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Biomedical subjects

A Mijović

Publications and source records attributed to A Mijović.

At least 19 recordsLinked to original sources

The myelodysplastic syndromes: towards a functional classification.

The French-American-British classification of myelodysplastic syndromes (MDS) has contributed greatly to better communication and conduct of clinical trials. However, the advent of novel cytogenetic, immunological and molecular techniques in recent years warrant some alterations to this purely morphological classification. This review aims at highlighting the advances which reflect more closely the unique biological and clinical features of various subtypes of MDS. We propose a comprehensive classification of MDS, to include the newly defined categories, as well as those not included in previous classifications, such as the therapy-induced and hereditary MDS. We hope that this classification will help in focusing attention on the biological features of MDS, the understanding of which will be crucial to combat this disease.

Adult↗

Myelosuppressive chemotherapy to mobilize normal stem cells in chronic myeloid leukemia.

Ten patients with Ph+ chronic myeloid leukemia (CML) were treated with idarubicin, cytarabine and etoposide followed by G-CSF to harvest Ph-negative progenitor cells. Six were in first chronic phase (CP1), and four beyond CP1. Between two and six aphereses (median 3, total 36) were performed starting 9-26 days (median 14.5) after chemotherapy when the leukocyte count was 0.6-4.7 x 10(9)/l (median 1.2). 1.3-3.6 x 10(8) mononuclear cells/kg (median 2.8), 0-128.4 x 10(4) CFU-GM/kg (median 1.2; seven patients) and 0.3-25.1 x 10(6) CD34+ cells/kg (median 9.8; seven patients) were collected. Seven of 27 harvests showing metaphases were 100% Ph-negative, 11 partially Ph-negative, and nine were 100% Ph+. All three patients with 100% Ph-negative collections were in CP1 and within 4-26 months of diagnosis. Four of six CP1 patients showed significant cytogenetic response compared with none of four beyond CP1 (P = 0.036). The absolute neutrophil count remained < 0.5 x 10(9)/l for 9-44 days (median 15.5) following chemotherapy. Four patients (three Ph-negative) were autografted after 16 mg/kg busulfan (n = 2) or 200 mg/m2 melphalan (n = 2). One of the three patients receiving Ph-negative cells died of graft failure, and two are alive with 15% and 50% Ph-negative cells at 15 and 11 months on interferon-alpha. We conclude that it is possible to harvest Ph-negative cells after myelosuppressive chemotherapy in some CML patients treated early in the course of CP1. However, in view of lack of consistent response, investigation of alternative approaches is necessary.

Adolescent↗

Drug-induced agranulocytosis: bone marrow granulocytic progenitor cells.

Bone marrow CFU-GM and cluster forming cells were studied in ten patients in different stages of drug-induced agranulocytosis using a methylcellulose cell culture technique in vitro. In the aplastic phase of the disease (A), the number of both CFU-GM and cluster forming cells was decreased in comparison to normal values. In the regenerative phase of the disease (R), the number of both granulocytic progenitors increased but did not reach normal values. In patients considered to be recovered from acute agranulocytosis (Rec), a decreased number of progenitors persisted indicating residual damage at this granulocytic cell level. It is suggested that agranulocytosis is due to isolated damage of granulocytic cells and predictable cascade of events within different cell compartments could be used as an in vivo model for investigation of the regulation of granulopoiesis.

Agranulocytosis↗

Erythropoiesis in paroxysmal nocturnal hemoglobinuria.

Ten patients with paroxysmal nocturnal hemoglobinuria were studied. The diagnosis was made on the basis of hemolytic anemia, a positive Ham test and hemosiderinuria. Six patients had primary paroxysmal nocturnal hemoglobinuria evolved from aplastic anemia. These four patients also had a milder form of the disease, Over long periods of the follow-up, large variations of hemoglobin values and red blood cell counts were observed. Both absolute and percent reticulocyte counts were increased. Erythroblast counts in the bone marrow were 3-5 times higher than normal. Reticulocyte counts in the bone marrow were 3-5 times higher than normal. Reticulocyte counts showed wide variations but substantially smaller than those in autoimmune hemolytic anemias. Serum iron was either normal or increased, while the bone marrow iron store was high or low. However, the finding of urinary hemosiderin in all cases spoke against depletion of iron stores. The red blood cell life span was moderately shortened. Kinetic studies with 59Fe showed a high red blood cell iron incorporation, while the curves frequently had irregular shapes (broken curve) or an early, abrupt fall. Studies of late erythroid progenitors (CFU-E) indicated that this compartment was preserved. Even after long observation periods was no stem cell pool depletion due to an increased red blood cell demand observed.

Anemia, Aplastic↗

Chronic myeloid leukemia associated with pure red cell aplasia and terminating in promyelocytic transformation.

After intermittent treatment with busulphan over a 7-year period for chronic myeloid leukemia (CML) in chronic phase, a 39-year-old female developed leukocytosis in association with pure red cell aplasia (PRCA). Bone marrow examination confirmed erythroid aplasia, and culture revealed a total absence of erythroid progenitor cells. The patient then was treated with azathioprine, corticosteroids, cyclophosphamide, plasma exchange, and cyclosporin A, but she remained erythroblastopenic and transfusion dependent for more than a year, at which time a promyelocytic transformation supervened. The authors propose that this sequence of events, hitherto unreported, is a manifestation of the multistep progression of CML.

Adult↗

Acute erythremic myelosis (DiGuglielmo) following atypical aplastic anemia.

A patient presented with acute erythromyelosis (DiGuglielmo) which was developed after 3 yr of aplastic anemia. Aplastic anemia differed from the classical form, since erythroid cells and megakaryocytes were relatively preserved in the bone marrow. Treatment with androgens induced the increase of hematocrit and reticulocyte as well as general improvement. The sudden appearance of hemorrhagic syndrome due to thrombocytopenia was associated with aggravation of anemia and granulocytopenia. In the bone marrow, giant multinuclear proerythroblasts with bizarre nuclear morphology and PAS positivity with coarse granules was found. Serum erythropoietin (Ep) level was high. Bone marrow cells culture in vitro revealed two types of erythroid colonies: typical and giant multinuclear cells, both benzidine-positive. The number of colonies was irrespective to the Ep dose. "Autonomous" Ep independent growth of these colonies was also demonstrated. The number of colonies was more than 3 times higher per number of cells seeded when compared to normals, which indicated malignant proliferation and Ep independent growth. Treatment with 6-mercaptopurine and transfusions was without effect and the patient died after 15 days with signs of cerebral bleeding.

Acute Disease↗

Myelopoiesis and erythropoiesis of bone marrow cells cultured in vitro in patients recovered from aplastic anaemia.

Methylcellulose culture assay was used to detect committed haemopoietic stem cells, CFU-C and CFU-E, in aplastic anaemia patients with autologous haemopoietic reconstitution. Severe diminution of CFU-C was found in all the patients studied and the absence of a dose-response to colony stimulating factor (CSF) was demonstrated. A reduced number of CFU-E and lower erythropoietin (Ep) sensitivity of those progenitors was detected as well. Autologous serum added to the bone marrow cultures of these patients enhanced the growth of CFU-C but inhibited CFU-E growth. According to the results presented, some residual damage at the stem cell level is suggested.

Adult↗

A case of chronic myeloid leukemia without Ph1 translocation.

A case of chronic myeloid leukemia (CML) with a short survival (11 months) is described. Cytogenetic peculiarities of the bone marrow cells analyzed by G-banding consisted of a Ph1 chromosome with no translocation and a translocation t(5;13). Hematological characteristics were marked leukocytosis and massive splenomegaly. After treatment with busulfan complete hematological remission was achieved, followed by the appearance of a normal clone. However, 6 months later the patient entered the blastic crisis and a hyperdiploid clone appeared. The usual chemotherapy was given, but the patient responded only partially and died with a prevalence of pathologic myeloblasts in the bone marrow, corresponding to progression of the hyperdiploid clone.

Adult↗

[Immunoneutropenia].

A patient with two episodes of acute agranulocytosis was described. Recovery was followed by an unusually slow increase in the number of peripheral blood granulocytes in spite of the presence of granulocyte precursors in the bone marrow. High level of circulating immune complexes as well as an increased number of immunoglobulins on the surface of granulocyte membrane was demonstrated throughout the course of the disease. When the level of CIC and the number of Ig-NG decreased and attained normal values, the number of granulocytes increased rapidly. The possibility that immune complexes were responsible for this neutropenia was suggested.

Adult↗

[Aspirin-like defect - a hereditary thrombocytopathy due to impaired release of platelet adenosine diphosphate].

This report presents the case of a 36 year old woman with an inborn haemorrhagic syndrome, who exhibited a lifelong history of spontaneous bruising, nose bleeding, prolonged bleeding after tooth extraction, and menometrorrhagia. The routine tests of haemostasis were consistent with impaired platelet functions. The diagnosis of the "Aspirin-like defect" was made on the basis of the following findings: the bleeding time was prolonged, whereas the platelet count and morphology were normal; platelet retention in glass bead filters was unmeasurable. ADP-induced platelet aggregation was normal, while it was markedly reduced with collagen and epinephrine. The platelet ADP and ATP content, as well as the ATP/ADP ratio were within normal limits. Aggregation of platelets pre-incubated with aspirin was only slightly reduced when induced by ADP, collagen, or epinephrine. These findings suggest that the thrombocytopathy in our patient is due to an impaired ADP release from the platelet granules containing normal quantities of adenine nucleotides. A similar disorder is observed in normal subjects after aspirin ingestion, and therefore the defect described in this paper is referred to as the "Aspirin-like" defect.

Adenosine Diphosphate↗