Jaime S. Green

Early cytomegalovirus reactivation remains associated with increased transplant-related mortality in the current era: a CIBMTR analysis

Single-center studies have reported an association between early (before day 100) cytomegalovirus (CMV) reactivation and decreased incidence of relapse for acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation. To substantiate these preliminary findings, the Center for International Blood and Marrow Transplant Research (CIBMTR) Database was interrogated to analyze the impact of CMV reactivation on hematologic disease relapse in the current era. Data from 9469 patients transplanted with bone marrow or peripheral blood between 2003 and 2010 were analyzed according to 4 disease categories: AML (n = 5310); acute lymphoblastic leukemia (ALL, n = 1883); chronic myeloid leukemia (CML, n = 1079); and myelodysplastic syndrome (MDS, n = 1197). Median time to initial CMV reactivation was 41 days (range, 1-362 days). CMV reactivation had no preventive effect on hematologic disease relapse irrespective of diagnosis. Moreover, CMV reactivation was associated with higher nonrelapse mortality [relative risk [RR] among disease categories ranged from 1.61 to 1.95 and P values from .0002 to <.0001; 95% confidence interval [CI], 1.14-2.61). As a result, CMV reactivation was associated with lower overall survival for AML (RR = 1.27; 95% CI, 1.17-1.38; P <.0001), ALL (RR = 1.46; 95% CI, 1.25-1.71; P <.0001), CML (RR = 1.49; 95% CI, 1.19-1.88; P = .0005), and MDS (RR = 1.31; 95% CI, 1.09-1.57; P = .003). In conclusion, CMV reactivation continues to remain a risk factor for poor posttransplant outcomes and does not seem to confer protection against hematologic disease relapse.

Novel H1N1 Influenza in Hematopoietic Stem Cell Transplantation Recipients: Two Centers’ Experiences

Respiratory virus infections, such as influenza A, cause significant morbidity in hematopoietic stem cell transplantation (HSCT) recipients. The clinical characteristics and impact of infection with the novel H1N1 virus in this patient population is not yet well defined, however. HSCT recipients diagnosed with proven or probable H1N1 during the 2009 pandemic were identified and charts were retrospectively reviewed with analysis of clinical descriptions, risk factors, diagnosis, treatments, and outcomes. Twenty-seven patients from two medical centers were identified. Fever and cough were the most common presenting symptoms. The incidence of influenza lower respiratory tract infection (LRTI) was 52% (14/27). Compared with patients with LRTI, those with influenza upper respiratory tract infection (URTI) were more likely to have a classic influenza-like syndrome. Compared to patients with URTI, those with LRTI were started on antiviral therapy significantly later after symptom onset (3.0 days vs 6.58 days after onset of symptoms; P = .03; 95% confidence interval [CI], 0.29-6.8). Overall influenza-related 30-day mortality was 22% (6/27), and that in patients with LRTI was 43% (6/14). Chronic steroid use (≥20 mg/day of prednisone equivalent) at the time of presentation was associated with LRTI (P = .006) and mortality (P = .003) on univariate analysis. Five cases were hospital-acquired. In this first season of the novel H1N1 pandemic, infection in HSCT often presented as an atypical severe illness with a high incidence of LRTI and high mortality.

Identification of Bacteria in Formalin-Fixed, Paraffin-Embedded Heart Valve Tissue via 16S rRNA Gene Nucleotide Sequencing

ABSTRACT We applied 16S rRNA gene sequencing to identify bacterial species present in formalin-fixed, paraffin-embedded heart valve tissue. In 40% (12/30) of the cases, we were able to identify the bacterium to the species-genus level. For more recent cases (≤4 years), the success rate was significantly improved, to 70% (P < 0.001).

Persistent Neutrophilic Meningitis in an Immunocompetent Patient after Basilar Skull Fracture: Case Report

BackgroundPersistent neutrophilic meningitis is an unusual form of chronic meningitis that is defined as clinical meningitis with a neutrophilic pleocytosis that persists for greater than 7 days despite empiric antimicrobial therapy. Although numerous disease processes can cause this syndrome, the majority of cases are due to opportunistic pathogens infecting immunocompromised hosts.Case PresentationA 47 year-old female presented after basilar skull fracture with persistent neutrophilic meningitis unresponsive to empiric broad-spectrum antibiotics. After more than weeks of intensive therapy, 4 hospitalizations and 3 relapses, Nocardia cyriacigeorgica was identified from cerebral spinal fluid. Induction therapy was begun with Ceftriaxone and trimethoprim-sulfamethoxazole (TMP-SMX) for 6 weeks followed by therapy with TMP-SMX and doxycycline for one year. The patient made a complete recovery without sequelae.ConclusionsDue to the difficulty in obtaining a microbiologic diagnosis, appropriate treatment in cases of persistent neutrophilic meningitis is often delayed leading to morbidity, This case highlights a number of the unique features of Nocardia meningitis and the importance of considering Nocardia infection as a cause of persistent neutrophilic meningitis even in immunocompetent patients.

Human Herpesvirus 6 is Associated with Status Epilepticus and Hyponatremia after Umbilical Cord Blood Transplantation

This article describes a case involving a 65-year-old man who experienced nonconvulsive status epilepticus after undergoing an allogenic hematopoietic cell transplantation to treat chronic lymphocytic leukemia. The authors describe the diagnostic work-up and treatment of human herpesvirus 6 infection, and discuss other potential causes of nonconvulsive status epilepticus in similar scenarios.

Absence of early HHV-6 reactivation after cord blood allograft predicts powerful graft-versus-tumor effect

Approximately 75% of cord blood transplant (CBT) recipients experience human herpes virus‐6 (HHV‐6) reactivation. Considering the immunomodulatory effects of HHV‐6, we hypothesized that early HHV‐6 reactivation may influence the risk of relapse of the underlying hematologic malignancy. In 152 CBT recipients with hematological malignancies, we determined the association between HHV‐6 reactivation by day +28 and 2‐year cumulative incidence of relapse. In univariate analysis, the absence of HHV‐6 reactivation (n = 32) was associated with less relapse (26 [18‐35]% vs. 7 [0‐17]% in groups with vs. without HHV‐6 reactivation, respectively; P = .03). This difference was due to a remarkably low relapse incidence among patients without HHV‐6 reactivation. In multivariable analysis, the absence of HHV‐6 reactivation was associated with less relapse (hazard ratio [95% confidence interval]: 0.2 [0.05‐0.9], P = .03). This association was independent of patient‐, disease‐, and transplant‐related characteristics known to influence the risk of relapse. Natural killer cell and T‐cell reconstitution at day +28 were similar between patients with vs. without HHV‐6 reactivation. Our results suggest that CB allografts not complicated by HHV‐6 reactivation by day +28 have a powerful graft‐versus‐tumor effect. Knowledge about early HHV‐6 reactivation may stratify patients at day +28 into low vs. high relapse risk groups.

Reactivation of Chagas disease among heart transplant recipients in the United States, 2012-2016

Heart transplantation has been shown to be a safe and effective intervention for progressive cardiomyopathy from chronic Chagas disease. However, in the presence of the immunosuppression required for heart transplantation, the likelihood of Chagas disease reactivation is significant. Reactivation may cause myocarditis resulting in allograft dysfunction and the rapid onset of congestive heart failure. Reactivation rates have been well documented in Latin America; however, there is a paucity of data regarding the risk in non‐endemic countries.

Evaluation and Management of Bacterial and Fungal Infections in Patients with a Hematological Malignancy: A 2018 Update

Bacterial and fungal infections continue to be an unwelcome complication of the treatment of patients with hematological malignancies despite much progress in the oncologic management in recent years. Some new treatment advances and modalities have offered hope to entire new patient populations, but have also opened the door for opportunistic and invasive organisms. Developments in antimicrobial agents, diagnostic methods, and infection control practices have unfortunately not been able to keep up with rapid developments in oncologic therapies nor antimicrobial resistance. Understanding and control of risk factors for antineoplastic therapy-associated immune-suppression, antimicrobial mechanisms and effects, and changing microbial characteristics are key factors to prevention and treatment of bacterial and fungal infection in this complex patient population. This chapter aims to provide a solid understanding of all these principles and factors to enable educated decision-making, considering guidelines and evidence when these exist, and rational recommendations when evidence is lacking for a particular topic.

Strongyloides hyperinfection following hematopoietic stem cell transplant in a patient with HTLV‐1‐associated T‐cell leukemia

Strongyloides stercoralis has the potential to cause accelerated autoinfection in immunocompromised hosts. Screening tests for strongyloidiasis may be falsely negative in the setting of immunosuppression. We report a case of Strongyloides hyperinfection syndrome in a patient with human T‐lymphotropic virus type 1‐associated T‐cell leukemia early after hematopoietic stem cell transplant. The diagnosis was made by stool ova and parasite examination, despite a negative screening enzyme‐linked immunosorbent assay. Because of anticipated prolonged neutropenia, an extended course of treatment was utilized.

The challenges of treating aspergillus abdominal aneurysm after hematopoietic cell transplant: Rapid voriconazole metabolizer

Mycotic aneurysms are a fatal manifestation of disseminated fungal infections in immunocompromised hosts. We present a patient with an Aspergillus mycotic aneurysm after hematopoietic cell transplant. Due to CYP2C19 rapid metabolizer phenotype (*1/*17), therapeutic levels of voriconazole were unobtainable. Successful therapy was achieved with posaconazole salvage therapy and early, aggressive surgery. This case demonstrates the consequences of voriconazole rapid metabolism and the potential impact of genetic variants.