Maintenance therapy with hypomethylating agents for patients with acute myeloid leukemia in first remission not eligible for allogeneic hematopoietic cell transplantation: A systematic review and meta-analysis.

BACKGROUND: Older patients encompass about 75 % of patients with acute myeloid leukemia (AML). Today therapeutic options to prevent relapse in older patients who managed to achieve complete remission (CR) after intensive chemotherapy are scarce. Recent randomized controlled trials (RCTs) have aimed to reduce the risk of relapse by means of post-CR maintenance therapy. METHODS: We performed a systematic review and meta-analysis of RCTs comparing the efficacy and safety of maintenance with hypomethylating agents (HMA) vs. observation, conventional care or placebo in older patients with AML who are not candidates for allogeneic hematopoietic transplantation (allo-HCT). We searched Cochrane Library, PubMed and conference proceedings up to August 2021. RESULTS: Six trials were included. Treatment with hypomethylating agents significantly improved overall survival (HR 0.80, 95 % CI 0.70 to 0.91, I2 = 30 %), and disease control (HR 0.80, 95 % CI 0.70 to 0.91, I2 = 0). A significant decrease was seen in both one year mortality (Risk Ratio [RR] 0.61, 95 % CI 0.48 to 0.77, I2 = 0) and mortality at the end of follow-up (RR 0.77, 95 % CI 0.67 to 0.88, I2 = 0). The rate of relapse at 6 months and at one-two years was lower in the HMA arm vs. control (RR, 0.59; 95 % CI, 0.47-0.72; RR, 0.74, I2 = 0; 95 % CI 0.69 - 0.91, I2 = 41 %, respectively). HMA were associated with a statistically non-significant increase in the risk of serious adverse events (RR 3.44, 95 % CI 0.93-12.74, I2 = 80 %). CONCLUSIONS: Our meta-analysis shows that in older patients who are not candidates for allo-HCT, maintenance therapy with HMA improves OS and disease control without a statistically significant increase in adverse events.

Antibacterial prophylaxis with ciprofloxacin for patients with multiple myeloma and lymphoma undergoing autologous haematopoietic cell transplantation: a quasi-experimental single-centre before-after study.

OBJECTIVES: We aimed to study whether ciprofloxacin prophylaxis reduces infectious complications in patients undergoing autologous haematopoietic cell transplantation (AHCT). METHODS: This is a quasi-experimental, retrospective, before-after study. We compared the incidence of bacterial-related complications among 356 patients with multiple myeloma (MM) (n = 202) and lymphoma (n = 154) who underwent AHCT with (n = 177) or without (n = 179) ciprofloxacin prophylaxis between 03/2007 and 10/2012 and between 10/2012 and 07/2016, respectively, at a single centre. RESULTS: Febrile neutropaenia, bacteraemia, and pneumonia were significantly more common among patients who underwent AHCT during the second study period and did not receive antibacterial prophylaxis compared with patients who underwent AHCT during the first study period and received antibacterial prophylaxis (89.9% (161/179) vs. 83.1% (147/177), difference 6.9%, 95% CI 0-14.1%, P = 0.002; 15.1% (27/179) vs. 4.5% (8/177), difference 10.6%, 95% CI 4.4-16.9%, p < 0.0001; 12.3% (22/179) vs. 6.2% (11/177), difference 6.1%, 95% CI 0-12.3%, p = 0.04, respectively). The number-needed-to-treat to prevent one episode of bacteraemia, pneumonia, and febrile neutropaenia was 8.6, 8.5, and 13.7, respectively. Patients with ciprofloxacin prophylaxis had higher rates of ciprofloxacin-resistant bacteraemia (62.5% (5/8) vs. 18.5% (5/27), difference 44%, 95% CI 7-70%, p = 0.01). In multivariate analysis, ciprofloxacin prophylaxis significantly decreased the odds of bacteraemia (OR 0.19, 95% CI 0.07-0.52; p < 0.0001) and pneumonia (OR 0.37, 95% CI 0.16-0.85, p = 0.02). CONCLUSION: According to our single-centre experience, patients with MM and lymphoma undergoing AHCT may benefit from antibacterial prophylaxis with ciprofloxacin.

Erythrodermic mycosis fungoides and Sézary syndrome treated with extracorporeal photopheresis as part of a multimodality regimen: A single-centre experience.

BACKGROUND: Extracorporeal photopheresis (ECP) is recommended for the erythrodermic mycosis fungoides (MF) and Sezary syndrome (SS) alone or in combination with other therapies. The possibility of a differential response in the blood and skin has hardly been addressed in the literature. OBJECTIVES: To evaluate the clinical response rate of patients with erythrodermic MF and SS to ECP as part of a multimodality approach and to compare the kinetics of the blood and skin responses in the presence of leukaemic involvement. METHODS: Twenty patients were treated with ECP and other modalities at a tertiary medical centre in 2003-2013. Ten patients had SS, 1 CD8-positive patch-stage MF with leukaemic involvement and nine erythrodermic MF. Clinical and outcome data were collected retrospectively from the medical files. Response was evaluated overall and for blood and skin separately. RESULTS: Adjunctive therapies were interferon-α, narrow-band ultraviolet B, psoralen and ultraviolet A, isotretinoin, acitretin, methotrexate, prednisone, topical nitrogen mustard and total skin or localized hands/feet electron beam radiotherapy. Overall response was documented in 13 patients (65%)--complete 30%, partial 35%--and maintained for >2 years in 38.5%. In patients with leukaemic involvement (n = 11), the blood response occurred earlier than skin response (P = 0.008) and was maintained longer (P = 0.03). In three of the patients with a complete blood response, the skin response was partial (n = 2) or absent (n = 1). CONCLUSION: Extracorporeal photopheresis as part of a multimodality approach yields a high durable clinical response in patients with erythrodremic MF and SS. The kinetics of the response differ between the blood and skin. The blood response occurs earlier and lasts longer; it does not necessarily predict the clinical skin response. Further studies are needed to determine if there is a survival advantage to a blood response in the absence of a skin response.

Fever and rash in children: important diagnostic considerations.

The association of fever with illness has been known for years. A febrile child may have rash, and physicians need to know when this symptom combination is a benign versus a pathologic clinical presentation. In other terms, potential etiologies are either infectious or non-infectious. With scrupulous, methodical history taking and careful, serial physical examination, the treating physician will find hints to assess and solidify an appropriate diagnosis, and chose an appropriate treatment.

Systemic arthritis in children: a review of clinical presentation and treatment.

Systemic juvenile idiopathic arthritis (sJIA) constitutes a small part of juvenile idiopathic arthritis (JIA), yet has a disproportionally higher rate of mortality. Despite being grouped under JIA, it is considered to be a multifactorial autoinflammatory disease. The objective of this paper is to review the epidemiology, pathogenesis, genetics, clinical manifestations, complications, therapy, prognosis, and outcome of sJIA. The presentation and clinical manifestations of sJIA have not changed much in the past several decades, but the collective understanding of the pathogenesis and the development of new targeted therapies (particularly the biologic agents) have transformed and improved the disease outcome for children with sJIA.

New antibiotic substance produced by Salmonella typhimurium LT2.

Salmonella typhimurium LT2 excreted under certain conditions an antibiotic substance designated typhimuricin. It is suggested that the LT2 "cryptic" plasmid is involved in its production and in the immunity to it. Preliminary characterization of typhimuricin is presented.

Mutagenic and colicine-inducing activity of two antioxidants: pyrogallol and purpurogallin.

The antioxidants pyrogallol and its oxidative derivative, purpurogallin, both induce colicine E2 as well as base substitution and frameshift mutations. Because of the bactericidal effect of purpurogallin, its mutagenicity could be best demonstrated by short-term exposure followed by dilution on the test plates. The colicine-inducing potential of purpurogallin was also observed when tested directly on the plates.

The lethal effect and the inhibition of colicin production by leucine on a phenylalanine requiring E. coli strain as a function of age and dilution of culture.

The lethal effect caused by leucine on a phenylalanine requiring strain of Escherichia coli K-12 (7), was found to be strongly affected by the age of the culture. Early log cells were the least sensitive, while older cells became more sensitive to leucine. Another important factor affecting the sensitivity of this strain to leucine in liquid medium was the range of dilution of the culture. The age sensitive culture reacted to leucine only when its dilution was at a certain specific range. The sensitivity to leucine of a culture treated at the "right" age and at the proper dilution was proportional to the concentration of leucine. Colicine production was studied with cultures treated in various ways using a colicinogenic derivative of the leucine sensitive strain. It was found that leucine in a rather high concentration (2 mg/ml) prevented colicine production when given in the absence of phenylalanine, while phenylalanine at a very low dose (0.2 microgram/ml) could reverse this inhibition. The effect of leucine on colicine production, like lethality, operated only under certain conditions of culture dilution, but unlike lethality, was not very sensitive to the age of the culture. Tryptophane was found to resemble leucine in its effects on viability and on colicine production in liquid medium. Its effect was likewise reversed by a small amount of phenylalanine, and like leucine, tryptophane acted best only under very specific conditions of culture dilution.

A simple plate test for screening colicine-inducing substances as a tool for the detection of potential carcinogens.

A simple and rapid plate test is described for screening substances that induce colicine E2. By using chemicals activated with microsomal enzymes and a permeable (rfa) tester bacterium that is also deficient in DNA repair (uvrB), the range of inducing substances that can be detected has been extended. The possible correlation between colicine-inducing substances and carcinogens is discussed.

Mode of action of pesticin.

The mode of action of pesticin, a bacteriocin produced by many strains of Pasturella pestis, was studied. Pesticin action on macromolecular synthesis of a sensitive strain of Escherichia coli, strain phi, was found to have features similar to those of colicin E2-317 acting on the same strain. After exposure to pesticin, deoxyribonucleic acid synthesis was arrested and ribonucleic acid was degraded, but little effect was observed on protein synthesis. Pesticin, like colicin E2-317, induced lysogenic E. coli phi (P1), but, unlike the colicin, was active in the presence of dinitrophenol. Trypsin was found to reverse pesticin action up to 15 min after its addition at 40 C to E. coli phi. Pesticin action was studied on three sensitive bacterial strains, P. pestis 2C, P. pseudotuberculosis, and E. coli strain phi, which vary widely in their optimal growth temperature. P. pestis grows best at 29 C, P. pseudotuberculosis at 37 C, and E. coli phi at 40 C. It was found that pesticin action on all three strains was optimal at 40 C. Whereas the titer of pesticin was the same on all three strains when determined on agar, E. coli phi was the most sensitive to pesticin action in broth. No action of pesticin in broth on P. pseudotuberculosis was observed unless Ca ions were added. The effect was not immediate; that is, the cells had to be grown in a medium containing Ca(++) before they displayed sensitivity to pesticin.