Mediastinal malignant teratoma and acute myeloid leukemia in a patient with Klinefelter's syndrome--comparison of DNA content in the two malignancies.
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Biomedical subjects
Publications and source records attributed to B Labar.
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Correlation between the FAB classification and immunophenotype was studied in 169 consecutive adult patients with acute leukaemia (AL). The lineage of leukaemic cells could be determined in the majority of cases, whereas 3 patients (1.8%) remained unclassified. In 22 out of 71 patients (31%) with acute myeloid leukaemia (AML) FAB M1 and M2 types, and in 5 out of 16 patients (31%) with chronic myeloid leukaemia (CML) in myeloid blast crisis, leukaemic cells did not express myeloid lineage-related markers, indicating asynchronous expression of cell markers in a substantial proportion of patients. Flow cytometric two-colour immunofluorescence revealed mixed AL immunophenotype in 6 out of 169 patients (3.4%). This group included five CD2+AML (5% of AML tested) and one undifferentiated AL expressing CD10(CALLA), CDw65(VIM-2). The former group included FAB M1, M2, M3 and M4 forms of AML with a single cell population, and an AML M2 patient with both cytochemically and immunologically two separate populations of leukaemic cells. This further illustrates the heterogeneity of the target cell(s) for leukaemogenesis and the level of differentiation of AML cells. However, there was no difference in the treatment response and the remission duration between AML patients and patients with mixed phenotype AML.
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Between October 1988 and December 1990, 60 patients with leukaemia (25 with AML, 19 ALL and 16 CML) undergoing BMT were randomised in a double-blind clinical trial to receive prostaglandin E2 (PGE) (Prostin E2, 0.5 mg per tablet) or placebo for prophylaxis of oral mucositis. Patients had to dissolve tablets in the mouth three times daily starting 7 days before BMT and continuing until 21 days after BMT. The incidence of severe oral mucositis was similar for both groups, 55% in patients receiving PGE and 52% in patients receiving placebo. The duration of severe mucositis did not differ between PGE and placebo groups (chi-square 0.95, p = NS). The incidence of HSV infection was significantly higher in patients receiving PGE. Patients with HSV infection receiving PGE also had a higher incidence of severe oral mucositis. The results presented indicate that PGE is not effective for prophylaxis of oral mucositis in BMT recipients.
To assess the effects of GM-CSF in patients with myelodysplasia, a total of 101 patients with refractory anemia (RA), RA with ringed sideroblasts (RARS), and RA with an excess of blasts provided that the percentage of blasts in the bone marrow did not exceed 10% (RAEB) were enrolled in the EORTC Leukemia Cooperative Group study 06885. They were randomized to receive two daily subcutaneous injections of rhGM-CSF (mammalian, glycosylated, Sandoz/Schering-Plough) at a daily dose of either 108 micrograms glycoprotein (group I) or 216 micrograms glycoprotein (group II) for 8 weeks. Response was defined as an increase in Hb (greater than 2.5 g%), neutrophil count (more than 100%), or platelet count (more than 100%) without progression of the disease. After exclusion of 19 patients who did not meet the entry criteria, 82 were evaluated. Fifty-four patients (66%) responded (27 of 42 patients in group I and 27 of 40 in group II). Progressive disease was seen in two patients of group I and in four of group II. Two of the latter developed leukemia. All responses were reflected in the granulocytic series. In two patients platelet numbers also increased. Cytogenetic analysis, successfully performed in 43 cases, showed that 14 of 16 patients with normal karyotypes responded, compared with 14 of 27 patients with abnormal karyotypes (p = 0.008). In some cases GM-CSF was reduced in dose or discontinued prematurely due to side effects so that only 35% of all evaluable patients finished 8 weeks of treatment without a change of dose.
Symptomatic patients with myelodysplastic syndromes (MDS) and 10-30% blasts in the bone marrow were treated with low-dose AraC (2 x 10 mg/m2 subcutaneously (sc) days 1-14) and GM-CSF (fully glycosylated, Sandoz/Schering-Plough, 2 x 150 micrograms protein/day sc) given either subsequently (days 15-21) or simultaneously (days 8-14 and one week rest). Evaluations were carried out after three courses (nine weeks); responding patients could be continued for two further cycles. Eighty-two patients with refractory anaemia and excess of blasts (RAEB), with (RAEBt) or without transformation, were evaluable: 45 RAEB and 37 RAEBt, mean age 64 years (range 17-80 years). A complete remission was achieved in 14 cases (17%), 11 had a good response (13%), and 12 a partial response (15%). Stable disease was found in 21 cases (26%). There were 12 cases of toxic death (15%), progression was noted in eight patients (10%), and death due to disease in three (4%). No difference existed between the two treatment arms with respect to response. Major adverse events during treatment were haemorrhage (25%), infections (23%), and fever with GM-CSF (21%). GM-CSF did not induce leukaemia nor contribute to haemorrhage induced by AraC, but gave rise to an overall response rate of 46% which is high and relatively durable as compared to other treatments in this disease.
Cytochemical analysis of leukemic blasts from 46 patients with acute myeloblastic M2 leukemia (according to the FAB classification) was performed before and after cytostatic therapy, and compared with findings obtained in 20 age- and sex-matched control subjects. Cytochemical findings for myeloperoxidase (MPO), Sudan black B, acid phosphatase and alpha-naphthyl-acetate esterase (ANAE) were related to the achievement of the first complete remission (CR), i.e. data were compared after the patients had been divided into CR and non-CR groups. The analysis clearly showed that a high proportion of myeloperoxidase- and, to a lesser extent, Sudan black B-positive blasts before treatment may have constituted a significantly unfavourable prognostic factor.
Paraffin-embedded histopathologic specimens, taken before the commencement of therapy from 14 low-grade and 21 high-grade malignant lymphoma patients, and 9 normal lymph nodes were utilized to analyze six cell DNA-related parameters. The flow cytometry technique was used to determine cell-cycle G0/G1, S and G2/M phases, and silver staining to enumerate nuclear organized regions (AgNORs); nucleus surface area was determined by an image-analyzing system. The six parameters and natural logarithm of cell proportion in the S-phase (LS) were determined according to the histologic tumor type and achievement of the first complete remission (CR). All parameters except cell proportion in G1/M cycle phase differed significantly with respect to histologic cell type, but were not related to the achievement of first CR. Inasmuch as the parameters significantly correlated with each other, multivariate discriminant analysis and proportional hazard regression were applied to estimate their discriminant/predictive values with respect to tumor malignancy. AgNORs proved to be far superior in all three clinical parameters, S-phase was significantly predictive for the achievement of first CR, and LS for tumor histology type. The statistical model applied narrowed down the analysis of seven parameters to two with respect to tumor histology type (AgNORs and LS) and achievement of first CR (AgNORs and S), but only to one for overall patient survival (AgNORs). Only the model for tumor histology type discrimination was statistically significant (R2 = 0.904, p < 0.001). It appears that AgNORs may be of utmost predictive importance for the clinical outcome in NHL.
A patient developed pure red cell aplasia after ABO incompatible BMT for leukemia. He did not respond to plasma exchange. Antilymphocyte globulin therapy was followed by complete and permanent erythroid recovery with disappearance of recipient-derived isoagglutinins.
From June 1986 to June 1990, 64 patients with leukaemia (25 acute myelogenous leukaemia, 21 acute lymphoblastic leukaemia and 18 chronic myeloid leukaemia) undergoing marrow transplantation were randomized to receive cyclophosphamide (CY) and fractionated total body irradiation (TBI) without lung shielding (n = 33) or CY and fractionated TBI with lung shielding (n = 31, control group) as conditioning. Patients conditioned with TBI without lung shielding received a significantly higher total lung dose compared with the control group (p less than 0.0001). The 3-year leukaemia-free survival for patients receiving TBI without lung shielding is 54 +/- 18% versus 51 +/- 18% for patients receiving TBI with lung shielding (p = ns). There was no significant difference in the probability of leukaemia relapse (22 +/- 18% for TBI without lung shielding versus 24 +/- 18% for control group; p = ns). The probability of interstitial pneumonitis is 15 +/- 14% for TBI without lung shielding and 5 +/- 5% for TBI with lung shielding (p = ns). A higher incidence of lung fungal infection (15 versus 3%) and interstitial pneumonitis (12 versus 3%) has been documented in patients receiving TBI without lung shielding compared with the control group. The results indicate that higher radiation dose to the lung did not increase antileukaemic efficacy of TBI but seemed to be associated with the increased pulmonary toxicity.
Twenty-one newly diagnosed adult AML patients were treated with high dose Ara-C (HD-ARA-C) as a single induction treatment with the dose of 2 g/m2 q 12 hours x 12. Seventy-six percent (16/21) responded with complete remission. Three patients died in induction in pancytopenia, another one died on day 44 in CR due to bleeding of pulmonary aspergilloma. This treatment seems to be highly efficient for remission induction, but requires an adequate transfusion and other supportive measures. The overall toxicity was transient and seems acceptable. However, the remission duration is unacceptably short, the consolidation with the same treatment seems to be inadequate. More aggressive treatment in postinduction period seems to be warranted.
We compared the cellular composition of the first 1.0 ml volume bone marrow aspirate with that of an aliquot from the total bone marrow harvest at the end of the procedure in 17 healthy bone marrow donors. Each sample was assayed for its content of red blood cells, nucleated cells, CD2+, CD4+, CD8+, CD19+, HLA-DR+, CD56+, CD13+, CD33+, CD34+ and KiM8+ cells and CFU-GM. On the basis of data obtained, we estimated that the first 1.0 ml samples had 8.0 +/- 5.2% (SD) and the transplant samples 20.8 +/- 8.5% contamination with nucleated blood cells. The calculation revealed that both types of bone marrow samples had 100% volume contamination with peripheral blood, i.e. that bone marrow cells were aspirated within blood fluid volume. Nucleated cell concentration was 3-fold, and CFU-GM concentration 10-fold lower in the transplant than in the first-puncture 1.0 ml bone marrow samples. Various marker-positive cells appeared in transplant samples in concentrations that depended on their abundance in the first-puncture 1.0 ml and blood samples. Taken together, our data suggest that bone marrow harvesting would be substantially improved if individual aspirates were small in volume and taken from bone puncture sites as distant as possible.
From May 1985 to July 1989, 76 patients with leukemia (30 acute myelogenous leukemia, 24 acute lymphoblastic leukemia and 22 chronic myeloid leukemia) were randomized to receive either cyclosporin (CSP) alone (n = 39) or CSP combined with methotrexate (CSP + MTX, n = 37) for graft-versus-host disease (GVHD) prophylaxis. Patients were conditioned with total body radiation and cyclophosphamide followed by bone marrow infusion from an HLA-identical sibling. Engraftment of the transplanted bone marrow was similar in both groups. The incidence of moderate to severe acute GVHD was significantly higher in the CSP group compared with the CSP + MTX group (20 (51%) versus 9 (25%), chi 2 = 4.76, p less than 0.02). There was no significant difference in the incidence of chronic GVHD. Survival was significantly better for the CSP + MTX group (63 +/- 16%) compared to CSP alone (42 +/- 18%). Leukemia-free survival tended to be better for the CSP + MTX group (55 +/- 17% versus 32 +/- 16%).
The expression of progenitor cell-associated antigen CD34, defined with monoclonal antibody BI-3C5, was investigated in cells from 109 patients with leukaemia. No reactivity was found in chronic leukaemias, whereas 31% of acute myelogenous leukaemia (AML) and most non-T, non-B acute lymphoblastic leukaemia (ALL) expressed CD34. Examples of BI-3C5+ AML included M1 and M2 FAB types only; all but one were myeloperoxidase positive. In combination with pan-myeloid markers, BI-3C5 is useful for identification of immature myeloid cells.
Bone marrow and peripheral blood of 25 healthy bone marrow donors from our allogeneic bone marrow transplantation program were assessed for cell subsets bearing T11(CD2), T4(CD4), T8(CD8), B1(CD20) J5(CALLA, CD10), Mo1(CD11b), MY7(CD13). Mo2(CD14), MY9(CD33) and NKH-1 antigens. Bone marrow cell samples were taken for analysis at the start or at the end of the harvesting procedure of aspiration from the iliac crest. All samples were analysed on a flow cytometer at the lymphocyte window as obtained on the two-parameter (L90oLSxFALS) scatter diagram. There were no differences in the lymphocyte subset composition of bone marrow samples taken at the start or at the end of the harvesting procedure. In contrast to the majority of literature data, a high CD4/CD8 ratio was detected in bone marrow samples: it did not differ from that in the peripheral blood. The proportions of CD2 and CD4 T cell markers in the bone marrow correlated with those in the peripheral blood, thus further documenting a substantial bone marrow contamination with peripheral blood cells. A relatively large aspirate volume (4-5 ml) obtained from individual aspiration sites was identified as the only factor possibly accounting for the high-level contamination of bone marrow samples with peripheral blood. This conclusion was corroborated by low T cell proportions and low CD4/CD8 ratios found in the bone marrow washed from bone fragments and in bone marrow samples aspirated at first bone puncture in a volume of 1.0 ml. Taken together, these findings imply that less vigorous suction may decrease the number of T lymphocytes in bone marrow harvested for transplantation purposes.
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