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  1. Fulltext MDM2 promotor polymorphism and disease characteristics in chronic lymphocytic leukemia: results of an individual patient data-based meta-analysis
    Benner A, Mansouri L, Rossi D, Majid A, Willander K, Parker A, et al.
    Haematologica, 2014 Aug;99(8):1285-91.
    PMID: 25082786 DOI: 10.3324/haematol.2013.101170
    A number of single nucleotide polymorphisms have been associated with disease predisposition in chronic lymphocytic leukemia. A single nucleotide polymorphism in the MDM2 promotor region, MDM2SNP309, was shown to soothe the p53 pathway. In the current study, we aimed to clarify the effect of the MDM2SNP309 on chronic lymphocytic leukemia characteristics and outcome. We performed a meta-analysis of data from 2598 individual patients from 10 different cohorts. Patients' data and genetic analysis for MDM2SNP309 genotype, immunoglobulin heavy chain variable region mutation status and fluorescence in situ hybridization results were collected. There were no differences in overall survival based on the polymorphism (log rank test, stratified by study cohort; P=0.76; GG genotype: cohort-adjusted median overall survival of 151 months; TG: 153 months; TT: 149 months). In a multivariable Cox proportional hazards regression analysis, advanced age, male sex and unmutated immunoglobulin heavy chain variable region genes were associated with inferior survival, but not the MDM2 genotype. The MDM2SNP309 is unlikely to influence disease characteristics and prognosis in chronic lymphocytic leukemia. Studies investigating the impact of individual single nucleotide polymorphisms on prognosis are often controversial. This may be due to selection bias and small sample size. A meta-analysis based on individual patient data provides a reasonable strategy for prognostic factor analyses in the case of small individual studies. Individual patient data-based meta-analysis can, therefore, be a powerful tool to assess genetic risk factors in the absence of large studies.
  2. Fulltext Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation: A Randomized Clinical Trial
    Bastidas A, de la Serna J, El Idrissi M, Oostvogels L, Quittet P, López-Jiménez J, et al.
    JAMA, 2019 07 09;322(2):123-133.
    PMID: 31287523 DOI: 10.1001/jama.2019.9053
    Importance: Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster.

    Objective: To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients.

    Design, Setting, and Participants: Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT.

    Interventions: Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n = 922) or placebo (n = 924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter.

    Main Outcomes and Measures: The primary end point was occurrence of confirmed herpes zoster cases.

    Results: Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P 

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