Publications by authors named "Aliyah Baluch"

13 Publications

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Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma.

Haematologica 2021 04 1;106(4):978-986. Epub 2021 Apr 1.

Dept. of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, USA.

CD19 CAR T-cell therapy with axicabtagene ciloleucel (axi-cel) for relapsed or refractory (R/R) large B cell lymphoma (LBCL) may lead to durable remissions, however, prolonged cytopenias and infections may occur. In this single center retrospective study of 85 patients, we characterized immune reconstitution and infections for patients remaining in remission after axi-cel for LBCL. Prolonged cytopenias (those occurring at or after day 30 following infusion) were common with >= grade 3 neutropenia seen in 21/70 (30-0%) patients at day 30 and persisting in 3/31 (9-7%) patients at 1 year. B cells were undetectable in 30/34 (88-2%) patients at day 30, but were detected in 11/19 (57-9%) at 1 year. Median IgG levels reached a nadir at day 180. By contrast, CD4 T cells decreased from baseline and were persistently low with a median CD4 count of 155 cells/μl at 1 year after axi-cel (n=19, range 33 - 269). In total, 23/85 (27-1%) patients received IVIG after axi-cel, and 34/85 (40-0%) received G-CSF. Infections in the first 30 days occurred in 31/85 (36-5%) patients, of which 11/85 (12-9%) required intravenous antibiotics or hospitalization ("severe") and were associated with cytokine release syndrome (CRS), neurotoxicity, tocilizumab use, corticosteroid use, and bridging therapy on univariate analyses. After day 30, 7 severe infections occurred, with no late deaths due to infection. Prolonged cytopenias are common following axi-cel therapy for LBCL and typically recover with time. Most patients experience profound and prolonged CD4 T cell immunosuppression without severe infection.
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http://dx.doi.org/10.3324/haematol.2019.238634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017820PMC
April 2021

Early Antimicrobial De-escalation and Stewardship in Adult Hematopoietic Stem Cell Transplantation Recipients: Retrospective Review.

Open Forum Infect Dis 2017 11;4(4):ofx226. Epub 2017 Dec 11.

Department of Infectious Diseases, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Background: Antimicrobial stewardship in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients remains underutilized in North America. European guidelines advise de-escalation of broad-spectrum therapy after 72 hours in select patients with neutropenic fever of unknown origin. This is not commonplace in the United States, as current guidelines recommend broad-spectrum therapy until neutrophil engraftment. If de-escalating after at least 5 days of broad-spectrum therapy and defervescence in neutropenic allo-HSCT recipients does not predispose them to recurrent fever or infection, the practice could afford several benefits.

Methods: The primary end point was rate of recurrent fever. Secondary outcomes included -associated infections, length of stay, intensive care unit (ICU) admission incidence, in-hospital mortality rate, need for re-escalation of therapy, rate of positive blood cultures for patients who had recurrent fevers, overall antimicrobial utilization from neutropenic fever onset, and pharmacoeconomic impact.

Results: A total of 120 patients were assessed in 2 groups as cohort 1 (n = 46), which received early de-escalation, and cohort 2 (n = 74), which did not. The primary end point met criteria for noninferiority, as 7 patients (15%) in cohort 1 had recurrent fever within the specified time frame compared with 14 (19%) in cohort 2 (90% CI, -0.0878 to 0.1629, = .026). Patients in cohort 1 received significantly less gram-positive broad-spectrum antimicrobials, with trends toward lower use of broad-spectrum gram-negative agents and lower associated costs and no differences in length of stay, ICU admission incidence, need for re-escalation of therapy, rate of culture-positive bacteremia after de-escalation or discontinuation of broad-spectrum therapy, or in-hospital mortality rate.

Conclusions: De-escalating after at least 5 days of broad-spectrum therapy and defervescence did not appear to affect the rate of recurrent fever. This allowed for significant reductions in gram-positive broad-spectrum antimicrobial utilization, with trends toward lower use of broad-spectrum gram-negative agents and associated costs and no difference in clinical outcomes compared with those continuing such therapy until neutrophil engraftment.
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http://dx.doi.org/10.1093/ofid/ofx226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726466PMC
December 2017

Fever in Patients With Cancer.

Cancer Control 2017 Apr;24(2):193-197

Division of Infectious Diseases, Moffitt Cancer Center, Tampa, FL.

Background: The definition of fever is flexible and depends on the clinical context. Fever is frequently observed in patients with cancer.

Methods: Infectious and noninfectious causes of fever in patients with various oncological and hematological malignancies and the usefulness of biomarkers are discussed.

Results: To treat patients in a timely manner and to minimize morbidity and mortality, it is paramount that health care professionals determine the cause of fever. The usefulness of biomarkers in febrile patients with cancer continues to be controversial.

Conclusions: Fever is frequently seen in patients with cancer and can be associated with a variety of infectious and noninfectious causes. The utility of acute-phase reactants, such as erythrocyte sedimentation rate, C-reactive protein, and procalcitonin, along with a nonsteroidal anti-inflammatory drug challenge should be further evaluated as adjunct tools for the workup of fever in patients with cancer.
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http://dx.doi.org/10.1177/107327481702400212DOI Listing
April 2017

Successful management of Mycobacterium haemophilum lower extremity cutaneous infection in a matched-unrelated donor stem cell transplant recipient.

Transpl Infect Dis 2017 Feb 16;19(1). Epub 2016 Dec 16.

Department of Pharmacy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

Nontuberculous mycobacterial infections can often occur in individuals with adequate immune function. Such infections typically have cutaneous involvement and are caused by rapidly growing mycobacterium. Other nontuberculous mycobacteria species, like Mycobacterium haemophilum, almost always present as opportunistic infections occurring in severely immunocompromised hosts. Here, we present a complicated and protracted course of diagnosing M. haemophilum lower extremity cutaneous infection in a matched-unrelated donor stem cell transplant recipient.
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http://dx.doi.org/10.1111/tid.12627DOI Listing
February 2017

State of the Globe: The Rippling Effect of Multidrug-Resistant Gram-negative Infections.

Authors:
Aliyah Baluch

J Glob Infect Dis 2015 Oct-Dec;7(4):125-6

Division of Infectious Diseases, Moffitt Cancer Center, Tampa, FL, USA.

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http://dx.doi.org/10.4103/0974-777X.170494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693302PMC
January 2016

Baseline serum interleukin-6 to interleukin-2 ratio is associated with the response to seasonal trivalent influenza vaccine in solid organ transplant recipients.

Vaccine 2015 Dec 10;33(51):7176-7182. Epub 2015 Nov 10.

Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada. Electronic address:

Background: The analysis of pre- and post-vaccination B-cell-associated cytokines might be useful in predicting the immunogenicity of seasonal trivalent influenza vaccine (TIV) in solid organ transplant (SOT) recipients.

Methods: We performed a subanalysis of a clinical trial that compared the safety and efficacy of high-dose intradermal (ID) versus intramuscular (IM) TIV in SOT recipients. Serum levels of selected cytokines (interferon [IFN]-γ, interleukin [IL]-2, IL-4, IL-5, IL-6, IL-12 and IL-21, and tumor necrosis factor [TNF]-α) were measured pre- and one month post-vaccination in 155 patients (with 84 and 71 receiving the ID and IM vaccines, respectively). Cytokine profiles were compared according to vaccine response (seroconversion [≥4-fold increase in hemagglutination inhibition antibody titers] to ≥1 influenza vaccine antigen).

Results: Mean baseline IL-6 levels were higher (1.20 versus 0.65pg/mL; P-value=0.021) and IL-2 levels were lower (0.01 versus 0.50pg/mL; P-value=0.051) in patients achieving vaccine response. After adjusting for clinical variables, baseline IL-6/IL-2 ratio remained predictive of vaccine response (odds ratio per 10-unit increment: 1.06; 95% confidence interval: 1.02-1.10; P-value=0.002). Vaccination induced an increase in TNF-α (P-value <0.0001) and a decrease in IL-5 levels (P-value=0.0007). There were no significant differences in cytokine kinetics between vaccine responders and non-responders. Mean baseline TNF-α levels were higher in patients experiencing moderate-to-severe adverse events after vaccination (1.93 versus 1.72pg/mL; P-value=0.009).

Conclusions: Baseline serum IL-6 and IL-2 levels, two cytokines that modulate the role of CD4(+) T follicular helper cells and the terminal differentiation of B-cells, predict vaccine response in SOT recipients.
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http://dx.doi.org/10.1016/j.vaccine.2015.10.134DOI Listing
December 2015

Effect of Immunosuppression on T-Helper 2 and B-Cell Responses to Influenza Vaccination.

J Infect Dis 2015 Jul 14;212(1):137-46. Epub 2015 Jan 14.

Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.

Background: Influenza vaccine immunogenicity is suboptimal in immunocompromised patients. However, there are limited data on the interplay of T- and B- cell responses to vaccination with simultaneous immunosuppression.

Methods: We collected peripheral blood mononuclear cells from transplant recipients before and 1 month after seasonal influenza vaccination. Before and after vaccination, H1N1-specific T- and B-cell activation were quantified with flow cytometry. We also developed a mathematical model using T- and B-cell markers and mycophenolate mofetil (MMF) dosage.

Results: In the 47 patients analyzed, seroconversion to H1N1 antigen was demonstrated in 34%. H1N1-specific interleukin 4 (IL-4)-producing CD4(+) T-cell frequencies increased significantly after vaccination in 53% of patients. Prevaccine expression of H1N1-induced HLA-DR and CD86 on B cells was high in patients who seroconverted. Seroconversion against H1N1 was strongly associated with HLA-DR expression on B cells, which was dependent on the increase between prevaccine and postvaccine H1N1-specific IL-4(+)CD4(+) T cells (R(2) = 0.35). High doses of MMF (≥ 2 g/d) led to lower seroconversion rates, smaller increase in H1N1-specific IL-4(+)CD4(+) T cells, and reduced HLA-DR expression on B cells. The mathematical model incorporating a MMF-inhibited positive feedback loop between H1N1-specific IL-4(+)CD4(+) T cells and HLA-DR expression on B cells captured seroconversion with high specificity.

Conclusions: Seroconversion is associated with influenza-specific T-helper 2 and B-cell activation and seems to be modulated by MMF.
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http://dx.doi.org/10.1093/infdis/jiv015DOI Listing
July 2015

IL-28B is a key regulator of B- and T-cell vaccine responses against influenza.

PLoS Pathog 2014 Dec 11;10(12):e1004556. Epub 2014 Dec 11.

Department of Medicine and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.

Influenza is a major cause of morbidity and mortality in immunosuppressed persons, and vaccination often confers insufficient protection. IL-28B, a member of the interferon (IFN)-λ family, has variable expression due to single nucleotide polymorphisms (SNPs). While type-I IFNs are well known to modulate adaptive immunity, the impact of IL-28B on B- and T-cell vaccine responses is unclear. Here we demonstrate that the presence of the IL-28B TG/GG genotype (rs8099917, minor-allele) was associated with increased seroconversion following influenza vaccination (OR 1.99 p = 0.038). Also, influenza A (H1N1)-stimulated T- and B-cells from minor-allele carriers showed increased IL-4 production (4-fold) and HLA-DR expression, respectively. In vitro, recombinant IL-28B increased Th1-cytokines (e.g. IFN-γ), and suppressed Th2-cytokines (e.g. IL-4, IL-5, and IL-13), H1N1-stimulated B-cell proliferation (reduced 70%), and IgG-production (reduced>70%). Since IL-28B inhibited B-cell responses, we designed antagonistic peptides to block the IL-28 receptor α-subunit (IL28RA). In vitro, these peptides significantly suppressed binding of IFN-λs to IL28RA, increased H1N1-stimulated B-cell activation and IgG-production in samples from healthy volunteers (2-fold) and from transplant patients previously unresponsive to vaccination (1.4-fold). Together, these findings identify IL-28B as a key regulator of the Th1/Th2 balance during influenza vaccination. Blockade of IL28RA offers a novel strategy to augment vaccine responses.
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http://dx.doi.org/10.1371/journal.ppat.1004556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263767PMC
December 2014

Influenza vaccination in oncology patients.

Curr Infect Dis Rep 2013 Dec;15(6):486-90

Division of Infectious Diseases, Moffitt Cancer Center, University of South Florida College of Medicine, 12902 Magnolia Drive, MCC-IHM, Tampa, FL, 33612, USA,

It is well established that the immunological response to the seasonal trivalent influenza vaccine is attenuated in cancer patients. Furthermore, rates of seroprotection and seroconversion vary by malignancy type and are higher in patients with solid tumors, as compared either with those with hematologic malignancies or with allogeneic hematopoietic stem cell recipients. In 2009, a novel influenza strain prompted development of new vaccines and evaluation of alternative dosing strategies in an attempt to increase the rates of seroconversion in immunocompromised patients, further complicating this issue. Recent literature has demonstrated that the use of myeloablative chemotherapy regimens and biologics is correlated with decreased immunogenicity and response to influenza vaccines. Much debate still exists as to the optimal timing of influenza vaccination. Delaying vaccination from 1 week following standard chemotherapy up to 6 months following rituximab is increasingly supported by studies in this heterogeneous population.
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http://dx.doi.org/10.1007/s11908-013-0368-7DOI Listing
December 2013

Early identification and control of carbapenemase-producing Klebsiella pneumoniae, originating from contaminated endoscopic equipment.

Am J Infect Control 2013 Jun 18;41(6):562-4. Epub 2012 Nov 18.

Department of Infectious Diseases and International Medicine, University of South Florida, College of Medicine, Tampa, FL, USA.

Klebsiella producing carbapenemase is an emerging pathogen. We report transmission of this organism by contaminated endoscopic instruments. Quick identification of source, staff education, contact precautions, and emphasis on hand and environmental hygiene led to case control and prevention of outbreak.
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http://dx.doi.org/10.1016/j.ajic.2012.07.008DOI Listing
June 2013

An analysis of regulatory T-cell and Th-17 cell dynamics during cytomegalovirus replication in solid organ transplant recipients.

PLoS One 2012 11;7(11):e43937. Epub 2012 Oct 11.

Alberta Transplant Institute and Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada.

Background: CMV-specific T-cells are crucial to control CMV-replication post-transplant. Regulatory T-cells (T-regs) are associated with a tolerant immune state and may contribute to CMV-replication. However, T-cell subsets such as T-regs and IL-17 producing T-cells (Th-17) are not well studied in this context. We explored T-regs and Th-17 frequencies during CMV-replication after transplantation.

Methods: We prospectively evaluated 30 transplant patients with CMV-viremia. We quantified CMV-specific CD4(+) and CD8(+) T-cells, T-regs (CD4(+)CD25(+)FoxP3(+)) and Th-17 frequencies using flow-cytometry and followed patients requiring anti-viral treatment. Two subsets were compared: anti-viral treatment requirement (n = 20) vs. spontaneous clearance of viremia (n = 10).

Results: Higher initial CMV-specific CD4(+) T-cells and lower T-regs were observed in patients with spontaneous clearance (p = 0.043; p = 0.021 respectively). Using a ratio of CMV-specific CD4(+) T-cells to T-regs allowed prediction of viral clearance with 80% sensitivity and 90% specificity (p = 0.001). One month after stop of treatment, the same correlation was observed in patients protected from CMV-relapse. The ratio of CMV-specific CD4(+) T-cells to T-regs allowed prediction of relapse with 85% sensitivity and 86% specificity (p = 0.004). Th-17 responses were not correlated with virologic outcomes.

Conclusions: This study provides novel insights into T-regs and Th-17 subpopulations during CMV-replication after transplantation. These preliminary data suggest that measurement of CMV-specific CD4(+) T-cells together with T-regs has value in predicting spontaneous clearance of viremia and relapse.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0043937PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3469568PMC
March 2013

Humoral immune response following seasonal influenza vaccine in islet transplant recipients.

Cell Transplant 2013 21;22(3):469-76. Epub 2012 Sep 21.

Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada.

Annual influenza vaccine is recommended for organ transplant recipients, but immunogenicity is known to be suboptimal. Islet transplant recipients receive immunosuppressive therapy, but there are no data on the immunogenicity of influenza vaccine in this population. In this prospective cohort study, adult islet transplant recipients at least 3 months posttransplant were enrolled. All patients received the 2010-2011 seasonal influenza vaccine. Serum was obtained pre- and postvaccination to determine humoral response to each of the three influenza strains included in the vaccine. Adverse effects of vaccine were also noted. A total of 61 islet transplant recipients were enrolled and completed the study protocol. The median time from last transplant was 1.9 years (range 0.26-11.4 years), and most patients had undergone multiple prior islet transplant procedures (90.2%). Overall immunogenicity of the vaccine was poor. Seroconversion rates to H1N1, H3N2, and B antigens were 34.4%, 29.5%, and 9.8%, respectively. In the subset not seroprotected at baseline, a protective antibody titer postvaccination was achieved in 58.6%, 41.9%, and 34.5% of patients, respectively. Patients within the first year of transplant were significantly less likely to seroconvert to at least one antigen (23.5% vs. 54.5%; p = 0.029). Alemtuzumab recipients trended toward lower seroconversion rates (25% vs. 51%; p = 0.11). No vaccine-related safety concerns were identified. Seasonal influenza vaccine had suboptimal immunogenicity in islet transplant recipients especially those who were less than 1 year posttransplant or had received alemtuzumab induction. Novel strategies for protection in this group of patients need further study.
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http://dx.doi.org/10.3727/096368912X656135DOI Listing
September 2013

Long term immune responses to pandemic influenza A/H1N1 infection in solid organ transplant recipients.

PLoS One 2011 14;6(12):e28627. Epub 2011 Dec 14.

Alberta Institute of Transplant Sciences, University of Alberta, Edmonton, Alberta, Canada.

In solid organ transplant (SOT) recipients it is unknown if natural infection with influenza confers protection from re-infection with the same strain during the next influenza season. The purpose of this study was to determine if infection with pandemic influenza A/H1N1 (pH1N1) resulted in a long-term immunologic response. Transplant recipients with microbiologically proven pH1N1 infection in 2009/2010 underwent humoral and cell-mediated immunity (CMI) testing for pH1N1 just prior to the next influenza season. Concurrent testing for A/Brisbane/59/2007 was done to rule-out cross-reacting antibody. We enrolled 22 adult transplant patients after pH1N1 infection. Follow up testing was done at a median of 7.4 months (range 5.8-15.4) after infection. After excluding those with cross-reactive antibody, 7/19 (36.8%) patients were seroprotected. Detectable pH1N1-specific CD4+ and CD8+ interferon-γ producing T-cells were found in 11/22 (50%) and 8/22 (36.4%) patients respectively. Humoral immunity had a significant correlation with a CD4 response. This is the first study in transplant patients to evaluate long-term humoral and cellular response after natural influenza infection. We show that a substantial proportion of SOT recipients with previous pH1N1 infection lack long-term humoral and cellular immune responses to pH1N1. These patients most likely are at risk for re-infection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0028627PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237471PMC
August 2012