Page 1892 - Hematology_ Basic Principles and Practice ( PDFDrive )

1674 Part X Transplantation

chronic GVHD need to continue prophylaxis for the duration of by neutropenia in the preengraftment period, can greatly increase the
their immunosuppression. 1 risk of invasion and systemic yeast infections. Presence of indwelling
Human polyomavirus type I, also known as BK virus, can cause central venous catheters and alteration of normal surface flora arising
hemorrhagic cystitis in the early posttransplant period. Urine PCR from antibiotics are additional risk factors for Candida infections. 1
can identify BK virus and distinguish it from hemorrhagic cystitis Clinical manifestations can range from localized mucocutaneous
caused by other infections (e.g., adenovirus) and urotoxic agents (e.g., to disseminated deep-tissue infection. A high index of suspicion is
cyclophosphamide). Quinolone antibiotics suppress BK virus replica- needed for the diagnosis of Candida infections, especially in patients
tion in vivo and in vitro and may have a role as prophylaxis in patients with persistent febrile neutropenia, since blood cultures are usually
1
at high risk for hemorrhagic cystitis. Along with bladder irrigation not very sensitive for isolation and identification of Candida spp.
or forced polyuria intravesical or intravenous cidofovir has been used Oral and esophageal candidiasis frequently occurs in the early post-
1
for the treatment of BK virus hemorrhagic cystitis. Rarely, BK virus transplant period and should be treated aggressively as these can serve
encephalitis has been described postallogeneic HCT. Another as portals for subsequent systemic infection. Venous catheter infec-
polyoma virus, John Cunningham virus, can reactivate in immuno- tions can be difficult to eradicate with antifungal agents alone and
compromised HCT recipients and lead progressive multifocal leuko- necessitate removal of the central line. Patients with candidemia are
encephalopathy, a fatal demyelinating disease of the central nervous also at risk for endovascular infections such as endocarditis, throm-
system. Severe immune deficiency is the primary risk factor for these bophlebitis or endophthalmitis. Hepatosplenic candidiasis is the most
opportunistic infections, and treatment is primarily supportive and common manifestation of disseminated candidiasis, although it is
aimed at an improving immune function, if possible. increasingly rare with widespread use of effective anticandida azoles
HHV-6 can also reactivate from latency post-HCT, with incidence and echinocandins. Specific signs or symptoms related to organ
ranging from 20% in recipients of grafts from matched sibling involvement may be absent and the diagnosis frequently has to be
donors, 46% in URDs, and 69% of recipients of UCB grafts, at a made by abdominal CT scan imaging.
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median of 23 days after HCT. Although reactivation is common, Prophylaxis with fluconazole is recommended in the preengraft-
routine surveillance is not necessary. Rather, preemptive treatment of ment and early postengraftment periods, especially among allogeneic
a high viral load (>25,000 copies) with ganciclovir or foscarnet, in HCT recipients. 1,14,15 In patients who are at high-risk for mold infec-
the presence of symptoms (headache, mental status changes, unex- tions, caspofungin, micafungin, voriconazole, or posaconazole can be
plained fever and/or rash, delayed engraftment or marrow suppres- considered as they have antimold activity. Candida krusei and Candida
sion) should be considered. Reactivation of HHV-6 is common and glabrata are intrinsically resistant to fluconazole and other agents
is rarely associated with poor post-HCT outcomes. (e.g., posaconazole, voriconazole, or micafungin) should be preferred
for prophylaxis in patients colonized with fluconazole-resistant
Candida species. Itraconazole is another active agent, but its use is
Acquired Viral Infections limited by its tolerability, absorption, and toxicities. Cross-resistance
to azoles can occur among Candida species. Antifungal agents for
HCT recipients can be prone to community-acquired respiratory treatment of suspected or known invasive candidiasis include vori-
viral (CRV) infections with influenza, parainfluenza, and respiratory conazole or posaconazole, echinocandins or an amphotericin formu-
syncytial virus (RSV). As upper respiratory infections can progress to lation, especially when infection occurs in the setting of ongoing
more serious lower respiratory infections and certain CRVs can be fluconazole prophylaxis. 15
treated, appropriate diagnostic testing (e.g., nasopharyngeal swabs)
should be considered to identify the virus if possible. Zanamivir or
oseltamivir can be used for chemoprophylaxis and prompt treatment Aspergillus Infections
of influenza. Aerosolized and possibly oral ribavarin can be considered
in patients with RSV infection, especially if they are early post- Most mold infections in HCT recipients are caused by Aspergillus
transplantation or have lower respiratory tract involvement. fumigatus, Aspergillus flavus, and Aspergillus niger, which gain entry
Adenovirus infections can occasionally occur after allogeneic through breakdown of mucosal surfaces in the nasal passages, sinuses,
HCT, especially among recipients of T-cell depleted or mismatched and the lower respiratory tract. Aspergillus infections can occur early
grafts and in patients with GVHD. Novel antivirals are needed to after HCT (during the neutropenic phase) or later, especially com-
treat respiratory viral infections in HCT recipients. An inhaled plicating the immunosuppression associated with acute or chronic
antiviral, DAS181, cleaves sialic acid-containing receptors on the GVHD. Risk factors for Aspergillus infections include allogeneic
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surface of host respiratory epithelial cells, thus preventing influenza (more than autologous) HCT, prolonged neutropenia, and GVHD.
and parainfluenza attachment to and infection of respiratory cells, is Transplantation for diseases that cause extended neutropenia or
currently undergoing clinical study. 12 neutrophil dysfunction pretransplantation (e.g., aplastic anemia and
MDS, Fanconi anemia, or chronic granulomatous disease) also
increases the risk. Prior history of Aspergillus infection has also been
Fungal Infections observed to be a risk factor for recrudescence after HCT.
Aspergillus occurring in the posttransplant setting can be difficult
Invasive fungal infections are among the leading causes of mortality to diagnose premortem. Hence, a high index of suspicion and an
in HCT recipients. The vast majority of fungal infections in this aggressive approach is required to establish its diagnosis and initiate
setting are caused by yeasts (Candida spp.) or molds (Aspergillus spp.). therapy. Since the nasal passages and tracheobronchial tree are the
most common portals of entry for Aspergillus spp., these two sites
are also the most common sites of infection. Sinusitis is frequently
Candida Infections symptomatic and more advanced disease can be associated with
erosion, vascular invasion and necrosis of surrounding structures.
Candida albicans has been the leading cause of yeast infections in Pulmonary manifestations typically include nodular infiltrates,
HCT recipients, but the current widespread use of azole prophylaxis usually distributed along the lung periphery, with pleuritic pain or
in the early transplant period has reduced the overall incidence, but cough as an initial symptom. Frank consolidation (with a halo sign
led to the emergence of a variety of non-albicans species, such as on CT scan) or cavitary lesions can be seen in more advanced stages
Candida tropicalis, Candida krusei and Candida glabrata, as important of pulmonary involvement. Aspergillus has angioinvasive properties
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pathogens. These yeasts are normal inhabitants of the skin, oral and and can present with hemoptysis or with intravascular dissemination
gastrointestinal mucosa which overgrow as normal commensal flora to the skin or brain.
are disrupted by broad-spectrum antibacterials. Breakdown of these Blood cultures have a very low sensitivity in detecting Aspergillus
mucosal surfaces caused by radiation and chemotherapy, compounded and diagnosis has to rely on demonstration of typical fungal