow biopsy showed erythroid hyperplasia with megaloblastic and dyserythropoietic features, increase in myeloblasts greater than 5% (10/15 cases), positive PAS staining of erythroid precursors (12/12 cases), and erythrophagocytosis by abnormal erythroid precursors (6/15 cases). Abnormalities were noted in monocytic and megakaryocytic cell lines, and it was concluded that erythroleukemia is probably a stem cell disorder. Response to chemotherapy was poor with median survival of four months from initial diagnosis. Intracranial hemorrhage and bacterial or fungal infection were the most frequent cause of death.

Adult↗

PubMed1979

Histopathology of bone marrow in human chronic leukemias.

Among the patients with chronic myeloproliferative diseases including clinical symptoms of chronic myelogenous leukemia--CML--two varying compartments with substantially differing histology of hemopoiesis were found: one with predominating granulopoiesis for which the usual term of chronic granylocytic leukemia--CGL--seems inadequate. The other with proliferation of granylopoiesis and megakaryopoiesis as a neoplasia with a mixed cellularity is observed to be different in its clinical course: there are often a leukemic or subleukemic cell counts, but mostly considerable increased platelets in the peripheral blood; there is a prolonged period of latency, a higher age group, an infrequent occurrence of blastic crisis and a regular outcome into myelofibrosis. This entity of chronic megakaryocytic granulocytic myelosis--CMGM--can be seen very frequently among myeloproliferative diseases. Among a total of 718 core biopsies from the bone marrow the CMGM-patients are up to 29% compared with 21% of the typical one-cell-line disease CGL. The Ph1-chromosome may be presented in the CMGM-entity likewise.

Bone Marrow↗

PubMed1991

Treatment of thrombocytosis in chronic myeloproliferative disorders with interferon alfa-2b.

Thirty-six patients with chronic myeloproliferative disorders (CMPD) with thrombocytosis (essential thrombocythaemia 19 patients, chronic megakaryocytic granulocytic myelosis five, polycythaemia vera six, chronic myelogenous leukaemia six) were treated with interferon alfa-2b to reduce the platelet count. The pre-treatment platelet count was in the range 450-700 x 10(9)/L in eight patients, 700-1000 x 10(9)/L in eight and above 1000 x 10(9)/L in 20. In the induction phase of treatment 22 patients were treated with interferon alfa-2b 3 million units (MU) daily subcutaneously for 2 months or until the platelet count returned to normal, if earlier. Fourteen patients received 5 MU interferon alfa-2b daily in the same way. In the maintenance phase the doses were reduced to 3 MU and 5 MU thrice weekly, respectively. Complete response (CR), defined as a reduction of platelet count to below 450 x 10(9)/L, was achieved in 78% of patients (within 2 months of induction in 64%). The platelet depleting effect was dose dependent: CR in 2 months in 52% on 3 MU interferon alfa-2b versus 75% on 5 MU. Reduction of interferon dose was followed by an increase in platelet count in 39% of patients. The white cell count fell by 50% in Philadelphia-negative CMPD. Side effects were common, though generally mild, but led to withdrawal of treatment in six patients. Three patients suffered cerebrovascular events during treatment and one shortly thereafter.

Adult↗

PubMed1975

[Eosinophil leucocytes in csf after myelography (author's transl)].

2 cases one of polyneuropathy and one of funicular myelosis, in which myelography was performed, are reported. After the insertion of the contrast medium an increase of eosinophil leucocytes was observed. In one case an additional increase of IgG and IgA, as well as a penetration of macromolecular proteins and an increase of the total protein, was detected. The second case showed an increase in haptoglobulin in addition to the cellular reaction described. After removal of the contrast medium, the CSF became normal in both cases. These changes were on one hand interpreted as a functional lesion of the barrier, and on the other hand as a special cellular and humoral immune reaction. This could be distinctly detected in the lumbar CSF while in the suboccipital CSF there was only an indication of it. This emphasizes the assumption of a pathological reaction in the section of the cerebrospinal region that was in contact with the contrast medium (allergen-hyperergic reaction of the vascular fibrous tissue of the leptomeninges). No marked changes were observed in the serum.

Adult↗

PubMed1981

Congenital erythroleukemia. A case report.

The disease of a four week old boy is described, which presented with papulous skin infiltrations, lethargy, anemia and bilateral testicular swelling. The investigation of bone marrow, cerebrospinal fluid and skin biopsy revealed infiltration by a leukemic process which could be identified by means of cytology and cytochemistry as erythroleukemia at the stage of erythremic myelosis. Death occurred 20 days after the onset of symptoms. Only one previous report of congenital erythroleukemia could be found in the literature. The findings are briefly discussed.

Biopsy↗

PubMed1977

Selective vitamin B12 malabsorption (Imerslund-Gräsbeck syndrome). Studies on gastroenterological and nephrological problems.

In a girl 10 years of age with selective vitamin B12 malabsorption associated with proteinuria and residual symptoms of funicular myelosis an extensive study of the intestinal and nephrologic functions was done. Repeated Schilling tests pointed to a malabsorption pattern of vitamin B12. Gastric acid and intrinsic factor secretion as well as gastric morphology were normal. There were no antibodies against intrinsic factor and parietal cells in serum. Ileal mucosa showed on light- and electron-microscopy no pathologic changes. Pancreatic exocrine function as well as pH and calcium concentrations in the lumen of the gut were within the normal range. A general malabsorption syndrome could be excluded. A high selective glomerular proteinuria was found through different methods. Inulin clearance was slightly reduced, PAH clearance, however, markedly so. There was no further evidence for renal tubular dysfunction. Renal biopsy showed a minimal proliferative intercapillary glomerulonephritis (minimal changes). In electron-microscopic studies a fusion of a part of the foot processes of the podocytes was found. No familialhistory of the syndrome could be demonstrated in our patient.

Anemia, Macrocytic↗

PubMed1976

Originalarbeiten.

In 5 cases of polycythaemia vera and 2 cases with other myeloproliferative disorders accompanied by thrombocythaemia (megakaryocytic myelosis), the megakaryocytes were differentiated and studied by use of the combined application of cytophotometric determination of the DNA content and autoradiography with tritiated thymidine (3H-TdR) in vitro. A shift to the right of the megakaryocyte series, occurence of high polyploidy cells at 64c and a decrease of the 3H-TdR-labeling indices were observed. The data suggest a disturbance of the rhythmical polyploidization of the megakaryocytes, consisting of an elevated proportion of rest cells at the different ploidy stages. The maturation capacity of megakaryocytes may be related more to the resting than to the DNA synthesizing cells.

Adult↗