Page 1683 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 93 Late Complications of Hematologic Diseases and Their Therapies 1501

increased treatment intensity, younger age at treatment exposure, and survivors had mild or greater deficits, a proportion that was signifi-
female sex. 169,172–176 Neurocognitive deficits usually become evident cantly higher than that among the controls (17.5%). Neurocognitive
within 1–2 years following cranial radiation and are progressive in sequelae among adults undergoing HCT include slowed reaction
nature. The decline over time is typically reflective of the child’s time, reduced attention and concentration, and difficulties in reason-
failure to acquire new abilities or information at a rate similar to ing and problem solving, memory impairment, problems with execu-
peers, rather than because of a progressive loss of skills and knowledge. tive functioning and processing speed, and cognitive impairment. 186–189
Survivors of childhood ALL are at risk for neurocognitive problems, Reduced memory function is associated with older age, longer interval
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generally characterized by reduced attention, processing speed, execu- since HCT, chronic GVHD, and long-term cyclosporine use.
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tive function, and global intellectual function. Affected children Other predictors include fatigue and poor physical functioning.
with information-processing deficits exhibit academic difficulties and Lower education level and poorer social functioning appear to impact
are prone to problems with receptive and expressive language, atten- cognitive performance. It is therefore prudent to query post-HCT
tion span, and visual and perceptual motor skills. The deficits patients regarding perceived deficits in neuropsychological function-
observed after chemotherapy alone are restricted to attention, execu- ing and to refer patients with these problems to a neuropsychologist
tive function, and complex fine-motor functioning; global intellectual who is experienced in the follow-up care of HCT patients.
function is relatively preserved. Neurocognitive function in long-term The COG LTFU guidelines recommend a baseline neuropsycho-
survivors of childhood cancer appears particularly vulnerable to the logical evaluation for patients who received therapy that may affect
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effects of fatigue and sleep disruption. The neurocognitive impair- neurocognitive function. This should be repeated as clinically indi-
ment observed in survivors of childhood ALL persists into adulthood; cated and at key transition points (e.g., transitioning from grade
this impairment is associated with reduced educational attainment school to middle/high school); an annual assessment of their voca-
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and unemployment, independent living, and health care use. 179 tional or educational progress should also be monitored. Joint rec-
A spectrum of neuropathological syndromes related to leukoen- ommendations for monitoring long-term survivors of HCT by the
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cephalopathy may occur in survivors of childhood hematologic EBMT/CIBMTR/ASBMT suggest that all recipients of HCT should
malignancies, including radionecrosis, necrotizing leukoencephalopa- undergo clinical evaluation for symptoms or signs of neurologic
thy, mineralizing microangiopathy and dystrophic calcification, cer- dysfunction at 1 year after HCT. Additional tests such as neuropsy-
ebellar sclerosis, and spinal cord dysfunction, manifesting clinically chologic testing may be warranted for those with symptoms or
as ataxia, spasticity, dysarthria, hemiparesis, or seizures. Imaging signs. 83
abnormalities may or may not be evident in these patients. Leuko-
encephalopathy has been primarily associated with methotrexate-
induced injury of white matter. However, cranial irradiation may play OTHER TOXICITIES
an additive role through disruption of the blood–brain barrier, allow-
ing greater exposure of the brain to systemic therapy. Although some Ocular Effects
abnormalities have been detected by diagnostic imaging studies, the
abnormalities observed have not been well demonstrated to correlate Survivors of hematologic malignancies are at risk for the development
with clinical findings and neurocognitive status. In a recent study, of cataracts as a consequence of therapy with corticosteroids, cranial
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brain grey and white matter volume and diffusion tensor imaging was irradiation, 191,192 TBI, or busulfan. In a cohort of childhood ALL
compared between survivors treated with and without radiation and survivors who were treated with chemotherapy with or without
healthy controls. ALL survivors had a lower ratio of white matter to cranial radiation and received a mean cumulative prednisone equiva-
2
intracranial volume in frontal and temporal lobes compared with lent dose of 5.2 gm/m , cumulative incidence of cataracts was 26 ±
control subjects. ALL survivors treated with chemotherapy alone 8.1% at 25 years; cranial radiation was the only significant risk
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performed worse in processing speed, verbal selective reminding, and factor. Belkacemi et al studied 1063 patients who underwent
academics compared with population norms but performed better HCT for acute leukemia; the overall 10-year incidence of cataracts
than survivors treated with cranial RT on verbal selective reminding, in this group of patients was 50%. Single-dose TBI was associated
processing speed, and memory span. There were significant associa- with a 60% incidence of cataracts, fractionated TBI was associated
tions between neurocognitive performance and brain imaging, par- with a 43% incidence for those receiving six or fewer fractions, and
ticularly for frontal and temporal white and grey matter volume. ALL a 7% incidence was reported for those receiving more than six frac-
survivors treated with chemotherapy alone demonstrated significant tions. Factors independently associated with an increased risk for
long-term differences in neurocognitive function and altered neuro- cataract formation in this cohort were older age (>23 years), alloge-
anatomical integrity. 181 neic bone marrow transplantation, higher dose rate (>0.04 Gy/min),
Long-term survivors of childhood HL may also be at risk for and steroid administration for longer than 100 days. Xerophthalmia
neurocognitive impairment. This is associated with radiologic indices may also occur as a late complication because of decreased lacrima-
suggestive of reduced brain integrity and occurs in the presence of tion resulting from damage to the lacrimal gland during radiation or,
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symptoms of cardiopulmonary dysfunction. 182 in HCT patients, from chronic GVHD. Westeneng et al fol-
Many survivors of adult-onset hematologic malignancies also lowed 101 adults up to 24 months after allogeneic HCT and reported
experience impairments of neurocognitive function, including ocular GVHD in 54% of patients, manifesting mainly as xerophthal-
memory loss, distractibility, and difficulty performing multiple tasks. mia and conjunctivitis; blepharitis and uveitis were encountered less
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These patients may also concurrently suffer from mood disturbances often. Tabbara et al reported major ocular complications in 13%
and symptoms that compromise their ability to function adequately, of 620 patients (age range: 9–65 years) after allogeneic HCT; com-
including fatigue and pain. 183 plications included chronic ocular GVHD, corneal ulcers, cataracts,
HCT survivors are also at risk for neurocognitive late effects. glaucoma, cytomegalovirus retinitis, fungal endophthalmitis, and the
Prospective, longitudinal evaluations of intellectual and adaptive acquisition of allergic conjunctivitis from atopic donors.
functioning of children receiving a transplant have revealed declines
in intellectual function, particularly among those less than 6 years of
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age at transplantation. Among the adult populations, a prospective Audiologic Effects
longitudinal study design was used to describe neurocognitive func-
tion over 5 years after allogeneic HCT for cancer survivors and Survivors of hematologic malignancies who received platinum che-
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compared with matched controls. Survivors recovered significant motherapy, those who had cranial irradiation at a young age (especially
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cognitive function from posttransplantation (80 days) to 5 years in during infancy), and those who required supportive therapy with
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all tests except verbal recall. Between 1 and 5 years, verbal fluency aminoglycoside antibiotics are at risk for therapy-related hearing
improved, as did executive function, but motor dexterity did not, loss. Hearing loss associated with ototoxic agents is generally sensori-
remaining significantly below population norms. Over 40% of the neural in origin and is usually irreversible. Although a low incidence