University of Wisconsin Hematology

Infections in the immunocompromised host

General

  1. Manzo and Bhatt. The human microbiome in hematopoiesis and hematologic disorders. Blood 2015;126:311
  2. Pizzo PA. Management of Patients With Fever and Neutropenia Through the Arc of Time: A Narrative Review. Ann Intern Med 2019;170:389
  3. Mullighan et al. Mannose-binding lectin status is associated with risk of major infection following myeloablative sibling allogeneic hematopoietic stem cell transplantation. Blood 2008;112:2120
  4. Straka et al. Testing G-CSF responsiveness predicts the individual susceptibility to infection and consecutive treatment in recipients of high-dose chemotherapy. Blood 2011;117:2121(“G-CSF responsiveness appears as a signature of the myeloid marrow reserve predicting defense against neutropenic infection after intensive chemotherapy”)
  5. DesJardin et al. Clinical utility of blood cultures drawn from indwelling central venous catheters in hospitalized patients with cancer. Ann Intern Med 1999;131:641
  6. Klastersky et al. The Multinational Association for Supportive Care in Cancer Risk Index: A Multinational Scoring System for Identifying Low-Risk Febrile Neutropenic Cancer Patients. J Clin Oncol 2000;18:3038
  7. Talcott et al. Safety of Early Discharge for Low-Risk Patients With Febrile Neutropenia: A Multicenter Randomized Controlled Trial. J Clin Oncol 2011;29:3977(Home antibiotic therapy as safe as hospital care)
  8. Kern et al. Oral Antibiotics for Fever in Low-Risk Neutropenic Patients With Cancer: A Double-Blind, Randomized, Multicenter Trial Comparing Single Daily Moxifloxacin With Twice Daily Ciprofloxacin Plus Amoxicillin/Clavulanic Acid Combination Therapy—EORTC Infectious Diseases Group Trial XV. J Clin Oncol 2013;31:1149
  9. Bucaneve et al. Results of a Multicenter, Controlled, Randomized Clinical Trial Evaluating the Combination of Piperacillin/Tazobactam and Tigecycline in High-Risk Hematologic Patients With Cancer With Febrile Neutropenia. J Clin Oncol 2014;32:1463(Adding tigecycline increased rate of treatment success from 44% to 68%)
  10. Aguilar-Guisado et al. Optimisation of empirical antimicrobial therapy in patients with haematological malignancies and febrile neutropenia (How Long study): an open-label, randomised, controlled phase 4 trial. Lancet Haematol 2017;4:e583(Safe to stop antibiotics in high-risk patients who have recovered clinically and have been afebrile for 72 hours; with editorial)

Prophylaxis

  1. Dadwal et al. How I prevent viral reactivation in high-risk patients. Blood 2023;141:2062
  2. Hill and Seo. How I prevent infections in patients receiving CD19-targeted chimeric antigen receptor T cells for B-cell malignancies. Blood 2020;136:925
  3. Bucaneve et al. Levofloxacin to Prevent Bacterial Infection in Patients with Cancer and Neutropenia. NEJM 2005;353:977
  4. Cullen et al. Antibacterial Prophylaxis after Chemotherapy for Solid Tumors and Lymphomas. NEJM 2005;353:988  (Levofloxacin reduced incidence of fever, probable infection, and hospitalization)
  5. Therriault et al. Characterization of Bacterial Infections in Allogeneic Hematopoietic Stem Cell Transplant Recipients Who Received Prophylactic Levofloxacin With Either Penicillin or Doxycycline. Mayo Clin Proc 2010;85:711 (Prophylaxis may increase incidence of resistant gram negative infections)
  6. Gafter-Gvili et al. Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients.  Ann Intern Med 2005;142:979
  7. Bow et al. Quinolone-based antibacterial chemoprophylaxis in neutropenic patients: effect of augmented gram-positive activity on infectious morbidity. Ann Intern Med 1996;125:183
  8. Robenshtok et al. Antifungal Prophylaxis in Cancer Patients After Chemotherapy or Hematopoietic Stem-Cell Transplantation: Systematic Review and Meta-Analysis. J Clin Oncol 2007;25:5471
  9. Ullmann et al. Posaconazole or Fluconazole for Prophylaxis in Severe Graft-versus-Host Disease. NEJM 2007;356:335
  10. Cornely et al. Posaconazole vs. Fluconazole or Itraconazole Prophylaxis in Patients with Neutropenia. NEJM 2007;356:348    (Posaconazole superior, gave survival advantage)
  11. Wingard et al. Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation. Blood 2010; 116:5111(No difference in fungus-free survival)
  12. Fisher et al. Effect of Caspofungin vs Fluconazole Prophylaxis on Invasive Fungal Disease Among Children and Young Adults With Acute Myeloid Leukemia. A Randomized Clinical Trial. JAMA 2019;322:1673(Caspofungin superior)
  13. Erard et al. One-year acyclovir prophylaxis for preventing varicella-zoster virus disease after hematopoietic cell transplantation: no evidence of rebound varicella-zoster virus disease after drug discontinuation. Blood 2007;110:3071
  14. Hill et al. Oral brincidofovir decreases the incidence of HHV-6B viremia after allogeneic HCT. Blood 2020;135:1447
  15. Wilcox et al. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. NEJM 2017;376:305

Fungal infection

  1. Nucci and Anaissie. How we treat invasive fungal diseases in patients with acute leukemia: the importance of an individualized approach. Blood 2014;124:3858
  2. Bow. E. Of Yeasts and Hyphae: A Hematologist’s Approach to Antifungal Therapy. Hematology 2006;361
  3. Walsh et al.  Caspofungin versus Liposomal Amphotericin B for Empirical Antifungal Therapy in Patients with Persistent Fever and Neutropenia. NEJM 2004;351:1391
  4. Thompson et al. Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (ReSTORE): a multicentre, double-blind, double-dummy, randomised phase 3 trial. Lancet 2023;401:49 (Weekly rezafungin non-inferior to daily caspofungin)
  5. Walsh et al. Liposomal amphotericin B for empirical therapy in patients with persistent fever and netropenia. NEJM 1999;340:764
  6. DeShazo et al. Fungal sinusitis. NEJM 1997;337:254
  7. Gerber et al. Reversible skeletal disease and high fluoride serum levels in hematologic patients receiving voriconazole. Blood 2012;120:2390
  8. Kontoyiannis and Lewis. How I treat mucormycosis. Blood 2011;118:1216

Aspergillus

  1. Thompson and Young. Aspergillus infections. NEJM 2021;385:1496
  2. Bergeron et al. The strategy for the diagnosis of invasive pulmonary aspergillosis should depend on both the underlying condition and the leukocyte count of patients with hematologic malignancies. Blood 2012;119:1831(Airway-invasive disease more common in non-leukemics and patients with ANC>100; angioinvasive disease found in leukemics and those with severe neutropenia)
  3. Meersseman et al. Galactomannan in Bronchoalveolar Lavage Fluid. A Tool for Diagnosing Aspergillosis in Intensive Care Unit Patients. Am J Respir Crit Care Med 2008;177:27(GM in BAL fluid much more sensitive than serum GM)
  4. Bochud et al. Toll-like Receptor 4 Polymorphisms and Aspergillosis in Stem-Cell Transplantation. NEJM 2008;359:1766
  5. Cunha et al. Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation. NEJM 2014;370:421(Donor genotype correlates with fungal infection risk)
  6. Marr et al. Combination Antifungal Therapy for Invasive Aspergillosis: A Randomized Trial. Ann Intern Med 2015;162:81(Dual therapy with echinocandin more effective than voriconazole alone)
  7. Matt et al. Predicting Outcome After Lung Resection for Invasive Pulmonary Aspergillosis in Patients With Neutropenia. Chest 2004;126:1783
  8. Maertens et al. Screening for circulating galactomannan as a noninvasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation recipients: a prospective validation. Blood 2001;97:1604
  9. Herbrecht et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. NEJM 2002;347:408
  10. Maertens et al. Posaconazole versus voriconazole for primary treatment of invasive aspergillosis: a phase 3, randomised, controlled, non-inferiority trial. Lancet 2021;397:499 (Posaconazole non-inferior, better tolerated)

Candida

  1. Kulbert and Arendrup. Invasive candidiasis. Mayo Clin Proc 2015;373:1445
  2. Mora-Duarte et al.  Comparison of caspofungin and amphotericin B for invasive candidiasis.  NEJM 2002;347:2020
  3. Kuse et al. Micafungin versus liposomal amphotericin B for candidemia and invasive candidiasis: a phase III randomised double-blind trial. Lancet 2007;269:1519
  4. Zhai et al. High-resolution mycobiota analysis reveals dynamic intestinal translocation preceding invasive candidiasis. Nat Med 2020;26:59
  5. Reboli et al. Anidulafungin versus fluconazole for invasive candidiasis. NEJM 2007;356:2472

Viral infections

 

  1. Blanchette et al. Influenza Vaccine Effectiveness Among Patients With Cancer: A Population-Based Study Using Health Administrative and Laboratory Testing Data From Ontario, Canada. J Clin Oncol 2019;37:2795 (Vaccine appeared to be effective in 20% of solid tumor pts, 8% of those with heme malignancy)
  2. Hall et al. Influenza Vaccination Strategies in Patients with Hematologic Cancer. NEJM 2025;392:306 (Augmented vaccine strategies have limited benefit; worst responses in patients receiving B-cell depleting therapies)
  3. Wade J. Viral Infections in Patients with Hematological Malignancies. Hematology 2006;368
  4. Torres and McDonald. How I treat hepatitis C virus infection in patients with hematologic malignancies. Blood 2016;128:1449
  5. Lok et al. Reactivation of Hepatitis B During Immunosuppressive Therapy: Potentially Fatal Yet Preventable. Ann Intern Med 2012;156:743
  6. Pleyer et al. Effect of Bruton tyrosine kinase inhibitor on efficacy of adjuvanted recombinant hepatitis B and zoster vaccines. Blood 2021;137:185 (“Nearly absent” response to Hep B vaccine; no effect on recall immune response to zoster vaccine)
  7. Liang R. How I treat and monitor viral hepatitis B infection in patients receiving intensive immunosuppressive therapies or undergoing hematopoietic stem cell transplantation. Blood 2009;113:3147
  8. Niitsu et al. Prospective analysis of hepatitis B virus reactivation in patients with diffuse large B-cell lymphoma after rituximab combination chemotherapy. J Clin Oncol 2010;28:5097(12% of patients with evidence of prior HBV infection relapsed during or after rituximab treatment)
  9. Zurawska et al. Hepatitis B virus screening before chemotherapy for lymphoma: a cost-effectivness analysis. J Clin Oncol 2012;30:3167(Most cosf-effective to screen everyone; 10-fold decrease in HBV reactivation rate)
  10. Seto et al. Hepatitis B Reactivation in Patients With Previous Hepatitis B Virus Exposure Undergoing Rituximab-Containing Chemotherapy for Lymphoma: A Prospective Study. J Clin Oncol 2014;32:3736(41% reactivation rate in 2 yrs in anti-HBc positive patients with undetactable serum HBV DNA)
  11. Boeckh M. Complications, Diagnosis, Management, and Prevention of CMV Infections: Current and Future. Hematology 2011:305
  12. Boeckh and Ljungman. How we treat cytomegalovirus in hematopoietic cell transplant recipients. Blood 2009;113:5711
  13. El Chaer et al. How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients. Blood 2016;128:2624
  14. O’Brien et al. Valganciclovir prevents cytomegalovirus reactivation in patients receiving alemtuzumab-based therapy. Blood 2008;111:1816
  15. Einsele et al. How I treat CMV reactivation after allogeneic hematopoietic stem cell transplantation. Blood 2020;135:1619
  16. Milano et al. Intensive strategy to prevent CMV disease in seropositive umbilical cord blood transplant recipients. Blood 2011;118:5689
  17. Boeckh et al. Valganciclovir for the Prevention of Complications of Late Cytomegalovirus Infection After Allogeneic Hematopoietic Cell Transplantation: A Randomized Trial. Ann Intern Med 2015;162:1(Prophylaxis no more effective than treatment guided by PCR testing for virus)
  18. Marty et al. Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation. NEJM 2018;378:2433(CMV infection rate 37% vs 61% in control group; all-cause mortality 21% vs 25%))
  19. Zerr et al. HHV-6 reactivation and its effect on delirium and cognitive functioning in hematopoietic cell transplantation recipients. Blood 2011;117:5243
  20. Hill et al. Oral brincidofovir decreases the incidence of HHV-6B viremia after allogeneic HCT. Blood 2020;135:1447
  21. Versluis et al. Hepatitis E virus: an underestimated opportunistic pathogen in recipients of allogeneic hematopoietic stem cell transplantation. Blood 2013;122:1079
  22. Erard et al. BK DNA viral load in plasma: evidence for an association with hemorrhagic cystitis in allogeneic hematopoietic cell transplant recipients. Blood 2005;106:1130
  23. Boeckh et al. Long-term acyclovir for prevention of varicella zoster virus disease after allogeneic hematopoietic cell transplantation�a randomized double-blind placebo-controlled study. Blood 2006;107:1800
  24. Englund et al. Brief Communication: Fatal Human Metapneumovirus Infection in Stem-Cell Transplant Recipients. Ann Intern Med 2006;144:344
  25. Scheinberg et al. Distinct EBV and CMV reactivation patterns following antibody-based immunosuppressive regimens in patients with severe aplastic anemia. Blood 2007; 109:3219(Subclinical, self-limited reactivation of EBV and CMV common after ATG-based treatment of AA)
  26. Casper et al. How I treat influenza in patients with hematologic malignancies. Blood 2010;115:1331
  27. Lindemans et al. How I treat adenovirus in hematopoietic stem cell transplant receipients. Blood 2010;116:5476
  28. Schwartz et al. Norovirus gastroenteritis causes severe and lethal complications after chemotherapy and hematopoietic stem cell transplantation. Blood 2011;117:5850
  29. Waghmare et al. How I treat respiratory viral infections in the setting of intensive chemotherapy or hematopoietic cell transplantation. Blood 2016;127:2682
  30. Shah and Chemaly.Management of RSV infections in adult recipients of hematopoietic stem cell transplantation. Blood 2011;117:2755
  31. Chemaly et al. The characteristics and outcomes of parainfluenza virus infections in 200 patients with leukemia or recipients of hematopoietic stem cell transplantation. Blood 2012;119:2738
  32. Waghmare et al. Clinical disease due to enterovirus D68 in adult hematologic malignancy patients and hematopoietic cell transplant recipients. Blood 2015;125:1724
  33. Leen et al. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood 2013;121:5113
  34. Neil and DeAngelis. Progressive multifocal leukoencephalopathy and hematologic malignancies: a single cancer center retrospective review. Blood Adv 2017;1:2041
  35. Muftuoglu et al. Allogeneic BK Virus–Specific T Cells for Progressive Multifocal Leukoencephalopathy. NEJM 2018;379:1443
  36. Cortese et al. Pembrolizumab Treatment for Progressive Multifocal Leukoencephalopathy. NEJM 2019;380:1597
  37. Progressive multifocal leukoencephalopathy in patients treated with chimeric antigen receptor T cells. Blood 2023;141:67 (Occurs in about 1/1000 recipients)
  38. Keller and Bollard. Virus-specific T-cell therapies for patients with primary immune deficiency. Blood 2020;135:620

COVID-19

  1. Pagano et al. Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from the EPICOVIDEHA survey. Blood 2022;140:2773 (Mortality 9% in vaccinated patients; monoclonal Ab/antivirals beneficial)
  2. Langerbeins and Hallek. COVID-19 in patients with hematologic malignancy. Blood 2022;140:236
  3. Chaer et al. How I treat and prevent COVID-19 in patients with hematologic malignancies and recipients of cellular therapies. Blood 2022;140:673
  4. Mato et al. Outcomes of COVID-19 in patients with CLL: a multicenter international experience. Blood 2020;136:1134(High mortality in both treated and untreated patients)
  5. Herishanu et al. Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia. Blood 2021;137:3165(Poor responses, particularly in patients under treatment)
  6. Hueso et al. Convalescent plasma therapy for B-cell–depleted patients with protracted COVID-19. Blood 2020;136:2290
  7. Aydillo et al. Shedding of Viable SARS-CoV-2 after Immunosuppressive Therapy for Cancer. NEJM 2020;383:2586(HSCT or CAR-T patients may shed viable virus for 2+ months after infection)
  8. Vijenthira et al. Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients. Blood 2020;136:2881(34% mortality rate, regardless of whether or not patient being actively treated)
  9. Chari et al. Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set. Blood 2020’136:3033
  10. Herishanu et al. Efficacy of a third BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL who failed standard 2-dose vaccination. Blood 2022;139:678 (About 25% responded to 3rd dose)
  11. Niemann et al. Patients with CLL have a lower risk of death from COVID-19 in the Omicron era. Blood 2022;140:445
  12. Shen et al. Multiple COVID-19 vaccine doses in CLL and MBL improve immune responses with progressive and high seroconversion. Blood 2022;140:2709
  13. Tadmore et al. Effectiveness of nirmatrelvir plus ritonavir treatment for patients with chronic lymphocytic leukemia during the Omicron surge. Blood 2023;141:2239

Pneumocystis

  1. Thomas and Limper.  Pneumocystis pneumonia.  NEJM 2004;350:2487

Pulmonary infiltrates

  1. Shorr et al.  Pulmonary Infiltrates in the Non-HIV-Infected Immunocompromised Patient. Etiologies, Diagnostic Strategies, and Outcomes. Chest 2004;125:260
  2. Heussel et al. Early detection of pneumonia in febrile neutropenic patients: use of thin-section CT. AJR 1997;169:1347
  3. Cockerill et al. Open lung biopsy in immunocompromised patients. Arch Intern Med 1985; 145:1398
  4. Englund et al. Brief Communication: Fatal Human Metapneumovirus Infection in Stem-Cell Transplant Recipients. Ann Intern Med 2006;144:344
  5. Wingard et al. How I manage pulmonary nodular lesions and nodular infiltrates in patients with hematologic malignancies or undergoing hematopoietic cell transplantation. Blood 2012;120:1791

Other infectious syndromes

  1. Leffler and Lamont. Clostridium difficile infection. NEJM 2015;372:1539
  2. Bartlett J.  Narrative Review: The New Epidemic of Clostridium difficile�Associated Enteric Disease. Ann Intern Med 2006;145:758
  3. Loo et al. Host and pathogen factors for Clostridium difficile infection and colonization. NEJM 2011;365:1693
  4. Talbot et al. Persistent fever after recovery from granulocytopenia in acute leukemia. Arch Intern Med 1988; 148:129

Catheter-related infections

  1. Safdar et al. Meta-Analysis: Methods for Diagnosing Intravascular Device�Related Bloodstream Infection. Ann Intern Med 2005;142:451