Introduction
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a vital treatment for various benign and malignant diseases, with over 50,000 procedures performed globally each year.
Pulmonary complications are a significant cause of morbidity and mortality in alloHSCT recipients, including non-infectious and infectious causes.
Despite antimicrobial prophylaxis and infection prevention measures, bacterial infections remain a major problem, affecting up to 20-30% of recipients.
The immunocompromised state post-alloHSCT is due to factors such as high-intensity chemotherapy, disruption of mucosal barriers, prolonged neutropenia, and delayed immune recovery.
Graft-versus-host disease (GVHD) is another concern, requiring immunosuppression and affecting the risk of opportunistic infections.
The risk of infection and GVHD varies based on factors like conditioning regimens, donor type, recipient traits, HLA match, and cell source
We hereby present all other cases reported in the literature of bacterial pathogens causing pneumonia in the chronic GVHD population.
Pathogenesis of Bacterial Pneumonia
Bacteria can reach the lungs through inhalation, aspiration, migration, or hematogenous spread. Lung protection mechanisms include mucociliary clearance and immune defenses, usually effective in a healthy host.
Infections trigger immune reactions that can lead to pneumonia, characterized by radiographic changes, fever, leukocytosis, and cough.
Cancer and its treatments can weaken the immune response and create structural defects, increasing the risk of acquiring infections, especially in hospitalized patients. Impaired immunity can obscure pneumonia symptoms, causing delayed diagnosis.
Graft-versus-host disease (GVHD) patients are at higher risk of bacterial pneumonias due to chronic inflammation, airway and lung damage, and immune deficiencies.
Treating GVHD with immunosuppression further increases the susceptibility to bacterial infections.
Methods
We conducted a systematic review using EMBASE, MEDLINE, and CINAHL databases. Our search strategy involved three key concepts: hematopoietic transplant, chronic GVHD, and bacterial pneumonia.
We used filters to exclude conference abstracts, and the results were categorized into case reports, non-case report reviews, and other articles.
No language or publication date filters were applied. We identified duplicates using EndNote and Zotero tools. After deduplication, we reviewed 225 unique records and selected the most relevant 40 articles for inclusion, excluding cases of pneumonia caused by Streptococcus pneumoniae or Haemophilus influenzae.
Mycobacterium Tuberculosis
Tuberculosis (TB) incidence varies widely globally, with a higher risk in highly endemic regions. Among hematopoietic stem cell transplant (HSCT) recipients, alloHSCT patients are at a threefold greater risk of developing active TB, especially affecting the lungs, and those with chronic GVHD are more susceptible due to prolonged immune dysfunction.
Certain GVHD treatments, such as corticosteroids, ruxolitinib, and anti-CD52 therapies, increase the risk of active TB, which can have a mortality rate of up to 50%.
Imaging findings for TB are diverse, and while nucleic acid testing is fairly sensitive and specific, culture remains the gold standard for diagnosis. Treating latent TB in alloHSCT patients with abnormal test results is crucial to prevent reactivation.
Nontuberculous Mycobacterial Infections
Nontuberculous mycobacterial (NTM) infections are more common in alloHSCT recipients, especially those with pulmonary chronic GVHD, with up to 2.9% of alloHSCT patients affected.
The treatment and clinical presentation of NTM infections in these patients resemble the general population.
The use of macrolides for post-alloHSCT patients with bronchiolitis obliterans syndrome (BOS) is controversial, as recent data suggest potential negative outcomes.
The chronic immunocompromised state and immunosuppressant use in alloHSCT recipients contribute to the higher incidence of NTM infections.
Liue et al. conducted a study in an Asian academic center, identifying 17 patients with NTM infection among those with chronic GVHD. They reported different NTM species and discussed patient characteristics.
Legionnaires’ Disease
Legionella is a Gram-negative bacterium found in water sources, commonly causing pneumonia known as Legionnaires’ disease (LD).
It was first identified in 1976 during an outbreak at an American Legion convention due to hotel air conditioning contamination.
Legionella pneumophila serogroup 1 is the primary human disease-causing species. Better diagnostic methods have increased Legionellosis awareness, with a 217% increase in cases from 2000 to 2009 in the US.
Immunocompromised individuals, including those with cancer, organ transplants, or on immunosuppressive medications, are at higher risk for LD, especially if their cellular immunity is impaired.
The bacterium is often acquired through community exposure or nosocomial outbreaks, including transplant centers.
Nocardia
Nocardia is a common Gram-positive bacterium found in soil and water. Pulmonary infections, often acquired through inhalation, can manifest as acute, subacute, or chronic illnesses with symptoms like fever and cough. Central nervous system infection can occur in up to 20-50% of cases.
In alloHSCT recipients, nocardiosis is rare, with an incidence between 0.3% and 1.7%. Trimethoprim-sulfamethoxazole (TMP-SMX) is commonly used for prophylaxis against Pneumocystis jiroveci pneumonia (PJP) and can also prevent Nocardia infection.
However, some recipients may develop nocardiosis despite TMP-SMX prophylaxis. Using alternatives to PJP prophylaxis, like atovaquone, increases the risk of nocardiosis.
Pseudomonas Aeruginosa
Pseudomonas aeruginosa is a Gram-negative bacterium commonly found in environmental reservoirs. It’s highly adaptable and can survive on various surfaces, including medical equipment.
This opportunistic pathogen is associated with a range of healthcare-associated infections, including ventilator-associated pneumonia, bloodstream infections, surgical site infections, urinary tract infections, and more.
Pseudomonas aeruginosa is known for its antibiotic resistance, adaptability, and virulence factors, making it a significant contributor to nosocomial infections. It can be especially dangerous for immunocompromised individuals and those with structural lung diseases, hematological neoplasms, and other risk factors.
Preventative and Mitigation Measures
To reduce the risk of infection in alloHSCT recipients, various prevention strategies are essential. These include emphasizing hand hygiene, avoiding contact with sick individuals, and maintaining sterile hospital environments. Regular dental care is also crucial. Vaccination is a critical component of infection prevention.
Its effectiveness can be influenced by factors like the type of HSCT, timing of immunization, age at transplantation, and the presence of chronic GVHD. Even with vaccination, patients may still have compromised immune systems, necessitating additional precautions. Active GVHD, its treatment, and recent rituximab use can impact vaccine responses.
AlloHSCT recipients should receive vaccinations for Streptococcus pneumoniae, Haemophilus influenzae type b, SARS-CoV-2, and seasonal influenza, among others. In cases of profound hypogammaglobulinemia (Ig levels <400 mg/dL) in the first 200 days post-transplant, intravenous immunoglobulin (IVIG) may be considered.
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