Page 1898 - Hematology_ Basic Principles and Practice ( PDFDrive )

1680 Part X Transplantation

TABLE Screening Guidelines for Common Cancers After differentiate into effector cells and recruit mononuclear phagocytes
109.6 Hematopoietic Cell Transplantation and neutrophils and possibly NK cells which ultimately yield host
tissue destruction, primarily through apoptosis. T-cell depletion of
Site Screening Recommendations the graft reduces the risk of acute and chronic GVHD, albeit at the
Breast Mammogram annually starting at age 40 years; in women cost of increasing risks of disease relapse caused by blunting of the
who have received ≥20 Gy to the chest region begin at graft-versus-tumor response. Alternative mechanisms may also be
age 25 years or 8 years after radiation, whichever is later involved in the pathogenesis of chronic GVHD including autoreac-
tivity, loss of self-tolerance and B-cell dysregulation. 42
Cervix Pap smear every year (for regular Pap test) or every 2 years
(for liquid-based Pap test); may screen every 2–3 years
after 30 years of age if patient has three consecutive Acute Graft-Versus-Host Disease
normal tests
Colorectal Beginning at age 50 years, fecal occult blood annually and/ Risk Factors and Clinical Features
or flexible sigmoidoscopy every 5 years, or double
contrast barium enema every 5 years, or colonoscopy Up to 50% of patients receiving HLA-identical sibling-donor and up
every 10 years; certain high-risk groups (e.g., patients to 90% of patients receiving URD HCT develop acute GVHD.
with inflammatory bowel disease) may need earlier Donor-recipient HLA disparity is the most important risk factor for
initiation and more frequent screening acute GVHD. Additional risk factors include increasing recipient and
Lung Yearly pulmonary exam with imaging as appropriate donor age, use of alloimmunized donors such as parous women, and
HCT from unrelated instead of sibling donors. Among recipients of
Oral Yearly oral cavity exam
UCB, acute GVHD occurs in 20% to 60% of patients; incidence of
Thyroid Yearly thyroid exam acute GVHD, though of only moderate severity, may be higher
Skin Yearly skin exam among recipients of double UCB transplantation. 43
Pap, Papanicolaou. Skin, liver, and gastrointestinal tract are the most common sites
of GVHD. Acute GVHD of the skin is characterized by a maculo-
papular rash that, when severe, can lead to bullae or even resemble
toxic epidermal necrolysis. Hepatic involvement manifests as choles-
and presence of medical late effects. Although chronic GVHD is a tatic hepatitis with marked elevation of serum bilirubin and alkaline
strong predictor of poor QOL, the overall health and functional phosphatase, but usually only mild transaminase alterations. In the
status improves with resolution of GVHD and eventually reaches a intestine, upper gastrointestinal tract GVHD can produce nausea,
level comparable with that seen in patients with no history of chronic vomiting and anorexia, whereas small bowel and colon GVHD
GVHD. Gender specific differences in QOL have also been observed produces large volume secretory diarrhea. The diagnosis is clinical
with females more likely to report impairments in psychologic and but frequently requires histologic confirmation to distinguish it from
sexual domains. Cognitive deficits, particularly involving executive other frequent toxicities in the early posttransplantation period (e.g.,
function, memory and motor skills, have been reported in 30% to hypersensitivity drug rash, drug-induced cholestasis, SOS, or infec-
60% of HCT survivors. The risk of developing these neuropsycho- tious enteritis). The histologic hallmark of acute GVHD is apoptosis
logical sequelae is increased in patients receiving transplantation at of the proliferative and regenerative cell layer of the epidermis,
an older age, although a recent prospective study did not identify any intestinal or biliary epithelium.
association of cognitive deficit with intensity of conditioning, cyclo- Acute GVHD is graded according to organs involved (skin, liver
sporine, length of inpatient stay, or the development of GVHD. 40 or gastrointestinal tract) and the extent (stage) of each organ involve-
ment. Mild to moderate (grade I or II) GVHD is characterized by
limited organ involvement and carries an excellent prognosis. Severe
GRAFT-VERSUS-HOST DISEASE (grade III or IV) GVHD has extensive multiorgan involvement with
significant morbidity and poor survival, commonly evolves to chronic
GVHD is a clinicopathologic syndrome initiated by T cell–mediated GVHD and is associated with an increased risk of secondary oppor-
alloreactivity that commonly occurs as a complication of allogeneic tunistic infections.
HCT and leads to significant morbidity and mortality (also see
Chapter 108). It is usually classified as acute GVHD or chronic
GVHD. Acute GVHD may be further characterized as classic acute Prophylaxis of Graft-Versus-Host Disease
GVHD (onset ≤100 days) and persistent, recurrent or late-onset
acute GVHD (onset >100 days). In the absence of clinical features The most effective techniques for GVHD prevention have involved
characteristic of acute GVHD, chronic GVHD is called classic ex vivo depletion of donor T-lymphocytes, most often coupling
chronic GVHD. When features of both acute and chronic GVHD immunologic recognition (monoclonal anti–T-cell antibodies) with
appear together, it is classified as overlap syndrome, based upon a depletion techniques (immunomagnetic beads, complement cytotox-
consensus conference proposed definition. Recent revisions lend icity or toxin immunoconjugates). Immunomagnetic selection of
lesser support for maintaining this overlap syndrome as an indepen- CD34+ cells from the graft (negatively selecting out T cells) has been
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dent category. 41 used more widely in recent years. Although vigorous T-cell deple-
Current understanding of the pathogenesis of GVHD suggests tion prevents acute GVHD, it also may increase the risks of graft
that alloreactive donor T-lymphocytes recognize histocompatibility failure and neoplastic relapse after transplantation.
antigens on host cells and initiate secondary inflammatory injury, Pharmacologic immunosuppression administered in the first
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leading to the clinical symptoms of GVHD. This alloreactive several months after transplantation can prevent or blunt the initiat-
response can be initiated or accelerated by conditioning regimen- ing T-cell recognition and proliferative response that triggers GVHD
induced tissue injury with release of proinflammatory cytokines, and can allow development of immune system tolerance and complete
primarily IL-1 and TNF-α. GVHD is more frequent and more severe lymphohematopoietic chimerism. Methotrexate, corticosteroids,
in recipients of partially matched transplants, suggesting that major ATG, cyclosporine, tacrolimus, MMF and sirolimus have been used
histocompatibility complex encoded molecules may be the prime for prophylaxis of GVHD and have successfully reduced both the
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antigenic targets initiating the alloreactive T-cell response. Minor frequency and the severity of clinical GVHD. Despite the potential
histocompatibility antigens also play an important role in its patho- role of inflammatory cytokines in initiation and amplification of
genesis, especially in HLA-identical sibling donor grafts. Activated GVHD, clinical blockade of IL-1, IL-2, or TNF-α has not been
donor-derived T-cells produce IL-2 and interferon-γ, expand and effective in GVHD prophylaxis. Current therapies being tested in