Medical Biology - Research Publications
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ItemSuccessful identification of predictive profiles for infection utilising systems-level immune analysis: a pilot study in patients with relapsed and refractory multiple myeloma(WILEY, 2021)OBJECTIVES: Patients with multiple myeloma (MM) are at increased risk for infection. Clinical assessment of infection risk is increasingly challenging in the era of immune-based therapy. A pilot systems-level immune analysis study to identify predictive markers for infection was conducted. METHODS: Patients with relapsed and/or refractory MM (RRMM) who participated in a treatment trial of lenalidomide and dexamethasone were evaluated. Data on patient demographics, disease and episodes of infection were extracted from clinical records. Peripheral blood mononuclear cells (PBMCs) collected at defined intervals were analysed, with or without mitogen re-stimulation, using RNA sequencing and mass cytometry (CyTOF). CyTOF-derived cell subsets and RNAseq gene expression profiles were compared between patients that did and did not develop infection to identify immune signatures that predict infection over a 3-month period. RESULTS: Twenty-three patients participated in the original treatment trial, and we were able to access samples from 17 RRMM patients for further evaluation in our study. Nearly half the patients developed an infection (8/17) within 3 months of sample collection. Infections were mostly clinically diagnosed (62.5%), and the majority involved the respiratory tract (87.5%). We did not detect phenotypic or numerical differences in immune cell populations between patients that did and did not develop infections. Transcriptional profiling of stimulated PBMCs revealed distinct Th2 immune pathway signatures in patients that developed infection. CONCLUSION: Immune cell counts were not useful predictors of infection risk. Functional assessment of stimulated PBMCs has identified potential immune profiles that may predict future infection risk in patients with RRMM.
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ItemCytomegalovirus DNAemia and disease: natural history and management in settings other than allogeneic stem cell transplantation(Ferrata Storti Foundation, 2005-12)Background and Objectives. Despite increasing intensity and profound immunosuppressionassociated with newer therapies for hematologic malignancies, little information exists regarding cytomegalovirus (CMV) reactivation in settings other than allogeneic stem cell transplantation (SCT).Design and Methods. We reviewed the epidemiology of CMV disease in patients who were CMV polymerase chain reaction (PCR) positive during treatment for hematologic malignancies without allogeneic SCT from June 1999 to June 2004.Results. Thirty-six patients with CMV reactivation were identified. Of these, 92% were undergoing investigation for fever. Fifteen patients with CMV DNAemia were treatedwith ganciclovir without CMV disease developing. Notably, 20 patients with untreated CMV DNAemia did not develop CMV disease during a median follow-up of 3.5 (1-19)months. The highest rates of reactivation were observed with HyperCVAD (7.8%) and alemtuzumab (50%).Interpretation and Conclusions. We recommend that screening for CMV DNAemia be instituted and pre-emptive therapy contemplated for asymptomatic CMV reactivationonly in patients receiving alemtuzumab therapy, but not routinely for other patients outside the allogeneic SCT setting. Indeed for such patients, detection of isolated CMV DNAemia does not imply the need for immediate therapy and future studies are needed to validate PCR detection of CMV DNA and CMV DNA titers as predictors for CMV disease.