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.

Replacing carmustine by thiotepa and cyclophosphamide for autologous stem cell transplantation in Hodgkin's and non-Hodgkin's B-cell lymphoma.

This study aimed to compare the real-life results of TECAM, a thiotepa-based conditioning regimen consisting of thiotepa (40 mg/m2 days -5 to -2), etoposide (200 mg/m2 days -6 to -3), cytarabine (200 mg/m2 days -4 to -1), cyclophosphamide (60 mg/kg day -3), and melphalan (60 mg/m2 days -2 to -1) with that of the conventional carmustine-based regimen BEAM. We reviewed 125 consecutive patients who underwent a first autologous transplantation (ASCT) for B-cell lymphomas at a large tertiary transplantation center between 1999 and 2014. TECAM (n=65) and BEAM (n=60) had comparable results (3yPFS 49 vs 62%, P=0.16; 3yOS 64 vs 71%, P=0.44; TRM 1.6 vs 5%, P=0.35) without a difference in toxicity or time to engraftment. Notably, comparable outcomes were observed even though patients treated with TECAM were older (55 vs 44) and had a trend towards more prior lines of therapy (>2 prior lines: 43 vs 27%, P=0.08). In this regard, 23% of TECAM patients were over the age of 65 yet could withstand therapy with similar results to younger patients. We conclude that, replacing carmustine by thiotepa and cyclophosphamide for ASCT conditioning, has comparable efficacy and safety profiles with a possible advantage in older patients.

Genotype-phenotype correlations between GBA mutations and Parkinson disease risk and onset.

BACKGROUND: Mutations in GBA and LRRK2 genes have been implicated in Parkinson disease (PD), particularly in Ashkenazi Jews. METHODS: An Israeli Ashkenazi cohort of 420 patients with PD, 333 elderly controls, and 3,805 young controls was screened for eight GBA mutations, which are associated with mild (N370S, R496H) and severe (84GG, IVS2 + 1, V394L, D409H, L444P, RecTL) Gaucher disease. Patients with PD and elderly controls were also genotyped for LRRK2 G2019S. RESULTS: GBA carrier frequency was 17.9% in patients with PD compared to 4.2% in elderly and 6.35% in young controls. The proportion of severe mutation carriers among PD patient GBA carriers was 29% compared to 7% among young controls. Severe and mild GBA mutations increased the risk of developing PD by 13.6- and 2.2-fold, and affected the average age at PD onset (AAO), 55.7 and 57.9 years, compared to 60.7 years in patients without known GBA or LRRK2 mutations. CONCLUSIONS: These data demonstrate genotype-phenotype correlations between different GBA mutations and Parkinson disease (PD) risk and AAO in Ashkenazi Jews. Additionally, an earlier AAO was observed in LRRK2 G2019S carrier PD patients. Finally, these data demonstrate that a surprisingly high frequency, more than one third of our patient population, carried a mutation in GBA or LRRK2.

The LRRK2 G2019S mutation in Ashkenazi Jews with Parkinson disease: is there a gender effect?

BACKGROUND: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic determinant of Parkinson disease (PD) identified to date, and have been implicated in both familial and sporadic forms of the disease. The G2019S change in LRRK2 exon 41 has been associated with disease at varying frequencies in Asian, European, North American, and North African populations, and is particularly prevalent among Ashkenazi Jews. METHODS: We assessed the occurrence of the LRRK2 G2019S, I2012T, I2020T, and R1441G/C/H mutations in our cohort of Jewish Israeli patients with PD, and determined the LRRK2 haplotypes in 76 G2019S-carriers detected and in 50 noncarrier Ashkenazi patients, using six microsatellite markers that span the entire gene. RESULTS: Only the G2019S mutation was identified among our patients with PD, 14.8% in the Ashkenazi and 2.7% in the non-Ashkenazi patients, and in 26% and 10.6% of the Ashkenazi familial and apparently sporadic cases. The carrier frequencies in the Ashkenazi and non-Ashkenazi control samples were 2.4% and 0.4%. A common shared haplotype was detected in all non-Ashkenazi and half-Ashkenazi carriers and in all full-Ashkenazi carriers tested, except two. Women and patients with a positive family history of PD were significantly over-represented among the G2019S mutation carriers. Age at disease onset was similar in carriers and noncarriers. CONCLUSIONS: Our data suggest that the LRRK2 G2019S mutation plays an important role in the causality of familial and sporadic Parkinson disease (PD) in Israel and that gender affects its frequency among patients. Although testing symptomatic patients may help establish the diagnosis of PD, the value of screening asymptomatic individuals remains questionable until the penetrance and age-dependent risk of this mutation are more accurately assessed, and specific disease prevention or modifying interventions become available.

Genome-wide expression analysis of cultured trophoblast with trisomy 21 karyotype.

BACKGROUND: The pathologic features of Down syndrome are assumed to be the result of over-expression of genes located on chromosome 21 and/or a more global transcriptional misregulation that crosses chromosomal borders. METHODS: To address this issue, four RNA samples from trisomy 21 placentas and four samples from normal first trimester pregnancies were analyzed using Affymetrix U95v2 microarray. Statistical and bioinformatic analyses were employed to compare global gene expression, functional classes, and pathways to differentiate between placentas taken from trisomy 21 and from normal pregnancies. RESULTS: About 750 genes were significantly over-expressed in trisomy 21. This list contains an approximately 4.5-fold over-abundance of genes that map to chromosome 21, compared to that which could be expected for this chromosome, on the microarray. Among the classes of genes that best discriminated the trisomy 21 and normal karyotype, we found genes that are also implicated in Alzheimer disease and genes that are associated with ubiquitination and proteosomal degradation. Finally, using the top 10 most discriminating genes, eight samples taken from a different database were correctly classified as either trisomy 21 or normal. CONCLUSIONS: Our results demonstrate that gene expression in trisomy 21 affected placentas significantly differs from that of chromosomally normal placentas, and this difference is only partially explained by over-expression of genes from chromosome 21. Our findings suggest that specific highly discriminatory genes may be potential targets for further research and development of novel prenatal diagnosis techniques.

Coping with the stress of immigration among new immigrants to Israel from Commonwealth of Independent States (CIS) who were exposed to Chernobyl: the effect of age.

This study examined the differential effect of age on coping and psychological measures among immigrants from Commonwealth of Independent States (CIS) to Israel. Some of these immigrants originated in the Republics adjacent to the Chernobyl Power Plant, site of the 1986 accident. The sample consisted of 708 immigrants who were interviewed between the years 1993-1995 with an average age of 47.5 (sd 11.8). This sample was reinterviewed approximately a year and three months later (n = 520). The sample included two exposure groups--high exposed and low exposed based on the estimated levels of ground cesium contamination from the IAEA maps and a comparison group matched by age, gender, and year of immigration. Those over the age of sixty-five were disadvantaged, compared to those aged fifty to sixty-four, and younger, when it came to the tasks of immigrant absorption; learning the language, working and acquiring an income, and establishing alternative social networks which could offer support in times of illness. The psychological variables showed that over time, somatization, depression, and post-traumatic stress disorder (PTSD) symptoms related to Chernobyl improved, however at a much slower pace for older immigrants (aged 55 and over) compared to younger ones.