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CHAPTER 94: Hematopoietic Stem Cell Transplantation and Graft-Versus-Host Disease 889

Infection: Infections of the liver may include those due to bacteria, fun- Chronic kidney disease (CKD) is one of the long-term complica-
gus, or virus. Bacteremias due to resistant gram-negative bacteria and tions of HSCT. Although now well recognized, its incidence, etiology,
gram-positive bacteria such as VRE may result in liver abscesses and clinical course remain controversial. While it may develop as a
and should be treated with antibiotics appropriate to the sensitivities. consequence of AKI, it has also been associated with older age, lower
Fungal infections of the liver may be due to yeast or molds. Yeast infec- pretreatment glomerular filtration rate, female gender, use of TBI and
tions have become less common since the practice of administering fludarabine in the conditioning regimen, GVHD, use of calcineurin
prophylaxis with antifungal agents such as fluconazole. The develop- inhibitors (CNI), and a variety of other factors. The cumulative inci-
ment of abscesses on imaging studies is best addressed with a CT-guided dence in HSCT patients for development of moderate and severe CKD
needle biopsy for culture. B-glucan and galactomannan are two serologic has been reported to be 12% to 29% and 3% to 3.6%, respectively, in
studies, which may be helpful in diagnosing invasive fungal infections retrospective cohort analyses. A recent systematic review reported an
when biopsy is not safe. If biopsy is not possible, antifungal prophylaxis incidence of 16.6%. In older patients undergoing allogeneic T cell–
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should be advanced to treatment dosing, and should include an agent depleted HSCT, the incidence of sustained CKD was almost 50% at
of broader spectrum of activity. Classes of antifungal agents currently 2 years even in the absence of calcineurin inhibitors. Sixteen percent of
available include liposomal amphotericin B, azoles, and echinocandins. the patients in the same study, all in the group that received TBI, devel-
Infectious disease consultation may be helpful in determining the appro- oped thrombotic microangiopathy, a more serious renal complication of
priate choice for a particular pathogen. transplantation. The clinical manifestations of this thrombotic micro-
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Viruses are less often the etiology of liver infections. Patients who angiopathy include renal insufficiency, microangiopathic hemolytic
are known to be hepatitis B antibody positive prior to transplant should anemia, thrombocytopenia, hypertension, and in some cases neurologic
undergo evaluation for viral load and if negative are managed with deficits. Although CKD is a slowly progressive disorder, the critical care
entecavir for prophylaxis throughout the transplant and posttransplant physician may be called upon to intervene in the setting of an acute
period until immune recovery as these patients are at risk of reactiva- deterioration due to infection or other precipitating event. Avoidance of
tion. For those patients with a viral load, infectious disease and hepa- nephrotoxins and close fluid and electrolyte management to maintain
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tology consult are obtained prior to proceeding to stem cell transplant adequate renal perfusion may help avoid the need for hemodialysis or
for assessment of eligibility for antiviral treatment and to proceed to renal replacement therapy.
transplant. Those patients who are known to be infected with hepatitis
C also undergo infectious disease and hepatology consultation for evalu- REJECTION/GRAFT FAILURE
ation of viral load, eligibility for treatment with antiviral agents, and
eligibility for HSCT. In a patient with known hepatitis B or C infection Rejection of the graft is an immune-mediated process that results from
and increasing transaminases, viral load should be monitored and if inadequate suppression of the patient’s immune system during the
increasing, should be considered for antiviral therapy. Management of conditioning. Immunologically competent cells of the patient (host)
such patients in the critical care setting should include a consultation destroy the transplanted stem cells from the donor—it is a form of “host
with the infectious disease service. Adenovirus in a patient with known versus graft”—HVG. Patients who fail to demonstrate hematologic
viremia can involve the liver and can result in fulminant hepatitis and recovery by day 30 or those who begin count recovery and subsequently
liver failure. Although there is no specific therapy, in vitro data showing lose their peripheral blood counts should be evaluated for rejection.
activity of cidofovir have led to its use in vivo. The mortality rate for a Evaluation should include a bone marrow aspiration and biopsy with
fulminant disseminated viremia is high. assessment of status of disease, cellularity and chimerism (quantita-
tion of donor and host components in the marrow). If there are still
RENAL COMPLICATIONS adequate peripheral blood counts, immunophenotyping of peripheral
blood mononuclear cells, as well as peripheral blood chimerism of
The renal complications associated with HSCT are generally divided polymorphonuclear leukocytes, T and B cells should be obtained. A
into early and late, resulting in acute and chronic renal insufficiency. predominance of host cells in these studies should raise concern for
The early complications are often related to the conditioning used for rejection. Studies suggesting rejection would require treatment of the
the transplant and to the medications needed for immunosuppression to patient with additional immunosuppressive conditioning and a second
prevent GVHD in the allogeneic setting. Several studies have reported graft. The risk of rejection is highest in patients who have been very
the incidence of acute kidney injury (AKI) according to the Acute heavily transfused prior to the transplant, those who have received
Kidney Injury Network (AKIN) or Risk, Injury, Failure, Loss, End- unrelated or mismatched grafts, and those who receive umbilical cord
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stage kidney disease (RIFLE) criteria in patients undergoing HSCT. blood transplants due to the naïve nature of the cord blood immune
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The incidence of acute renal failure during HSCT has been reported to system. Rejection is only observed with allogeneic HSCT and occurs
be in the 30% to 50% range. 74,75 Causes of renal insufficiency posttrans- more frequently when reduced intensity conditioning (RIC) is used
plant include side effects of the conditioning, volume depletion due to compared to myeloablative conditioning.
nausea, vomiting, and diarrhea, hypotension and sepsis, nephrotoxic Graft failure is a nonimmune-mediated process that results from
medications including aminoglycoside antibiotics, amphotericin, and inadequate stem cell numbers or injury to the stem cells from medi-
calcineurin inhibitors, and VOD. Mortality rates for patients with AKI cations or infection resulting in myelosuppression. Evaluation of this
increase with the severity of the renal insufficiency. One of the major condition is similar to that for rejection; however, the studies would
cofactors in poorer outcome of patients with AKI is the limitation it show full donor chimerism in the setting of a hypoplastic or aplastic
imposes in adequately administering GVHD prophylaxis with calci- bone marrow. Treatment would be infusion of a second graft without
neurin inhibitors. The inability to use calcineurin inhibitors frequently the need for additional conditioning. In order to avoid additional risk of
leads to the development of GVHD, manifested as nausea, vomiting, and GVHD, a T cell–depleted stem cell boost can be considered, merely to
diarrhea, and the need for additional immunosuppressives, resulting in provide additional CD34+ stem cells alone. Graft failure can be seen in
infections, sepsis, hypotension, and the need for more antimicrobials. autologous or allogeneic HSCT.
ICU management is frequently needed for these patients with severe The risk of death from graft rejection or graft failure is high due to the
forms of AKI, especially those with higher grade acute GVHD and those prolonged period of neutropenia and the high risk of a life-threatening
with sepsis. Studies in ICU patients have consistently shown high rates infection. In the case of cord blood transplants with graft failure, the source
of mortality in patients requiring hemodialysis early posttransplant. As of stem cells for a second transplant is usually another cord blood. Studies
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expected, the incidence of AKI is generally less for autologous compared that report using the same adult donor or a second adult donor have failed
to allogeneic HSCT patients. to consistently demonstrate an advantage of one over the other. 22,23

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