Interleukin 4 responses in acute leukaemia patients with severe chemotherapy-induced leucopenia

T lymphocyte functions in acute leukaemia patients with severe chemotherapy-induced leucopenia were investigated using 3 different approaches: (i) analysis of serum concentrations of the T cell cytokine interleukin 4 (IL4) demonstrated that serum IL4 levels increased during complicating bacterial infections. However, this response was modulated by a concomitant increase in serum levels of the potential IL4 antagonist soluble IL4 receptor alpha chain (sIL4R alpha). (ii) Even during leucopenia a subset of T lymphocytes derived from leucopenic patients expressed the activation markers CD25 (IL2 receptor), CD71 (transferrin receptor) and HLA-DR. (iii) Subsets of circulating CD4+ and CD8+ T lymphocytes could undergo clonogenic proliferation in vitro, and a majority of these clones secreted IL4. CD4+ clones showed higher IL4 levels than CD8+ clones. Our results indicate that T lymphocytes can be activated and contribute to cytokine responses in acute leukaemia patients with severe chemotherapy-induced cytopenia.     

Pulmonary infiltrates in neutropenic patients with acute leukemia during chemotherapy: outcome and prognostic factors

STUDY OBJECTIVE: To determine predictors of mortality from pulmonary infiltrates in neutropenic patients with acute leukemia during chemotherapy, and the significance of those factors related to the underlying malignancy and its therapy as well as of those related to the severity of the illness associated with pulmonary infiltrates. DESIGN: A historical cohort study. SETTING: A university teaching hospital and tertiary referral center. PATIENTS AND METHODS: Overall, 53 patients with neutropenia during chemotherapy and with first episodes of pulmonary infiltrates during a 4-year period were studied. Prognostic analysis included 38 variables. Multivariate analyses were performed by logistic regression. RESULTS: The survival rate from pneumonia was 57% (30/53). The following eight parameters were significantly associated with death in univariate analysis: comorbidity present; development of "late" pulmonary infiltrates (> or = 14 days after hospital admission); heart rate > or = 100 beats/min; a ratio heart rate/systolic blood pressure (HR/SBP) > or = 1.2; urea nitrogen > 7 mmol/L; radiographic score > or = 3; neutropenia < 1.0x10(9)/L at the treatment end point; and failed complete remission. In a multivariate model including only parameters available at diagnosis of pulmonary infiltrates, the presence of a ratio HR/SBP > or = 1.2 and of a radiographic score > or = 3 remained independently associated with death. In a second model also including the evolutionary parameter neutropenia < or = 1.0x10(9)/L at the treatment end point, both parameters remained significant together with neutropenia <1.0x 10(9)/L at the treatment end point. The presence of a ratio HR/SBP > or = 1.2 was a strong marker of early death. CONCLUSION: Both therapy- and malignancy-associated neutropenia as well as the severity of illness associated with pulmonary infiltrates are independent prognostic factors. Patients with a ratio HR/SBP > or = 1.2 at diagnosis of pulmonary infiltrates suffer from potentially reversible acute illness, are at risk for early death and, therefore, may be appropriate candidates for treatment in an ICU.     

Haematopoietic response and bcl-2 expression in patients with acute myeloid leukaemia

In the Bethesda System for reporting cervicovaginal cytology results, 1 criterion for smear adequacy is an adequate squamous component. The accuracy of a cytologist's estimate that 10% of the slide is covered by squamous cells, the adequacy threshold, has not been determined. The percentage of the surface of a glass slide covered by squamous cells was independently estimated by 4 cytologists on 2 occasions by microscopic examination of 83 buccal smears prepared to display estimated coverage of 1% to 20% of the slide surface. The accuracy of visual estimates was compared with measurements by the TracCell System. Each observer made a third set of estimates after receiving 5 slides with known coverage. Median coverage by visual estimation ranged from 4% to 25%, but as measured by the TracCell system was 2%. Median estimated coverage was significantly different for 2 of 4 observers between first and second viewings and between all but 1 pair of observers. For all observers, it was significantly higher than the true coverage. A visual estimate of 10% coverage corresponded to a true median coverage of 3%. When provided with a physical standard, the median estimated coverage by 3 of 4 observers was not statistically different from the true coverage, and interobserver kappa values improved. Unaided visual estimation of the adequacy of squamous cell coverage is neither reproducible nor accurate. What most cytologists consider "adequate" coverage represents only 3% coverage. The availability of a physical standard dramatically increases reproducibility and accuracy.     

Cytochemical demonstration of 5-formyl-tetrahydrofolate cyclodehydrase activity in leucocytes of patients with acute leukaemia

The activity of 5-formyl-tetrahydrofolate cyclodehydrase has been studied cytochemically in leucocytes of children with acute leukaemia. Comparison of enzymatic activity in the same types of cells showed no significant variation between normal controls and the patients with acute leukaemia. The blast cells were weakly positive or negative. This finding is of very interest as the blast cells are capable of division. Probably the enzyme appears in the blast cells at some stage of the cell cycle. 2 populations of lymphocytes were observed, 1 positive with a few granules and 1 negative. A reduction of enzyme activity was observed after prophylactic cranial irradiation and methotrexate decreased enzyme activity in some patients.     

The causes and prophylaxis of postoperative gastrointestinal hemorrhage in patients with acute gastroduodenal bleeding

The work discusses the neurochemical correlates of rat brain dopamin-synaptic activity after injection of 0.5 mg/kg rudotel (medazepam) as compared with intact animals. The parameters of functioning of D2-receptors in [3H]-dopamine binding, the content of catecholamines and their metabolites (high-performance liquid chromatography with electrochemical detection) were studied in the dopaminergic system in different brain areas (the striatum, frontal cortex, amygdala, hippocampus, hypothalamus, and accumbence).     

Fusarium fungaemia in severely neutropenic patients

We report two cases of Fusarium infection with evidence of fungaemia in severely neutropenic patients with leukaemia. One patient was a 65-year-old woman with chronic lymphocytic leukaemia infected by Fusarium verticillioides. The other patient was a 45-year-old woman with acute myeloblastic leukaemia infected by Fusarium spp. Fungaemia was the only evident manifestation of these fungal infections.     

Efficacy of itraconazole in the prevention of fungal infections among neutropenic patients with hematologic malignancies and intensive chemotherapy. A double blind, placebo controlled study

We studied the efficacy and safety of itraconazole for the prevention of fungal infection in neutropenic patients given cytotoxic chemotherapy for hematologic malignancies. Patients were randomly allocated to receive either itraconazole (200 mg bd) or placebo in addition to oral amphotericin B until the patient either developed fungal infection or had completed antileukemic treatment. Forty six patients (83 neutropenic episodes) treated with itraconazole and 46 placebo treated patients (84 neutropenic episodes) were evaluable. No specific toxicity was noted. Nine fungal infections developed in the itraconazole group, of which four were histologically or microbiologically proven and 15 in the patients given placebo (eight proven) (p < 0.12). All these patients received IV amphotericin B. The incidence of Candida albicans infections tended to be lower in the itraconazole group, but overall, there was no measurable improvement in the prevention of fungal infections and mortality by itraconazole.     

Structural and functional analysis of the cytidine deaminase gene in patients with acute myeloid leukaemia

Gene transfer of the cytidine deaminase (CDD) cDNA has recently been shown to induce cellular resistance to cytarabine (AraC) in vitro. To investigate the role for CDD in acute myeloid leukaemia (AML) we analysed the CDD activity and CDD gene structure in blast material from well-defined patients with untreated and AraC refractory (RF) AML. Median CDD activity in previously untreated AML was significantly lower than in RF-AML blasts (P=0.015) and was significantly lower in patients with complete remission than with blast persistence following induction chemotherapy (P=0.043). Structural investigation of the CDD gene by Southern analyses and RT-PCR showed no detectable aberrations. Sequence analysis of the CDD cDNA from nine RF-AML patients showed inconsistent aberrations in three patients. Semiquantitative assessment of CDD mRNA expression revealed a significant correlation with CDD activity. In conclusion, concordant with another recent study our data suggest a correlation of pretherapeutic CDD activity with induction treatment response. Besides the previously described prognostic impact of mdrl expression, this result could be useful for the development of risk-adapted AML treatment strategies and warrants further studies of CDD activity in well-defined cohorts of AML patients and of the mechanisms involved in the regulation of CDD activity.     

Piperacillin-tazobactam as empiric monotherapy in febrile neutropenic patients with haematological malignancies

To examine the relationship between apolipoprotein E (apoE) phenotype and life span, we measured the frequently of the apoE phenotype and allele in 54 Japanese centenarians who lived in the Tokyo metropolitan area in 1994, 1995, and 1996. The control group consisted of 973 subjects, 883 healthy volunteers who were described previously and 90 healthy people who came to the Keio health consulting center. The apoE phenotypes in the centenarians was 2 E2/E2 (3.7%), 5 E2/E3 (9.3%), 38 E3/E3 (70.4%), and 9 3E/E4 (16.7%). No other phenotype was observed. In the control group, the phenotypes were 2 E2/E2 (0.2%), 57 E2/E3 (5.9%) 712 E3/E3 (73.2%), and 179 E3/E4 (18.4%). The frequency of E2 was higher in the centenarians. The frequencies of the apoE allele in the centenarians and the control subjects were epsilon 2 8.3% vs. 3.5%, epsilon 3 83.3% vs. 85.4%, and epsilon 4 8.3% vs. 10.9%. The frequency of the apoE allele differed significantly between centenarians and control subjects (chi 2 = 6.84, p = 0.033). Levels of serum cholesterol and apolipoprotein B were significantly lower in the E2/E2 + E2/E3 centenarians. Studies of the frequency of the apoE allele in Japanese, French, and Finnish subjects showed that epsilon 2 is more frequent and epsilon 4 is less frequent in centenarians. These data show the apoE phenotype may affect life span: epsilon 2 is positively and epsilon 4 is negatively associated with longevity.     

Detection of clonal immunoglobulin gene rearrangements in the PBPC harvests of patients with acute lymphoblastic leukaemia

We have used a fluorescently based PCR technique to detect rearrangements in the immunoglobulin heavy chain (IgH) gene in the presentation BM of five patients with adult ALL and have looked for similar rearrangements in their PBPC. Using this approach we have been able to demonstrate clonal rearrangements in the PBPC of two of five patients. Remission BM samples taken 6-12 weeks prior to leucapheresis failed to show a clonal rearrangement in either patient. The significance of these results is discussed.     

Biology of acute leukaemia

The leukaemias vary in their response to therapy. In acute myeloid leukaemia, for instance, response to therapy is poorer in older than in younger patients. One explanation for this is that in older patients the acute myeloid leukaemia is more likely to have arisen from a pluripotent stem cell than from a lineage-restricted progenitor cell; the former has a high self-renewal capacity, an active drug-efflux pump, and high content of anti-apoptotic proteins, all of which contribute to chemoresistance. Unravelling the biology of the leukaemias should help in the development of novel therapies.     

Chemotherapy of acute myeloblastic leukaemia with DAM regimen

32 patients of denovo-ANLL were treated with Doxorubicin, Ara-C and 6-Mercaptopurine (DAM) regimen. Remission induction was instituted with 1-3 cycles of DAM regimen and maintenance was given by 6-MP continuously with intermittent DA (1,5) regimen. In the remission induction, Doxorubicin 30 mg/m2 for 3 days, Ara-C 150 mg/m2 for 5 days and 6-Mp 100 mg/m2 daily was given. Complete remission (CR) was observed in 60% cases. The probability of 2 years disease-free survival of patients with complete remission is 56.73%.     

Treatment and prophylaxis of acute disorders of the cerebral blood circulation in patients with diabetes mellitus

Experiments were conducted on young female rats with the aid of morphological, morphometric and histochemical methods; a study was made of the adrenal glands, mammary and the thyroid glands under conditions of castration and administration of synestrol, progesterone, both sex hormones, hydrocortisone. Sex hormones proved to produce a fulminant growth of the glandular tree against the background of reduction of the functional activity of the thyroid gland and relatively high indices of the hormonal activity of the fasciculo-reticular zone of the adrenal glands. A harmonious development of the glandular tree of the mammary glands was noted only under the effect of a simultaneous administration of synesterol and progesteron. A shift in the hormonal balance in the direction of synestrol caused the appearance of pathological deviations in the mammary glands by the type of cystic mastopathy. Under conditions of castration hydrocortisone produced a moderate stimulating influence on the mammary glands only in case of a prolonged action.