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Biomedical subjects

D Fiere

Publications and source records attributed to D Fiere.

At least 73 records · Page 4Linked to original sources
PubMed1990

Pre-clinical evaluation of anti-lacto-N-fucopentaose III (CD15) monoclonal antibodies for ex vivo bone marrow purging in acute myeloid leukemia.

In order to eliminate residual leukemic cells from the marrow of patients with acute myeloid leukemia (AML) prior to autologous bone marrow transplantation, the optimal conditions of utilization of three CD15 murine monoclonal antibodies (MoAb) were investigated. The VIM-D5 MoAb was used with rabbit complement (C'), whereas the 8.27 and SMY15A MoAbs were used in the presence of human C'. These antibodies were also tested after fixation on magnetic beads. In a culture assay in semi-solid medium with a mixture of normal marrow and 1% HL60 cells, a lysis of clonogenic cells greater than 99% was achieved with the three antibodies and two rounds of complement, or with antibody-coated magnetic beads. Cultures of leukemic clonogenic cells (CFU-L) were performed in 47 cases. An inhibition equal to or greater than 90% was achieved in seven cases with VIM-D5, 16 cases with 8.27 and 11 cases with SMY15A and C'. The correlation with cytotoxicity of fresh cells was low. Twenty cases were purged with antibody-coated beads. An inhibition equal to or greater than 90% was observed in 10 cases with VIM-D5, 11 cases with 8.27 and 12 cases with SMY15A. The mean recovery of normal CFU-GM was higher than 70% and that of BFU-E higher than 95% with any method of treatment. It is concluded that efficient marrow purging of clonogenic AML cells can be achieved in some cases without toxicity for normal progenitors. The addition of other MoAbs seems necessary to obtain a significant purge in a majority of cases.

Antibodies, Monoclonal↗
PubMed1989

Influence of cigarette smoking on the presentation and course of chronic myelogenous leukemia.

It is known that cigarette smoking induces leukocytosis and increased genetic instability in normal individuals. Therefore, a retrospective review was conducted of 173 patients with chronic myelogenous leukemia to detect a possible influence of cigarette smoking on initial characteristics at the time of presentation and on the course of this disease. Thirty-nine patients (23%) were smoking 5 cigarettes/d or more at time of diagnosis. Cigarette smoking was significantly related to male sex (P = 0.0005) and younger age at diagnosis (P = 0.02) and smokers tended to have lower leukocyte counts (P = 0.07) than nonsmokers. Cigarette smoking was significantly associated with early blast crisis (P less than 0.0001) and short survival (P less than 0.0001). Other characteristics associated with a poor prognosis included hepatomegaly, anemia, and a high percentage of peripheral blast cells at time of diagnosis. When studied in a multivariate analysis, cigarette smoking remained the strongest prognostic factor for both occurrence of blast crisis (P = 0.0003) and overall survival (P = 0.0001). Other poor prognosis factors found in the multivariate analysis included a high percentage of blasts in the peripheral blood at time of diagnosis and high platelet count. It is possible that cigarette smoke may act as a promoter or cocarcinogen in the transformation of chronic myelogenous leukemia.

Blast Crisis↗
PubMed1989

[Treatment of acute myeloblastic leukemia in aged patients].

Approximately 55 per cent of patients with acute myelogenous leukaemia (AML) are over 60 years of age, which raises therapeutic problems since the intensive chemotherapy generally used in younger patients is very toxic in the elderly. The three main therapeutic alternatives offered to the physician in elderly patients are: (1) initial therapeutic abstention followed by palliative chemotherapy habitually using hydroxyurea when control of hyperleukocytosis is required; (2) intensive chemotherapy with anthracyclines and cytosine arabinoside (araC) based regimens, which induces complete remission in 45 to 50 per cent of the cases at the price of an initial toxic death rate of approximately 30 per cent, with 5 to 15 per cent of the patients possibly being cured, and (3) low-dose araC inducing complete remission, generally of shorter duration, in 25 to 30 per cent of the patients with about 10 per cent toxic deaths. In the absence of randomized trial comparing these approaches, there are no objective criteria enabling precise therapeutic indications to be defined. Poor initial general condition and a past history of myelodysplastic syndrome are widely accepted factors of poor prognosis whatever the therapeutic strategy used.

Aged↗
PubMed1989

Phase II trial of plicamycin and hydroxyurea in acute myelogenous leukemia.

A total of 23 patients with high-risk acute myelogenous leukemia (AML) at diagnosis (2 patients), relapsing AML (14) or resistant AML (6) were treated with 25 micrograms/kg i.v. plicamycin every other day for 3 weeks and 500-4,000 mg hydroxyurea per day p. o. according to the WBC count. Aplasia was observed in only two patients. Severe extrahematologic toxicity included sepsis (four cases), vomiting (four patients), toxic hepatitis (three cases), and fibrinopenia (one patient). No partial or complete responses were observed. The 95% confidence interval limit of the overall response rate (CR + PR) was 0-14%.

Bone Marrow↗
PubMed1989

Cell kinetics in acute lymphoblastic leukaemia: comparative analysis between adults and children.

Cell kinetics were studied in 124 patients with acute lymphoblastic leukaemia (ALL) by flow cytometry, comparing cell cycle characteristics between adults (57 cases) and children (67 cases). S, G2 + M and the low protein content fraction of G1 (LPC fraction) were determined and studied in relation to other clinical and biological features. No difference was found between adults and children in the distribution of these variables. The proliferative rates according to organomegaly, leukocytosis, the FAB cytological groups and the immunological groups did not present any significant differences between the two groups of patients. However, cell cycle did seem to have a very different prognostic value for adults and for children. G2 + M was a strong prognostic indicator for childhood ALL: duration of CR and survival were significantly longer when G2 + M was higher (P less than 0.01). In adults, survival was longer for intermediary (between 3.8 and 5.8%) and high (over 7.2%) G2 + M values (P less than 0.01). The negative correlation between S and G2 + M observed in adults and the absence of correlation in children raise the possibility of differences in duration of the different phases for the two groups and perhaps an accumulation of cells in G2 or tetraploidy in some cases.

Adolescent↗
PubMed1989

Surface marker expression in adult acute myeloid leukaemia: correlations with initial characteristics, morphology and response to therapy.

The clinical significance of surface markers was investigated in 145 cases of acute myeloid (AML) or undifferentiated leukaemia (AUL), using a panel of six monoclonal antibodies directed to NHL-30.5 antigen (expressed on poorly differentiated myeloid cells), CD13, CD14, CD15, CD33 and CD34 antigens. Expression of CD14 was correlated with higher leucocyte count, higher serum lactate dehydrogenase level and presentation with extramedullary disease. There was no strict correlation with the French-American-British classification. However, the expression of CD14 was associated with monocytic subtypes. CD15 was mainly expressed in M2 and M3 subtypes, and NHL-30.5 and CD34 antigens in AUL and M1 leukaemias. All patients were treated with the same intensive induction treatment. Staining by three antibodies had a prognostic value. The complete remission (CR) rates were 38% (26/68) in NHL-30.5-positive versus 75% (62/77) in NHL-30.5-negative cases (P less than 10(-5), 50% (37/74) in CD34-positive versus 72% (51/71) in CD34-negative cases (P = 0.007) and 70% (77/110) in CD15-positive versus 31% (11/35) in CD15-negative cases (P less than 10(-4). Expression of NHL-30.5 and CD34 antigen was associated with shorter survival (P less than 10(-3) and P less than 10(-2) respectively), whereas survival was longer in CD15-positive cases (P less than 10(-3). In multivariate analysis, expression of NHL-30.5 antigen, absence of CD15, and high LDH level were associated with poor survival. CR duration was not influenced by any of the factors studied, including antigen expression. These results suggest that leukaemias with less differentiated phenotype have a lower response rate to induction treatment.

Acute Disease↗
PubMed1989

[Comparison of the antiemetic effectiveness of high-dose corticosteroids with synacthene in nausea induced by chemotherapy: results of a randomized study].

One hundred two patients submitted to intensive chemotherapy were included in a randomized study with cross over comparing for the second course two anti-emetics: tetracosactide (D1: 3 mg, D2 and D3: 2 mg/d) and methylprednisolone (D1: 240 mg, D2 and D3: 160 mg/d). Most patients presented with malignant lymphoma. All patients experienced nausea and emesis during first course of chemotherapy. Results were similar in both groups, respectively for tetracosactide and methylprednisolone: no nausea 37 versus 40%, less than 3 emesis 69% versus 73%. Secondary effects were observed in 5 and 8% of cases. Tetracosactide with a schedule of 7 mg for 3 days gives the same results than methylprednisolone 560 mg for 3 days in chemotherapy induced nausea and emesis prevention.

Adolescent↗
PubMed1988

Treatment of acute myeloid leukemia in elderly patients. A retrospective study.

In an attempt to rationalize the use of therapy in acute myeloblastic leukemia (AML) in elderly patients, 69 cases of primary AML in patients older than 60 years of age were reviewed retrospectively. Therapy was empirical and 12 patients received supportive care (SC) only, 35 received aggressive chemotherapy (AC), and 22 received low-dose cytosine arabinoside (LD-araC). Patients receiving SC only often had a poor Karnofski index and their median survival was 17 days. Aggressive chemotherapy yielded complete remissions (CR) in 48% of the patients, whereas 23% of the patients had resistant disease (RD) and 29% had other failures (OF). Low-dose araC, which was administered to patients significantly older than those receiving AC, yielded 23% CR, 68% RD, and 9% OF, with important hematologic toxicity in most patients. Median survival was 211 days in patients receiving AC and 235 days in patients treated with LD-araC. Survival beyond 2 years from diagnosis was noted in the AC group only. A low Karnofski index was the strongest factor in poor prognosis, while age was not a prognostic factor. The initial characteristics of the patients did not allow us to define groups of patients who should be treated by either AC or LD-araC. We concluded that the decision to treat patients actively should rely more on the patient's general condition and socio-economical criteria than on age.

Aged↗
PubMed1988

Hypereosinophilic syndrome with multiple organ dysfunction treated by allogeneic bone marrow transplantation.

A 26-year-old man with hypereosinophilic syndrome who had initial neurologic, cardiac, and pulmonary dysfunction, high eosinophil count, thrombocytopenia, and bone marrow fibrosis had only a transient response to conventional treatment with corticosteroids and hydroxyurea. He therefore received human lymphocyte antigen-identical allogeneic bone marrow transplantation (BMT) after conditioning with cytoxan and fractionated total body irradiation. Hematologic recovery was prompt, with normalization of blood counts and bone marrow. The patient died less than 3 months after transplantation from diffuse cytomegalovirus infection. Potential interest of BMT in patients with resistant hypereosinophilic syndrome and features of poor prognosis is discussed.

Adult↗
PubMed1988

Expression of immunological markers on leukemic cells before and after cryopreservation and thawing.

We have studied the effects of cryopreservation on the viability and on the expression of surface antigens of acute leukemia cells. Marrow samples were obtained at initial diagnosis from 89 patients with acute myeloid leukemia (AML), acute undifferentiated leukemia (AUL), and acute lymphoid leukemia (ALL). In AML, the mean viability was greater than 90% in the types M1, M4, and M5 of the French-American-British classification, 79% in M2, and 3% in M3 types. The viability was 74% in AUL. In ALL, the viability was 95% for pre-B leukemias, but only 2% in T-cell leukemias. The expression of myeloid antigens was studied before and after freezing and thawing using three monoclonal antibodies (NHL30.5, against poorly differentiated granulocytic leukemias, VIMC6 against differentiated granulocytic leukemias and granulocytes; and UCHM1 or CRIS-6, against monocytic leukemias and monocytes). The percentage of cells stained by NHL30.5 and UCHM1 or CRIS-6 was very similar before and after cryopreservation. For VIMC6, the mean staining after cryopreservation was 60% of the initial one. In pre-B ALL, the stainings by anti common ALL antigen before and after cryopreservation were also very similar. We conclude that leukemic cryopreserved cells are suitable for immunologic studies. The recovery is, however, very low in promyelocytic AML and T-cell ALL.

Acute Disease↗
PubMed1988

Expression of CD 19 antigen on acute monoblastic leukemia cells at diagnosis and after TPA-induced differentiation.

We have previously shown that CD 19, a B-lymphoid differentiation antigen, is expressed on acute myeloid leukemia cells. In this study, the expression of CD 19 and CD 14 (a monocytic antigen) was investigated in 18 cases of acute monoblastic leukemia. The staining by anti-CD 19 antibody (SB4) ranged between 26 and 81% of the cells, and was significantly correlated with the staining by anti-CD 14. Double stainings confirmed that the antigens were expressed on the same cells. After a 48-hr culture in the presence of TPA, most cells became adherent and lost CD 19 antigen, whereas CD 14 was still expressed with only minimal changes. It is concluded that CD 19 antigen is expressed on more immature stages of monoblastic leukemias. The hypothesis that CD 19 could be an early monocytic differentiation antigen is discussed.

Antigens, CD19↗
PubMed1988

Evaluation of a Candida antigen detection test (Cand-Tec) in the diagnosis of deep candidiasis in neutropenic patients.

The diagnostic efficiency of a serum Candida antigen detection test Cand-Tec test) was prospectively investigated in 104 leukemic patients treated by intensive chemotherapy or allogeneic bone marrow transplantation. Candida antigen titers were determined on admission and then weekly as long as patients remained neutropenic. Nine patients had a proven disseminated yeast infection (diagnosed only at autopsy in five cases). The highest Candida antigen titers were 1:2 in two patients and 1:4 or more in seven patients (sensitivity: 76% for this last titer). This highest titer was observed 12 days before to 3 days after the diagnosis. Seven out of the 97 patients without proven deep candidiasis had a maximum titer of 1:4 (specificity: 93%). The positive predictive value was 50% for a titer of 1:4 and 24% for a titer of 1:2, whereas the negative predictive value was 100% for a titer of 1:4 and 97% for a titer of 1:2. Patients with elevated titers were mostly treated by chemotherapy, were older and had a worse prognosis than those with negative titers, although the duration of neutropenia was similar. It is concluded that Candida antigen detection is a reliable method of diagnosis of deep candidiasis in neutropenic patients. The clinical interest in this test, with special regard to empiric antifungal therapy, is discussed.

Agranulocytosis↗
PubMed1988

Acute leukaemia with t(4;11) in patients previously exposed to carcinogens.

We report three cases of acute leukaemia with t(4;11) (q21;q23), one of them of undifferentiated and the other two of lymphoid phenotype, occurring after adjuvant radiochemotherapy for breast cancer (two cases) or occupational exposure to radiation (one case). Although the myeloid phenotype and characteristic chromosomal anomalies usually observed in secondary leukaemia were lacking, our observations raise the possibility of causal relationship between exposure to carcinogens and the occurrence of a leukaemia with t(4;11).

Acute Disease↗
PubMed1988

Acute leukaemia following high-dose chemoradiotherapy with bone marrow rescue for ovarian teratoma.

A case of acute leukaemia following intensive chemo- and radiotherapy for solid tumour is reported. A 15-year-old girl received four courses of chemotherapy with adriamycin, cyclophosphamide and cisplatinum after the surgical diagnosis of ovarian immature teratoma. An intensification treatment was performed with cyclophosphamide and total body irradiation, followed by marrow rescue. The diagnosis of myelomonocytic acute leukaemia was performed 8 months later. The patient died after a transient improvement following a treatment by hydroxyurea. The roles of the primary tumour, of the chemotherapy and of the marrow transplantation in the occurrence of leukaemia are discussed.

Acute Disease↗
PubMed1988

Initial clonal acute lymphoblastic transformation of chronic lymphocytic leukemia with (11;14) and (8;12) chromosome translocations and acquired homozygosity.

A 69-year-old woman presented with chronic lymphocytic leukemia (CLL) diagnosed after bone marrow recovery following intensive chemotherapy for acute lymphoblastic leukemia. The retrospective diagnosis of initial blastic transformation of CLL was made. The patient eventually died, 5 months after initial blastic phase, from a blastic relapse of her CLL. Immunologic and karyotypic studies of the lymphoid cells at different times during the evolution of the disease provided evidence that both the small lymphocytes and the large blastic cells originated from the same clone since they carried the same surface markers and the same (11;14) (q13;q32) translocation. A subpopulation of cells carried in addition a t(8;12) (q24;q22) together with the loss of the normal chromosome 8 and homozygosity for the abnormal der(8). The possibility that this second population might correspond to the blast cells and that the occurrence of the t(8;12) with homozygosity might be linked to blastic transformation of the CLL is discussed.

Aged↗
PubMed1988

[Early bacterial infections after allogenic bone marrow grafts].

The bacterial infections occurring during the period of neutropenia have been reviewed in a series of 100 allogeneic bone marrow transplant patients. Forty episodes of septicaemia were observed, in 37 patients, with a large majority of Gram positive organisms (thirty cases). Only one case of major local infection occurred (Gram negative meningitis). A non-bacterial infection was seen in 10 patients, and 36 patients presented with fever of unknown origin. Three patients who failed to engraft died of bacterial infection. Surveillance cultures showed that upper respiratory tract was a frequent site of invasion, not only for Gram positive, but also for Gram negative organisms (Pseudomonas aeruginosa).

Adolescent↗
PubMed1987

Incidence and prognosis of cytomegalovirus infections following allogenic bone marrow transplantation.

The incidence and the outcome of cytomegalovirus (CMV) infections were evaluated in 83 adult recipients of allogenic bone marrow transplantation. Virological and serological surveillance was performed weekly for 3 months posttransplant, and then every other week or every month until 1 year. CMV infection occurred in 45 patients, with a cumulative risk of 62% at 1 year and 66% at 2 years. In multivariate analysis, two factors significantly influenced the incidence of CMV infection: patients with pretransplant positive anti-CMV titres had a risk of infection of 72% at 1 year versus 33% for patients with negative titres. Patients with acute myeloid leukemia were also infected more frequently (85% at 1 year) than patients with acute lymphoblastic leukemia (56%), chronic granulocytic leukemia (45%), or aplastic anemia (47%). In both univariate and multivariate analysis, CMV infection was not associated with a worse prognosis. However, 5 (out of 10) cases of lethal interstitial pneumonitis were associated with CMV, and two patients died of possible CMV encephalitis. All these patients had been suffering from severe acute or chronic graft versus host disease.

Adult↗