Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma
2021; 5 (1): 143–55
Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma.
2021; 5 (1): 143–55
Fungal prostatitis due to endemic mycoses and Cryptococcus: A multicenter case series.
Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed large B-cell lymphoma (LBCL). We evaluated the long-term course of hematologic recovery, immune reconstitution, and infectious complications in 41 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) at a single center. Grade 3+ cytopenias occurred in 97.6% of patients within the first 28 days postinfusion, with most resolved by 6 months. Overall, 63.4% of patients received a red blood cell transfusion, 34.1% of patients received a platelet transfusion, 36.6% of patients received IV immunoglobulin, and 51.2% of patients received growth factor (granulocyte colony-stimulating factor) injections beyond the first 28 days postinfusion. Only 40% of patients had recovered detectable CD19+ B cells by 1 year, and 50% of patients had a CD4+ T-cell count <200 cells per μL by 18 months postinfusion. Patients with durable responses to axi-cel had significantly longer durations of B-cell aplasia, and this duration correlated strongly with the recovery of CD4+ T-cell counts. There were significantly more infections within the first 28 days compared with any other period of follow-up, with the majority being mild-moderate in severity. Receipt of corticosteroids was the only factor that predicted risk of infection in a multivariate analysis (hazard ratio, 3.69; 95% confidence interval, 1.18-16.5). Opportunistic infections due to Pneumocystis jirovecii and varicella-zoster virus occurred up to 18 months postinfusion in patients who prematurely discontinued prophylaxis. These results support the use of comprehensive supportive care, including long-term monitoring and antimicrobial prophylaxis, beyond 12 months after axi-cel treatment.
View details for DOI 10.1182/bloodadvances.2020002732
View details for PubMedID 33570626
Eremothecium coryli bloodstream infection in a patient with acute myeloid leukemia: first case report of human infection
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
2019; 95 (1): 77–79
Missed diagnosis and misdiagnosis of infectious diseases in hematopoietic cell transplant recipients: an autopsy study.
2019; 3 (22): 3602–12
Fungal prostatitis is exceedingly rare with mostly case reports.Electronic medical records at three medical centers were searched for cases of fungal prostatitis due to endemic mycoses and Cryptococcus over the preceding 10 years.Seven cases were identified from 105 600 prostate biopsies within the Southern California Permanente Medical Group for an incidence of 0.0066%. An additional eight cases were identified from two other health care systems. Excluding four patients without available clinical data, 11 patients were reviewed, most of whom underwent biopsy due to elevated prostate-specific antigen. Four were asymptomatic and the remainder had nonspecific signs or symptoms. All biopsies revealed granulomatous inflammation and fungal organisms. Seven patients had coccidioidomycosis, three patients had cryptococcosis (confirmed in two cases and suspected by organism morphology in the other), and one patient had likely histoplasmosis based on organism morphology. Prolonged antifungal treatment was standard; outcomes were favorable.Fungal prostatitis due to endemic mycoses and Cryptococcus is uncommon and associated with favorable outcomes but generally involves prolonged therapy.
View details for DOI 10.1002/pros.24034
View details for PubMedID 32572997
Use of Alternative Agents for Prevention of Opportunistic Infections in Heart and Lung Transplant Recipients
CLINICAL INFECTIOUS DISEASES
2018; 67 (10): 1637–39
Echinocandin prophylaxis in patients undergoing haematopoietic cell transplantation and other treatments for haematological malignancies.
The Journal of antimicrobial chemotherapy
2018; 73 (suppl_1): i60–i72
Hematopoietic cell transplantation (HCT) is potentially curative for patients with hematologic disorders, but carries significant risks of infection-related morbidity and mortality. Infectious diseases are the second most common cause of death in HCT recipients, surpassed only by progression of underlying disease. Many infectious diseases are difficult to diagnose and treat, and may only be first identified by autopsy. However, autopsy rates are decreasing despite their value. The clinical and autopsy records of adult HCT recipients at our center who underwent autopsy between 1 January 2000 and 31 December 2017 were reviewed. Discrepancies between premortem clinical diagnoses and postmortem autopsy diagnoses were evaluated. Of 185 patients who underwent autopsy, 35 patients (18.8%) had a total of 41 missed infections. Five patients (2.7%) had >1 missed infection. Of the 41 missed infections, 18 (43.9%) were viral, 16 (39.0%) were fungal, 5 (12.2%) were bacterial, and 2 (4.9%) were parasitic. According to the Goldman criteria, 31 discrepancies (75.6%) were class I, 5 (12.2%) were class II, 1 (2.4%) was class III, and 4 (9.8%) were class IV. Autopsies of HCT recipients frequently identify clinically significant infectious diseases that were not suspected premortem. Had these infections been suspected, a change in management might have improved patient survival in many of these cases. Autopsy is underutilized and should be performed regularly to help improve infection-related morbidity and mortality. Illustrative cases are presented and the lessons learned from them are also discussed.
View details for DOI 10.1182/bloodadvances.2019000634
View details for PubMedID 31743391
Prevention and Management of Tuberculosis in Solid Organ Transplant Recipients.
Infectious disease clinics of North America
2018; 32 (3): 703–18
Antifungal prophylaxis is the standard of care for patients undergoing intensive chemotherapy for haematological malignancy or haematopoietic cell transplantation (HCT). Prophylaxis with azoles reduces invasive fungal infections and may reduce mortality. However, breakthrough infections still occur, and the use of azoles is sometimes complicated by pharmacokinetic variability, drug interactions, adverse events and other issues. Echinocandins are highly active against Candida species, including some organisms resistant to azoles, and have some clinical activity against Aspergillus species as well. Although currently approved echinocandins require daily intravenous administration, the drugs have a favourable safety profile and more predictable pharmacokinetics than mould-active azoles. Clinical data support the efficacy and safety of echinocandins for antifungal prophylaxis in haematology and HCT patients, though data are less robust than for azoles. Notably, sparse evidence exists supporting the use of echinocandins as antifungal prophylaxis for patients with significant graft-versus-host disease (GvHD) after HCT. Two drugs that target (1,3)-β-d-glucan are in development, including an oral glucan synthase inhibitor and an echinocandin with unique pharmacokinetics permitting subcutaneous and weekly administration. Echinocandins are a reasonable alternative to azoles and other agents for antifungal prophylaxis in patients undergoing intensive chemotherapy for haematological malignancy or those receiving HCT, excluding those with significant GvHD.
View details for PubMedID 29304213
Infectious Complications of Multiple Sclerosis Therapies: Implications for Screening, Prophylaxis, and Management.
Open forum infectious diseases
2018; 5 (8): ofy174
Solid organ transplant recipients are at an increased risk of tuberculosis and transplant candidates should be screened early in their evaluation with a detailed history, tuberculin skin test or tuberculosis interferon-gamma release assay, and chest radiograph. For latent tuberculosis treatment, isoniazid and rifamycin-based regimens have advantages and disadvantages; treatment decisions should be customized. Tuberculosis after solid organ transplantation generally occurs after months or years; early infections should raise the possibility of donor-derived infections. Tuberculosis diagnosis and treatment in solid organ transplant recipients may be complicated by protean manifestations, drug interactions, and adverse drug reactions.
View details for PubMedID 30146031
HHV-6 and Septic Shock: Tenuous Proof of Causation.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Multiple sclerosis therapies include interferons, glatiramer, and multiple immunosuppressive drugs. Discerning infectious risks of immunosuppressive drugs requires understanding their mechanisms of action and analyzing interventional studies and postmarketing observational data. Though identical immunosuppressive therapies are sometimes used in non-neurologic conditions, infectious risks may differ in this population. Screening for and treatment of latent tuberculosis (TB) infection should be prioritized for patients receiving alemtuzumab; ocrelizumab is likely not associated with an increased risk of TB. Hepatitis B virus (HBV) reactivation can be devastating for patients treated with ocrelizumab and alemtuzumab, whereas the small molecule oral agents do not likely pose substantial risk of HBV. Progressive multifocal leukoencephalopathy is a particular concern with natalizumab. Alemtuzumab, and possibly natalizumab and fingolimod, risks herpes virus reactivation and may warrant prophylaxis. Unusual opportunistic infections have been described. Vaccination is an important tool in preventing infections, though vaccine timing and contraindications can be complex.
View details for PubMedID 30094293
View details for PubMedCentralID PMC6080056
Use of Alternative Agents for Prevention of Opportunistic Infections in Heart and Lung Transplant Recipients.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Micafungin Versus Posaconazole Prophylaxis in Acute Leukemia or Myelodysplastic Syndrome: A Randomized Study.
The Journal of infection
Bonnafous and others present the case of a patient who became ill three weeks after liver transplantation, developing multiple organ failure and episodes of apparent septic shock culminating in death. The authors attribute the illness to reactivation of donor-derived chromosomally-integrated human herpesvirus 6 (HHV-6) infection.1 While HHV-6 is often considered a potential etiologic agent in immunocompromised patients with encephalitis and other diseases, proof of a causal relationship is tenuous. This article is protected by copyright. All rights reserved.
View details for DOI 10.1111/ajt.14983
View details for PubMedID 29939480
The Brief Case: Anaerobiospirillum succiniciproducens Bacteremia and Pyomyositis.
Journal of clinical microbiology
2017; 55 (3): 665-669
Closing the Brief Case: Anaerobiospirillum succiniciproducens Bacteremia and Pyomyositis.
Journal of clinical microbiology
2017; 55 (3): 986-987
Toxoplasma Encephalitis in Atypical Hosts at an Academic Cancer Center.
Open forum infectious diseases
2016; 3 (2): ofw070-?
To compare the effectiveness and tolerability of micafungin versus posaconazole during chemotherapy-induced neutropenia in acute leukemia (AL) and myelodysplastic syndrome (MDS).Patients with AL or MDS undergoing chemotherapy were randomized to open-label micafungin 100 mg intravenously daily or posaconazole suspension 400 mg orally twice daily until neutrophil recovery, up to 28 days. Patients were followed for 12 weeks. The primary endpoint was prophylaxis failure (premature discontinuation due to infection, intolerance, adverse event, or death). Time to failure and survival were calculated by Kaplan-Meier analysis.From March 2011 to May 2016, 113 patients who received at least 2 doses of prophylaxis were analyzed (58 patients randomized to micafungin and 55 to posaconazole). Prophylaxis failure occurred in 34.5% and 52.7% of patients on micafungin and posaconazole, respectively (P = 0.0118). The median number of days on prophylaxis was 16 [interquartile range (IQR) 12-20] for micafungin and 13 [IQR 6-16] for posaconazole (P = 0.01). Micafungin failures were largely due to antifungal treatment; posaconazole failures were mostly due to gastrointestinal intolerance or adverse effects. IFI incidence and survival were similar between study arms.Our data support micafungin as alternative antifungal prophylaxis in patients with AL and MDS.
View details for DOI 10.1016/j.jinf.2018.03.015
View details for PubMedID 29746955
Toxoplasma encephalitis is a well recognized complication of acquired immune deficiency syndrome, solid organ transplantation, and allogeneic hematopoietic stem cell transplantation (HSCT). However, patients with hematologic malignancies not treated with allogeneic HSCT may also develop this condition, which requires high clinical suspicion and consideration for prophylactic therapy.
View details for DOI 10.1093/ofid/ofw070
View details for PubMedID 27096140