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PubMed2001

Infectious complications in children with acute lymphoblastic leukemia and T-cell lymphoma--a rationale for tailored supportive care.

Infections still remain a major cause of therapy-associated morbidity and death in patients with malignant diseases. To further lower the risk of serious and long-lasting infections by additional supportive measures, detailed information on the frequency and characteristic features of infections is needed. Therefore, patient data from 112 children with acute lymphoblastic leukemia and T-cell lymphoma who were treated according to the COALL-05-92 protocol in our department were analyzed for differences in the frequency and origin of febrile episodes in relation to age, immunological type of leukemia, treatment in group assessed as being at high or low risk of relapse, actual occurrence of relapse, and course of chemotherapy. At the time of diagnosis, low-risk patients more commonly presented with febrile episodes than high-risk patients. In total, patients developed a fever in 313 (24%) of 1,307 evaluated chemotherapy cycles. Febrile episodes were associated with microbiologically or clinically documented infections in 60% of all cases, while in 40% the fever was of unknown origin. Gram-positive pathogens had a markedly higher incidence than gram-negative or fungal ones. The incidence of febrile episodes during therapy appeared to be correlated with certain chemotherapeutic drug combinations. The highest rate was found after high-dose cytarabine and asparaginase causing a long period of leukopenia. However, after other chemotherapy courses with a similar duration of leukopenia the incidence of febrile episodes was significantly lower, suggesting that specific interactions of different chemotherapeutic agents with the immune response might be an important factor in development of infections. Individual factors might also account for an increased incidence of infections, since the number of high-risk patients with recurrent infections was significantly higher than expected on the basis of statistical evaluation. In conclusion, our findings suggest that the risk of infections during chemotherapy may not only be influenced by leukopenia, but that drug-specific effects of the various chemotherapeutic agents and individual factors may also be important contributory factors. These observations must be further expanded in prospective studies so that new tailored supportive care protocols can be elaborated.

Adolescent↗
PubMed1999

Interleukin-2-activated autologous bone marrow and peripheral blood stem cells in the treatment of acute leukemia and lymphoma.

In this pilot trial of interleukin (IL)-2-treated autologous bone marrow (BM) and peripheral stem cell (PSC)-supported high-dose chemoradiotherapy, we report 36 patients with poor-prognosis leukemia and lymphoma who received BM and/or granulocyte colony-stimulating factor (G-CSF)-mobilized autologous PSCs that had been exposed to IL-2 for 24 hours ex vivo. Patients then received IL-2 by low-dose continuous intravenous (i.v.) infusion until hematologic reconstitution and then by intermediate-dose continuous i.v. infusion for six 2-week maintenance cycles given at 1-month intervals. The median Day to neutrophils over 500/microL was 22 with BM and 10 with PSCs (p = 0.01). The median Day to platelets >20,000/microL was 50 for BM and 25 for PSCs, and to platelets >50,000/microL was 138 for BM and 34 for PSCs (p not significant). After the first three patients received IL-2 at 2 mIU x m(-2) x day(-1) and had slow reconstitution, four patients were treated without IL-2 until the maintenance phase following reconstitution. The remaining 29 patients received the initial "post-infusion" IL-2 at 1 mIU x m(-2) x day(-1). Toxicities associated with the infusion of IL-2-activated cells consisted of chills and fever in about one-half of the patients and transient hypotension in 12%. Low-dose IL-2 by continuous i.v. infusion in the early posttransplant period was associated with exacerbation of fever, diarrhea, and altered mental status in a minority of patients. The major dose-limiting toxicities of maintenance IL-2 were fever, fatigue, gastrointestinal symptoms, skin rash, and dyspnea. Among 24 lymphoma patients, nine are in continuous complete remission (CCR) from 18-48 months, and 15 have died (12 due to relapse and three of therapy-related toxicities). Of 12 acute leukemia patients, two with acute lymphoblastic leukemia (ALL) are in CCR at 38 and 43 months, and one patient who was in cytogenetic but not molecular remission of Philadelphia chromosome-positive ALL died of progressive leukemia at Day 108. Three of nine with myeloid leukemia are in CCR at 21, 46, and 53 months; one is in hematologic and cytogenetic remission of acute promyelocytic leukemia at 55 months with multiple new cytogenetic abnormalities; one is alive at 54 months with pancytopenia after incomplete hematologic recovery followed by multiple new cytogenetic abnormalities (myelodysplasia); and one had an unrelated donor transplant after relapsing 4 months following protocol therapy. One myeloid leukemia patient remains without evidence of relapse, but is transfusion-dependent at 15 months following transplant.

Acute Disease↗
PubMed1993

Transient wheeze. Eosinophilic bronchobronchiolitis in acute eosinophilic pneumonia.

The clinicopathologic features of five patients with acute eosinophilic pneumonia who presented with transient wheeze as well as acute onset of high fever, severe hypoxemia, and diffuse pulmonary infiltrates are described. Eosinophilic pneumonia was diagnosed by bronchoalveolar lavage and transbronchial lung biopsy. The illness resolved rapidly with or without corticosteroid therapy. No relapse occurred. To characterize the transient wheeze, a transbronchoscopic bronchial biopsy and pulmonary function tests were performed. Specimens of bronchial wall revealed eosinophil infiltration into the bronchial mucosa. Pulmonary function tests demonstrated reduced diffusing capacity and small airway dysfunction. These findings suggested that eosinophil infiltration into the bronchial mucosa might temporarily cause transient wheeze, different from bronchial asthma, due to small airway dysfunction in acute eosinophilic pneumonia.

Acute Disease↗
PubMed2000

Non-Hodgkin's lymphoma presenting as anasarca: probably mediated by tumor necrosis factor alpha (TNF-alpha).

Two patients presented with anasarca, fevers and sweats. Subsequent evaluation revealed aggressive lymphoproliferative disease. Both patients were treated with CHOP chemotherapy. One patient responded with spontaneous, vigorous diuresis and complete resolution of the edema. She relapsed two months later with recurrent edema that responded a second time to salvage chemotherapy. The second patient died of gram positive sepsis a week after diagnosis. As anasarca is an unusual presenting symptom of non-Hodgkin's lymphoma, we postulated that the malignant cells were secreting a cytokine that resulted in "vascular leakage" of fluid and development of diffuse edema. Several serum cytokine levels were tested. Both patients had elevated TNF-alpha levels, which could have been the cause of the edema; or there might be yet another unidentified mediator that was responsible for the anasarca. We report these two cases to bring to attention the unusual nature of this presentation.

Adult↗
PubMed1999

[An autopsy case of interstitial pneumonia probably induced by Sho-saiko-to].

A 66-year-old woman had been treated for 3 years by her local physician with Sho-saiko-to for chronic hepatitis C virus (HCV) infection and liver cirrhosis. She was admitted to our hospital because of cough, fever, and infiltrative shadows on chest x-ray films. Sho-saiko-to-induced pneumonitis was diagnosed and steroid therapy started. Though a temporary improvement was observed, interstitial pneumonitis relapsed and the patient died of respiratory failure and liver dysfunction. Autopsy findings showed diffuse alveolar damage and honeycombing. Furthermore, reverse-transcriptase polymerase chain reaction techniques detected HCV-RNA in specimens of fibrotic lung tissue. For comparison, HCV-RNA was not histologically detected in lung tissue specimens from 4 control subjects who were positive for HCV antibodies but who did not have interstitial lung disease. It was speculated that the progression of interstitial pneumonia in the present case may have been caused by HCV in combination with Sho-saiko-to-induced lung injury.

Aged↗
PubMed2000

Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) for previously treated patients with relapsed or primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation.

We used the CAG regimen (low-dose cytarabine [10 mg/m2 per 12 hours, days 1-14], aclarubicin [14 mg/m2 per day, days 1-4], and granulocyte colony-stimulating factor [200 micrograms/m2 per day, days 1-14]) for the treatment of patients with primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation (RAEB-T) in addition to relapsed AML. Forty-three of 69 (62%) patients achieved complete remission (CR), including 29 of 35 (83%) patients with relapsed AML, 1 of 8 patients with primary resistant AML, 5 of 8 elderly patients with previously untreated AML, and 8 of 18 patients with previously untreated secondary AML or RAEB-T. Ten of 22 (45%) patients > or = 65 years old achieved CR. The patients who achieved CR received at least 1 course of modified CAG therapy as the first consolidation therapy, followed by various second consolidation and intensification therapies. The median disease-free survival and overall survival were 8 and 15 months, respectively, for relapsed AML; 11 and 8 months for the elderly patients; and 8 and 17 months for secondary AML and RAEB-T. Myelosuppression was mild to moderate, and other than fever, severe nonhematologic toxicity was rare. CAG as the induction therapy seems promising for the treatment of various categories of poor-prognosis AML.

Aclarubicin↗
PubMed2002

A comparison of prophylactic efficacy of tilmicosin and a new formulation of oxytetracycline in feedlot calves.

Two replicated-pen field studies were performed under commercial feedlot conditions in western Canada to compare the administration of long-acting oxytetracycline at 30 mg/kg body weight (BW) versus tilmicosin at 10 mg/kg BW to feedlot calves upon arrival at the feedlot. Ten thousand nine hundred and eighty-nine, recently weaned, auction market derived, crossbred beef steer and bull calves were randomly allocated upon arrival at the feedlot to one of 2 experimental groups as follows: oxytetracycline, which received intramuscular long-acting oxytetracycline (300 mg/mL formulation) at a rate of 30 mg/kg BW; or tilmicosin, which received subcutaneous tilmicosin (300 mg/mL formulation) at a rate of 10 mg/kg BW. There were 20 pens in each experimental group. In Study 1 and in the combined analysis, the initial undifferentiated fever (UF) treatment rate was significantly (P < 0.05) higher in the oxytetracycline group as compared with the tilmicosin group. There were no significant (P > or = 0.05) differences in first UF relapse, second UF relapse, third UF relapse, overall chronicity, overall rail, overall mortality, bovine respiratory disease (BRD) mortality, hemophilosis mortality, arthritis mortality, or miscellaneous mortality rates between the experimental groups in either study or in the combined analysis. In addition, there were no significant (P > or = 0.05) differences in initial weight, final weight, weight gain, days on feed, daily dry matter intake, average daily gain, or the dry matter intake to gain ratio between the experimental groups in either study or in the combined analyses. In the economic analysis, there was a net economic advantage of $5.22 CDN per animal in the oxytetracycline group, due to a lower prophylactic cost, even though the UF therapeutic cost was higher.

Animals↗
PubMed2006

Leukocytosis and retinoic acid syndrome in patients with acute promyelocytic leukemia treated with arsenic trioxide.

OBJECTIVE: To study the incidence of leukocytosis and retinoic acid (RA) syndrome in newly diagnosed and relapsed acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (ATO). METHODS: Thirty patients with newly diagnosed or relapsed APL received ATO for remission induction at the dose of 10 mg/d. RA syndrome was defined when patient was with one or more of the following signs or symptoms: fever, dyspnea, serous cavity effusion, muscular pain, pulmonary infiltration, weight gain, or pulmonary infiltration on chest X-ray. RESULTS: Twenty-three (77% ) patients achieved complete remission, mean time to remission was 37.1 days. Leukocytosis was observed in 14 (47%) patients, mean time to leukocytosis was 12.7 days, median baseline leukocyte count for patients with leukocytosis was 3.1 x 10(9)/L, which was higher than that for patients who did not develop leukocytosis (2.6 x 10(9)/L, z = -2.635, P = 0.008). No other cytotoxic therapy was administered, and the leukocytosis resolved in all cases. The RA syndrome was observed in 9 (30%) patients, mean time to diagnose of RA syndrome was 13.9 days, median baseline leukocyte count for patients with RA syndrome was 3.6 x 10(9)/L, which was higher than that for patients who did not develop RA syndrome (2.6 x 10(9)/L, z = -1.909, P = 0.046). No patient died of RA syndrome. CONCLUSION: Leukocytosis and RA syndrome are associated with ATO and baseline leukocyte count respectively, and there is distinct link between leukocytosis and RA syndrome.

Adolescent↗
PubMed1993

[Roxithromycin in the treatment of community-acquired pneumonia].

BACKGROUND: The aim of the present study was to prospectively evaluate the efficacy and tolerance of roxithromycin in the empiric treatment of extra-hospitalary pneumonias in immunocompetent adult patients. METHODS: Over a 12 month period 101 patients with extra-hospitalary pneumonia who attended the Emergency Department were studied. Of these, 53 were treated as out patients (5 with amoxicillin-clavulanic, 25 with erythromycin and 23 with roxithromycin at daily doses of 300 mg for 10 days). The treatment was randomly chosen, with no patient selection, thus making heterogeneous groups and, therefore, the study could not be comparative. RESULTS: In patients receiving roxithromycin, an etiologic diagnosis was achieved in 15 cases (65.3%), with Mycoplasma pneumoniae, being the most frequent pathogen (10 cases), followed by Streptococcus pneumoniae (3), Chlamydia pneumoniae (1) and Haemophilus influenzae (1). The mean duration of fever was 1.9 days, 6.7 days for respiratory manifestations and resolution of the radiographic infiltrate 11.6 days. The evolution was good in all the patients with no secondary effects or relapse occurring in any patient. CONCLUSION: Roxithromycin is an effective, safe and comfortable antibiotic in the treatment of infections of the lower respiratory tract acquired in the community.

Adolescent↗
PubMed1998

[Treatment of pneumonia caused by Legionella with azithromycin].

Nineteen patients with pneumonia caused by Legionella, who did not need to be admitted to ICU were treated with 500 mg/day of azithromycin. The etiological diagnosis was made retrospectively by detecting Legionella pneumophila in the urine of nine patients and/or by serology (seroconversion or single titer 1/256) in 19 cases. None of them met the criteria for ICU admittance nor had received prior treatment with antibiotics which were potentially active against L. pneumophila. Serology tests and radiography of the thorax were carried out on all the patients in the study during their convalescence period. The average age (+/- SD) of the group was 58.5 +/- 16.2 years. The average respiratory frequency (+/- SD) 26 +/- 6 breaths per minute; the radiologic extension was of one lobule in 18 cases and two lobules in one case. No patients showed bilateral disease. Arterial gasometry (FiO2 0.21) showed a pO2 average of (+/- SD) 53 +/- 14 mmHg and the hemogram an average of 6.700 leukocytes/mm3 (range: 4,200-41-800). All the patients progressed favorably. The average duration of fever was 1.8 days; the average stay (+/- SD) was 6.1 +/- 2 days. The treatment was well tolerated. One month after discharge radiographies were clear for all patients. There were no relapses. In conclusion, 3-day administration of azithromycin was found to be a useful guide in the treatment of community acquired pneumonia caused by Legionella in patients whose clinical situation does not require ICU administration and allows for oral administration.

Adult↗
PubMed1982

Q fever endocarditis.

Despite a worldwide distribution of Coxiella burnetii, only single cases of Q fever endocarditis have been reported outside Great Britain and Australia. We present 10 patients; five were female, only four had a history of environmental exposure, and the mitral valve was involved as commonly as the aortic stenosis, and three patients had a prosthetic valve. We confirm the importance of hepatic involvement, thrombocytopenia and hypergammaglobulinemia as diagnostic features. Diagnosis was established by finding and elevated complement-fixing antibody to Phase I C. burnetii antigen. Tetracycline, with or without lincomycin or cotrimoxazole, was used in nine patients, and one patient received cotrimoxazole as as the sole antibiotic agent. Optimal duration of therapy is unknown. In one patient, relapse followed when treatment was stopped after 18 months. Valve replacement was necessary in five patients, because of hemodynamic problems. Five patients died, and the means survival is 36 months with a range of five to 66 months. We suggest that Q fever endocarditis is frequently missed, and we recommend clinicians to consider the diagnosis in all cases of culture-negative endocarditis.

Adult↗
PubMed2005

[Bronchiolitis obliterans organizing pneumonia following radiotherapy].

INTRODUCTION: Pulmonary complications of radiotherapy are rare, but bronchiolitis obliterans organizing pneumonia (BOOP) is observed in 2.5% of cases. It can develop after radiation treatment of breast cancer as well as, more rarely, lung cancer, sarcoma, Hodgkin's disease or malignant thymoma. CASE: Ten months after radiotherapy for breast cancer, a 52 year-old woman developed migratory alveolar opacities outside the radiation field. Their improvement with corticosteroid treatment led to the diagnosis of BOOP. DISCUSSION: BOOP, which resembles infectious pneumonia, can develop 2-7 months after the end of radiotherapy and is seen especially in women aged 50-60 years with fever and coughs resistant to antibiotics. Dyspnea is far rarer. Imaging reveals patchy infiltrates with widespread bilateral, mobile lesions extended over and above the radiation field. Biopsy is required to confirm diagnosis; sections, which may or may not come from the radiation field, reveal the nonspecific granulomatous alveolar infiltrates typical of BOOP. Other causes should be eliminated (toxic, immune, iatrogenic or even idiopathic infection and recurrent early neoplastic relapse). Association with hormone therapy does not influence the course of BOOP. Outcome with corticosteroid treatment is excellent.

Adrenal Cortex Hormones↗
PubMed2003

Treatment of typhoid fever in children with a flexible-duration of ceftriaxone, compared with 14-day treatment with chloramphenicol.

Although the efficacy of ceftriaxone in typhoid fever is well documented, the precise duration of ceftriaxone therapy in children with typhoid fever is not established and varies from 3 to 14 days in the literature. In a prospective, randomized study ceftriaxone was compared with chloramphenicol for treatment of 72 children who had bacteriologically confirmed typhoid fever. Ceftriaxone was given at a dose of 75 mg/kg per day (maximally 2 g/day) intravenously, in two doses until defervescence and continued 5 days after that time. Chloramphenicol was given at a dose of 75 mg/kg per day (maximally 2 g/day) in four doses for 14 days. Mean defervescence time was in 5.4 days in the ceftriaxone group and 4.2 days in the chloramphenicol group (P=0.04). Clinical cure without complications was achieved in all patients in both groups. No patient relapsed in the ceftriaxone group, and four patients relapsed in the chloramphenicol group (P=0.048). The overall results of this study suggest that a flexible-duration of ceftriaxone therapy given until defervescence time, followed by an additional 5 days of therapy is a reasonable alternative to conventional 14-day chloramphenicol treatment in children with typhoid fever.

Adolescent↗
PubMed1985

[High-dose cytosine arabinoside in the treatment of recurrent or acute refractory myeloid leukemias].

10 adult patients (age 27-62 years) with refractory or relapsed acute nonlymphocytic leukemia were treated with high dose cytosine arabinoside (HDAraC: 3 g/m2 q 12 h by IV infusion, d 1-6) either alone (7 patients) or with additional treatment, consisting of bone marrow transplantation (1 patient), m-AMSA (1pt.) and VP16 (1 patient). All patients had received conventional dose AraC (CDAraC); 8 patients were resistant to CDAraC, having failed 1 or more courses of CDAraC just before treatment with HDAraC. Recovery of granulocyte count (0,5 X 10(9)L) occurred at a median of 26 d (23-27 d) after initial therapy, and recovery of platelet counts (50 X 10(9)/L) at a median of 24 d (22-27 d). 6 patients became severely septic, 3 of them requiring granulocyte transfusions. Consequently, sophisticated blood banking facilities and supportive care are required. The non-myeloid toxicities associated with HDAraC were not severe. Vomiting (9/10), erythematous skin rash (4/10), conjunctivitis and photophobia (2/10) were found most commonly. CNS-toxicity, pulmonary toxicity or drug fever were not observed. 4 patients achieved a complete remission and 1 a partial remission. 2 patients failed to respond and 3 patients died during the period of pancytopenia. Thus, HDAraC is effective treatment for refractory or relapsed ANLL, even in cases of apparent resistance to CDAraC.

Adult↗