Pocket Oncology (Pocket Notebook Series), 1st Ed.

INFECTIONS IN THE TRANSPLANT HOST

Lalitha Parameswaran and Monika K. Shah

Background

Infxn occurring after HSCT cause ↑ morbidity & mortality. RF for infxn include skin breakdown & mucositis from conditioning, use of central venous catheters, neutropenia, & immunodeficiency (N Engl J Med2006;17:1813).

Stages of Transplant and Related Infections

Pre & tx of infxn in HSCT pts is based on understanding the type of pretransplant conditioning regimen, type of graft used, the different stages of immune recovery after transplant, & the infxn a/w each of those stages (MMWR Recomm Rep 2000;49(RR-10):1)

Bacterial Infections

• Blood stream infxn during HSCT: Commonly seen during conditioning & pre-engraftment phases

Gram-negative bacteria have slowly been replaced by gram-positive organisms (inc. Coagulase-negative Staphylococci, Enterococcus, & Staphylococcus aureus) as causative agents of bacteremia after HSCT

Bacteremia is more common in allogeneic vs. in autologous transplants (Ann Hematol 2005;84:40)

• Intestinal domination by single organisms, like Vancomycin-resistant Enterococcus & Gram-negative bacilli may represent a major RF for development of bacteremia in HSCT (Clin Infect Dis 2012;55:905)

Viral Infections

• CMV causes the most sev. & clinically evident disease

Definition of Infxn: Recovery of DNA from sterile sites (ie, blood); Definition of Disease: End-organ damage caused by CMV, inc. pneumonitis, hepatitis, colitis, chorioretinitis, & encephalitis

Pts at ↑ risk for CMV infxn: (1) High-dose corticosteroids & MMF; (2) use of anti-T-cell strategies including T-cell depleted grafts; (3) positive CMV serostatus of the recipient (Biol Blood Marrow Transplant2003;9:543)

Pts w/↑ risk for CMV disease: Chronic GVHD (p = 0.001) & prior antiviral Rx for more than 4 wks (p = 0.007) (Blood 1995;86:2815)

Monitoring of CMV by checking PCR in blood allows prompt start of preemptive antiviral Rx, w/c ↓ the incidence of CMV disease, CMV-related mortality & duration of antiviral Rx.

Foscarnet, Ganciclovir: Drugs of choice for preemptive Rx. Their use ↓ the incidence of CMV disease to <5%. No difference in survival between the two drugs. S/e may limit their use, neutropenia is >w/Ganciclovir (p = 0.04) & renal insufficiency is >w/Foscarnet (p = 0.4) (Blood 2002;99:1159)

• HSV/VZV reactivation: Can occur at early or late stages after HSCT.

ACV Ppx is effective in preventing reactivation. It should be administered to all HSCT pts during pretransplant conditioning.

• EBV reactivation: Correlates w/post-transplant lymphoproliferative disorder. Rituximab is the tx of choice.

• HHV-6 reactivation: Occurs early after HSCT in about half of all allo-HSCT recipients.

Its high prevalence makes it difficult to make disease associations.

Most significant manifestation: Encephalitis although it can also delay engraftment (Bone Marrow Transplant 2008;42:227)

• Adenovirus reactivation: The relative contribution of Adenovirus as a viral cause of mortality has ↑ in the last decade.

Viral load ≥10 copies may correlate w/development of Adenovirus disease (Biol Blood Marrow Transplant 2012;12:1)

Fungal Infections

• Invasive Aspergillosis: Most common invasive fungal infxn.

Voriconazole is the tx of choice. It has better response & ↑ survival; as well as potential ↓ s/e than Amphotericin B (N Engl J Med 2002;347:408)

• Other relevant fungi: Species of Candida & non Aspergillus molds.

Candida causes earlier infxn after HSCT (∼60 d) compared to molds (∼120 d) (Clin Infect Dis 2010;50:1091)

• Incidence of nonAspergillus mold infxn (ie, Mucormycosis, Fusarium, Scedosporium, Dematiaceous) has ↑ during the last decade.

Reasons are unclear but ≠ survival, changes in immunosuppression & use of antifungals may be RF(Emerg Infect Dis 2011;17:1856)

• Post-HSCT pts are at ↑ risk for PCP. Prompt recognition & tx may ↑ survival.

TMP-SMX is the first-line agent for tx & Ppx. Second-line agents (dapsone, clindamycin/primaquine, pentamidine, atovaquone) are ↓ effective than TMP-SMX for both tx & Ppx.

Parasitic Infections

• Toxoplasma gondii reactivation: Most important parasitic infxn in pts following HSCT.

Disseminated disease can occur. CNS > lungs > heart are main organs involved; hepatitis, nephritis, & chorioretinitis also reported.

Early onset (before d 60): Worse prognosis vs. late disease (Clin Infect Dis 2000;31:1188)

Dx: May be difficult, requires a ↑ degree of clinical suspicion; molecular methods such as PCR & histopathologic analysis of tissues are mainstay of dx (Leukemia Lymphoma 2010;51:1530)

• Strongyloides stercolaris: Causes hyperinfection syndrome after HSCT

Pretransplantation testing & preemptive tx strategies should be considered in pts from endemic areas.