Impaired release of colony stimulating activity by monocytes from Hodgkin's disease in response to phorbol myristate acetate activation.

We assessed the humoral effect of resting and phorbol esters preincubated monocytes from Hodgkin's disease patients (HDMo) and healthy subjects (nMo), on granulocyte progenitors (CFU-dG) growth using a double diffusion chamber technique. The release of colony stimulating activity and indomethacin-dependent inhibitors by resting HDMo and nMo was found to be cell-concentration dependent. However, phorbol myristate acetate preincubated HDMo (PMA-HDMo) in contrast to nMo at low concentrations (2.5 x 10(4] were unable to increase the CFU-dG growth stimulation. On the other hand, at a higher cell number (5 x 10(4], phorbol treated HDMo stimulated the myeloid colony formation, whereas nMo suppressed the CFU-dG proliferation. Further enhancement of HDMo and nMo concentrations induced a pronounced inhibition of CFU-dG-derived colony formation, caused by an increased PGE2 production. After incubation with the cyclooxygenase inhibitor-indomethacin, PMA-HDMo showed considerably more granulocyte colony formation than nMo. Our results suggest that the observed abnormalities in the function of HDMo could be associated with an excessive production of PGE2 and a general dysfunction of these cells in Hodgkin's disease.

[Coexistence of Hodgkin's disease and myelodysplastic syndrome with late conversion to acute myeloblastic leukemia]. / Wspólistnienie ziarnicy zlosliwej i zespolu mielodysplastycznego z pózniejsza konwersja w ostra bialaczke szpikowa.

A case of coexistence of Hodgkin's disease with myelodysplastic syndrome followed by conversion to acute myeloid leukaemia is reported. Possible pathogenetic determinants of this coexistence are discussed.

[Significance of histologic bone marrow evaluation in diagnosis of chronic granulocytic leukemia. I. Reticulin fibrosis]. / Znaczenie oceny histologicznej szpiku w diagnostyce przewleklej bialaczki szpikowej. I. Wlóknienie retikulinowe.

The aim of the study was the evaluation of bone marrow reticulin fibrosis in non-treated patients suffering from chronic granulocytic leukaemia (cgl). We have examined 40 patients (19 female and 21 male, average age 41.2 years) with chronic phase, Ph'-positive cgl. Reticulin fibrosis grade I and II (according to Dekmezian and co.) was detected in 47.5% of patients and grade III and IV in 42.5%. Statistically significant correlation was found between reticulin fibrosis intensity and spleen size, platelets count and Sokal index. We believe that reticulin fibrosis assessment is of prognostic value.

[Effect of activated monocytes on the growth of cloned granulocytic progenitor cells]. / Wplyw aktywowanych monocytów na wzrost klonalny komórek ukierunkowanych szeregu granulocytarnego.

The humoral effect of resting and phorbol myristate acetate (PMA) preincubated normal monocytes on granulocytic progenitor growth in double diffusion chamber culture (CFU-dG) was assayed. The activation of monocytes by PMA was confirmed in NBT reduction test (increased formazan content) and by enhanced superoxide anions production compared with resting cells. The activatory and inhibitory effect of monocytes on granulocytic colony formation was cell-concentration dependent. The maximal CFU-dG growth promoting effects was seen at 5 X 10(4) of resting monocytes, whereas PMA-treated cells exerted their optimal stimulatory activity at lower cell number (2.5 X 10(4)). Further increase of monocyte concentration resulted in diminished CFU-dG proliferation. It is shown that the decline of colony count at high monocyte number was caused by indomethacin-dependent inhibitors.

[Significance of histologic bone marrow evaluation in diagnosis of chronic granulocytic leukemia. II. Megakaryocytes]. / Znaczenie oceny histologicznej szpiku w diagnostyce przewleklej bialaczki szpikowej. II Megakariocyty.

In 40 non-treated, ph1-positive patients with chronic granulocytic leukaemia (CGL) statistically significant correlation between the number of megakaryocytes and Sokal's index was found. The comparison of the data concerning megakaryocytic-granulocytic type (with increased number of megakaryocytes) CGL and granulocytic type (classical) revealed that patients with increased number of megakaryocytes in bone marrow had significantly greater spleen, larger number of leukocytes, platelets and myeloblasts in peripheral blood, more advanced bone marrow fibrosis and higher Sokal's index. These data seem to suggest that patients with megakaryocytic-granulocytic type of CGL have worse prognosis than with classical type.

[Significance of histologic bone marrow evaluation in chronic granulocytic leukemia diagnosis. III. Myeloblasts and promyelocytes]. / Znaczenie oceny histologicznej szpiku w diagnostyce przewleklej bialaczki szpikowej. III Mieloblasty i promielocyty.

The aim of the study was to assessment of the relationship between the number of myeloblasts in trephine biopsy in patients with chronic granulocytic leukaemia and Sokal's index. We have not found any correlation between these values. Further analysis revealed however that Sokal's index < 0.8 still qualified patients with evident signs of disease progress (increased number of layers of myeloblasts and promyelocytes in peri-trabecular and perivascular regions) to low risk group. We therefore conclude that bone marrow histology examination in chronic granulocytic leukaemia may bring valuable information concerning the real state of the disease.

[Neutrophils do not affect clonal growth of granulocyte progenitor cells cultured in vivo in diffuse chambers]. / Granulocyty obojetnochlonne nie wplywaja na wzrost klonalny komórek ukierunkowanych szeregu granulocytarnego w hodowli w komorach dyfuzyjnych in vivo.

The effect of polymorphonuclear leukocytes on the growth of granulocytic progenitors in the diffusion chamber culture (CFU-dG) has been studied. It has been shown that peripheral blood neutrophils do not affect the myeloid colony formation in this culture system. The inhibition of CFU-dG growth, observed in the presence of peripheral blood leukocytes was dependent on prostaglandins release from monocytes.

Activated lymphocytes in the marrow cell suspension decrease the mafosfamide-induced CFU-GM cytotoxicity.

The aim of the study was to assess whether other cells, besides erythrocytes, may influence the cytotoxic effect of mafosfamide (maf) during ex vivo bone marrow purging from residual tumor cells before autologous transplantation. It was shown that the presence of normal granulocytes, blast cells from acute myeloid leukemia-patients (AML) and lymphoma cells from patients with chronic lymphocytic leukemia (CLL) during maf incubation did not change the maf-induced growth inhibition of CFU-GM. Similar observation was made in experiments with resting lymphocytes. However, when phytohaemagglutinin- and pokeweed mitogen-preincubated lymphocytes were present in the marrow cell suspension, significant decline of the maf-related CFU-GM cytotoxicity was observed. These results suggest that besides erythrocytes also the activated lymphocytes in the marrow mononuclear suspension may change the final effect of maf purging.

[Formation of mixed colonies by progenitor cells of chronic myeloid leukemia cultured in vivo]. / Wytwarzanie kolonii mieszanych przez komórki macierzyste przewleklej bialaczki szpikowej w hodowli in vivo.

The clonal growth of multipotential progenitor cells of chronic myeloid leukemia (CML) in diffusion chamber implanted into peritoneal cavity of neutropenic and anemic rats was assessed. CML precursors formed in methylcellulose culture enriched with medium conditioned by phytohemagglutinin activated lymphocytes mixed neutrophilic-erythroid colonies, in number significantly higher then normal cells. Mixed colonies produced by CML cells, in contrast to the normal precursors, contained also macrophages, eosinophils and megakaryocytes. We conclude that modified diffusion chamber culture technique may be a suitable tool for multipotential progenitor study in CML.

[Cytochemical evaluation of blast cells in acute myeloblastic leukemia after induction of their maturation in liquid culture--diagnostic usefulness]. / Ocena cytochemiczna komórek blastycznych ostrych bialaczek szpikowych indukowanych do dojrzewania w warunkach hodowli plynnej--przydatnosc diagnostyczna.

We have performed the cytochemical analysis (myeloperoxidase, ASD-chloroacetate and acid alpha-naphthylacetate esterases, Sudan black B) of blast cells from 25 acute leukemia patients, after 3, 5 and 7 days of liquid culture with conditioned medium from phytohemagglutinin stimulated leukocytes (PHA-LCM). In case of acute myeloid leukemia blast cells an increase of percentage of positive cells simultaneously with the enhancement of the cytochemical reactions was observed. This method may be useful for the precise diagnosis of poorly differentiated blasts with weak expression of cytochemical phenotype.

Ambulatory electrocardiographic evaluation of the heart in patients treated by megachemotherapy and bone marrow transplantation.

The aim of the study was evaluation of the frequency of conduction defects and cardiac arrhythmias before and one month (once a week) after bone marrow transplantation (BMT). It was evaluated by 24-hour electrocardiography based on the Holter's method. There were 50 patients (mean age 29.0 years) examined who were treated with megachemotherapy based on BuCy2, BuCy4 (busulphan and cyclophosphamide), BEAM (carmustine, etoposide, cytarabine, melphalan) and dexaBEAM (dexa-dexamethason) programs before BMT. No heart conduction defects occurred. The mean heart rate increased after BMT. Tachycardia (> 100/min) was observed in 92.5-98.1% of patients and bradycardia (< 60/min) in 41.6-68.0% patients. In 6% of patients bradycardia below 40/min occurred. The heart rate was increased in patients who previously used anthracycline antibiotics, had anaemia or fever, and in patients after autologous BMT (p < 0.05). The complex ventricular extrasystoles were detected in 20% of patients before megachemotherapy. They were more frequently observed in patients with hypokalemia (p < 0.05). After therapy these extrasystoles were observed in a total of 24% patients. There was a statistically significant correlation between this kind of extrasystole and age. The extrasystoles developed mainly in young men. In 10% they occurred de novo and also mainly in men. The heart failure (III degrees, IV degrees according to NYHA) occurred in 14% of patients and death caused by heart (or multiorgan) damage in 18%. Older patients and those who had higher mean heart rate during the first month after BMT were dying more frequently (p < 0.05).

[Effects of alternating as well as long-term intensive polychemotherapy in the remission-maintaining treatment of patients with acute myelocytic leukemia]. / Wyniki naprzemiennie powtarzanej oraz dlugotrwalej, intensywnej polichemioterapii w leczeniu podtrzymujçym remisje u chorych na ostre bialaczki szpikowe.

The paper presents the results of 2 year maintenance treatment of patients with acute myeloid leukemias using cyclic, rotating and intensive polychemotherapy. Complete remission (CR) was achieved in 22 out of 33 patients with doxorubicin (60 mg/m2; 1-3 days) and cytosine arabinoside (100 mg/m2; 1-7 days). All patients in CR entered into the authors' programme of intensification therapy consisting of two consecutive polychemotherapy cycles, using various combinations of amsacrine, doxorubicin, cytosine arabinoside, etoposide and 6-thioguanine repeated every 3-4 months. The mean survival so far is 18 months (range, 1-52 months). The projected 3-years survival rate in complete remission concerns 33% of the patients treated. Relapses occurred in 50% of the patients, within 10 months (range 1-35 mos.) after CR. Our results indicate that intensive cyclic polychemotherapy markedly prolongs the survival of AML patients. The high frequency of relapses during the first year after CR indicates the necessity to enhance the degree of aggressiveness of treatment shortly after a complete remission has been obtained.

[Effectiveness of empirical antibiotic therapy in the control of infections in patients with acute leukemia during severe neutropenia]. / Skutecznosc antybiotykoterapii empirycznej w zwalczaniu zakazen u chorych na ostre bialaczki w czasie glebokiej neutropenii.

The clinical efficacy of empiric antibiotic treatment regimen for infection in 38 neutropenic patients with acute leukemia during induction and intensification therapy was evaluated. The therapy, which was applied in 74 episodes of fever in patients with neutrophil count less then 0.5 G/l, consisted of three sets of antibiotics (gentamycin + carbenicillin or azlocillin, amikacin + cephradine++ or cefuroxime, netilmicin+cefotaxime or ceftazidime) used one after another in case of persistence of fever in spite of 72 hours of treatment: In addition, flucytosine was applied in case of stable fever after 72 hours of antibiotic therapy. Flucytosine was replaced by amphotericin after 72 hours of ineffective treatment. The response rate of 68% and 96% was observed for patients during induction and intensification chemotherapy respectively. Low clinical efficiency of gentamicin and carbenicillin/azlocillin during induction treatment indicates that the therapy with antibiotics of broader range of activity is needed for this group of patients.