Page 1686 - Hematology_ Basic Principles and Practice ( PDFDrive )

1504 Part VIII Comprehensive Care of Patients with Hematologic Malignancies

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of thyroid cancer. Thyroid cancer develops after a latency of 8.5 for females who received radiation with potential impact to the breast
years and is associated with an excellent outcome. (i.e., radiation doses of 20 Gy or higher to the mantle, mediastinal,
whole lung, and axillary fields): monthly breast self-examination
beginning at puberty; annual clinical breast examinations beginning
Subsequent Central Nervous System Tumors at puberty until age 25 years; and a clinical breast examination every
6 months, with annual mammograms and magnetic resonance images
Meningiomas and gliomas develop after cranial radiation for manage- beginning 8 years after radiation or at age 25 years (whichever occurs
ment of CNS disease among ALL or NHL patients. Gliomas occurred later). Females who received TBI or cumulative chest radiation doses
a median of 9 years from the original diagnosis; for meningiomas, of 10–19 Gy should be counseled regarding the benefits and risks/
the latency is 17 years. For gliomas, the excess RR per Gy was highest harms of screening; if a decision is made to screen, the same recom-
among children exposed at less than 5 years of age. The overall SIR mendations apply as for those women who received radiation doses
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was 8.7 for the gliomas, and the excess absolute risk was 1.9 per 1000 of 20 Gy or higher. Screening of those at risk for early-onset
person-years. 219,230,232,268–272 The risk for second brain tumors demon- colorectal cancer (i.e., radiation doses of ≥30 Gy to the abdomen,
strates a linear relation with radiation dose; the dose–response appears pelvis, or spine) should include colonoscopy every 5 years beginning
weaker for gliomas than for meningiomas. 268,269,273 Possible effects of at age 35 years or 10 years following radiation (whichever occurs
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chemotherapy on the risk of second brain tumors have also been last). Joint recommendations for monitoring long-term survivors of
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described by some. Increased exposure to intrathecal methotrexate HCT by the EBMT/CIBMTR/ASBMT suggest that all recipients of
significantly increases risk of meningioma. 273 HCT should be advised of the risks for subsequent malignancies and
encouraged to perform screening self-examinations, such as breast
Therapy-Related Myelodysplastic Syndrome/Acute and skin examinations. All patients should be advised to avoid high-
risk behaviors, including avoidance of tobacco or excessive unpro-
Myeloid Leukemia tected exposure of skin to ultraviolet light. 83
Several studies have described an increased risk for t-MDS/AML after
autologous HCT, particularly for HL or NHL; pretransplantation Late Mortality
therapy with alkylating agents, topoisomerase II inhibitors, and RT;
use of peripheral blood hematopoietic cells; stem cell mobilization Childhood cancer survivors remain at risk for disease-associated and
with etoposide; difficult stem cell harvests; conditioning with TBI; treatment-associated late mortality, and the excess mortality persists
+
number of CD34 cells infused; and a history of multiple trans- long after diagnosis. 220,280,281 Overall mortality among survivors has
plants. 224,226 Thus t-MDS/AML after autologous HCT is the result been described to be eightfold that of the general population. Recur-
of cumulative toxicity that includes pre-HCT chemotherapy (alkyl- rent disease is the most common cause of premature death. Increases
ators and topoisomerase II inhibitors), topoisomerase II inhibitors in cause-specific mortality are seen for deaths due to SMNs, cardiac,
used for stem cell mobilization, and transplantation-related condi- and pulmonary causes. Extended follow-up of these cohorts demon-
tioning. The diagnosis of t-MDS/AML after autologous HCT confers strates changing patterns of cancer-specific mortality with increasing
a uniformly poor prognosis, with a median survival of 6 months in time from diagnosis. 27,280 Thus excess risk for deaths from recurrence
patients treated with conventional chemotherapy. declines with time, while the excess risk for deaths from SMNs and
cardiovascular causes increases; subsequent to 45 years from diagnosis,
recurrence accounted for only 7% of the excess number of deaths
Subsequent Skin Cancer while SMNs and cardiovascular causes accounted for 51% and 26%
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of the excess number of deaths respectively. Childhood cancer
Among allogeneic HCT recipients, the incidence of BCCs is 6.5% survivors are at a 15-fold increased risk of SMN-related deaths, 8.8-
at 20 years, whereas the incidence for squamous cell carcinoma (SCC) fold increased risk of pulmonary deaths, and 7-fold increased risk of
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is 3.4%. TBI increases the risk for BCC, especially in younger death due to cardiac causes when compared with the general popula-
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patients. SCC risk is increased among patients with acute GVHD, tion. The high burden of morbidity carried by HCT recipients can
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whereas chronic GVHD is associated with both BCC and SCC. result in premature death. Mortality rates are fourfold to ninefold
Immunologic alterations predispose patients to SCC of the buccal higher than in the expected population for at least 30 years following
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cavity particularly, hence the association with chronic GVHD. In HCT, producing an estimated lower life expectancy of 30% compared
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patients with prolonged immunosuppression, oncogenic viruses such with the general population, regardless of current age. Relapse of
as human papillomavirus contribute to SCC of the skin and buccal primary disease and chronic GVHD are the main causes of premature
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mucosa. BCC is one of the most frequent SMNs in childhood death. Nonrelapse-related mortality is greater among patients who
cancer survivors. 219,276 Childhood cancer survivors are at a fivefold are over 18 years of age when undergoing HCT, as well as among
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increased risk of NMSC compared with the general population. those with chronic GVHD. Compared with the general population,
Ninety percent of patients have previously received RT; 90% of allogeneic HCT recipients are 3.6 times more likely to die of SMNs,
tumors occur within the radiation field. Radiation is associated with 15.1 times more likely to die of pulmonary complications, and 2.3
a sixfold increase in risk. 278 times more likely to die of a cardiac compromise. However, the
conditional survival probability at 10–20 years after allogeneic HCT
exceeds 80% for those individuals who were alive and disease free
Recommendations for Screening and Follow-Up 2–5 years after HCT. 283,284 On the other hand, autologous HCT
recipients demonstrate a conditional 5-year survival that approaches
The elevated risk of breast cancer noted among survivors of child- 75% among those who have survived 2 or more years and approaches
hood and adolescent cancers supports the importance of evidence- 90% among those who have survived 10 years after HCT. Among
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based screening guidelines for this high-risk group. Because those who survive the first 10 years, nonrelapse-related mortality
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outcome after breast cancer is closely linked to stage at diagnosis, exceeds relapse-related mortality. Primary disease and subsequent
close surveillance resulting in early diagnosis should confer survival malignancies are the most common cause of death. 227
advantage. Mammography, the most widely accepted screening tool
for breast cancer in the general population, may not be the ideal
screening tool by itself for radiation-related breast cancers, occurring Psychosocial Effects
in relatively young women with dense breasts, hence the American
Cancer Society recommends including adjunct screening with mag- Survivors of hematopoietic malignancies are at risk for adverse psy-
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netic resonance imaging. Thus the following are recommendations chosocial outcomes that may affect their overall quality of life,