Page 1887 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 109

COMPLICATIONS AFTER HEMATOPOIETIC CELL

TRANSPLANTATION

Shernan G. Holtan, Navneet S. Majhail, and Daniel J. Weisdorf

The high-dose therapy used in hematopoietic cell transplantation reconstitution and the lack of immunosuppressive drug therapy.
(HCT) results in toxicities induced directly by the treatment and Immune reconstitution can take up to 2 years to fully recover in
secondarily by the prolonged immunodeficiency and extended allogeneic HCT recipients and may be incomplete because of ongoing
recovery process. Identification of risk factors for particular complica- GVHD. Patients with chronic GVHD can be functionally asplenic
tions allows the design of risk-specific supportive care regimens that and be at risk for infections by encapsulated bacteria including pneu-
may reduce the morbidity and mortality accompanying transplanta- mococcus or H. influenza. In addition, chronic GVHD patients on
tion. HCT-related complications can be broadly classified into long-term immunosuppression remain susceptible to fungi (Aspergil-
infections, early noninfectious complications (within 3 months of lus spp., Candida spp. and Pneumocystis jiroveci) and viruses including
HCT), late noninfectious complications (after 3 months of HCT), CMV and varicella zoster virus (VZV). Additional factors that can
and graft-versus-host disease (GVHD) (Table 109.1). delay immune reconstitution include donor-recipient HLA disparity,
with depletion of T cells either through ex vivo graft manipulation or
in vivo with antithymocyte globulin (ATG) or alemtuzumab. URDs
INFECTIONS and possibly UCB as a graft source may also augment infection risks.
2,3
Antimicrobial prophylaxis should continue beyond the initial post-
Infections are among the most frequent causes of nonrelapse mortal- transplant period, typically for at least 3–6 months after cessation of
ity in HCT recipients and cause significant morbidity, both in the all immunosuppression, especially in patients being treated for chronic
early and late transplant period (Table 109.2). Immune defects occur- GVHD. Some centers use total T cell (CD3+) and particularly CD4
ring in the posttransplant period can be divided into predictable cell levels as surrogate markers of T-cell recovery and to guide decisions
phases based on time from engraftment (sustained absolute neutro- regarding the intensity and duration of infection surveillance and
phil count >500/µL), with characteristic infections in each phase antimicrobial prophylaxis. Supplemental intravenous immunoglobu-
(Fig. 109.1). Antimicrobial prophylaxis regimens tailored to address lin (IVIg) has been considered for patients with persistent hypogam-
the risk of specific infections during these time periods are effective maglobulinemia (immunoglobulin G [IgG] levels <400 mg/dL), but
in limiting the incidence of posttransplant opportunistic infections its prophylactic use is costly, does not prolong survival or prevent late
(Table 109.3). Evidence-based guidelines for preventing infectious infections, and may impair humoral immune reconstitution. Patients
complications in HCT recipients have been published and can be with GVHD and those with indwelling venous access undergoing
used as a reference for determining infection risk and assigning endoscopy or dental procedures should receive antibiotics for endo-
antimicrobial prophylaxis for individual patients. 1 carditis prophylaxis. Published guidelines are available for immuniza-
Engraftment generally occurs within 7–14 days in autologous and tion of HCT survivors (Table 109.4). 1
10–28 days in allogeneic HCT recipients. Recipients of grafts from Based on the type and dose of conditioning chemotherapy and
unrelated donors (URD) or umbilical cord blood (UCB) tend to radiation, recipients of nonmyeloablative or reduced-intensity condi-
engraft later compared with sibling donors; marrow grafts recover a tioning (NMA/RIC) regimens can exhibit varying degrees of myelo-
4
bit more slowly than filgrastim-mobilized peripheral blood stem cell suppression. The incidence of bacterial infections is lower in NMA/
(PBSC) grafts. Importantly, up to 5% of URDs (or potentially greater RIC recipients because of the shorter duration of posttransplant
if human leukocyte antigen [HLA]-mismatched) and approximately neutropenia. However, the degree of lymphodepletion tends to be
10% of UCB grafts may fail to engraft leading to prolonged neutro- comparable with that seen with myeloablative regimens and the risks
penia and extended transfusion dependence. In addition to neutro- of invasive aspergillosis and CMV reactivation remain unchanged.
penia, the main risk factors for infection during this preengraftment Among UCB HCT recipients, neutrophil engraftment and
phase are disruption of mucocutaneous barriers and indwelling immune reconstitution can be delayed and a higher incidence of
venous catheters. Bacterial infections can occur in up to 30% of bacterial and viral infections in the early posttransplant period has
transplant recipients during this initial period and usually arise from been reported. Overall, the risk of serious infections among children
normal flora of the skin (coagulase-negative Staphylococcus), orophar- receiving UCB grafts is comparable with that of URD marrow and is
2
ynx, and gastrointestinal tract (Streptococcus viridans, Enterococcus lower than that of a T-cell depleted graft source. Among adult UCB
spp. and enteric gram-negative bacilli). Colonizing yeasts or inhaled HCT recipients, the incidence of infections is higher in the early
airborne molds also invade because of neutropenia and disruption of posttransplant period; however, infections do not compromise the
normal host flora and can lead to systemic mycotic infections (most risks of overall and nonrelapse mortality compared with URD HCT. 2
often candida or aspergillus spp.) in 10% to 15% of patients. Reac- The approach to managing posttransplant infections is generally
tivation of latent herpes viruses (herpes simplex, cytomegalovirus similar to that for infections in patients with cancer, especially acute
[CMV] or human herpesvirus [HHV]-6 can occur, but may be leukemia (Chapter 89). However, certain infections, particularly
contained by antiviral prophylaxis. caused by viruses and fungi, are more common in the HCT popula-
The predominant immunologic defects seen in the early and late tion and are discussed in further detail here.
postengraftment period are impairments of cellular and humoral
immune systems. This underlying severe immune dysfunction is
enhanced and prolonged by acute and chronic GVHD and by corti- Febrile Neutropenia
costeroids and the immunosuppressive agents used for GVHD pre-
vention and treatment. The incidence of late opportunistic infections A large proportion of patients develop fever in the early posttrans-
is much lower in autologous HCT recipients because of faster immune plantation period though an infectious pathogen is identified in only

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