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Biomedical subjects

E Elonen

Publications and source records attributed to E Elonen.

At least 55 records · Page 3Linked to original sources

Impact of leucocyte-depleted blood components on the haematological recovery and prognosis of patients with acute myeloid leukaemia. Finnish Leukemia Group.

Use of leucocyte-depleted blood components reduces refractoriness to platelet transfusions, but the cost-effectiveness of this policy has been in doubt. We retrospectively analysed data of 115 patients with acute myeloid leukaemia (AML), treated according to a standardized cytostatic protocol. Fifty patients had received standard (STD) platelet concentrates (PCs) and red blood cell concentrates (RBCs). Sixty-five patients had received leucocyte-depleted (L-D) components, with fewer than one million leucocytes per unit. Refractory patients (22% of the STD group and 3% of the L-D group) were excluded from further observations. There were no differences between the groups during the first cytostatic treatment period. Thereafter, significantly fewer PCs and RBCs were transfused to the L-D group. In the L-D group, granulocytopenia (< 0.5 x 10(9)/l) and thrombocytopenia (< 50 x 10(9)/l) were shorter, the lowest leucocyte counts were higher, serious infections were less common (44% v 59%), and the patients spent fewer days in hospital. The median relapse-free survival (RFS) was longer in the L-D group than in the STD group. We conclude that leucocyte depletion of blood components has favourable effects on the recovery of haematopoiesis, consumption of blood components, occurrence of serious infections, and relapse-free survival in AML.

Acute Disease↗

Clinical significance of P-glycoprotein expression in acute leukaemia as analysed by immunocytochemistry.

Multidrug resistance, mediated by the overexpression of an energy-dependent transport protein, P-glycoprotein, has been one of the major targets of interest in solving the mechanisms of clinical drug resistance of malignant cells. To evaluate the correlation between P-glycoprotein overexpression and the response to chemotherapy, we analysed cytospin preparations of gradient-separated blood or bone marrow mononuclear cells from 79 patients with acute leukaemia by means of the P-glycoprotein-directed monoclonal antibody JSB-1 and immunocytochemistry using the alkaline phosphatase-antialkaline phosphatase technique. P-glycoprotein expression was detected in all disease phases of acute leukaemia. Thirteen out of 51 patients at diagnosis, 10/29 patients in relapse or during residual disease and 8/27 patients in remission overexpressed P-glycoprotein. Seven out of the 8 positive remission samples were collected between the cycles of consolidation treatment. Our results suggest that increased P-glycoprotein expression in samples collected between the cycles of consolidation treatment during remission may be induced in normal leukocytes by cytotoxic drug treatment, infections, or by some physiological mechanisms related to the disease. Patients older than 45 years of age were significantly more often P-glycoprotein-positive (11/25) at diagnosis than younger patients (2/26). P-glycoprotein expression at diagnosis was significantly correlated with a low remission rate after the first cycle of induction therapy. Of 34 P-glycoprotein-negative patients, 25 achieved remission after the first cycle as compared to 4/12 of the P-glycoprotein-positive patients. Our results indicate that the method used is specific and sensitive enough for the analysis of P-glycoprotein expression and that the expression at initial presentation is inversely correlated with the outcome of induction therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Corticosteroid is not beneficial in multiple-drug combination chemotherapy for multiple myeloma. Finnish Leukaemia Group.

In a randomised multicentre trial a combination of methylprednisolone, vincristine, lomustine, cyclophosphamide and melphalan (MOCCA) was compared with the same regimen omitting methylprednisolone after the first course (COLA) in previously untreated patients with multiple myeloma. The MOCCA arm showed a response rate of 72% among 79 patients and the COLA arm a response rate of 60% among 59 patients. This difference was not statistically significant. The median survival time was 56 months in the MOCCA arm and 61 months in the COLA arm. There was a slight increase of early deaths (within the first 6 months) in the MOCCA arm as compared with the COLA arm. We conclude that, in multidrug therapies, the continuation of corticosteroid at conventional dosage beyond the first course does not improve response rate or survival time in multiple myeloma.

Adult↗

Value of maintenance therapy with chemotherapy or interferon during remission of acute myeloid leukaemia.

108 consecutive patients with de novo acute myeloid leukaemia at ages 15 to 59 years were treated in a prospective controlled multicentre trial. Induction with combination TAD resulted in a complete remission in 85 cases (79%). After a cyclic consolidation programme for 6 months, 73% of the remissions continued. The maintenance therapy was at random either nothing, or alpha interferon, or monthly 5 day courses with thioguanine and cytarabine. The median duration of all remissions was 13 months; that of those in the control and interferon arms 15 months each, and in the chemotherapy arm 18 months. The median survival of all the 108 patients was 16 months; that of those in the control arm 20 months, in the interferon arm 33 months and in the chemotherapy arm 26 months. At 5 yr, 31%, 22% and 31%, respectively, were alive. The survival curves did not differ from each other significantly. Maintenance treatment after an intensive induction and a moderately intensive consolidation was of no benefit in this study. Interferon did not improve the prognosis.

Acute Disease↗

Prognostic subgroups in B-cell chronic lymphocytic leukemia defined by specific chromosomal abnormalities.

BACKGROUND AND METHODS: Specific chromosomal abnormalities have been shown to affect the overall survival of patients with acute leukemia, but the possibility that specific chromosomal defects may influence the course of B-cell chronic lymphocytic leukemia (CLL) is controversial. We assessed this possibility as follows: blood mononuclear cells from 433 patients with B-cell CLL in five European centers were cultured with B-cell mitogens, and banded metaphases were studied. RESULTS: Three hundred ninety-one patients could be evaluated cytogenetically, and 218 had clonal chromosomal changes. The most common abnormalities were trisomy 12 (n = 67) and structural abnormalities of chromosome 13 (n = 51; most involving the site of the retinoblastoma gene) and of chromosome 14 (n = 41). Patients with a normal karyotype had a median overall survival of more than 15 years, in contrast to 7.7 years for patients with clonal changes. Patients with single abnormalities (n = 113) did better than those with complex karyotypes (P less than 0.001). Patients with abnormalities involving chromosome 14q had poorer survival than those with aberrations of chromosome 13q (P less than 0.05). Among patients with single abnormalities, those with trisomy 12 alone had poorer survival than patients with single aberrations of chromosome 13q (P = 0.01); the latter had the same survival as those with a normal karyotype. A high percentage of cells in metaphase with chromosomal abnormalities, indicating highly proliferative leukemic cells, was associated with poor survival (P less than 0.001). Cox proportional-hazards analysis identified age, sex, the percentage of cells in metaphase with chromosomal abnormalities, and the clinical stage of the disease (Binet classification system) as independent prognostic variables. CONCLUSIONS: Chromosomal analysis provides prognostic information about overall survival in addition to that supplied by clinical data in patients with B-cell CLL.

Adult↗

Development of acute myelocytic leukemia in patients with Crohn's disease.

In our hospital within one year two patients with Crohn's disease were seen who developed an acute myelocytic leukemia. A review of the literature reveals eight previously reported patients with both Crohn's disease and leukemia. Six of the reported 10 patients have had acute myelocytic leukemia and, interestingly, three of them, including our two patients, have shown monocytic differentiation (FAB type M4). It has been suggested that the relative risk of leukemia, especially acute myelocytic leukemia, is increased in patients suffering from ulcerative colitis. More data of patients with Crohn's disease and acute leukemia are needed to evaluate the possible association between these diseases.

Crohn Disease↗

A cluster of seven cases of Clostridium tertium septicemia in neutropenic patients.

A cluster of seven febrile and severely neutropenic patients who developed Clostridium tertium septicemia during a 13-month period is described. The patients had received third generation cephalosporins for 7 to 13 days (mean 9 days) at the time Clostridium tertium was isolated from blood cultures. Two patients had perirectal and one patient pericaecal cellulitis. The organism was also isolated from bronchial secretions in one patient. No patient had diarrhea. Five of six strains tested were resistant to clindamycin (MIC 2-8 micrograms/ml), and six of seven strains moderately resistant to penicillin (MIC 1-4 micrograms/ml). In one patient Clostridium tertium grew from blood cultures although metronidazole had been administered for two days. Six patients recovered on antibiotic therapy. In view of the unusual susceptibility pattern of Clostridium tertium, an accurate diagnosis of infection with this organism is important for the choice of an appropriate antimicrobial treatment.

Adult↗

Intensive chemotherapy with combinations containing anthracyclines for refractory and relapsing multiple myeloma. Finnish Leukaemia Group.

94 patients with refractory multiple myeloma were treated in a multicentre trial with combinations of cytotoxic drugs including anthracyclines. All were refractory to a 5-drug combination containing 3 alkylating agents, vincristine and methylprednisolone (MOCCA). With a combination of epirubicin and iphosphamide a 50% response was achieved in 9% of 22 patients. The response rate after schedule VAP (vincristine, doxorubicin and prednisolone) was 8% of 13 patients and that after schedule VAD (vincristine, doxorubicin and dexamethasone) 20% of 59 patients. The previous chemotherapy had lasted for less than 12 months in 13 cases from among all these patients, and 5 of these (38%) responded. In contrast, there were only 10 responders (12%) among the 81 patients with longer previous chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Erythromycin ethylsuccinate, base and acistrate in the treatment of upper respiratory tract infection: two comparative studies of tolerability.

The efficacy and tolerability of erythromycin ethylsuccinate, erythromycin base and erythromycin acistrate were studied in two separate randomized studies in 80 and 82 primary health care patients with upper respiratory tract infections. In Study I, the patients were given either ethylsuccinate 666 mg tid or base 500 mg qid for ten days. Possible side-effects, abdominal pain, nausea, diarrhoea and vomiting, were recorded daily by the patient. Study II followed the same design as Study I with the exception of the side-effect evaluation method. Patients were given in a randomized fashion ethylsuccinate 666 mg tid, or acistrate 400 mg qid. Side-effect evaluation was based on a 10-cm analogue visual scale to record abdominal pain, while nausea, vomiting and diarrhoea were recorded as daily frequencies. These studies indicated that erythromycin ethylsuccinate caused significantly less abdominal pain than the base form (chi 2-test), but there were no significant differences in tolerance between the ethylsuccinate and acistrate forms. Other tolerance parameters revealed no real differences. The clinical response was good with all erythromycin preparations at the doses used in this study.

Adolescent↗

Characterization of neoplastic and reactive cells in T-cell lymphomas with cytogenetic, surface marker, and DNA methods.

Three patients with T-cell lymphoma were studied with a combined cytogenetic-immunological analysis (MAC) as well as by Southern blotting analysis. The MAC method, which allows simultaneous study of both chromosomes and immunophenotype of a mitotic cell, revealed that in each case the karyotypically abnormal and, therefore, neoplastic cells originated from different stages of T-cell maturation. In one case the abnormality was seen in cells expressing CD3 and CD10, in the second in cells expressing CD3 and CD8, and in the third case in cells expressing CD4 but not CD3. Mitoses were frequent also in non-neoplastic cells, but these mitoses were normal. Southern blotting analysis revealed TCR beta rearrangements in all patients. In addition, one patient displayed TCR gamma rearrangement, and one patient a rearrangement in the IgH joining region.

Aged↗

Immunoglobulin kappa and lambda light chain dual genotype rearrangement in a patient with kappa-secreting B-CLL.

The cytogenetics, immunophenotype and immunoglobulin gene rearrangements were analysed in a consecutive series of 56 patients with lymphoma or lymphatic leukaemia. One patient with B-CLL showed monoclonal rearrangements of the constant mu, kappa and lambda genes. The immunophenotype was kappa-secreting indicating expression of one immunoglobulin light kappa allele. Clones of kappa producing B-cells usually show germline lambda genes. The present case may thus be interpreted as a failure of the mechanisms controlling isotypic exclusion at the gene level. Further studies are needed to determine the frequency of such events and whether the patients show distinct clinical or other features.

B-Lymphocytes↗

Cytogenetic and immunologic characterization of mitotic cells in chronic lymphocytic leukaemia.

Lymphocytes from 14 patients with chronic B-cell leukaemia (B-CLL) and one with chronic T-cell leukaemia (T-CLL) were studied by the MAC (Morphology, Antibodies, Chromosomes) method, which allows simultaneous analysis of the morphology, immunologic phenotype and karyotype of the same mitotic cell. Use of the MAC-method in present studies has yielded new information about the cytogenetics of CLL. Although most of the interphase cells from patients with B-CLL were positive for B-cell markers, many of the mitotic cells turned out to be T cells, supporting the notion that the cells studied by conventional chromosome analysis are often non-neoplastic T cells. In some B-CLL cases with normal karyotype in the conventional chromosome study, however, most of the mitotic cells were B cells, indicating that neoplastic B cells may also have a normal karyotype. The patient with T-CLL had normal karyotype even though most of the mitoses were T cells. The chromosome abnormalities found were restricted to cells with light chain clonality. Our results show that clonal chromosome abnormalities do occur in neoplastic B cells of patients with B-CLL.

Aged↗

An outbreak of invasive aspergillosis in a haematologic unit.

Within a period of 15 months 8 cases of invasive pulmonary aspergillosis were seen in a haematologic unit; 7 of them between January and October 1984. No previous cases of invasive aspergillosis had been encountered during the existence of the unit since 1979. Environmental studies did not prove a single likely source for the fungal spores. Previous window renovation with concomitant fiber deposits on ventilation grids, poor sealing of air filter fittings in patient rooms, occasional ventilation through windows in the ward, and low speed of booster fans in the ventilation system may have created a condition favourable for the entry of Aspergillus fumigatus spores into the patient rooms. Environmental sanitation including cleaning of the ventilation ducts and change of filters in the ventilation system stopped the outbreak. Two sporadic cases have appeared during a follow-up period of 26 months.

Acute Disease↗